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Topical gel for epidermolysis bullosa shows ongoing benefit
GLASGOW, Scotland – the phase 3 safety and efficacy study of the treatment.
Over 200 patients from the trial, including 105 who began treatment with a control gel, continued taking oleogel-S10 after 90 days. The current interim analysis at 12 months indicates there was a 55% reduction in the proportion of the body affected, compared with baseline.
Moreover, reductions in skin activity scores seen in the double-blind phase of the trial were maintained during the open-label extension. About 6% of patients experienced adverse events that led to withdrawal from the study.
The results show that oleogel-S10 was associated with “accelerated wound healing,” said study presenter Tracey Cunningham, MD, chief medical officer, Amryt Pharmaceuticals DAC, Dublin, which is developing the topical agent. “There were no new safety signals with this longer exposure to oleogel-S10, and patients had sustained improvement in wound burden,” she added.
The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 6.
In April, European Medicines Agency recommended approval of oleogel-S10 for the treatment of partial-thickness skin wounds associated with dystrophic and junctional EB for patients aged 6 months and older.
However, just a month earlier, the U.S. Food and Drug Administration declined to approve the topical agent for use in EB, even after it extended its review by 3 months to include additional analyses of data previously submitted by the company.
In the post-presentation discussion, Dr. Cunningham said that the FDA had “not been satisfied at this point with the information that we have given them,” adding, “We don’t agree with the decision, and we will be appealing.”
Raman K. Madan, MD, a dermatologist at Northwell Health, Huntington, New York, who was not involved in the study, said that the reductions in wound healing seen in the study are “meaningful” and that the numbers represent a “big breakthrough.”
He told this news organization that there are “very few products on the market” for EB and that having an option for patients “would be amazing.”
“The big issue here would be cost and coverage for patients,” he said. If approved, “hopefully” it will be affordable, he added.
Dr. Madan noted that from his perspective, the majority of the reactions to the topical gel were “mild,” and there are “a lot of confounding factors” underlying the number of serious adverse events. “These patients with epidermolysis are prone to some of these issues regardless of treatment,” he said.
During her presentation, Dr. Cunningham noted that EB is a rare, debilitating condition that is characterized by varying degrees of skin fragility, blisters, and impaired wound healing that in turn lead to serious complications that affect quality of life.
While wound management is a “fundamental priority” for patients living with EB, she said, there is a “high, unmet” clinical need.
To those ends, EASE was the largest randomized controlled phase 3 efficacy and safety study in EB. In the study, 252 patients were allocated to receive oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing.
The double-blind phase of the trial met its primary endpoint: A higher proportion of patients who were given oleogel-S10 achieved first complete closure of the EB target wound by day 45, compared with patients who were given control gel, at 41.3% versus 28.9%. This equated to a relative risk of wound closure by day 45 of 1.44, or an odds ratio of 1.84 (P = .013).
However, as reported at the time by this news organization, the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of oleogel-S10 patients achieving wound closure, versus 43.9% of those in the control group.
Dr. Cunningham discussed the open-label extension, which involved 205 patients from the double-blind phase (mean age, of 16.3 years) treated with oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing for 24 months.
In presenting the results of the first 12 months of the open-label extension, she said that oleogel-S10 led to “consistent” reductions in the body surface area percentage (BSAP) affected by EB. The overall reduction from baseline was 55% after receiving treatment for 15 months.
Between day 90 and month 12 of the open-label extension, the absolute BSAP was reduced from 7.4% to 5.4% for patients who had received oleogel-S10 from the start of the study. For those who started in the control group and then switched to the oleogel-S10 arm during the open-label extension, the reduction was from 8.3% to 6.4%.
Dr. Cunningham pointed out that a 1% reduction in BSAP equates approximately to the palmar surface of the hand.
Scores on the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Skin activity subscale indicated that the reductions achieved in the double-blind phase of the trial were maintained.
Among patients who received oleogel-S10 from the start of the trial, EBDASI Skin scores were reduced from 19.6 at baseline to 13.5 at 12 months’ follow-up in the open-label extension. The reduction was from 19.6 to 13.5 for those who began the trial taking control gel.
Dr. Cunningham showed that adverse events of any grade were seen in 72.0% of patients who began taking oleogel-S10 at the start of the trial and in 69.5% of those who began the trial taking control gel.
Serious adverse events were recorded in 23.0% and 20.0% of patients, respectively, while 6.0% of those who initially received oleogel-S10 and 6.7% of those initially assigned to control gel experienced adverse events that led to study withdrawal during the open-label phase.
The most frequently reported adverse events in the open-label extension were wound complications, seen in 39.5% of patients; anemia, seen in 14.1%; wound infection, seen in 9.3%; pyrexia, seen in 8.3%; and pruritus, seen in 5.9%. No more details regarding adverse events were provided.
The study was funded by Amryt Pharmaceuticals DAC. Dr. Cunningham is an employee of Amryt Pharmaceuticals. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
GLASGOW, Scotland – the phase 3 safety and efficacy study of the treatment.
Over 200 patients from the trial, including 105 who began treatment with a control gel, continued taking oleogel-S10 after 90 days. The current interim analysis at 12 months indicates there was a 55% reduction in the proportion of the body affected, compared with baseline.
Moreover, reductions in skin activity scores seen in the double-blind phase of the trial were maintained during the open-label extension. About 6% of patients experienced adverse events that led to withdrawal from the study.
The results show that oleogel-S10 was associated with “accelerated wound healing,” said study presenter Tracey Cunningham, MD, chief medical officer, Amryt Pharmaceuticals DAC, Dublin, which is developing the topical agent. “There were no new safety signals with this longer exposure to oleogel-S10, and patients had sustained improvement in wound burden,” she added.
The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 6.
In April, European Medicines Agency recommended approval of oleogel-S10 for the treatment of partial-thickness skin wounds associated with dystrophic and junctional EB for patients aged 6 months and older.
However, just a month earlier, the U.S. Food and Drug Administration declined to approve the topical agent for use in EB, even after it extended its review by 3 months to include additional analyses of data previously submitted by the company.
In the post-presentation discussion, Dr. Cunningham said that the FDA had “not been satisfied at this point with the information that we have given them,” adding, “We don’t agree with the decision, and we will be appealing.”
Raman K. Madan, MD, a dermatologist at Northwell Health, Huntington, New York, who was not involved in the study, said that the reductions in wound healing seen in the study are “meaningful” and that the numbers represent a “big breakthrough.”
He told this news organization that there are “very few products on the market” for EB and that having an option for patients “would be amazing.”
“The big issue here would be cost and coverage for patients,” he said. If approved, “hopefully” it will be affordable, he added.
Dr. Madan noted that from his perspective, the majority of the reactions to the topical gel were “mild,” and there are “a lot of confounding factors” underlying the number of serious adverse events. “These patients with epidermolysis are prone to some of these issues regardless of treatment,” he said.
During her presentation, Dr. Cunningham noted that EB is a rare, debilitating condition that is characterized by varying degrees of skin fragility, blisters, and impaired wound healing that in turn lead to serious complications that affect quality of life.
While wound management is a “fundamental priority” for patients living with EB, she said, there is a “high, unmet” clinical need.
To those ends, EASE was the largest randomized controlled phase 3 efficacy and safety study in EB. In the study, 252 patients were allocated to receive oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing.
The double-blind phase of the trial met its primary endpoint: A higher proportion of patients who were given oleogel-S10 achieved first complete closure of the EB target wound by day 45, compared with patients who were given control gel, at 41.3% versus 28.9%. This equated to a relative risk of wound closure by day 45 of 1.44, or an odds ratio of 1.84 (P = .013).
However, as reported at the time by this news organization, the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of oleogel-S10 patients achieving wound closure, versus 43.9% of those in the control group.
Dr. Cunningham discussed the open-label extension, which involved 205 patients from the double-blind phase (mean age, of 16.3 years) treated with oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing for 24 months.
In presenting the results of the first 12 months of the open-label extension, she said that oleogel-S10 led to “consistent” reductions in the body surface area percentage (BSAP) affected by EB. The overall reduction from baseline was 55% after receiving treatment for 15 months.
Between day 90 and month 12 of the open-label extension, the absolute BSAP was reduced from 7.4% to 5.4% for patients who had received oleogel-S10 from the start of the study. For those who started in the control group and then switched to the oleogel-S10 arm during the open-label extension, the reduction was from 8.3% to 6.4%.
Dr. Cunningham pointed out that a 1% reduction in BSAP equates approximately to the palmar surface of the hand.
Scores on the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Skin activity subscale indicated that the reductions achieved in the double-blind phase of the trial were maintained.
Among patients who received oleogel-S10 from the start of the trial, EBDASI Skin scores were reduced from 19.6 at baseline to 13.5 at 12 months’ follow-up in the open-label extension. The reduction was from 19.6 to 13.5 for those who began the trial taking control gel.
Dr. Cunningham showed that adverse events of any grade were seen in 72.0% of patients who began taking oleogel-S10 at the start of the trial and in 69.5% of those who began the trial taking control gel.
Serious adverse events were recorded in 23.0% and 20.0% of patients, respectively, while 6.0% of those who initially received oleogel-S10 and 6.7% of those initially assigned to control gel experienced adverse events that led to study withdrawal during the open-label phase.
The most frequently reported adverse events in the open-label extension were wound complications, seen in 39.5% of patients; anemia, seen in 14.1%; wound infection, seen in 9.3%; pyrexia, seen in 8.3%; and pruritus, seen in 5.9%. No more details regarding adverse events were provided.
The study was funded by Amryt Pharmaceuticals DAC. Dr. Cunningham is an employee of Amryt Pharmaceuticals. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
GLASGOW, Scotland – the phase 3 safety and efficacy study of the treatment.
Over 200 patients from the trial, including 105 who began treatment with a control gel, continued taking oleogel-S10 after 90 days. The current interim analysis at 12 months indicates there was a 55% reduction in the proportion of the body affected, compared with baseline.
Moreover, reductions in skin activity scores seen in the double-blind phase of the trial were maintained during the open-label extension. About 6% of patients experienced adverse events that led to withdrawal from the study.
The results show that oleogel-S10 was associated with “accelerated wound healing,” said study presenter Tracey Cunningham, MD, chief medical officer, Amryt Pharmaceuticals DAC, Dublin, which is developing the topical agent. “There were no new safety signals with this longer exposure to oleogel-S10, and patients had sustained improvement in wound burden,” she added.
The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 6.
In April, European Medicines Agency recommended approval of oleogel-S10 for the treatment of partial-thickness skin wounds associated with dystrophic and junctional EB for patients aged 6 months and older.
However, just a month earlier, the U.S. Food and Drug Administration declined to approve the topical agent for use in EB, even after it extended its review by 3 months to include additional analyses of data previously submitted by the company.
In the post-presentation discussion, Dr. Cunningham said that the FDA had “not been satisfied at this point with the information that we have given them,” adding, “We don’t agree with the decision, and we will be appealing.”
Raman K. Madan, MD, a dermatologist at Northwell Health, Huntington, New York, who was not involved in the study, said that the reductions in wound healing seen in the study are “meaningful” and that the numbers represent a “big breakthrough.”
He told this news organization that there are “very few products on the market” for EB and that having an option for patients “would be amazing.”
“The big issue here would be cost and coverage for patients,” he said. If approved, “hopefully” it will be affordable, he added.
Dr. Madan noted that from his perspective, the majority of the reactions to the topical gel were “mild,” and there are “a lot of confounding factors” underlying the number of serious adverse events. “These patients with epidermolysis are prone to some of these issues regardless of treatment,” he said.
During her presentation, Dr. Cunningham noted that EB is a rare, debilitating condition that is characterized by varying degrees of skin fragility, blisters, and impaired wound healing that in turn lead to serious complications that affect quality of life.
While wound management is a “fundamental priority” for patients living with EB, she said, there is a “high, unmet” clinical need.
To those ends, EASE was the largest randomized controlled phase 3 efficacy and safety study in EB. In the study, 252 patients were allocated to receive oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing.
The double-blind phase of the trial met its primary endpoint: A higher proportion of patients who were given oleogel-S10 achieved first complete closure of the EB target wound by day 45, compared with patients who were given control gel, at 41.3% versus 28.9%. This equated to a relative risk of wound closure by day 45 of 1.44, or an odds ratio of 1.84 (P = .013).
However, as reported at the time by this news organization, the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of oleogel-S10 patients achieving wound closure, versus 43.9% of those in the control group.
Dr. Cunningham discussed the open-label extension, which involved 205 patients from the double-blind phase (mean age, of 16.3 years) treated with oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing for 24 months.
In presenting the results of the first 12 months of the open-label extension, she said that oleogel-S10 led to “consistent” reductions in the body surface area percentage (BSAP) affected by EB. The overall reduction from baseline was 55% after receiving treatment for 15 months.
Between day 90 and month 12 of the open-label extension, the absolute BSAP was reduced from 7.4% to 5.4% for patients who had received oleogel-S10 from the start of the study. For those who started in the control group and then switched to the oleogel-S10 arm during the open-label extension, the reduction was from 8.3% to 6.4%.
Dr. Cunningham pointed out that a 1% reduction in BSAP equates approximately to the palmar surface of the hand.
Scores on the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Skin activity subscale indicated that the reductions achieved in the double-blind phase of the trial were maintained.
Among patients who received oleogel-S10 from the start of the trial, EBDASI Skin scores were reduced from 19.6 at baseline to 13.5 at 12 months’ follow-up in the open-label extension. The reduction was from 19.6 to 13.5 for those who began the trial taking control gel.
Dr. Cunningham showed that adverse events of any grade were seen in 72.0% of patients who began taking oleogel-S10 at the start of the trial and in 69.5% of those who began the trial taking control gel.
Serious adverse events were recorded in 23.0% and 20.0% of patients, respectively, while 6.0% of those who initially received oleogel-S10 and 6.7% of those initially assigned to control gel experienced adverse events that led to study withdrawal during the open-label phase.
The most frequently reported adverse events in the open-label extension were wound complications, seen in 39.5% of patients; anemia, seen in 14.1%; wound infection, seen in 9.3%; pyrexia, seen in 8.3%; and pruritus, seen in 5.9%. No more details regarding adverse events were provided.
The study was funded by Amryt Pharmaceuticals DAC. Dr. Cunningham is an employee of Amryt Pharmaceuticals. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
European survey finds wide variations in the use of phototherapy for atopic eczema
GLASGOW, Scotland – , which points to the need for management guidelines.
Over 140 phototherapy practitioners from 27 European countries responded to the survey. Of the practitioners surveyed, 96% used narrow-band ultraviolet B (NB-UVB), and about 50% prescribed psoralen and ultraviolet A (PUVA) for adults. Fewer than 10% did so for children.
There was considerable variation in prescribing practices, “especially when it comes to dosing and treatment duration,” said study presenter Mia Steyn, MD, dermatology registrar, St. John’s Institute of Dermatology, Guy’s and St. Thomas’s Hospital, London.
These results, she said, demonstrate that “an optimal treatment modality either is not known or agreed upon” and that studies are required to determine treatment efficacy, cost, and safety “in a range of skin types.”
Dr. Steyn said that what is needed first is a set of consensus treatment guidelines, “hopefully leading to a randomized controlled trial” that would compare the various treatment options.
The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 7.
Session co-chair Adam Fityan, MD, a consultant dermatologist at University Hospital Southampton NHS Foundation Trust, U.K., commented that the study was “fascinating” and “really helpful.”
Dr. Fityan, who was not involved with the survey, told this news organization that, “clearly, what we’ve seen is that there is a huge variation in the way everyone uses the different modalities of phototherapy.”
“Having that sort of knowledge will hopefully help us to think a bit more clearly about the regimens and protocols that we use and to maybe find the evidence that everyone needs to have the most effective protocol.”
The data from the study are also useful on an individual level, Dr. Fityan continued, as “you have no idea what anyone is doing” and whether “you are an outlier.”
Dr. Steyn said that phototherapy is commonly used for the treatment of atopic eczema, but the evidence for its efficacy, its impact on quality on life, its cost-effectiveness, and short- and long-term safety is “weak,” particularly in relation to real-life use.
Electronic survey
In lieu of a well-designed randomized controlled trial to answer these questions, the researchers set up a task force to assess how phototherapy is currently being used to treat atopic eczema across the United Kingdom and Europe so as to guide further research.
An electronic survey was devised, and 144 members of phototherapy groups from 27 European countries submitted their responses during 2020. Most responses came from the Netherlands (20), Italy (16), the United Kingdom (14), France (11), and Germany (10).
The results showed that NB-UVB was the most widely used modality of phototherapy, chosen by 96% of respondents. In addition, 17% of respondents said they also prescribed home-based NB-UVB, which was available in eight of the 27 countries.
When asked how they used NB-UVB, the majority (68%) of respondents said they had an age cutoff for use in children, which was set at an average age of 9 years and older, although the range was age 2 years to 16 years.
NBUVB was used as a second-line therapy instead of systemic treatments in up to 93% of adults and in 69% of children. It was used concomitantly with systemic treatment in up to 58% of adults and 11% of children, according to the survey responses.
For about 70% of respondents, the use of NB-UVB was determined by assessing the Fitzpatrick skin type, although almost 40% relied on clinical experience.
Frequency of treatment
NB-UVB was prescribed three times a week by 59% of respondents; 31% of respondents prescribed it twice a week; 7%, five times per week; and 2%, four times a week. The typical number of treatments was 21-30 for 53% of respondents, 0-20 treatments for 24%, and 31-40 treatments for 20%.
The dose was typically increased in 10% increments, although there were wide variations in how the treatment was stepped up. Dose was increased after each treatment by almost 50% of respondents, after every two treatments by almost 25%, and after every three treatments by approximately 15%.
For the majority (53%) of respondents, response to NBUVB was assessed after 7-15 treatments, while 43% waited until after 16-30 treatments. Success was defined as a 75% reduction in eczema from baseline by 56% of respondents, while 54% looked to patient satisfaction, and 47% relied on quality of life to determine success of treatment.
Maintenance NB-UVB was never used by 54% of respondents, but 44% said they used it occasionally, and 83% said they did not follow a weaning schedule at the end of treatment.
The most commonly reported adverse effects of NB-UVB were significant erythema, hyperpigmentation, and eczema flare, while the most commonly cited absolute contraindications included a history of melanoma, a history of squamous cell carcinoma, the use of photosensitizing medications, and claustrophobia.
Use of PUVA, UVA1
The next most commonly used phototherapy for atopic eczema was PUVA. Although it was available to 83% of respondents, only 52% of respondents had personally prescribed the treatment for adults, and only 7% prescribed it for children.
Of the respondents, 71% said they would switch from NB-UVB to PUVA if desired treatment outcomes were not achieved with the former, and 44% said they would “sometimes consider” PUVA as second-line therapy instead of systemic treatments. Only 13% said they would use it concomitantly with systemic treatment.
Ultraviolet A1 (UVA1) phototherapy was not widely available, with 66% of respondents declaring that they did not have access to this option and just 29% saying they prescribed it.
But when it was used, UVA1 was cited as being used often in adults by 24% of respondents, while 33% used it was used sometimes, and 43% said it was used rarely. It was used for children by 26% of respondents. In addition, 29% said they favored using UVA1 for chronic atopic eczema, and 33% favored using it for acute eczema while 38% had no preference over whether to use it for chronic versus acute atopic eczema.
Similarly to NB-UVB, there were wide variations in the use of PUVA and UVA1 by respondents in terms of dosing schedules, duration of treatment, and how response to treatment was measured.
No funding for the study has been reported. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
GLASGOW, Scotland – , which points to the need for management guidelines.
Over 140 phototherapy practitioners from 27 European countries responded to the survey. Of the practitioners surveyed, 96% used narrow-band ultraviolet B (NB-UVB), and about 50% prescribed psoralen and ultraviolet A (PUVA) for adults. Fewer than 10% did so for children.
There was considerable variation in prescribing practices, “especially when it comes to dosing and treatment duration,” said study presenter Mia Steyn, MD, dermatology registrar, St. John’s Institute of Dermatology, Guy’s and St. Thomas’s Hospital, London.
These results, she said, demonstrate that “an optimal treatment modality either is not known or agreed upon” and that studies are required to determine treatment efficacy, cost, and safety “in a range of skin types.”
Dr. Steyn said that what is needed first is a set of consensus treatment guidelines, “hopefully leading to a randomized controlled trial” that would compare the various treatment options.
The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 7.
Session co-chair Adam Fityan, MD, a consultant dermatologist at University Hospital Southampton NHS Foundation Trust, U.K., commented that the study was “fascinating” and “really helpful.”
Dr. Fityan, who was not involved with the survey, told this news organization that, “clearly, what we’ve seen is that there is a huge variation in the way everyone uses the different modalities of phototherapy.”
“Having that sort of knowledge will hopefully help us to think a bit more clearly about the regimens and protocols that we use and to maybe find the evidence that everyone needs to have the most effective protocol.”
The data from the study are also useful on an individual level, Dr. Fityan continued, as “you have no idea what anyone is doing” and whether “you are an outlier.”
Dr. Steyn said that phototherapy is commonly used for the treatment of atopic eczema, but the evidence for its efficacy, its impact on quality on life, its cost-effectiveness, and short- and long-term safety is “weak,” particularly in relation to real-life use.
Electronic survey
In lieu of a well-designed randomized controlled trial to answer these questions, the researchers set up a task force to assess how phototherapy is currently being used to treat atopic eczema across the United Kingdom and Europe so as to guide further research.
An electronic survey was devised, and 144 members of phototherapy groups from 27 European countries submitted their responses during 2020. Most responses came from the Netherlands (20), Italy (16), the United Kingdom (14), France (11), and Germany (10).
The results showed that NB-UVB was the most widely used modality of phototherapy, chosen by 96% of respondents. In addition, 17% of respondents said they also prescribed home-based NB-UVB, which was available in eight of the 27 countries.
When asked how they used NB-UVB, the majority (68%) of respondents said they had an age cutoff for use in children, which was set at an average age of 9 years and older, although the range was age 2 years to 16 years.
NBUVB was used as a second-line therapy instead of systemic treatments in up to 93% of adults and in 69% of children. It was used concomitantly with systemic treatment in up to 58% of adults and 11% of children, according to the survey responses.
For about 70% of respondents, the use of NB-UVB was determined by assessing the Fitzpatrick skin type, although almost 40% relied on clinical experience.
Frequency of treatment
NB-UVB was prescribed three times a week by 59% of respondents; 31% of respondents prescribed it twice a week; 7%, five times per week; and 2%, four times a week. The typical number of treatments was 21-30 for 53% of respondents, 0-20 treatments for 24%, and 31-40 treatments for 20%.
The dose was typically increased in 10% increments, although there were wide variations in how the treatment was stepped up. Dose was increased after each treatment by almost 50% of respondents, after every two treatments by almost 25%, and after every three treatments by approximately 15%.
For the majority (53%) of respondents, response to NBUVB was assessed after 7-15 treatments, while 43% waited until after 16-30 treatments. Success was defined as a 75% reduction in eczema from baseline by 56% of respondents, while 54% looked to patient satisfaction, and 47% relied on quality of life to determine success of treatment.
Maintenance NB-UVB was never used by 54% of respondents, but 44% said they used it occasionally, and 83% said they did not follow a weaning schedule at the end of treatment.
The most commonly reported adverse effects of NB-UVB were significant erythema, hyperpigmentation, and eczema flare, while the most commonly cited absolute contraindications included a history of melanoma, a history of squamous cell carcinoma, the use of photosensitizing medications, and claustrophobia.
Use of PUVA, UVA1
The next most commonly used phototherapy for atopic eczema was PUVA. Although it was available to 83% of respondents, only 52% of respondents had personally prescribed the treatment for adults, and only 7% prescribed it for children.
Of the respondents, 71% said they would switch from NB-UVB to PUVA if desired treatment outcomes were not achieved with the former, and 44% said they would “sometimes consider” PUVA as second-line therapy instead of systemic treatments. Only 13% said they would use it concomitantly with systemic treatment.
Ultraviolet A1 (UVA1) phototherapy was not widely available, with 66% of respondents declaring that they did not have access to this option and just 29% saying they prescribed it.
But when it was used, UVA1 was cited as being used often in adults by 24% of respondents, while 33% used it was used sometimes, and 43% said it was used rarely. It was used for children by 26% of respondents. In addition, 29% said they favored using UVA1 for chronic atopic eczema, and 33% favored using it for acute eczema while 38% had no preference over whether to use it for chronic versus acute atopic eczema.
Similarly to NB-UVB, there were wide variations in the use of PUVA and UVA1 by respondents in terms of dosing schedules, duration of treatment, and how response to treatment was measured.
No funding for the study has been reported. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
GLASGOW, Scotland – , which points to the need for management guidelines.
Over 140 phototherapy practitioners from 27 European countries responded to the survey. Of the practitioners surveyed, 96% used narrow-band ultraviolet B (NB-UVB), and about 50% prescribed psoralen and ultraviolet A (PUVA) for adults. Fewer than 10% did so for children.
There was considerable variation in prescribing practices, “especially when it comes to dosing and treatment duration,” said study presenter Mia Steyn, MD, dermatology registrar, St. John’s Institute of Dermatology, Guy’s and St. Thomas’s Hospital, London.
These results, she said, demonstrate that “an optimal treatment modality either is not known or agreed upon” and that studies are required to determine treatment efficacy, cost, and safety “in a range of skin types.”
Dr. Steyn said that what is needed first is a set of consensus treatment guidelines, “hopefully leading to a randomized controlled trial” that would compare the various treatment options.
The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 7.
Session co-chair Adam Fityan, MD, a consultant dermatologist at University Hospital Southampton NHS Foundation Trust, U.K., commented that the study was “fascinating” and “really helpful.”
Dr. Fityan, who was not involved with the survey, told this news organization that, “clearly, what we’ve seen is that there is a huge variation in the way everyone uses the different modalities of phototherapy.”
“Having that sort of knowledge will hopefully help us to think a bit more clearly about the regimens and protocols that we use and to maybe find the evidence that everyone needs to have the most effective protocol.”
The data from the study are also useful on an individual level, Dr. Fityan continued, as “you have no idea what anyone is doing” and whether “you are an outlier.”
Dr. Steyn said that phototherapy is commonly used for the treatment of atopic eczema, but the evidence for its efficacy, its impact on quality on life, its cost-effectiveness, and short- and long-term safety is “weak,” particularly in relation to real-life use.
Electronic survey
In lieu of a well-designed randomized controlled trial to answer these questions, the researchers set up a task force to assess how phototherapy is currently being used to treat atopic eczema across the United Kingdom and Europe so as to guide further research.
An electronic survey was devised, and 144 members of phototherapy groups from 27 European countries submitted their responses during 2020. Most responses came from the Netherlands (20), Italy (16), the United Kingdom (14), France (11), and Germany (10).
The results showed that NB-UVB was the most widely used modality of phototherapy, chosen by 96% of respondents. In addition, 17% of respondents said they also prescribed home-based NB-UVB, which was available in eight of the 27 countries.
When asked how they used NB-UVB, the majority (68%) of respondents said they had an age cutoff for use in children, which was set at an average age of 9 years and older, although the range was age 2 years to 16 years.
NBUVB was used as a second-line therapy instead of systemic treatments in up to 93% of adults and in 69% of children. It was used concomitantly with systemic treatment in up to 58% of adults and 11% of children, according to the survey responses.
For about 70% of respondents, the use of NB-UVB was determined by assessing the Fitzpatrick skin type, although almost 40% relied on clinical experience.
Frequency of treatment
NB-UVB was prescribed three times a week by 59% of respondents; 31% of respondents prescribed it twice a week; 7%, five times per week; and 2%, four times a week. The typical number of treatments was 21-30 for 53% of respondents, 0-20 treatments for 24%, and 31-40 treatments for 20%.
The dose was typically increased in 10% increments, although there were wide variations in how the treatment was stepped up. Dose was increased after each treatment by almost 50% of respondents, after every two treatments by almost 25%, and after every three treatments by approximately 15%.
For the majority (53%) of respondents, response to NBUVB was assessed after 7-15 treatments, while 43% waited until after 16-30 treatments. Success was defined as a 75% reduction in eczema from baseline by 56% of respondents, while 54% looked to patient satisfaction, and 47% relied on quality of life to determine success of treatment.
Maintenance NB-UVB was never used by 54% of respondents, but 44% said they used it occasionally, and 83% said they did not follow a weaning schedule at the end of treatment.
The most commonly reported adverse effects of NB-UVB were significant erythema, hyperpigmentation, and eczema flare, while the most commonly cited absolute contraindications included a history of melanoma, a history of squamous cell carcinoma, the use of photosensitizing medications, and claustrophobia.
Use of PUVA, UVA1
The next most commonly used phototherapy for atopic eczema was PUVA. Although it was available to 83% of respondents, only 52% of respondents had personally prescribed the treatment for adults, and only 7% prescribed it for children.
Of the respondents, 71% said they would switch from NB-UVB to PUVA if desired treatment outcomes were not achieved with the former, and 44% said they would “sometimes consider” PUVA as second-line therapy instead of systemic treatments. Only 13% said they would use it concomitantly with systemic treatment.
Ultraviolet A1 (UVA1) phototherapy was not widely available, with 66% of respondents declaring that they did not have access to this option and just 29% saying they prescribed it.
But when it was used, UVA1 was cited as being used often in adults by 24% of respondents, while 33% used it was used sometimes, and 43% said it was used rarely. It was used for children by 26% of respondents. In addition, 29% said they favored using UVA1 for chronic atopic eczema, and 33% favored using it for acute eczema while 38% had no preference over whether to use it for chronic versus acute atopic eczema.
Similarly to NB-UVB, there were wide variations in the use of PUVA and UVA1 by respondents in terms of dosing schedules, duration of treatment, and how response to treatment was measured.
No funding for the study has been reported. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
‘Myriad’ dermatologic reactions after COVID-19 vaccination
GLASGOW – Individuals given COVID-19 vaccination may experience a wide range of dermatologic reactions, some of which may be life-threatening, reveals a prospective Indian study that suggests histopathological assessment is key to understanding the cause.
Studying more than 130 patients who presented with vaccine-related dermatologic reactions, the researchers found that the most common acute adverse events were acute urticaria, generalized pruritus, and maculopapular rash.
Dermal hypersensitivity reactions occurred within 3 days of vaccination, which suggests the culprit is an immediate type 1 hypersensitivity reaction, said study presenter Alpana Mohta, MD, department of dermatology, Sardar Patel Medical College, Bikaner, Rajasthan, India. Most of the patients had received the AstraZeneca vaccine, she said.
, which occurred within 3-4 weeks of vaccination and could be a result of delayed hypersensitivity or a T cell–mediated skin reaction caused by “molecular mimicry with a viral epitope,” Dr. Mohta said.
The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 5.
Dr. Mohta said that, given the “surge” in the number of people who have been vaccinated, it is “imperative as dermatologists” to maintain a “very high index of suspicion to differentiate reactions caused by vaccination” from other causes, and a proper assessment should be performed in “every patient” who presents with a possible reaction.
She also emphasized that “since so many clinical [COVID-19] variants are being encountered,” histopathological assessment could “help in better understanding the underlying pathophysiology” of every reaction.
Dr. Mohta began her presentation by explaining that India is running one of the “world’s largest vaccination drives” for COVID-19, with almost 90% of adults fully vaccinated.
She added that studies have indicated that the incidence of cutaneous adverse reactions following COVID-19 vaccination ranges from 1.0% to 1.9% and that dermatologists have encountered a “plethora” of related reactions.
Dr. Mohta emphasized that the “myriad presentations” of these reactions means that correlating clinical and pathological findings is “key” to understanding the underlying pathophysiology.
She and her colleagues therefore conducted a prospective, hospital-based study of patients who self-reported mucocutaneous adverse reactions from April to December 2021, within 4 weeks of receiving a COVID-19 vaccine.
They gathered information on the patients’ signs and symptoms, as well as the date of vaccine administration and the type of vaccine given, alongside a detailed medical history, including previous allergies, prior COVID-19 infection, and any comorbidities.
The patients also underwent a clinical examination and laboratory investigations, and their cases were assessed by two senior dermatologists to determine whether the association between the adverse event and COVID-19 vaccination was likely causal.
Dr. Mohta said that 132 adult patients, with an average age of 38.2 years, were identified as having vaccine-related reactions.
This included 84 (63.6%) patients with a mild reaction, defined as resolving with symptomatic treatment; 43 (32.6%) patients with a moderate reaction, defined as extensive and lasting for more than 4 weeks; and five (3.8%) patients with severe reactions, defined as systemic and potentially life-threatening.
The mild group included 21 patients with acute urticaria, with a mean onset of 1.2 days following vaccination, as well as 20 cases of maculopapular rash, with a mean onset of 2.4 days; 18 cases of pityriasis rosea, with a mean onset of 17.4 days; and nine cases of eruptive pseudoangioma, with a mean onset of 3.5 days.
There were 16 cases of lichen planus in the moderate group, with a mean onset of 22.7 days after COVID-19 vaccination; nine cases of herpes zoster, with a mean onset of 15.3 days; and one case of pityriasis lichenoides et varioliformis acuta (PLEVA), among others.
The severe group included two cases of erythroderma, with a mean onset of 9 days after vaccination; one case of drug rash with eosinophilia and systemic symptoms (DRESS), with a mean onset of 20 days; and one case each of subacute cutaneous lupus erythematosus (SCLE) and bullous pemphigoid, with mean onsets of 15 days and 14 days, respectively.
Turning to the histopathological results, Dr. Mohta explained that only 57 patients from their cohort agreed to have a skin biopsy.
Results of those skin biopsies showed that 21 (36.8%) patients had vaccine-related eruption of papules and plaques, predominantly spongiotic dermatitis. This correlated with the clinical diagnoses of pityriasis rosea, maculopapular and papulosquamous rash, and DRESS.
Lichenoid and interface dermatitis were seen in 13 (22.8%) patients, which correlated with the clinical diagnoses of lichen planus, PLEVA, and SCLE. Eleven (19.3%) patients had a dermal hypersensitivity reaction, equated to the clinical diagnoses of urticaria, and eruptive pseudoangioma.
Dr. Mohta acknowledged that the study was limited by the inability to calculate the “true prevalence of vaccine-associated reactions,” and because immunohistochemistry was not performed.
Session chair Saleem Taibjee, MD, department of dermatology, Dorset County Hospital NHS Foundation Trust, Dorchester, United Kingdom, congratulated Dr. Mohta on her “very interesting” presentation, highlighting their “extensive experience in such a large cohort of patients.”
He asked what type of COVID-19 vaccines the patients had received, and whether Dr. Mohta could provide any “insights into which patients you can safely give the vaccine again to, and those [to whom] you may avoid giving further doses.”
Dr. Mohta said that the majority of the patients in the study received the AstraZeneca COVID-19 vaccine, as that was the one most commonly used in India at the time, with around 30 patients receiving the Indian Covishield version of the AstraZeneca vaccine. (The two-dose AstraZeneca vaccine, which is cheaper to manufacture and easier to store at typical refrigerated temperatures than mRNA-based vaccines, has been authorized by the World Health Organization, the European Medicines Agency, and over 50 countries but has not been authorized in the United States.)
She added that none of the patients in the study with mild-to-moderate skin reactions were advised against receiving further doses” but that those with severe reactions “were advised not to take any further doses.”
Consequently, in the case of mild reactions, “further doses are not a contraindication,” Dr. Mohta said, but patients with more severe reactions should be considered on a “case by case basis.”
A version of this article first appeared on Medscape.com.
GLASGOW – Individuals given COVID-19 vaccination may experience a wide range of dermatologic reactions, some of which may be life-threatening, reveals a prospective Indian study that suggests histopathological assessment is key to understanding the cause.
Studying more than 130 patients who presented with vaccine-related dermatologic reactions, the researchers found that the most common acute adverse events were acute urticaria, generalized pruritus, and maculopapular rash.
Dermal hypersensitivity reactions occurred within 3 days of vaccination, which suggests the culprit is an immediate type 1 hypersensitivity reaction, said study presenter Alpana Mohta, MD, department of dermatology, Sardar Patel Medical College, Bikaner, Rajasthan, India. Most of the patients had received the AstraZeneca vaccine, she said.
, which occurred within 3-4 weeks of vaccination and could be a result of delayed hypersensitivity or a T cell–mediated skin reaction caused by “molecular mimicry with a viral epitope,” Dr. Mohta said.
The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 5.
Dr. Mohta said that, given the “surge” in the number of people who have been vaccinated, it is “imperative as dermatologists” to maintain a “very high index of suspicion to differentiate reactions caused by vaccination” from other causes, and a proper assessment should be performed in “every patient” who presents with a possible reaction.
She also emphasized that “since so many clinical [COVID-19] variants are being encountered,” histopathological assessment could “help in better understanding the underlying pathophysiology” of every reaction.
Dr. Mohta began her presentation by explaining that India is running one of the “world’s largest vaccination drives” for COVID-19, with almost 90% of adults fully vaccinated.
She added that studies have indicated that the incidence of cutaneous adverse reactions following COVID-19 vaccination ranges from 1.0% to 1.9% and that dermatologists have encountered a “plethora” of related reactions.
Dr. Mohta emphasized that the “myriad presentations” of these reactions means that correlating clinical and pathological findings is “key” to understanding the underlying pathophysiology.
She and her colleagues therefore conducted a prospective, hospital-based study of patients who self-reported mucocutaneous adverse reactions from April to December 2021, within 4 weeks of receiving a COVID-19 vaccine.
They gathered information on the patients’ signs and symptoms, as well as the date of vaccine administration and the type of vaccine given, alongside a detailed medical history, including previous allergies, prior COVID-19 infection, and any comorbidities.
The patients also underwent a clinical examination and laboratory investigations, and their cases were assessed by two senior dermatologists to determine whether the association between the adverse event and COVID-19 vaccination was likely causal.
Dr. Mohta said that 132 adult patients, with an average age of 38.2 years, were identified as having vaccine-related reactions.
This included 84 (63.6%) patients with a mild reaction, defined as resolving with symptomatic treatment; 43 (32.6%) patients with a moderate reaction, defined as extensive and lasting for more than 4 weeks; and five (3.8%) patients with severe reactions, defined as systemic and potentially life-threatening.
The mild group included 21 patients with acute urticaria, with a mean onset of 1.2 days following vaccination, as well as 20 cases of maculopapular rash, with a mean onset of 2.4 days; 18 cases of pityriasis rosea, with a mean onset of 17.4 days; and nine cases of eruptive pseudoangioma, with a mean onset of 3.5 days.
There were 16 cases of lichen planus in the moderate group, with a mean onset of 22.7 days after COVID-19 vaccination; nine cases of herpes zoster, with a mean onset of 15.3 days; and one case of pityriasis lichenoides et varioliformis acuta (PLEVA), among others.
The severe group included two cases of erythroderma, with a mean onset of 9 days after vaccination; one case of drug rash with eosinophilia and systemic symptoms (DRESS), with a mean onset of 20 days; and one case each of subacute cutaneous lupus erythematosus (SCLE) and bullous pemphigoid, with mean onsets of 15 days and 14 days, respectively.
Turning to the histopathological results, Dr. Mohta explained that only 57 patients from their cohort agreed to have a skin biopsy.
Results of those skin biopsies showed that 21 (36.8%) patients had vaccine-related eruption of papules and plaques, predominantly spongiotic dermatitis. This correlated with the clinical diagnoses of pityriasis rosea, maculopapular and papulosquamous rash, and DRESS.
Lichenoid and interface dermatitis were seen in 13 (22.8%) patients, which correlated with the clinical diagnoses of lichen planus, PLEVA, and SCLE. Eleven (19.3%) patients had a dermal hypersensitivity reaction, equated to the clinical diagnoses of urticaria, and eruptive pseudoangioma.
Dr. Mohta acknowledged that the study was limited by the inability to calculate the “true prevalence of vaccine-associated reactions,” and because immunohistochemistry was not performed.
Session chair Saleem Taibjee, MD, department of dermatology, Dorset County Hospital NHS Foundation Trust, Dorchester, United Kingdom, congratulated Dr. Mohta on her “very interesting” presentation, highlighting their “extensive experience in such a large cohort of patients.”
He asked what type of COVID-19 vaccines the patients had received, and whether Dr. Mohta could provide any “insights into which patients you can safely give the vaccine again to, and those [to whom] you may avoid giving further doses.”
Dr. Mohta said that the majority of the patients in the study received the AstraZeneca COVID-19 vaccine, as that was the one most commonly used in India at the time, with around 30 patients receiving the Indian Covishield version of the AstraZeneca vaccine. (The two-dose AstraZeneca vaccine, which is cheaper to manufacture and easier to store at typical refrigerated temperatures than mRNA-based vaccines, has been authorized by the World Health Organization, the European Medicines Agency, and over 50 countries but has not been authorized in the United States.)
She added that none of the patients in the study with mild-to-moderate skin reactions were advised against receiving further doses” but that those with severe reactions “were advised not to take any further doses.”
Consequently, in the case of mild reactions, “further doses are not a contraindication,” Dr. Mohta said, but patients with more severe reactions should be considered on a “case by case basis.”
A version of this article first appeared on Medscape.com.
GLASGOW – Individuals given COVID-19 vaccination may experience a wide range of dermatologic reactions, some of which may be life-threatening, reveals a prospective Indian study that suggests histopathological assessment is key to understanding the cause.
Studying more than 130 patients who presented with vaccine-related dermatologic reactions, the researchers found that the most common acute adverse events were acute urticaria, generalized pruritus, and maculopapular rash.
Dermal hypersensitivity reactions occurred within 3 days of vaccination, which suggests the culprit is an immediate type 1 hypersensitivity reaction, said study presenter Alpana Mohta, MD, department of dermatology, Sardar Patel Medical College, Bikaner, Rajasthan, India. Most of the patients had received the AstraZeneca vaccine, she said.
, which occurred within 3-4 weeks of vaccination and could be a result of delayed hypersensitivity or a T cell–mediated skin reaction caused by “molecular mimicry with a viral epitope,” Dr. Mohta said.
The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 5.
Dr. Mohta said that, given the “surge” in the number of people who have been vaccinated, it is “imperative as dermatologists” to maintain a “very high index of suspicion to differentiate reactions caused by vaccination” from other causes, and a proper assessment should be performed in “every patient” who presents with a possible reaction.
She also emphasized that “since so many clinical [COVID-19] variants are being encountered,” histopathological assessment could “help in better understanding the underlying pathophysiology” of every reaction.
Dr. Mohta began her presentation by explaining that India is running one of the “world’s largest vaccination drives” for COVID-19, with almost 90% of adults fully vaccinated.
She added that studies have indicated that the incidence of cutaneous adverse reactions following COVID-19 vaccination ranges from 1.0% to 1.9% and that dermatologists have encountered a “plethora” of related reactions.
Dr. Mohta emphasized that the “myriad presentations” of these reactions means that correlating clinical and pathological findings is “key” to understanding the underlying pathophysiology.
She and her colleagues therefore conducted a prospective, hospital-based study of patients who self-reported mucocutaneous adverse reactions from April to December 2021, within 4 weeks of receiving a COVID-19 vaccine.
They gathered information on the patients’ signs and symptoms, as well as the date of vaccine administration and the type of vaccine given, alongside a detailed medical history, including previous allergies, prior COVID-19 infection, and any comorbidities.
The patients also underwent a clinical examination and laboratory investigations, and their cases were assessed by two senior dermatologists to determine whether the association between the adverse event and COVID-19 vaccination was likely causal.
Dr. Mohta said that 132 adult patients, with an average age of 38.2 years, were identified as having vaccine-related reactions.
This included 84 (63.6%) patients with a mild reaction, defined as resolving with symptomatic treatment; 43 (32.6%) patients with a moderate reaction, defined as extensive and lasting for more than 4 weeks; and five (3.8%) patients with severe reactions, defined as systemic and potentially life-threatening.
The mild group included 21 patients with acute urticaria, with a mean onset of 1.2 days following vaccination, as well as 20 cases of maculopapular rash, with a mean onset of 2.4 days; 18 cases of pityriasis rosea, with a mean onset of 17.4 days; and nine cases of eruptive pseudoangioma, with a mean onset of 3.5 days.
There were 16 cases of lichen planus in the moderate group, with a mean onset of 22.7 days after COVID-19 vaccination; nine cases of herpes zoster, with a mean onset of 15.3 days; and one case of pityriasis lichenoides et varioliformis acuta (PLEVA), among others.
The severe group included two cases of erythroderma, with a mean onset of 9 days after vaccination; one case of drug rash with eosinophilia and systemic symptoms (DRESS), with a mean onset of 20 days; and one case each of subacute cutaneous lupus erythematosus (SCLE) and bullous pemphigoid, with mean onsets of 15 days and 14 days, respectively.
Turning to the histopathological results, Dr. Mohta explained that only 57 patients from their cohort agreed to have a skin biopsy.
Results of those skin biopsies showed that 21 (36.8%) patients had vaccine-related eruption of papules and plaques, predominantly spongiotic dermatitis. This correlated with the clinical diagnoses of pityriasis rosea, maculopapular and papulosquamous rash, and DRESS.
Lichenoid and interface dermatitis were seen in 13 (22.8%) patients, which correlated with the clinical diagnoses of lichen planus, PLEVA, and SCLE. Eleven (19.3%) patients had a dermal hypersensitivity reaction, equated to the clinical diagnoses of urticaria, and eruptive pseudoangioma.
Dr. Mohta acknowledged that the study was limited by the inability to calculate the “true prevalence of vaccine-associated reactions,” and because immunohistochemistry was not performed.
Session chair Saleem Taibjee, MD, department of dermatology, Dorset County Hospital NHS Foundation Trust, Dorchester, United Kingdom, congratulated Dr. Mohta on her “very interesting” presentation, highlighting their “extensive experience in such a large cohort of patients.”
He asked what type of COVID-19 vaccines the patients had received, and whether Dr. Mohta could provide any “insights into which patients you can safely give the vaccine again to, and those [to whom] you may avoid giving further doses.”
Dr. Mohta said that the majority of the patients in the study received the AstraZeneca COVID-19 vaccine, as that was the one most commonly used in India at the time, with around 30 patients receiving the Indian Covishield version of the AstraZeneca vaccine. (The two-dose AstraZeneca vaccine, which is cheaper to manufacture and easier to store at typical refrigerated temperatures than mRNA-based vaccines, has been authorized by the World Health Organization, the European Medicines Agency, and over 50 countries but has not been authorized in the United States.)
She added that none of the patients in the study with mild-to-moderate skin reactions were advised against receiving further doses” but that those with severe reactions “were advised not to take any further doses.”
Consequently, in the case of mild reactions, “further doses are not a contraindication,” Dr. Mohta said, but patients with more severe reactions should be considered on a “case by case basis.”
A version of this article first appeared on Medscape.com.
U.K. survey: Dermatologists want training in prescribing antipsychotics for delusional infestation
GLASGOW – that also indicated there is a clear demand for training in prescribing these drugs.
Delusional infestation is a rare disorder characterized by an individual’s belief that his or her skin, body, or immediate environment is infested by small, living pathogens, despite a lack of any medical evidence. Most of these patients require antipsychotic medication to alleviate symptoms.
The survey of almost 80 dermatologists found that almost 90% had not prescribed antipsychotics in the previous month for patients with psychodermatology conditions and that the most common barrier to prescribing was lack of experience with the drugs.
This was reflected in only 10% of survey respondents who said they were “happy to” prescribe antipsychotics without consulting either dermatology or psychiatric colleagues, and less than half having attended a related course.
Yet the research, presented at the annual meeting of the British Association of Dermatologists, indicated that more than 75% of respondents would attend such a course to increase their confidence.
This finding, said study presenter Ling Li, MD, Churchill Hospital, Oxford (England) University Hospitals NHS Foundation Trust, shows that there is a “clear demand for training, particularly among all the registrars [residents] who we surveyed.”
Dr. Li noted that the UK’s Joint Royal Colleges of Physicians Training Board’s latest curriculum for dermatology training highlights psychocutaneous medicine as a key area, and “that will include antipsychotic medication.”
The BAD also recently published guidelines for the management of adults with delusional infestation, which includes a recommendation to conduct a survey on attitudes toward antipsychotic prescribing for the condition among U.K. dermatologists.
Heeding that call, Dr. Li and colleagues sent an email containing a 10-question online survey to members of the BAD and the British Society for Medical Dermatology. Questions covered familiarity with antipsychotics and frequency of prescribing, confidence around antipsychotics, and current training and future needs. Responses were received between February through April 2021.
Among the 79 respondents, 51 (65%) were consultants and 20 (25%) were dermatology registrars, with the remainder dermatology clinical fellows, foundation doctors, or other doctors. A total of 31 respondents had an average of more than 50 visits with patients per week, 18 had an average of 41-50 patient visits, and 13 had an average of 31-40 visits per week; the remainder had an average of 11-30 visits per week.
Most of the respondents (39) said they had seen 2-5 patients with psychodermatology conditions in the last 6 months, while 17 said they had seen 1 patient, 13 said they had seen more than 10 patients, and 6 said they had seen 6-10 patients (4 had seen none and 1 could not remember).
The most commonly prescribed antipsychotics for psychodermatology patients in the past 6 months were risperidone (Risperdal; prescribed by five respondents), followed by olanzapine (Zyprexa; by four respondents). Seventy respondents had not prescribed any antipsychotics.
Asked about how confident they felt about prescribing antipsychotic medication for patients with delusional infestation, 8 (10%) said they were happy to prescribe independently, while 42 (54%) said they were not at all confident. Another 10 (13%) respondents said they would be happy to prescribe the medications after liaising with a dermatology colleague, while 17 (22%) said they would prefer to consult with the psychiatry team.
The most common barrier to prescribing antipsychotic medications was a lack of experience with the drugs, cited by 66 respondents, followed by concerns over drug monitoring, cited by 43 respondents.
In addition, 42 respondents highlighted concerns over adverse effects, 36 cited lack of experience in psychodermatology clinics, and 19 cited lack of experience in discussing psychodermatologic conditions with patients. Other barriers mentioned by the respondents included difficulties with patient acceptance of a psychiatric medication prescribed by a dermatologist.
An audience member went further, saying that clinicians have been told not to “confront” such patients and that the temptation is therefore to cloak the discussion of antipsychotics in nonthreatening language so that it is more acceptable to the patient.
However, under the U.K. system, a letter with the results of the consultation, including information that an antipsychotic has been prescribed, must be sent to the patient’s family doctor along with a copy that goes to the patient. “The situation is almost impossible,” the audience member said, adding that there “must be some arrangement where in certain circumstances dermatologists could be allowed not to write to the patient” or alternatively, “write an entirely different letter” to the family doctor.
Session cochair Susannah Baron, MD, a consultant dermatologist at St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospital, London, said that, in these situations, it is “really helpful to talk about doses” with patients.
She explained that she uses the analogy of aspirin, which has different effects depending on the dose given, giving pain relief at high doses but primarily an antiplatelet effect at low doses.
In the case of an antipsychotic, it is helpful to explain to the patient that “you don’t think they’re psychotic, and you’re prescribing it in a very low dose, because what it can do is help with their symptoms,” Dr. Baron added. “You have to be very open because if you’re not, they go to the pharmacy, and the pharmacist says: ‘Why are you on an antipsychotic?’ ”
Further results from the survey revealed that 56 (71%) respondents did not have access to a specialist psychodermatology clinic, whereas 36 (46%) had not yet attended a psychodermatology course.
Despite these responses, 60 (77%) respondents said they would be interested in attending a training course for prescribing antipsychotics, which included all 20 of the registrars who took part in the survey. a psychodermatologist at Frimley Health Foundation Trust, Windsor, England, and lead author of the BAD guidelines, commented from the audience that the survey results were “sort of what we expected.”
She explained that the intention of the authors when developing the guidelines “was to be able to help our junior colleagues and our peers to be able to feel competent to discuss antipsychotics with patients with delusional infestation and also initiate management.”
Dr. Ahmed added: “Why we’re encouraging our colleagues to prescribe antipsychotics is the longer you leave this type of psychotic illness untreated, the worse the prognosis.”
No funding or relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
GLASGOW – that also indicated there is a clear demand for training in prescribing these drugs.
Delusional infestation is a rare disorder characterized by an individual’s belief that his or her skin, body, or immediate environment is infested by small, living pathogens, despite a lack of any medical evidence. Most of these patients require antipsychotic medication to alleviate symptoms.
The survey of almost 80 dermatologists found that almost 90% had not prescribed antipsychotics in the previous month for patients with psychodermatology conditions and that the most common barrier to prescribing was lack of experience with the drugs.
This was reflected in only 10% of survey respondents who said they were “happy to” prescribe antipsychotics without consulting either dermatology or psychiatric colleagues, and less than half having attended a related course.
Yet the research, presented at the annual meeting of the British Association of Dermatologists, indicated that more than 75% of respondents would attend such a course to increase their confidence.
This finding, said study presenter Ling Li, MD, Churchill Hospital, Oxford (England) University Hospitals NHS Foundation Trust, shows that there is a “clear demand for training, particularly among all the registrars [residents] who we surveyed.”
Dr. Li noted that the UK’s Joint Royal Colleges of Physicians Training Board’s latest curriculum for dermatology training highlights psychocutaneous medicine as a key area, and “that will include antipsychotic medication.”
The BAD also recently published guidelines for the management of adults with delusional infestation, which includes a recommendation to conduct a survey on attitudes toward antipsychotic prescribing for the condition among U.K. dermatologists.
Heeding that call, Dr. Li and colleagues sent an email containing a 10-question online survey to members of the BAD and the British Society for Medical Dermatology. Questions covered familiarity with antipsychotics and frequency of prescribing, confidence around antipsychotics, and current training and future needs. Responses were received between February through April 2021.
Among the 79 respondents, 51 (65%) were consultants and 20 (25%) were dermatology registrars, with the remainder dermatology clinical fellows, foundation doctors, or other doctors. A total of 31 respondents had an average of more than 50 visits with patients per week, 18 had an average of 41-50 patient visits, and 13 had an average of 31-40 visits per week; the remainder had an average of 11-30 visits per week.
Most of the respondents (39) said they had seen 2-5 patients with psychodermatology conditions in the last 6 months, while 17 said they had seen 1 patient, 13 said they had seen more than 10 patients, and 6 said they had seen 6-10 patients (4 had seen none and 1 could not remember).
The most commonly prescribed antipsychotics for psychodermatology patients in the past 6 months were risperidone (Risperdal; prescribed by five respondents), followed by olanzapine (Zyprexa; by four respondents). Seventy respondents had not prescribed any antipsychotics.
Asked about how confident they felt about prescribing antipsychotic medication for patients with delusional infestation, 8 (10%) said they were happy to prescribe independently, while 42 (54%) said they were not at all confident. Another 10 (13%) respondents said they would be happy to prescribe the medications after liaising with a dermatology colleague, while 17 (22%) said they would prefer to consult with the psychiatry team.
The most common barrier to prescribing antipsychotic medications was a lack of experience with the drugs, cited by 66 respondents, followed by concerns over drug monitoring, cited by 43 respondents.
In addition, 42 respondents highlighted concerns over adverse effects, 36 cited lack of experience in psychodermatology clinics, and 19 cited lack of experience in discussing psychodermatologic conditions with patients. Other barriers mentioned by the respondents included difficulties with patient acceptance of a psychiatric medication prescribed by a dermatologist.
An audience member went further, saying that clinicians have been told not to “confront” such patients and that the temptation is therefore to cloak the discussion of antipsychotics in nonthreatening language so that it is more acceptable to the patient.
However, under the U.K. system, a letter with the results of the consultation, including information that an antipsychotic has been prescribed, must be sent to the patient’s family doctor along with a copy that goes to the patient. “The situation is almost impossible,” the audience member said, adding that there “must be some arrangement where in certain circumstances dermatologists could be allowed not to write to the patient” or alternatively, “write an entirely different letter” to the family doctor.
Session cochair Susannah Baron, MD, a consultant dermatologist at St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospital, London, said that, in these situations, it is “really helpful to talk about doses” with patients.
She explained that she uses the analogy of aspirin, which has different effects depending on the dose given, giving pain relief at high doses but primarily an antiplatelet effect at low doses.
In the case of an antipsychotic, it is helpful to explain to the patient that “you don’t think they’re psychotic, and you’re prescribing it in a very low dose, because what it can do is help with their symptoms,” Dr. Baron added. “You have to be very open because if you’re not, they go to the pharmacy, and the pharmacist says: ‘Why are you on an antipsychotic?’ ”
Further results from the survey revealed that 56 (71%) respondents did not have access to a specialist psychodermatology clinic, whereas 36 (46%) had not yet attended a psychodermatology course.
Despite these responses, 60 (77%) respondents said they would be interested in attending a training course for prescribing antipsychotics, which included all 20 of the registrars who took part in the survey. a psychodermatologist at Frimley Health Foundation Trust, Windsor, England, and lead author of the BAD guidelines, commented from the audience that the survey results were “sort of what we expected.”
She explained that the intention of the authors when developing the guidelines “was to be able to help our junior colleagues and our peers to be able to feel competent to discuss antipsychotics with patients with delusional infestation and also initiate management.”
Dr. Ahmed added: “Why we’re encouraging our colleagues to prescribe antipsychotics is the longer you leave this type of psychotic illness untreated, the worse the prognosis.”
No funding or relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
GLASGOW – that also indicated there is a clear demand for training in prescribing these drugs.
Delusional infestation is a rare disorder characterized by an individual’s belief that his or her skin, body, or immediate environment is infested by small, living pathogens, despite a lack of any medical evidence. Most of these patients require antipsychotic medication to alleviate symptoms.
The survey of almost 80 dermatologists found that almost 90% had not prescribed antipsychotics in the previous month for patients with psychodermatology conditions and that the most common barrier to prescribing was lack of experience with the drugs.
This was reflected in only 10% of survey respondents who said they were “happy to” prescribe antipsychotics without consulting either dermatology or psychiatric colleagues, and less than half having attended a related course.
Yet the research, presented at the annual meeting of the British Association of Dermatologists, indicated that more than 75% of respondents would attend such a course to increase their confidence.
This finding, said study presenter Ling Li, MD, Churchill Hospital, Oxford (England) University Hospitals NHS Foundation Trust, shows that there is a “clear demand for training, particularly among all the registrars [residents] who we surveyed.”
Dr. Li noted that the UK’s Joint Royal Colleges of Physicians Training Board’s latest curriculum for dermatology training highlights psychocutaneous medicine as a key area, and “that will include antipsychotic medication.”
The BAD also recently published guidelines for the management of adults with delusional infestation, which includes a recommendation to conduct a survey on attitudes toward antipsychotic prescribing for the condition among U.K. dermatologists.
Heeding that call, Dr. Li and colleagues sent an email containing a 10-question online survey to members of the BAD and the British Society for Medical Dermatology. Questions covered familiarity with antipsychotics and frequency of prescribing, confidence around antipsychotics, and current training and future needs. Responses were received between February through April 2021.
Among the 79 respondents, 51 (65%) were consultants and 20 (25%) were dermatology registrars, with the remainder dermatology clinical fellows, foundation doctors, or other doctors. A total of 31 respondents had an average of more than 50 visits with patients per week, 18 had an average of 41-50 patient visits, and 13 had an average of 31-40 visits per week; the remainder had an average of 11-30 visits per week.
Most of the respondents (39) said they had seen 2-5 patients with psychodermatology conditions in the last 6 months, while 17 said they had seen 1 patient, 13 said they had seen more than 10 patients, and 6 said they had seen 6-10 patients (4 had seen none and 1 could not remember).
The most commonly prescribed antipsychotics for psychodermatology patients in the past 6 months were risperidone (Risperdal; prescribed by five respondents), followed by olanzapine (Zyprexa; by four respondents). Seventy respondents had not prescribed any antipsychotics.
Asked about how confident they felt about prescribing antipsychotic medication for patients with delusional infestation, 8 (10%) said they were happy to prescribe independently, while 42 (54%) said they were not at all confident. Another 10 (13%) respondents said they would be happy to prescribe the medications after liaising with a dermatology colleague, while 17 (22%) said they would prefer to consult with the psychiatry team.
The most common barrier to prescribing antipsychotic medications was a lack of experience with the drugs, cited by 66 respondents, followed by concerns over drug monitoring, cited by 43 respondents.
In addition, 42 respondents highlighted concerns over adverse effects, 36 cited lack of experience in psychodermatology clinics, and 19 cited lack of experience in discussing psychodermatologic conditions with patients. Other barriers mentioned by the respondents included difficulties with patient acceptance of a psychiatric medication prescribed by a dermatologist.
An audience member went further, saying that clinicians have been told not to “confront” such patients and that the temptation is therefore to cloak the discussion of antipsychotics in nonthreatening language so that it is more acceptable to the patient.
However, under the U.K. system, a letter with the results of the consultation, including information that an antipsychotic has been prescribed, must be sent to the patient’s family doctor along with a copy that goes to the patient. “The situation is almost impossible,” the audience member said, adding that there “must be some arrangement where in certain circumstances dermatologists could be allowed not to write to the patient” or alternatively, “write an entirely different letter” to the family doctor.
Session cochair Susannah Baron, MD, a consultant dermatologist at St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospital, London, said that, in these situations, it is “really helpful to talk about doses” with patients.
She explained that she uses the analogy of aspirin, which has different effects depending on the dose given, giving pain relief at high doses but primarily an antiplatelet effect at low doses.
In the case of an antipsychotic, it is helpful to explain to the patient that “you don’t think they’re psychotic, and you’re prescribing it in a very low dose, because what it can do is help with their symptoms,” Dr. Baron added. “You have to be very open because if you’re not, they go to the pharmacy, and the pharmacist says: ‘Why are you on an antipsychotic?’ ”
Further results from the survey revealed that 56 (71%) respondents did not have access to a specialist psychodermatology clinic, whereas 36 (46%) had not yet attended a psychodermatology course.
Despite these responses, 60 (77%) respondents said they would be interested in attending a training course for prescribing antipsychotics, which included all 20 of the registrars who took part in the survey. a psychodermatologist at Frimley Health Foundation Trust, Windsor, England, and lead author of the BAD guidelines, commented from the audience that the survey results were “sort of what we expected.”
She explained that the intention of the authors when developing the guidelines “was to be able to help our junior colleagues and our peers to be able to feel competent to discuss antipsychotics with patients with delusional infestation and also initiate management.”
Dr. Ahmed added: “Why we’re encouraging our colleagues to prescribe antipsychotics is the longer you leave this type of psychotic illness untreated, the worse the prognosis.”
No funding or relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
AT BAD 2022
No adverse impact of obesity in biologic-treated IBD
Patients with both inflammatory bowel disease (IBD) and obesity starting on new biologic therapies do not face an increased risk for hospitalization, IBD-related surgery, or serious infection, reveals a multicenter U.S. study published online in American Journal of Gastroenterology.
“Our findings were a bit surprising, since prior studies had suggested higher clinical disease activity and risk of flare and lower rates of endoscopic remission in obese patients treated with biologics,” Siddharth Singh, MD, MS, director of the IBD Center at the University of California, San Diego, told this news organization.
“However, in this study we focused on harder outcomes, including risk of hospitalization and surgery, and did not observe any detrimental effect,” he said.
Based on the findings, Dr. Singh believes that biologics are “completely safe and effective to use in obese patients.”
He clarified, however, that “examining the overall body of evidence, I still think obesity results in more rapid clearance of biologics, which negatively impacts the likelihood of achieving symptomatic and endoscopic remission.”
“Hence, there should be a low threshold to monitor and optimize biologic drug concentrations in obese patients. I preferentially use biologics that are dosed based on body weight in patients with class II or III obesity,” he said.
Research findings
Dr. Singh and colleagues write that, given that between 15% and 45% of patients with IBD are obese and a further 20%-40% are overweight, obesity is an “increasingly important consideration” in its management.
It is believed that obesity, largely via visceral adiposity, has a negative impact on IBD via increased production of adipokines, chemokines, and cytokines, such as tumor necrosis factor (TNF) alpha and interleukin-6, thus affecting treatment response as well as increasing the risk for complications and infections.
However, studies of the association between obesity and poorer treatment response, both large and small, have yielded conflicting results, potentially owing to methodological limitations.
To investigate further, Dr. Singh and colleagues gathered electronic health record data from five health systems in California on adults with IBD who were new users of TNF-alpha antagonists, or the monoclonal antibodies vedolizumab or ustekinumab, between Jan. 1, 2010, and June 30, 2017.
World Health Organization definitions were used to classify the patients as having normal BMI, overweight, or obesity, and the risk for all-cause hospitalization, IBD-related surgery, or serious infection was compared between the groups.
The team reviewed the cases of 3,038 patients with IBD, of whom 31.1% had ulcerative colitis. Among the participants, 28.2% were classified as overweight and 13.7% as obese. TNF-alpha antagonists were used by 76.3% of patients.
Patients with obesity were significantly older, were more likely to be of Hispanic ethnicity, had a higher burden of comorbidities, and were more likely to have elevated C-reactive protein levels at baseline.
However, there were no significant differences between obese and nonobese patients in terms of IBD type, class of biologic prescribed, prior surgery, or prior biologic exposure.
Within 1 year of starting a new biologic therapy, 22.9% of patients required hospitalization, whereas 3.3% required surgery and 5.8% were hospitalized with a serious infection.
Cox proportional hazard analyses showed that obesity was not associated with an increased risk for hospitalization versus normal body mass index (adjusted hazard ratio, 0.90; 95% confidence interval, 0.72-1.13), nor was it associated with IBD-related surgery (aHR, 0.62; 95% CI, 0.31-1.22) or serious infection (aHR, 1.11; 95% CI, 0.73-1.71).
The results were similar when the patients were stratified by IBD type and index biologic therapy, the researchers write.
When analyzed as a continuous variable, BMI was associated with a lower risk for hospitalization (aHR, 0.98 per 1 kg/m2; P = .044) but not with IBD-related surgery or serious infection.
Reassuring results for the standard of care
Discussing their findings, the authors note that “the discrepancy among studies potentially reflects the shortcomings of overall obesity measured using BMI to capture clinically meaningful adiposity.”
“A small but growing body of literature suggests visceral adipose tissue is a potentially superior prognostic measure of adiposity and better predicts adverse outcomes in IBD.”
Dr. Singh said that it would be “very interesting” to examine the relationship between visceral adiposity, as inferred from waist circumference, and IBD outcomes.
Approached for comment, Stephen B. Hanauer, MD, Clifford Joseph Barborka Professor, Northwestern University Feinberg School of Medicine, Chicago, said, “At the present time, there are no new clinical implications based on this study.”
He said in an interview that it “does not require any change in the current standard of care but rather attempts to reassure that the standard of care does not change for obese patients.”
“With that being said, the standard of care may require dosing adjustments for patients based on weight, as is already the case for infliximab/ustekinumab, and monitoring to treat to target in obese patients as well as in normal or underweight patients,” Dr. Hanauer concluded.
The study was supported by the ACG Junior Faculty Development Award and the Crohn’s and Colitis Foundation Career Development Award to Dr. Singh. Dr. Singh is supported by the National Institute of Diabetes and Digestive and Kidney Diseases and reports relationships with AbbVie, Janssen, and Pfizer. The other authors report numerous financial relationships. Dr. Hanauer reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients with both inflammatory bowel disease (IBD) and obesity starting on new biologic therapies do not face an increased risk for hospitalization, IBD-related surgery, or serious infection, reveals a multicenter U.S. study published online in American Journal of Gastroenterology.
“Our findings were a bit surprising, since prior studies had suggested higher clinical disease activity and risk of flare and lower rates of endoscopic remission in obese patients treated with biologics,” Siddharth Singh, MD, MS, director of the IBD Center at the University of California, San Diego, told this news organization.
“However, in this study we focused on harder outcomes, including risk of hospitalization and surgery, and did not observe any detrimental effect,” he said.
Based on the findings, Dr. Singh believes that biologics are “completely safe and effective to use in obese patients.”
He clarified, however, that “examining the overall body of evidence, I still think obesity results in more rapid clearance of biologics, which negatively impacts the likelihood of achieving symptomatic and endoscopic remission.”
“Hence, there should be a low threshold to monitor and optimize biologic drug concentrations in obese patients. I preferentially use biologics that are dosed based on body weight in patients with class II or III obesity,” he said.
Research findings
Dr. Singh and colleagues write that, given that between 15% and 45% of patients with IBD are obese and a further 20%-40% are overweight, obesity is an “increasingly important consideration” in its management.
It is believed that obesity, largely via visceral adiposity, has a negative impact on IBD via increased production of adipokines, chemokines, and cytokines, such as tumor necrosis factor (TNF) alpha and interleukin-6, thus affecting treatment response as well as increasing the risk for complications and infections.
However, studies of the association between obesity and poorer treatment response, both large and small, have yielded conflicting results, potentially owing to methodological limitations.
To investigate further, Dr. Singh and colleagues gathered electronic health record data from five health systems in California on adults with IBD who were new users of TNF-alpha antagonists, or the monoclonal antibodies vedolizumab or ustekinumab, between Jan. 1, 2010, and June 30, 2017.
World Health Organization definitions were used to classify the patients as having normal BMI, overweight, or obesity, and the risk for all-cause hospitalization, IBD-related surgery, or serious infection was compared between the groups.
The team reviewed the cases of 3,038 patients with IBD, of whom 31.1% had ulcerative colitis. Among the participants, 28.2% were classified as overweight and 13.7% as obese. TNF-alpha antagonists were used by 76.3% of patients.
Patients with obesity were significantly older, were more likely to be of Hispanic ethnicity, had a higher burden of comorbidities, and were more likely to have elevated C-reactive protein levels at baseline.
However, there were no significant differences between obese and nonobese patients in terms of IBD type, class of biologic prescribed, prior surgery, or prior biologic exposure.
Within 1 year of starting a new biologic therapy, 22.9% of patients required hospitalization, whereas 3.3% required surgery and 5.8% were hospitalized with a serious infection.
Cox proportional hazard analyses showed that obesity was not associated with an increased risk for hospitalization versus normal body mass index (adjusted hazard ratio, 0.90; 95% confidence interval, 0.72-1.13), nor was it associated with IBD-related surgery (aHR, 0.62; 95% CI, 0.31-1.22) or serious infection (aHR, 1.11; 95% CI, 0.73-1.71).
The results were similar when the patients were stratified by IBD type and index biologic therapy, the researchers write.
When analyzed as a continuous variable, BMI was associated with a lower risk for hospitalization (aHR, 0.98 per 1 kg/m2; P = .044) but not with IBD-related surgery or serious infection.
Reassuring results for the standard of care
Discussing their findings, the authors note that “the discrepancy among studies potentially reflects the shortcomings of overall obesity measured using BMI to capture clinically meaningful adiposity.”
“A small but growing body of literature suggests visceral adipose tissue is a potentially superior prognostic measure of adiposity and better predicts adverse outcomes in IBD.”
Dr. Singh said that it would be “very interesting” to examine the relationship between visceral adiposity, as inferred from waist circumference, and IBD outcomes.
Approached for comment, Stephen B. Hanauer, MD, Clifford Joseph Barborka Professor, Northwestern University Feinberg School of Medicine, Chicago, said, “At the present time, there are no new clinical implications based on this study.”
He said in an interview that it “does not require any change in the current standard of care but rather attempts to reassure that the standard of care does not change for obese patients.”
“With that being said, the standard of care may require dosing adjustments for patients based on weight, as is already the case for infliximab/ustekinumab, and monitoring to treat to target in obese patients as well as in normal or underweight patients,” Dr. Hanauer concluded.
The study was supported by the ACG Junior Faculty Development Award and the Crohn’s and Colitis Foundation Career Development Award to Dr. Singh. Dr. Singh is supported by the National Institute of Diabetes and Digestive and Kidney Diseases and reports relationships with AbbVie, Janssen, and Pfizer. The other authors report numerous financial relationships. Dr. Hanauer reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients with both inflammatory bowel disease (IBD) and obesity starting on new biologic therapies do not face an increased risk for hospitalization, IBD-related surgery, or serious infection, reveals a multicenter U.S. study published online in American Journal of Gastroenterology.
“Our findings were a bit surprising, since prior studies had suggested higher clinical disease activity and risk of flare and lower rates of endoscopic remission in obese patients treated with biologics,” Siddharth Singh, MD, MS, director of the IBD Center at the University of California, San Diego, told this news organization.
“However, in this study we focused on harder outcomes, including risk of hospitalization and surgery, and did not observe any detrimental effect,” he said.
Based on the findings, Dr. Singh believes that biologics are “completely safe and effective to use in obese patients.”
He clarified, however, that “examining the overall body of evidence, I still think obesity results in more rapid clearance of biologics, which negatively impacts the likelihood of achieving symptomatic and endoscopic remission.”
“Hence, there should be a low threshold to monitor and optimize biologic drug concentrations in obese patients. I preferentially use biologics that are dosed based on body weight in patients with class II or III obesity,” he said.
Research findings
Dr. Singh and colleagues write that, given that between 15% and 45% of patients with IBD are obese and a further 20%-40% are overweight, obesity is an “increasingly important consideration” in its management.
It is believed that obesity, largely via visceral adiposity, has a negative impact on IBD via increased production of adipokines, chemokines, and cytokines, such as tumor necrosis factor (TNF) alpha and interleukin-6, thus affecting treatment response as well as increasing the risk for complications and infections.
However, studies of the association between obesity and poorer treatment response, both large and small, have yielded conflicting results, potentially owing to methodological limitations.
To investigate further, Dr. Singh and colleagues gathered electronic health record data from five health systems in California on adults with IBD who were new users of TNF-alpha antagonists, or the monoclonal antibodies vedolizumab or ustekinumab, between Jan. 1, 2010, and June 30, 2017.
World Health Organization definitions were used to classify the patients as having normal BMI, overweight, or obesity, and the risk for all-cause hospitalization, IBD-related surgery, or serious infection was compared between the groups.
The team reviewed the cases of 3,038 patients with IBD, of whom 31.1% had ulcerative colitis. Among the participants, 28.2% were classified as overweight and 13.7% as obese. TNF-alpha antagonists were used by 76.3% of patients.
Patients with obesity were significantly older, were more likely to be of Hispanic ethnicity, had a higher burden of comorbidities, and were more likely to have elevated C-reactive protein levels at baseline.
However, there were no significant differences between obese and nonobese patients in terms of IBD type, class of biologic prescribed, prior surgery, or prior biologic exposure.
Within 1 year of starting a new biologic therapy, 22.9% of patients required hospitalization, whereas 3.3% required surgery and 5.8% were hospitalized with a serious infection.
Cox proportional hazard analyses showed that obesity was not associated with an increased risk for hospitalization versus normal body mass index (adjusted hazard ratio, 0.90; 95% confidence interval, 0.72-1.13), nor was it associated with IBD-related surgery (aHR, 0.62; 95% CI, 0.31-1.22) or serious infection (aHR, 1.11; 95% CI, 0.73-1.71).
The results were similar when the patients were stratified by IBD type and index biologic therapy, the researchers write.
When analyzed as a continuous variable, BMI was associated with a lower risk for hospitalization (aHR, 0.98 per 1 kg/m2; P = .044) but not with IBD-related surgery or serious infection.
Reassuring results for the standard of care
Discussing their findings, the authors note that “the discrepancy among studies potentially reflects the shortcomings of overall obesity measured using BMI to capture clinically meaningful adiposity.”
“A small but growing body of literature suggests visceral adipose tissue is a potentially superior prognostic measure of adiposity and better predicts adverse outcomes in IBD.”
Dr. Singh said that it would be “very interesting” to examine the relationship between visceral adiposity, as inferred from waist circumference, and IBD outcomes.
Approached for comment, Stephen B. Hanauer, MD, Clifford Joseph Barborka Professor, Northwestern University Feinberg School of Medicine, Chicago, said, “At the present time, there are no new clinical implications based on this study.”
He said in an interview that it “does not require any change in the current standard of care but rather attempts to reassure that the standard of care does not change for obese patients.”
“With that being said, the standard of care may require dosing adjustments for patients based on weight, as is already the case for infliximab/ustekinumab, and monitoring to treat to target in obese patients as well as in normal or underweight patients,” Dr. Hanauer concluded.
The study was supported by the ACG Junior Faculty Development Award and the Crohn’s and Colitis Foundation Career Development Award to Dr. Singh. Dr. Singh is supported by the National Institute of Diabetes and Digestive and Kidney Diseases and reports relationships with AbbVie, Janssen, and Pfizer. The other authors report numerous financial relationships. Dr. Hanauer reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Persistent abdominal pain: Not always IBS
Persistent abdominal pain may be caused by a whole range of different conditions, say French experts who call for more physician awareness to achieve early diagnosis and treatment so as to improve patient outcomes.
Benoit Coffin, MD, PhD, and Henri Duboc, MD, PhD, from Hôpital Louis Mourier, Colombes, France, conducted a literature review to identify rare and less well-known causes of persistent abdominal pain, identifying almost 50 across several categories.
“Some causes of persistent abdominal pain can be effectively treated using established approaches after a definitive diagnosis has been reached,” they wrote.
“Other causes are more complex and may benefit from a multidisciplinary approach involving gastroenterologists, pain specialists, allergists, immunologists, rheumatologists, psychologists, physiotherapists, dietitians, and primary care clinicians,” they wrote.
The research was published online in Alimentary Pharmacology and Therapeutics.
Frequent and frustrating symptoms
Although there is “no commonly accepted definition” for persistent abdominal pain, the authors said it may be defined as “continuous or intermittent abdominal discomfort that persists for at least 6 months and fails to respond to conventional therapeutic approaches.”
They highlight that it is “frequently encountered” by physicians and has a prevalence of 22.9 per 1,000 person-years, regardless of age group, ethnicity, or geographical region, with many patients experiencing pain for more than 5 years.
The cause of persistent abdominal pain can be organic with a clear cause or functional, making diagnosis and management “challenging and frustrating for patients and physicians.”
“Clinicians not only need to recognize somatic abnormalities, but they must also perceive the patient’s cognitions and emotions related to the pain,” they added, suggesting that clinicians take time to “listen to the patient and perceive psychological factors.”
Dr. Coffin and Dr. Duboc write that the most common conditions associated with persistent abdominal pain are irritable bowel syndrome and functional dyspepsia, as well as inflammatory bowel disease, chronic pancreatitis, and gallstones.
To examine the diagnosis and management of its less well-known causes, the authors conducted a literature review, beginning with the diagnosis of persistent abdominal pain.
Diagnostic workup
“Given its chronicity, many patients will have already undergone extensive and redundant medical testing,” they wrote, emphasizing that clinicians should be on the lookout for any change in the description of persistent abdominal pain or new symptoms.
“Other ‘red-flag’ symptoms include fever, vomiting, diarrhea, acute change in bowel habit, obstipation, syncope, tachycardia, hypotension, concomitant chest or back pain, unintentional weight loss, night sweats, and acute gastrointestinal bleeding,” the authors said.
They stressed the need to determine whether the origin of the pain is organic or functional, as well as the importance of identifying a “triggering event, such as an adverse life event, infection, initiating a new medication, or surgical procedure.” They also recommend discussing the patient’s diet.
There are currently no specific algorithms for diagnostic workup of persistent abdominal pain, the authors said. Patients will have undergone repeated laboratory tests, “upper and lower endoscopic examinations, abdominal ultrasounds, and computed tomography scans of the abdominal/pelvic area.”
Consequently, “in the absence of alarm features, any additional tests should be ordered in a conservative and cost-effective manner,” they advised.
They suggested that, at a tertiary center, patients should be assessed in three steps:
- In-depth questioning of the symptoms and medical history
- Summary of all previous investigations and treatments and their effectiveness
- Determination of the complementary explorations to be performed
The authors went on to list 49 rare or less well-known potential causes of persistent abdominal pain, some linked to digestive disorders, such as eosinophilic gastroenteritis, mesenteric panniculitis, and chronic mesenteric ischemia, as well as endometriosis, chronic abdominal wall pain, and referred osteoarticular pain.
Systemic causes of persistent abdominal pain may include adrenal insufficiency and mast cell activation syndrome, while acute hepatic porphyrias and Ehlers-Danlos syndrome may be genetic causes.
There are also centrally mediated disorders that lead to persistent abdominal pain, the authors noted, including postural orthostatic tachycardia syndrome and narcotic bowel syndrome caused by opioid therapy, among others.
Writing support for the manuscript was funded by Alnylam Switzerland. Dr. Coffin has served as a speaker for Kyowa Kyrin and Mayoly Spindler and as an advisory board member for Sanofi and Alnylam. Dr. Duboc reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Persistent abdominal pain may be caused by a whole range of different conditions, say French experts who call for more physician awareness to achieve early diagnosis and treatment so as to improve patient outcomes.
Benoit Coffin, MD, PhD, and Henri Duboc, MD, PhD, from Hôpital Louis Mourier, Colombes, France, conducted a literature review to identify rare and less well-known causes of persistent abdominal pain, identifying almost 50 across several categories.
“Some causes of persistent abdominal pain can be effectively treated using established approaches after a definitive diagnosis has been reached,” they wrote.
“Other causes are more complex and may benefit from a multidisciplinary approach involving gastroenterologists, pain specialists, allergists, immunologists, rheumatologists, psychologists, physiotherapists, dietitians, and primary care clinicians,” they wrote.
The research was published online in Alimentary Pharmacology and Therapeutics.
Frequent and frustrating symptoms
Although there is “no commonly accepted definition” for persistent abdominal pain, the authors said it may be defined as “continuous or intermittent abdominal discomfort that persists for at least 6 months and fails to respond to conventional therapeutic approaches.”
They highlight that it is “frequently encountered” by physicians and has a prevalence of 22.9 per 1,000 person-years, regardless of age group, ethnicity, or geographical region, with many patients experiencing pain for more than 5 years.
The cause of persistent abdominal pain can be organic with a clear cause or functional, making diagnosis and management “challenging and frustrating for patients and physicians.”
“Clinicians not only need to recognize somatic abnormalities, but they must also perceive the patient’s cognitions and emotions related to the pain,” they added, suggesting that clinicians take time to “listen to the patient and perceive psychological factors.”
Dr. Coffin and Dr. Duboc write that the most common conditions associated with persistent abdominal pain are irritable bowel syndrome and functional dyspepsia, as well as inflammatory bowel disease, chronic pancreatitis, and gallstones.
To examine the diagnosis and management of its less well-known causes, the authors conducted a literature review, beginning with the diagnosis of persistent abdominal pain.
Diagnostic workup
“Given its chronicity, many patients will have already undergone extensive and redundant medical testing,” they wrote, emphasizing that clinicians should be on the lookout for any change in the description of persistent abdominal pain or new symptoms.
“Other ‘red-flag’ symptoms include fever, vomiting, diarrhea, acute change in bowel habit, obstipation, syncope, tachycardia, hypotension, concomitant chest or back pain, unintentional weight loss, night sweats, and acute gastrointestinal bleeding,” the authors said.
They stressed the need to determine whether the origin of the pain is organic or functional, as well as the importance of identifying a “triggering event, such as an adverse life event, infection, initiating a new medication, or surgical procedure.” They also recommend discussing the patient’s diet.
There are currently no specific algorithms for diagnostic workup of persistent abdominal pain, the authors said. Patients will have undergone repeated laboratory tests, “upper and lower endoscopic examinations, abdominal ultrasounds, and computed tomography scans of the abdominal/pelvic area.”
Consequently, “in the absence of alarm features, any additional tests should be ordered in a conservative and cost-effective manner,” they advised.
They suggested that, at a tertiary center, patients should be assessed in three steps:
- In-depth questioning of the symptoms and medical history
- Summary of all previous investigations and treatments and their effectiveness
- Determination of the complementary explorations to be performed
The authors went on to list 49 rare or less well-known potential causes of persistent abdominal pain, some linked to digestive disorders, such as eosinophilic gastroenteritis, mesenteric panniculitis, and chronic mesenteric ischemia, as well as endometriosis, chronic abdominal wall pain, and referred osteoarticular pain.
Systemic causes of persistent abdominal pain may include adrenal insufficiency and mast cell activation syndrome, while acute hepatic porphyrias and Ehlers-Danlos syndrome may be genetic causes.
There are also centrally mediated disorders that lead to persistent abdominal pain, the authors noted, including postural orthostatic tachycardia syndrome and narcotic bowel syndrome caused by opioid therapy, among others.
Writing support for the manuscript was funded by Alnylam Switzerland. Dr. Coffin has served as a speaker for Kyowa Kyrin and Mayoly Spindler and as an advisory board member for Sanofi and Alnylam. Dr. Duboc reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Persistent abdominal pain may be caused by a whole range of different conditions, say French experts who call for more physician awareness to achieve early diagnosis and treatment so as to improve patient outcomes.
Benoit Coffin, MD, PhD, and Henri Duboc, MD, PhD, from Hôpital Louis Mourier, Colombes, France, conducted a literature review to identify rare and less well-known causes of persistent abdominal pain, identifying almost 50 across several categories.
“Some causes of persistent abdominal pain can be effectively treated using established approaches after a definitive diagnosis has been reached,” they wrote.
“Other causes are more complex and may benefit from a multidisciplinary approach involving gastroenterologists, pain specialists, allergists, immunologists, rheumatologists, psychologists, physiotherapists, dietitians, and primary care clinicians,” they wrote.
The research was published online in Alimentary Pharmacology and Therapeutics.
Frequent and frustrating symptoms
Although there is “no commonly accepted definition” for persistent abdominal pain, the authors said it may be defined as “continuous or intermittent abdominal discomfort that persists for at least 6 months and fails to respond to conventional therapeutic approaches.”
They highlight that it is “frequently encountered” by physicians and has a prevalence of 22.9 per 1,000 person-years, regardless of age group, ethnicity, or geographical region, with many patients experiencing pain for more than 5 years.
The cause of persistent abdominal pain can be organic with a clear cause or functional, making diagnosis and management “challenging and frustrating for patients and physicians.”
“Clinicians not only need to recognize somatic abnormalities, but they must also perceive the patient’s cognitions and emotions related to the pain,” they added, suggesting that clinicians take time to “listen to the patient and perceive psychological factors.”
Dr. Coffin and Dr. Duboc write that the most common conditions associated with persistent abdominal pain are irritable bowel syndrome and functional dyspepsia, as well as inflammatory bowel disease, chronic pancreatitis, and gallstones.
To examine the diagnosis and management of its less well-known causes, the authors conducted a literature review, beginning with the diagnosis of persistent abdominal pain.
Diagnostic workup
“Given its chronicity, many patients will have already undergone extensive and redundant medical testing,” they wrote, emphasizing that clinicians should be on the lookout for any change in the description of persistent abdominal pain or new symptoms.
“Other ‘red-flag’ symptoms include fever, vomiting, diarrhea, acute change in bowel habit, obstipation, syncope, tachycardia, hypotension, concomitant chest or back pain, unintentional weight loss, night sweats, and acute gastrointestinal bleeding,” the authors said.
They stressed the need to determine whether the origin of the pain is organic or functional, as well as the importance of identifying a “triggering event, such as an adverse life event, infection, initiating a new medication, or surgical procedure.” They also recommend discussing the patient’s diet.
There are currently no specific algorithms for diagnostic workup of persistent abdominal pain, the authors said. Patients will have undergone repeated laboratory tests, “upper and lower endoscopic examinations, abdominal ultrasounds, and computed tomography scans of the abdominal/pelvic area.”
Consequently, “in the absence of alarm features, any additional tests should be ordered in a conservative and cost-effective manner,” they advised.
They suggested that, at a tertiary center, patients should be assessed in three steps:
- In-depth questioning of the symptoms and medical history
- Summary of all previous investigations and treatments and their effectiveness
- Determination of the complementary explorations to be performed
The authors went on to list 49 rare or less well-known potential causes of persistent abdominal pain, some linked to digestive disorders, such as eosinophilic gastroenteritis, mesenteric panniculitis, and chronic mesenteric ischemia, as well as endometriosis, chronic abdominal wall pain, and referred osteoarticular pain.
Systemic causes of persistent abdominal pain may include adrenal insufficiency and mast cell activation syndrome, while acute hepatic porphyrias and Ehlers-Danlos syndrome may be genetic causes.
There are also centrally mediated disorders that lead to persistent abdominal pain, the authors noted, including postural orthostatic tachycardia syndrome and narcotic bowel syndrome caused by opioid therapy, among others.
Writing support for the manuscript was funded by Alnylam Switzerland. Dr. Coffin has served as a speaker for Kyowa Kyrin and Mayoly Spindler and as an advisory board member for Sanofi and Alnylam. Dr. Duboc reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ALIMENTARY PHARMACOLOGY AND THERAPEUTICS
Advance directives for psychiatric care reduce compulsory admissions
, new research shows.
Results of a randomized trial showed the peer worker PAD group had a 42% reduction in compulsory admission over the following 12 months. This study group also had lower symptom scores, greater rates of recovery, and increased empowerment, compared with patients assigned to usual care.
In addition to proving that PADs are effective in reducing compulsory admission, the results show that facilitation by peer workers is relevant, study investigator Aurélie Tinland, MD, PhD, Faculté de Médecine Timone, Aix-Marseille University, Marseille, France, told delegates attending the virtual European Psychiatric Association (EPA) 2022 Congress. The study was simultaneously published online in JAMA Psychiatry.
However, Dr. Tinland noted that more research that includes “harder to reach” populations is needed. In addition, greater use of PADs is also key to reducing compulsory admissions.
‘Most coercive’ country
The researchers note that respect for patient autonomy is a strong pillar of health care, such that “involuntary treatment should be unusual.” However, they point out that “compulsory psychiatric admissions are far too common in countries of all income levels.”
In France, said Dr. Tinland, 24% of psychiatric hospitalizations are compulsory. The country is ranked the sixth “most coercive” country in the world, and there are concerns about human rights in French psychiatric facilities.
She added that advance care statements are the most efficient tool for reducing coercion, with one study suggesting they could cut rates by 25%, compared with usual care.
However, she noted there is an “asymmetry” between medical professionals and patients and a risk of “undue influence” when clinicians facilitate the completion of care statements.
To examine the impact on clinical outcomes of peer-worker facilitated PADs, the researchers studied adults with a diagnosis of schizophrenia, bipolar I disorder, or schizoaffective disorder who were admitted to a psychiatric hospital within the previous 12 months. Peer workers are individuals who have lived experience with mental illness and help inform and guide current patients about care options in the event of a mental health crisis.
Study participants were randomly assigned 1:1 to an intervention group or a usual care control group. The intervention group received a PAD document and were assigned a peer worker while the usual care group received comprehensive information about the PAD concept at study entry and were free to complete it, but they were not connected with a peer worker.
The PAD document included information about future treatment and support preferences, early signs of relapse, and coping strategies. Participants could meet the peer worker in a place of their choice and be supported in drafting the document and in sharing it with health care professionals.
In all, 394 individuals completed the study. The majority (61%) of participants were male and 66% had completed post-secondary education. Schizophrenia was diagnosed in 45%, bipolar I disorder in 36%, and schizoaffective disorder in 19%.
Participants in the intervention group were significantly younger than those in the control group, with a mean of 37.4 years versus 41 years (P = .003) and were less likely to have one or more somatic comorbidities, at 61.2% versus 69.2%.
A PAD was completed by 54.6% of individuals in the intervention group versus 7.1% of controls (P < .001). The PAD was written with peer worker support by 41.3% of those in the intervention and by 2% of controls. Of those who completed a PAD, 75.7% met care facilitators, and 27.1% used it during a crisis over the following 12 months.
Results showed that the rate of compulsory admissions was significantly lower in the peer worker PAD group, at 27% versus 39.9% in control participants, at an odds ratio of 0.58 (P = .007).
Participants in the intervention group had lower symptoms on the modified Colorado Symptom Score than usual care patients with an effect size of -0.20 (P = .03) and higher scores on the Empowerment Scale (effect size 0.30, P = .003).
Scores on the Recovery Assessment Scale were also significantly higher in the peer worker PAD group versus controls with an effect size of 0.44 (P < .001). There were no significant differences, however, in overall admission rates, the quality of the therapeutic alliance, or quality of life.
Putting patients in the driver’s seat
Commenting on the findings, Robert Dabney Jr., MA, MDiv, peer apprentice program manager at the Depression and Bipolar Support Alliance, Chicago, said the study “tells us there are many benefits to completing a psychiatric advance directive, but perhaps the most powerful one is putting the person receiving mental health care in the driver’s seat of their own recovery.”
However, he noted that “many people living with mental health conditions don’t know the option exists to decide on their treatment plan in advance of a crisis.”
“This is where peer support specialists can come in. Having a peer who has been through similar experiences and can guide you through the process is as comforting as it is empowering. I have witnessed and experienced firsthand the power of peer support,” he said.
“It’s my personal hope and the goal of the Depression and Bipolar Support Alliance to empower more people to either become peer support specialists or seek out peer support services, because we know it improves and even saves lives,” Mr. Dabney added.
Virginia A. Brown, PhD, department of psychiatry & behavioral sciences, University of Texas at Austin Dell Medical School, noted there are huge differences between the health care systems in France and the United States.
She explained that two of the greatest barriers to PADs in the United States is that until 2016, filling one out was not billable and that “practitioners don’t know anything about advanced care plans.”
Dr. Brown said her own work shows that individuals who support patients during a crisis believe it would be “really helpful if we had some kind of document that we could share with the health care system that says: ‘Hey, look, I’m the designated person to speak for this patient, they’ve identified me through a document.’ So, people were actually describing a need for this document but didn’t know that it existed.”
Another problem is that in the United States, hospitals operate in a “closed system” and cannot talk to an unrelated hospital or to the police department “to get information to those first responders during an emergency about who to talk to about their wishes and preferences.”
“There are a lot of hurdles that we’ve got to get over to make a more robust system that protects the autonomy of people who live with serious mental illness,” Dr. Brown said, as “losing capacity during a crisis is time-limited, and it requires us to respond to it as a medical emergency.”
The study was supported by an institutional grant from the French 2017 National Program of Health Services Research. The Clinical Research Direction of Assistance Publique Hôpitaux de Marseille sponsored the trial. Dr. Tinland declares grants from the French Ministry of Health Directorate General of Health Care Services during the conduct of the study.
A version of this article first appeared on Medscape.com.
, new research shows.
Results of a randomized trial showed the peer worker PAD group had a 42% reduction in compulsory admission over the following 12 months. This study group also had lower symptom scores, greater rates of recovery, and increased empowerment, compared with patients assigned to usual care.
In addition to proving that PADs are effective in reducing compulsory admission, the results show that facilitation by peer workers is relevant, study investigator Aurélie Tinland, MD, PhD, Faculté de Médecine Timone, Aix-Marseille University, Marseille, France, told delegates attending the virtual European Psychiatric Association (EPA) 2022 Congress. The study was simultaneously published online in JAMA Psychiatry.
However, Dr. Tinland noted that more research that includes “harder to reach” populations is needed. In addition, greater use of PADs is also key to reducing compulsory admissions.
‘Most coercive’ country
The researchers note that respect for patient autonomy is a strong pillar of health care, such that “involuntary treatment should be unusual.” However, they point out that “compulsory psychiatric admissions are far too common in countries of all income levels.”
In France, said Dr. Tinland, 24% of psychiatric hospitalizations are compulsory. The country is ranked the sixth “most coercive” country in the world, and there are concerns about human rights in French psychiatric facilities.
She added that advance care statements are the most efficient tool for reducing coercion, with one study suggesting they could cut rates by 25%, compared with usual care.
However, she noted there is an “asymmetry” between medical professionals and patients and a risk of “undue influence” when clinicians facilitate the completion of care statements.
To examine the impact on clinical outcomes of peer-worker facilitated PADs, the researchers studied adults with a diagnosis of schizophrenia, bipolar I disorder, or schizoaffective disorder who were admitted to a psychiatric hospital within the previous 12 months. Peer workers are individuals who have lived experience with mental illness and help inform and guide current patients about care options in the event of a mental health crisis.
Study participants were randomly assigned 1:1 to an intervention group or a usual care control group. The intervention group received a PAD document and were assigned a peer worker while the usual care group received comprehensive information about the PAD concept at study entry and were free to complete it, but they were not connected with a peer worker.
The PAD document included information about future treatment and support preferences, early signs of relapse, and coping strategies. Participants could meet the peer worker in a place of their choice and be supported in drafting the document and in sharing it with health care professionals.
In all, 394 individuals completed the study. The majority (61%) of participants were male and 66% had completed post-secondary education. Schizophrenia was diagnosed in 45%, bipolar I disorder in 36%, and schizoaffective disorder in 19%.
Participants in the intervention group were significantly younger than those in the control group, with a mean of 37.4 years versus 41 years (P = .003) and were less likely to have one or more somatic comorbidities, at 61.2% versus 69.2%.
A PAD was completed by 54.6% of individuals in the intervention group versus 7.1% of controls (P < .001). The PAD was written with peer worker support by 41.3% of those in the intervention and by 2% of controls. Of those who completed a PAD, 75.7% met care facilitators, and 27.1% used it during a crisis over the following 12 months.
Results showed that the rate of compulsory admissions was significantly lower in the peer worker PAD group, at 27% versus 39.9% in control participants, at an odds ratio of 0.58 (P = .007).
Participants in the intervention group had lower symptoms on the modified Colorado Symptom Score than usual care patients with an effect size of -0.20 (P = .03) and higher scores on the Empowerment Scale (effect size 0.30, P = .003).
Scores on the Recovery Assessment Scale were also significantly higher in the peer worker PAD group versus controls with an effect size of 0.44 (P < .001). There were no significant differences, however, in overall admission rates, the quality of the therapeutic alliance, or quality of life.
Putting patients in the driver’s seat
Commenting on the findings, Robert Dabney Jr., MA, MDiv, peer apprentice program manager at the Depression and Bipolar Support Alliance, Chicago, said the study “tells us there are many benefits to completing a psychiatric advance directive, but perhaps the most powerful one is putting the person receiving mental health care in the driver’s seat of their own recovery.”
However, he noted that “many people living with mental health conditions don’t know the option exists to decide on their treatment plan in advance of a crisis.”
“This is where peer support specialists can come in. Having a peer who has been through similar experiences and can guide you through the process is as comforting as it is empowering. I have witnessed and experienced firsthand the power of peer support,” he said.
“It’s my personal hope and the goal of the Depression and Bipolar Support Alliance to empower more people to either become peer support specialists or seek out peer support services, because we know it improves and even saves lives,” Mr. Dabney added.
Virginia A. Brown, PhD, department of psychiatry & behavioral sciences, University of Texas at Austin Dell Medical School, noted there are huge differences between the health care systems in France and the United States.
She explained that two of the greatest barriers to PADs in the United States is that until 2016, filling one out was not billable and that “practitioners don’t know anything about advanced care plans.”
Dr. Brown said her own work shows that individuals who support patients during a crisis believe it would be “really helpful if we had some kind of document that we could share with the health care system that says: ‘Hey, look, I’m the designated person to speak for this patient, they’ve identified me through a document.’ So, people were actually describing a need for this document but didn’t know that it existed.”
Another problem is that in the United States, hospitals operate in a “closed system” and cannot talk to an unrelated hospital or to the police department “to get information to those first responders during an emergency about who to talk to about their wishes and preferences.”
“There are a lot of hurdles that we’ve got to get over to make a more robust system that protects the autonomy of people who live with serious mental illness,” Dr. Brown said, as “losing capacity during a crisis is time-limited, and it requires us to respond to it as a medical emergency.”
The study was supported by an institutional grant from the French 2017 National Program of Health Services Research. The Clinical Research Direction of Assistance Publique Hôpitaux de Marseille sponsored the trial. Dr. Tinland declares grants from the French Ministry of Health Directorate General of Health Care Services during the conduct of the study.
A version of this article first appeared on Medscape.com.
, new research shows.
Results of a randomized trial showed the peer worker PAD group had a 42% reduction in compulsory admission over the following 12 months. This study group also had lower symptom scores, greater rates of recovery, and increased empowerment, compared with patients assigned to usual care.
In addition to proving that PADs are effective in reducing compulsory admission, the results show that facilitation by peer workers is relevant, study investigator Aurélie Tinland, MD, PhD, Faculté de Médecine Timone, Aix-Marseille University, Marseille, France, told delegates attending the virtual European Psychiatric Association (EPA) 2022 Congress. The study was simultaneously published online in JAMA Psychiatry.
However, Dr. Tinland noted that more research that includes “harder to reach” populations is needed. In addition, greater use of PADs is also key to reducing compulsory admissions.
‘Most coercive’ country
The researchers note that respect for patient autonomy is a strong pillar of health care, such that “involuntary treatment should be unusual.” However, they point out that “compulsory psychiatric admissions are far too common in countries of all income levels.”
In France, said Dr. Tinland, 24% of psychiatric hospitalizations are compulsory. The country is ranked the sixth “most coercive” country in the world, and there are concerns about human rights in French psychiatric facilities.
She added that advance care statements are the most efficient tool for reducing coercion, with one study suggesting they could cut rates by 25%, compared with usual care.
However, she noted there is an “asymmetry” between medical professionals and patients and a risk of “undue influence” when clinicians facilitate the completion of care statements.
To examine the impact on clinical outcomes of peer-worker facilitated PADs, the researchers studied adults with a diagnosis of schizophrenia, bipolar I disorder, or schizoaffective disorder who were admitted to a psychiatric hospital within the previous 12 months. Peer workers are individuals who have lived experience with mental illness and help inform and guide current patients about care options in the event of a mental health crisis.
Study participants were randomly assigned 1:1 to an intervention group or a usual care control group. The intervention group received a PAD document and were assigned a peer worker while the usual care group received comprehensive information about the PAD concept at study entry and were free to complete it, but they were not connected with a peer worker.
The PAD document included information about future treatment and support preferences, early signs of relapse, and coping strategies. Participants could meet the peer worker in a place of their choice and be supported in drafting the document and in sharing it with health care professionals.
In all, 394 individuals completed the study. The majority (61%) of participants were male and 66% had completed post-secondary education. Schizophrenia was diagnosed in 45%, bipolar I disorder in 36%, and schizoaffective disorder in 19%.
Participants in the intervention group were significantly younger than those in the control group, with a mean of 37.4 years versus 41 years (P = .003) and were less likely to have one or more somatic comorbidities, at 61.2% versus 69.2%.
A PAD was completed by 54.6% of individuals in the intervention group versus 7.1% of controls (P < .001). The PAD was written with peer worker support by 41.3% of those in the intervention and by 2% of controls. Of those who completed a PAD, 75.7% met care facilitators, and 27.1% used it during a crisis over the following 12 months.
Results showed that the rate of compulsory admissions was significantly lower in the peer worker PAD group, at 27% versus 39.9% in control participants, at an odds ratio of 0.58 (P = .007).
Participants in the intervention group had lower symptoms on the modified Colorado Symptom Score than usual care patients with an effect size of -0.20 (P = .03) and higher scores on the Empowerment Scale (effect size 0.30, P = .003).
Scores on the Recovery Assessment Scale were also significantly higher in the peer worker PAD group versus controls with an effect size of 0.44 (P < .001). There were no significant differences, however, in overall admission rates, the quality of the therapeutic alliance, or quality of life.
Putting patients in the driver’s seat
Commenting on the findings, Robert Dabney Jr., MA, MDiv, peer apprentice program manager at the Depression and Bipolar Support Alliance, Chicago, said the study “tells us there are many benefits to completing a psychiatric advance directive, but perhaps the most powerful one is putting the person receiving mental health care in the driver’s seat of their own recovery.”
However, he noted that “many people living with mental health conditions don’t know the option exists to decide on their treatment plan in advance of a crisis.”
“This is where peer support specialists can come in. Having a peer who has been through similar experiences and can guide you through the process is as comforting as it is empowering. I have witnessed and experienced firsthand the power of peer support,” he said.
“It’s my personal hope and the goal of the Depression and Bipolar Support Alliance to empower more people to either become peer support specialists or seek out peer support services, because we know it improves and even saves lives,” Mr. Dabney added.
Virginia A. Brown, PhD, department of psychiatry & behavioral sciences, University of Texas at Austin Dell Medical School, noted there are huge differences between the health care systems in France and the United States.
She explained that two of the greatest barriers to PADs in the United States is that until 2016, filling one out was not billable and that “practitioners don’t know anything about advanced care plans.”
Dr. Brown said her own work shows that individuals who support patients during a crisis believe it would be “really helpful if we had some kind of document that we could share with the health care system that says: ‘Hey, look, I’m the designated person to speak for this patient, they’ve identified me through a document.’ So, people were actually describing a need for this document but didn’t know that it existed.”
Another problem is that in the United States, hospitals operate in a “closed system” and cannot talk to an unrelated hospital or to the police department “to get information to those first responders during an emergency about who to talk to about their wishes and preferences.”
“There are a lot of hurdles that we’ve got to get over to make a more robust system that protects the autonomy of people who live with serious mental illness,” Dr. Brown said, as “losing capacity during a crisis is time-limited, and it requires us to respond to it as a medical emergency.”
The study was supported by an institutional grant from the French 2017 National Program of Health Services Research. The Clinical Research Direction of Assistance Publique Hôpitaux de Marseille sponsored the trial. Dr. Tinland declares grants from the French Ministry of Health Directorate General of Health Care Services during the conduct of the study.
A version of this article first appeared on Medscape.com.
FROM EPA 2022
Adjunctive psychotherapy may offer no benefit in severe depression
Results of a cross-sectional, naturalistic, multicenter European study showed there were no significant differences in response rates between patients with major depressive disorder (MDD) who received combination treatment with psychotherapy and antidepressant medication in comparison with those who received antidepressant monotherapy, even when comparing different types of psychotherapy.
This “might emphasize the fundamental role of the underlying complex biological interrelationships in MDD and its treatment,” said study investigator Lucie Bartova, MD, PhD, Clinical Division of General Psychiatry, Medical University of Vienna.
However, she noted that patients who received psychotherapy in combination with antidepressants also had “beneficial sociodemographic and clinical characteristics,” which might reflect poorer access to “psychotherapeutic techniques for patients who are more severely ill and have less socioeconomic privilege.”
The resulting selection bias may cause patients with more severe illness to “fall by the wayside,” Dr. Bartova said.
Lead researcher Siegfried Kasper, MD, also from the Medical University of Vienna, agreed, saying in a press release that, by implication, “additional psychotherapy tends to be given to more highly educated and healthier patients, which may reflect the greater availability of psychotherapy to more socially and economically advantaged patients.”
The findings, some of which were previously published in the Journal of Psychiatry Research, were presented at the virtual European Psychiatric Association 2022 Congress.
Inconsistent guidelines
During her presentation, Dr. Bartova said that while “numerous effective antidepressant strategies are available for the treatment of MDD, many patients do not achieve a satisfactory treatment response,” which often leads to further management refinement and the use of off-label treatments.
She continued, saying that the “most obvious” approach in these situations is to try the available treatment options in a “systematic and individualized” manner, ideally by following recommended treatment algorithms.
Meta-analyses have suggested that standardized psychotherapy with fixed, regular sessions that follows an established rationale and is based on a defined school of thought is effective in MDD, “with at least moderate effects.”
Among the psychotherapy approaches, cognitive-behavioral therapy (CBT) is the “best and most investigated,” Dr. Bartova said, but international clinical practice guidelines “lack consistency” regarding recommendations for psychotherapy.
To examine the use and impact of psychotherapy for MDD patients, the researchers studied 1,410 adult inpatients and outpatients from 10 centers in eight countries who were surveyed between 2011 and 2016 by the European Group for the Study of Resistant Depression.
Participants were assessed via the Mini–International Neuropsychiatric Interview, the Montgomery-Åsberg Depression Rating Scale, and the Hamilton Depression Rating Scale.
Results showed that among 1,279 MDD patients who were included in the final analysis, 880 (68.8%) received only antidepressants, while 399 (31.2%) received some form of structured psychotherapy as part of their treatment.
These patients included 22.8% who received CBT, 3.4% who underwent psychoanalytic psychotherapy, and 1.3% who received systemic psychotherapy. The additional psychotherapy was not specified for 3.8%.
Dr. Bartova explained that the use of psychotherapy in combination pharmacologic treatment was significantly associated with younger age, higher educational attainment, and ongoing employment in comparison with antidepressant use alone (P < .001 for all).
In addition, combination therapy was associated with an earlier average age of MDD onset, lower severity of current depressive symptoms, a lower risk of suicidality, higher rates of additional melancholic features in the patients’ symptomatology, and higher rates of comorbid asthma and migraine (P < .001 for all).
There was also a significant association between the use of psychotherapy plus pharmacologic treatment and lower average daily doses of first-line antidepressant medication (P < .001), as well as more frequent administration of agomelatine (P < .001) and a trend toward greater use of vortioxetine (P = .006).
In contrast, among patients who received antidepressants alone, there was a trend toward higher rates of additional psychotic features (P = .054), and the patients were more likely to have received selective serotonin reuptake inhibitors as their first-line antidepressant medication (P < .001).
The researchers found there was no significant difference in rates of response, nonresponse, and treatment-resistant depression (TRD) between patients who received combination psychotherapy and pharmacotherapy and those who received antidepressants alone (P = .369).
Dr. Bartova showed that 25.8% of MDD patients who received combination therapy were classified as responders, compared with 23.5% of those given only antidepressants. Nonresponse was identified in 35.6% and 33.8% of patients, respectively, while 38.6% versus 42.7% had TRD.
Dr. Bartova and colleagues performed an additional analysis to determine whether there was any difference in response depending on the type of psychotherapy.
They divided patients who received combination therapy into those who had received CBT and those who had been given another form of psychotherapy.
Again, there were no significant differences in response, nonresponse, and TRD (P = .256). The response rate was 27.1% among patients given combination CBT, versus 22.4% among those who received another psychotherapy.
“Despite clinical guidelines and studies which advocate for psychotherapy and combining psychotherapy with antidepressants, this study shows that in real life, no added value can be demonstrated for psychotherapy in those already treated with antidepressants for severe depression,” Livia De Picker, MD, PhD, Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Belgium, said in the press release.
“This doesn’t necessarily mean that psychotherapy is not useful, but it is a clear sign that the way we are currently managing these depressed patients with psychotherapy is not effective and needs critical evaluation,” added Dr. De Picker, who was not involved in the research.
However, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, told this news organization that the current study “is a secondary analysis of a naturalistic study.”
Consequently, it is not possible to account for the “dose and duration, and quality, of the psychotherapy provided.”
Therefore, the findings simply suggest that “the kinds of psychotherapy provided to these patients was not so powerful that people who received it consistently did better than those who did not,” Dr. Thase said.
The European Group for the Study of Resistant Depression obtained an unrestricted grant sponsored by Lundbeck A/S. Dr. Bartova has relationships with AOP Orphan, Medizin Medien Austria, Universimed, Vertretungsnetz, Dialectica, Diagnosia, Schwabe, Janssen, Lundbeck, and Angelini. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
Results of a cross-sectional, naturalistic, multicenter European study showed there were no significant differences in response rates between patients with major depressive disorder (MDD) who received combination treatment with psychotherapy and antidepressant medication in comparison with those who received antidepressant monotherapy, even when comparing different types of psychotherapy.
This “might emphasize the fundamental role of the underlying complex biological interrelationships in MDD and its treatment,” said study investigator Lucie Bartova, MD, PhD, Clinical Division of General Psychiatry, Medical University of Vienna.
However, she noted that patients who received psychotherapy in combination with antidepressants also had “beneficial sociodemographic and clinical characteristics,” which might reflect poorer access to “psychotherapeutic techniques for patients who are more severely ill and have less socioeconomic privilege.”
The resulting selection bias may cause patients with more severe illness to “fall by the wayside,” Dr. Bartova said.
Lead researcher Siegfried Kasper, MD, also from the Medical University of Vienna, agreed, saying in a press release that, by implication, “additional psychotherapy tends to be given to more highly educated and healthier patients, which may reflect the greater availability of psychotherapy to more socially and economically advantaged patients.”
The findings, some of which were previously published in the Journal of Psychiatry Research, were presented at the virtual European Psychiatric Association 2022 Congress.
Inconsistent guidelines
During her presentation, Dr. Bartova said that while “numerous effective antidepressant strategies are available for the treatment of MDD, many patients do not achieve a satisfactory treatment response,” which often leads to further management refinement and the use of off-label treatments.
She continued, saying that the “most obvious” approach in these situations is to try the available treatment options in a “systematic and individualized” manner, ideally by following recommended treatment algorithms.
Meta-analyses have suggested that standardized psychotherapy with fixed, regular sessions that follows an established rationale and is based on a defined school of thought is effective in MDD, “with at least moderate effects.”
Among the psychotherapy approaches, cognitive-behavioral therapy (CBT) is the “best and most investigated,” Dr. Bartova said, but international clinical practice guidelines “lack consistency” regarding recommendations for psychotherapy.
To examine the use and impact of psychotherapy for MDD patients, the researchers studied 1,410 adult inpatients and outpatients from 10 centers in eight countries who were surveyed between 2011 and 2016 by the European Group for the Study of Resistant Depression.
Participants were assessed via the Mini–International Neuropsychiatric Interview, the Montgomery-Åsberg Depression Rating Scale, and the Hamilton Depression Rating Scale.
Results showed that among 1,279 MDD patients who were included in the final analysis, 880 (68.8%) received only antidepressants, while 399 (31.2%) received some form of structured psychotherapy as part of their treatment.
These patients included 22.8% who received CBT, 3.4% who underwent psychoanalytic psychotherapy, and 1.3% who received systemic psychotherapy. The additional psychotherapy was not specified for 3.8%.
Dr. Bartova explained that the use of psychotherapy in combination pharmacologic treatment was significantly associated with younger age, higher educational attainment, and ongoing employment in comparison with antidepressant use alone (P < .001 for all).
In addition, combination therapy was associated with an earlier average age of MDD onset, lower severity of current depressive symptoms, a lower risk of suicidality, higher rates of additional melancholic features in the patients’ symptomatology, and higher rates of comorbid asthma and migraine (P < .001 for all).
There was also a significant association between the use of psychotherapy plus pharmacologic treatment and lower average daily doses of first-line antidepressant medication (P < .001), as well as more frequent administration of agomelatine (P < .001) and a trend toward greater use of vortioxetine (P = .006).
In contrast, among patients who received antidepressants alone, there was a trend toward higher rates of additional psychotic features (P = .054), and the patients were more likely to have received selective serotonin reuptake inhibitors as their first-line antidepressant medication (P < .001).
The researchers found there was no significant difference in rates of response, nonresponse, and treatment-resistant depression (TRD) between patients who received combination psychotherapy and pharmacotherapy and those who received antidepressants alone (P = .369).
Dr. Bartova showed that 25.8% of MDD patients who received combination therapy were classified as responders, compared with 23.5% of those given only antidepressants. Nonresponse was identified in 35.6% and 33.8% of patients, respectively, while 38.6% versus 42.7% had TRD.
Dr. Bartova and colleagues performed an additional analysis to determine whether there was any difference in response depending on the type of psychotherapy.
They divided patients who received combination therapy into those who had received CBT and those who had been given another form of psychotherapy.
Again, there were no significant differences in response, nonresponse, and TRD (P = .256). The response rate was 27.1% among patients given combination CBT, versus 22.4% among those who received another psychotherapy.
“Despite clinical guidelines and studies which advocate for psychotherapy and combining psychotherapy with antidepressants, this study shows that in real life, no added value can be demonstrated for psychotherapy in those already treated with antidepressants for severe depression,” Livia De Picker, MD, PhD, Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Belgium, said in the press release.
“This doesn’t necessarily mean that psychotherapy is not useful, but it is a clear sign that the way we are currently managing these depressed patients with psychotherapy is not effective and needs critical evaluation,” added Dr. De Picker, who was not involved in the research.
However, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, told this news organization that the current study “is a secondary analysis of a naturalistic study.”
Consequently, it is not possible to account for the “dose and duration, and quality, of the psychotherapy provided.”
Therefore, the findings simply suggest that “the kinds of psychotherapy provided to these patients was not so powerful that people who received it consistently did better than those who did not,” Dr. Thase said.
The European Group for the Study of Resistant Depression obtained an unrestricted grant sponsored by Lundbeck A/S. Dr. Bartova has relationships with AOP Orphan, Medizin Medien Austria, Universimed, Vertretungsnetz, Dialectica, Diagnosia, Schwabe, Janssen, Lundbeck, and Angelini. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
Results of a cross-sectional, naturalistic, multicenter European study showed there were no significant differences in response rates between patients with major depressive disorder (MDD) who received combination treatment with psychotherapy and antidepressant medication in comparison with those who received antidepressant monotherapy, even when comparing different types of psychotherapy.
This “might emphasize the fundamental role of the underlying complex biological interrelationships in MDD and its treatment,” said study investigator Lucie Bartova, MD, PhD, Clinical Division of General Psychiatry, Medical University of Vienna.
However, she noted that patients who received psychotherapy in combination with antidepressants also had “beneficial sociodemographic and clinical characteristics,” which might reflect poorer access to “psychotherapeutic techniques for patients who are more severely ill and have less socioeconomic privilege.”
The resulting selection bias may cause patients with more severe illness to “fall by the wayside,” Dr. Bartova said.
Lead researcher Siegfried Kasper, MD, also from the Medical University of Vienna, agreed, saying in a press release that, by implication, “additional psychotherapy tends to be given to more highly educated and healthier patients, which may reflect the greater availability of psychotherapy to more socially and economically advantaged patients.”
The findings, some of which were previously published in the Journal of Psychiatry Research, were presented at the virtual European Psychiatric Association 2022 Congress.
Inconsistent guidelines
During her presentation, Dr. Bartova said that while “numerous effective antidepressant strategies are available for the treatment of MDD, many patients do not achieve a satisfactory treatment response,” which often leads to further management refinement and the use of off-label treatments.
She continued, saying that the “most obvious” approach in these situations is to try the available treatment options in a “systematic and individualized” manner, ideally by following recommended treatment algorithms.
Meta-analyses have suggested that standardized psychotherapy with fixed, regular sessions that follows an established rationale and is based on a defined school of thought is effective in MDD, “with at least moderate effects.”
Among the psychotherapy approaches, cognitive-behavioral therapy (CBT) is the “best and most investigated,” Dr. Bartova said, but international clinical practice guidelines “lack consistency” regarding recommendations for psychotherapy.
To examine the use and impact of psychotherapy for MDD patients, the researchers studied 1,410 adult inpatients and outpatients from 10 centers in eight countries who were surveyed between 2011 and 2016 by the European Group for the Study of Resistant Depression.
Participants were assessed via the Mini–International Neuropsychiatric Interview, the Montgomery-Åsberg Depression Rating Scale, and the Hamilton Depression Rating Scale.
Results showed that among 1,279 MDD patients who were included in the final analysis, 880 (68.8%) received only antidepressants, while 399 (31.2%) received some form of structured psychotherapy as part of their treatment.
These patients included 22.8% who received CBT, 3.4% who underwent psychoanalytic psychotherapy, and 1.3% who received systemic psychotherapy. The additional psychotherapy was not specified for 3.8%.
Dr. Bartova explained that the use of psychotherapy in combination pharmacologic treatment was significantly associated with younger age, higher educational attainment, and ongoing employment in comparison with antidepressant use alone (P < .001 for all).
In addition, combination therapy was associated with an earlier average age of MDD onset, lower severity of current depressive symptoms, a lower risk of suicidality, higher rates of additional melancholic features in the patients’ symptomatology, and higher rates of comorbid asthma and migraine (P < .001 for all).
There was also a significant association between the use of psychotherapy plus pharmacologic treatment and lower average daily doses of first-line antidepressant medication (P < .001), as well as more frequent administration of agomelatine (P < .001) and a trend toward greater use of vortioxetine (P = .006).
In contrast, among patients who received antidepressants alone, there was a trend toward higher rates of additional psychotic features (P = .054), and the patients were more likely to have received selective serotonin reuptake inhibitors as their first-line antidepressant medication (P < .001).
The researchers found there was no significant difference in rates of response, nonresponse, and treatment-resistant depression (TRD) between patients who received combination psychotherapy and pharmacotherapy and those who received antidepressants alone (P = .369).
Dr. Bartova showed that 25.8% of MDD patients who received combination therapy were classified as responders, compared with 23.5% of those given only antidepressants. Nonresponse was identified in 35.6% and 33.8% of patients, respectively, while 38.6% versus 42.7% had TRD.
Dr. Bartova and colleagues performed an additional analysis to determine whether there was any difference in response depending on the type of psychotherapy.
They divided patients who received combination therapy into those who had received CBT and those who had been given another form of psychotherapy.
Again, there were no significant differences in response, nonresponse, and TRD (P = .256). The response rate was 27.1% among patients given combination CBT, versus 22.4% among those who received another psychotherapy.
“Despite clinical guidelines and studies which advocate for psychotherapy and combining psychotherapy with antidepressants, this study shows that in real life, no added value can be demonstrated for psychotherapy in those already treated with antidepressants for severe depression,” Livia De Picker, MD, PhD, Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Belgium, said in the press release.
“This doesn’t necessarily mean that psychotherapy is not useful, but it is a clear sign that the way we are currently managing these depressed patients with psychotherapy is not effective and needs critical evaluation,” added Dr. De Picker, who was not involved in the research.
However, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, told this news organization that the current study “is a secondary analysis of a naturalistic study.”
Consequently, it is not possible to account for the “dose and duration, and quality, of the psychotherapy provided.”
Therefore, the findings simply suggest that “the kinds of psychotherapy provided to these patients was not so powerful that people who received it consistently did better than those who did not,” Dr. Thase said.
The European Group for the Study of Resistant Depression obtained an unrestricted grant sponsored by Lundbeck A/S. Dr. Bartova has relationships with AOP Orphan, Medizin Medien Austria, Universimed, Vertretungsnetz, Dialectica, Diagnosia, Schwabe, Janssen, Lundbeck, and Angelini. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
FROM EPA 2022
Hormonal contraceptives protective against suicide?
Contrary to previous analyses, new research suggests.
In a study of more than 800 women younger than age 50 who attempted suicide and more than 3,000 age-matched peers, results showed those who took hormonal contraceptives had a 27% reduced risk for attempted suicide.
Further analysis showed this was confined to women without a history of psychiatric illness and the reduction in risk rose to 43% among those who took combined hormonal contraceptives rather than progestin-only versions.
The protective effect against attempted suicide increased further to 46% if ethinyl estradiol (EE)–containing preparations were used. Moreover, the beneficial effect of contraceptive use increased over time.
The main message is the “current use of hormonal contraceptives is not associated with an increased risk of attempted suicide in our population,” study presenter Elena Toffol, MD, PhD, department of public health, University of Helsinki, told meeting attendees at the European Psychiatric Association 2022 Congress.
Age range differences
Dr. Toffol said there could be “several reasons” why the results are different from those in previous studies, including that the researchers included a “larger age range.” She noted it is known that “older women have a lower rate of attempted suicide and use different types of contraceptives.”
Dr. Toffol said in an interview that, although it’s “hard to estimate any causality” because this is an observational study, it is “tempting to speculate, and it is plausible, that hormones partly play a role with some, but not all, women being more sensitive to hormonal influences.”
However, the results “may also reflect life choices or a protective life status; for example, more stable relationships or more conscious and health-focused behaviors,” she said.
“It may also be that the underlying characteristics of women who are prescribed or opt for certain types of contraceptives are somehow related to their suicidal risk,” she added.
In 2019, the global age-standardized suicide rate was 9.0 per 100,000, which translates into more than 700,000 deaths every year, Dr. Toffol noted.
However, she emphasized the World Health Organization has calculated that, for every adult who dies by suicide, more than 20 people attempt suicide. In addition, data from the U.S. Centers for Disease Control and Prevention indicate that attempted suicides are three times more common among young women than in men.
“What are the reasons for this gender gap?” Dr. Toffol asked during her presentation.
“It is known that the major risk factor for suicidal behavior is a psychiatric disorder, and in particular depression and mood disorders. And depression and mood disorders are more common in women than in men,” she said.
However, there is also “growing interest into the role of biological factors” in the risk for suicide, including hormones and hormonal contraception. Some studies have also suggested that there is an increased risk for depression and “both completed and attempted suicide” after starting hormonal contraception.
Dr. Toffol added that about 70% of European women use some form of contraception and, among Finnish women, 40% choose a hormonal contraceptive.
Nested analysis
The researchers conducted a nested case-control analysis combining 2017 national prescription data on 587,823 women aged 15-49 years with information from general and primary healthcare registers for the years 2018 to 2019.
They were able to identify 818 cases of attempted suicide among the women. These were matched 4:1 with 3,272 age-matched healthy women who acted as the control group. Use of hormonal contraceptives in the previous 180 days was determined for the whole cohort.
Among users of hormonal contraceptives, there were 344 attempted suicides in 2017, at an incidence rate of 0.59 per 1,000 person-years. This compared with 474 attempted suicides among nonusers, at an incidence rate of 0.81 per 1000 person-years.
Kaplan-Meier analysis showed there was a significant difference in rates for attempted suicide among hormonal contraceptive users versus nonusers, at an incidence rate ratio of 0.73 (P < .0001) – and the difference increased over time.
In addition, the incidence of attempted suicide decreased with increasing age, with the highest incidence rate in women aged 15-19 years (1.62 per 1,000 person-years).
Conditional logistic regression analysis that controlled for education, marital status, chronic disease, recent psychiatric hospitalization, and current use of psychotropic medication showed hormonal contraceptive use was not linked to an increased risk of attempted suicide overall, at an odds ratio of 0.79 (95% confidence interval, 0.56-1.11).
However, when they looked specifically at women without a history of psychiatric illness, the association became significant, at an OR of 0.73 for attempted suicide among hormonal contraceptive users (95% CI, 0.58-0.91), while the relationship remained nonsignificant in women with a history of psychiatric disorders.
Further analysis suggested the significant association was confined to women taking combined hormonal contraceptives, at an OR of 0.57 for suicide attempt versus nonusers (95% CI, 0.44-0.75), and those use EE-containing preparations (OR, 0.54; 95% CI, 0.40-0.73).
There was a suggestion in the data that hormonal contraceptives containing desogestrel or drospirenone alongside EE may offer the greatest reduction in attempted suicide risk, but that did not survive multivariate analysis.
Dr. Toffol also noted that they were not able to capture data on use of intrauterine devices in their analysis.
“There is a growing number of municipalities in Finland that are providing free-of-charge contraception to young women” that is often an intrauterine device, she said. The researchers hope to include these women in a future analysis.
‘Age matters’
Commenting on the findings, Alexis C. Edwards, PhD, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, said the current study’s findings “made a lot of sense.” Dr. Edwards wasn’t involved with this study but conducted a previous study of 216,702 Swedish women aged 15-22 years that showed use of combination or progestin-only oral contraceptives was associated with an increased risk for suicidal behavior.
She agreed with Dr. Toffol that the “much larger age range” in the new study may have played a role in showing the opposite result.
“The trajectory that we saw if we had been able to continue following the women for longer – which we couldn’t, due to limitations of the registries – [was that] using hormonal contraceptives was going to end up being protective, so I do think that it matters what age you’re looking at,” she said.
Dr. Edwards noted the takeaway from both studies “is that, even if there is a slight increase in risk from using hormonal contraceptives, it’s short lived and it’s probably specific to young women, which is important.”
She suggested the hormonal benefit from extended contraceptive use could come from the regulation of mood, as it offers a “more stable hormonal course than what their body might be putting them through in the absence of using the pill.”
Overall, it is “really lovely to see very well-executed studies on this, providing more empirical evidence on this question, because it is something that’s relevant to anyone who’s potentially going to be using hormonal contraception,” Dr. Edwards said.
Clinical implications?
Andrea Fiorillo, MD, PhD, department of psychiatry, University of Campania “Luigi Vanvitelli,” Naples, Italy, said in a press release that the “striking” findings of the current study need “careful evaluation.”
They also need to be replicated in “different cohorts of women and controlled for the impact of several psychosocial stressors, such as economic upheavals, social insecurity, and uncertainty due to the COVID pandemic,” said Dr. Fiorillo, who was not involved with the research.
Nevertheless, she believes the “clinical implications of the study are obvious and may help to destigmatize the use of hormonal contraceptives.”
The study was funded by the Jane and Aatos Erkko Foundation, the Avohoidon Tsukimis äätiö (Foundation for Primary Care Research), the Yrj ö Jahnsson Foundation, and the Finnish Cultural Foundation. No relevant financial relationships were reported.
A version of this article first appeared on Medscape.com.
Contrary to previous analyses, new research suggests.
In a study of more than 800 women younger than age 50 who attempted suicide and more than 3,000 age-matched peers, results showed those who took hormonal contraceptives had a 27% reduced risk for attempted suicide.
Further analysis showed this was confined to women without a history of psychiatric illness and the reduction in risk rose to 43% among those who took combined hormonal contraceptives rather than progestin-only versions.
The protective effect against attempted suicide increased further to 46% if ethinyl estradiol (EE)–containing preparations were used. Moreover, the beneficial effect of contraceptive use increased over time.
The main message is the “current use of hormonal contraceptives is not associated with an increased risk of attempted suicide in our population,” study presenter Elena Toffol, MD, PhD, department of public health, University of Helsinki, told meeting attendees at the European Psychiatric Association 2022 Congress.
Age range differences
Dr. Toffol said there could be “several reasons” why the results are different from those in previous studies, including that the researchers included a “larger age range.” She noted it is known that “older women have a lower rate of attempted suicide and use different types of contraceptives.”
Dr. Toffol said in an interview that, although it’s “hard to estimate any causality” because this is an observational study, it is “tempting to speculate, and it is plausible, that hormones partly play a role with some, but not all, women being more sensitive to hormonal influences.”
However, the results “may also reflect life choices or a protective life status; for example, more stable relationships or more conscious and health-focused behaviors,” she said.
“It may also be that the underlying characteristics of women who are prescribed or opt for certain types of contraceptives are somehow related to their suicidal risk,” she added.
In 2019, the global age-standardized suicide rate was 9.0 per 100,000, which translates into more than 700,000 deaths every year, Dr. Toffol noted.
However, she emphasized the World Health Organization has calculated that, for every adult who dies by suicide, more than 20 people attempt suicide. In addition, data from the U.S. Centers for Disease Control and Prevention indicate that attempted suicides are three times more common among young women than in men.
“What are the reasons for this gender gap?” Dr. Toffol asked during her presentation.
“It is known that the major risk factor for suicidal behavior is a psychiatric disorder, and in particular depression and mood disorders. And depression and mood disorders are more common in women than in men,” she said.
However, there is also “growing interest into the role of biological factors” in the risk for suicide, including hormones and hormonal contraception. Some studies have also suggested that there is an increased risk for depression and “both completed and attempted suicide” after starting hormonal contraception.
Dr. Toffol added that about 70% of European women use some form of contraception and, among Finnish women, 40% choose a hormonal contraceptive.
Nested analysis
The researchers conducted a nested case-control analysis combining 2017 national prescription data on 587,823 women aged 15-49 years with information from general and primary healthcare registers for the years 2018 to 2019.
They were able to identify 818 cases of attempted suicide among the women. These were matched 4:1 with 3,272 age-matched healthy women who acted as the control group. Use of hormonal contraceptives in the previous 180 days was determined for the whole cohort.
Among users of hormonal contraceptives, there were 344 attempted suicides in 2017, at an incidence rate of 0.59 per 1,000 person-years. This compared with 474 attempted suicides among nonusers, at an incidence rate of 0.81 per 1000 person-years.
Kaplan-Meier analysis showed there was a significant difference in rates for attempted suicide among hormonal contraceptive users versus nonusers, at an incidence rate ratio of 0.73 (P < .0001) – and the difference increased over time.
In addition, the incidence of attempted suicide decreased with increasing age, with the highest incidence rate in women aged 15-19 years (1.62 per 1,000 person-years).
Conditional logistic regression analysis that controlled for education, marital status, chronic disease, recent psychiatric hospitalization, and current use of psychotropic medication showed hormonal contraceptive use was not linked to an increased risk of attempted suicide overall, at an odds ratio of 0.79 (95% confidence interval, 0.56-1.11).
However, when they looked specifically at women without a history of psychiatric illness, the association became significant, at an OR of 0.73 for attempted suicide among hormonal contraceptive users (95% CI, 0.58-0.91), while the relationship remained nonsignificant in women with a history of psychiatric disorders.
Further analysis suggested the significant association was confined to women taking combined hormonal contraceptives, at an OR of 0.57 for suicide attempt versus nonusers (95% CI, 0.44-0.75), and those use EE-containing preparations (OR, 0.54; 95% CI, 0.40-0.73).
There was a suggestion in the data that hormonal contraceptives containing desogestrel or drospirenone alongside EE may offer the greatest reduction in attempted suicide risk, but that did not survive multivariate analysis.
Dr. Toffol also noted that they were not able to capture data on use of intrauterine devices in their analysis.
“There is a growing number of municipalities in Finland that are providing free-of-charge contraception to young women” that is often an intrauterine device, she said. The researchers hope to include these women in a future analysis.
‘Age matters’
Commenting on the findings, Alexis C. Edwards, PhD, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, said the current study’s findings “made a lot of sense.” Dr. Edwards wasn’t involved with this study but conducted a previous study of 216,702 Swedish women aged 15-22 years that showed use of combination or progestin-only oral contraceptives was associated with an increased risk for suicidal behavior.
She agreed with Dr. Toffol that the “much larger age range” in the new study may have played a role in showing the opposite result.
“The trajectory that we saw if we had been able to continue following the women for longer – which we couldn’t, due to limitations of the registries – [was that] using hormonal contraceptives was going to end up being protective, so I do think that it matters what age you’re looking at,” she said.
Dr. Edwards noted the takeaway from both studies “is that, even if there is a slight increase in risk from using hormonal contraceptives, it’s short lived and it’s probably specific to young women, which is important.”
She suggested the hormonal benefit from extended contraceptive use could come from the regulation of mood, as it offers a “more stable hormonal course than what their body might be putting them through in the absence of using the pill.”
Overall, it is “really lovely to see very well-executed studies on this, providing more empirical evidence on this question, because it is something that’s relevant to anyone who’s potentially going to be using hormonal contraception,” Dr. Edwards said.
Clinical implications?
Andrea Fiorillo, MD, PhD, department of psychiatry, University of Campania “Luigi Vanvitelli,” Naples, Italy, said in a press release that the “striking” findings of the current study need “careful evaluation.”
They also need to be replicated in “different cohorts of women and controlled for the impact of several psychosocial stressors, such as economic upheavals, social insecurity, and uncertainty due to the COVID pandemic,” said Dr. Fiorillo, who was not involved with the research.
Nevertheless, she believes the “clinical implications of the study are obvious and may help to destigmatize the use of hormonal contraceptives.”
The study was funded by the Jane and Aatos Erkko Foundation, the Avohoidon Tsukimis äätiö (Foundation for Primary Care Research), the Yrj ö Jahnsson Foundation, and the Finnish Cultural Foundation. No relevant financial relationships were reported.
A version of this article first appeared on Medscape.com.
Contrary to previous analyses, new research suggests.
In a study of more than 800 women younger than age 50 who attempted suicide and more than 3,000 age-matched peers, results showed those who took hormonal contraceptives had a 27% reduced risk for attempted suicide.
Further analysis showed this was confined to women without a history of psychiatric illness and the reduction in risk rose to 43% among those who took combined hormonal contraceptives rather than progestin-only versions.
The protective effect against attempted suicide increased further to 46% if ethinyl estradiol (EE)–containing preparations were used. Moreover, the beneficial effect of contraceptive use increased over time.
The main message is the “current use of hormonal contraceptives is not associated with an increased risk of attempted suicide in our population,” study presenter Elena Toffol, MD, PhD, department of public health, University of Helsinki, told meeting attendees at the European Psychiatric Association 2022 Congress.
Age range differences
Dr. Toffol said there could be “several reasons” why the results are different from those in previous studies, including that the researchers included a “larger age range.” She noted it is known that “older women have a lower rate of attempted suicide and use different types of contraceptives.”
Dr. Toffol said in an interview that, although it’s “hard to estimate any causality” because this is an observational study, it is “tempting to speculate, and it is plausible, that hormones partly play a role with some, but not all, women being more sensitive to hormonal influences.”
However, the results “may also reflect life choices or a protective life status; for example, more stable relationships or more conscious and health-focused behaviors,” she said.
“It may also be that the underlying characteristics of women who are prescribed or opt for certain types of contraceptives are somehow related to their suicidal risk,” she added.
In 2019, the global age-standardized suicide rate was 9.0 per 100,000, which translates into more than 700,000 deaths every year, Dr. Toffol noted.
However, she emphasized the World Health Organization has calculated that, for every adult who dies by suicide, more than 20 people attempt suicide. In addition, data from the U.S. Centers for Disease Control and Prevention indicate that attempted suicides are three times more common among young women than in men.
“What are the reasons for this gender gap?” Dr. Toffol asked during her presentation.
“It is known that the major risk factor for suicidal behavior is a psychiatric disorder, and in particular depression and mood disorders. And depression and mood disorders are more common in women than in men,” she said.
However, there is also “growing interest into the role of biological factors” in the risk for suicide, including hormones and hormonal contraception. Some studies have also suggested that there is an increased risk for depression and “both completed and attempted suicide” after starting hormonal contraception.
Dr. Toffol added that about 70% of European women use some form of contraception and, among Finnish women, 40% choose a hormonal contraceptive.
Nested analysis
The researchers conducted a nested case-control analysis combining 2017 national prescription data on 587,823 women aged 15-49 years with information from general and primary healthcare registers for the years 2018 to 2019.
They were able to identify 818 cases of attempted suicide among the women. These were matched 4:1 with 3,272 age-matched healthy women who acted as the control group. Use of hormonal contraceptives in the previous 180 days was determined for the whole cohort.
Among users of hormonal contraceptives, there were 344 attempted suicides in 2017, at an incidence rate of 0.59 per 1,000 person-years. This compared with 474 attempted suicides among nonusers, at an incidence rate of 0.81 per 1000 person-years.
Kaplan-Meier analysis showed there was a significant difference in rates for attempted suicide among hormonal contraceptive users versus nonusers, at an incidence rate ratio of 0.73 (P < .0001) – and the difference increased over time.
In addition, the incidence of attempted suicide decreased with increasing age, with the highest incidence rate in women aged 15-19 years (1.62 per 1,000 person-years).
Conditional logistic regression analysis that controlled for education, marital status, chronic disease, recent psychiatric hospitalization, and current use of psychotropic medication showed hormonal contraceptive use was not linked to an increased risk of attempted suicide overall, at an odds ratio of 0.79 (95% confidence interval, 0.56-1.11).
However, when they looked specifically at women without a history of psychiatric illness, the association became significant, at an OR of 0.73 for attempted suicide among hormonal contraceptive users (95% CI, 0.58-0.91), while the relationship remained nonsignificant in women with a history of psychiatric disorders.
Further analysis suggested the significant association was confined to women taking combined hormonal contraceptives, at an OR of 0.57 for suicide attempt versus nonusers (95% CI, 0.44-0.75), and those use EE-containing preparations (OR, 0.54; 95% CI, 0.40-0.73).
There was a suggestion in the data that hormonal contraceptives containing desogestrel or drospirenone alongside EE may offer the greatest reduction in attempted suicide risk, but that did not survive multivariate analysis.
Dr. Toffol also noted that they were not able to capture data on use of intrauterine devices in their analysis.
“There is a growing number of municipalities in Finland that are providing free-of-charge contraception to young women” that is often an intrauterine device, she said. The researchers hope to include these women in a future analysis.
‘Age matters’
Commenting on the findings, Alexis C. Edwards, PhD, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, said the current study’s findings “made a lot of sense.” Dr. Edwards wasn’t involved with this study but conducted a previous study of 216,702 Swedish women aged 15-22 years that showed use of combination or progestin-only oral contraceptives was associated with an increased risk for suicidal behavior.
She agreed with Dr. Toffol that the “much larger age range” in the new study may have played a role in showing the opposite result.
“The trajectory that we saw if we had been able to continue following the women for longer – which we couldn’t, due to limitations of the registries – [was that] using hormonal contraceptives was going to end up being protective, so I do think that it matters what age you’re looking at,” she said.
Dr. Edwards noted the takeaway from both studies “is that, even if there is a slight increase in risk from using hormonal contraceptives, it’s short lived and it’s probably specific to young women, which is important.”
She suggested the hormonal benefit from extended contraceptive use could come from the regulation of mood, as it offers a “more stable hormonal course than what their body might be putting them through in the absence of using the pill.”
Overall, it is “really lovely to see very well-executed studies on this, providing more empirical evidence on this question, because it is something that’s relevant to anyone who’s potentially going to be using hormonal contraception,” Dr. Edwards said.
Clinical implications?
Andrea Fiorillo, MD, PhD, department of psychiatry, University of Campania “Luigi Vanvitelli,” Naples, Italy, said in a press release that the “striking” findings of the current study need “careful evaluation.”
They also need to be replicated in “different cohorts of women and controlled for the impact of several psychosocial stressors, such as economic upheavals, social insecurity, and uncertainty due to the COVID pandemic,” said Dr. Fiorillo, who was not involved with the research.
Nevertheless, she believes the “clinical implications of the study are obvious and may help to destigmatize the use of hormonal contraceptives.”
The study was funded by the Jane and Aatos Erkko Foundation, the Avohoidon Tsukimis äätiö (Foundation for Primary Care Research), the Yrj ö Jahnsson Foundation, and the Finnish Cultural Foundation. No relevant financial relationships were reported.
A version of this article first appeared on Medscape.com.
FROM EPA 2022
Post-hoc analysis offers hope for novel cholesterol drug
MILAN, Italy – The antisense oligonucleotide vupanorsen substantially reduces very-low-density-lipoprotein (VLDL) and remnant cholesterol levels in patients with raised lipids despite statin therapy, suggests a subanalysis of TRANSLATE-TIMI 70 that appears to offer more hope than the primary study findings.
Vupanorsen targets hepatic angiopoietin-like protein 3 (ANGPTL3), which inhibits enzymes involved in triglyceride and cholesterol metabolism.
Earlier this year, headline data from TRANSLATE-TIMI 70 suggested that the drug reduced triglycerides and non–high-density-lipoprotein cholesterol to a degree that was significant but not clinically meaningful for cardiovascular risk reduction.
Moreover, as reported by this news organization, there were safety concerns over increases in liver enzymes among patients taking the drug, as well as dose-related increases in hepatic fat.
As a result, Pfizer announced that it would discontinue its clinical development program for vupanorsen and return the development rights to Ionis, following the signing of a worldwide exclusive agreement in November 2019.
Now, Nicholas A. Marston, MD, MPH, cardiovascular medicine, Brigham and Women’s Hospital, Boston, has presented a post-hoc analysis of the phase 2b study, showing that the drug reduces VLDL and remnant cholesterol levels by up to 60%.
These were closely tied to reductions in ANGPTL3 levels, although substantial reductions in cholesterol levels were achieved even at less than maximal reductions in ANGPTL3, where the impact on safety outcomes was reduced.
Dr. Marston said that lower doses of vupanorsen, where the safety effects would be less, or other drugs that inhibit ANGPTL3, “may have an important role in patients with residual dyslipidemia despite current therapy.”
The results were presented at the 90th European Atherosclerosis Society Congress on May 23.
Dr. Marston told this news organization that some of the reductions they saw with the lower doses of vupanorsen were “just as good as any other therapy, and the safety profile was … much better than at the highest dose.”
They wanted to pursue the subgroup analysis, despite Pfizer’s announcement, partly to “learn something in terms of the potential efficacy of the ANGPTL3 pathway in general.”
Dr. Marston said that Ionis is now focused on ANGPTL3, and the current results suggest that it “works very well,” so if other drugs are able to achieve the same efficacy as vupanorsen “but without the effects,” then it may “get elbowed out.”
Børge G. Nordestgaard, MD, PhD, of Herlev and Gentofte Hospital, Copenhagen, who was not involved in the study, called the findings “very encouraging.”
He told this news organization that being able to reduce LDL cholesterol as well as VLDL and remnant cholesterol is “exactly what I would be dreaming about” with a drug like vupanorsen.
Dr. Nordestgaard nevertheless underlined that “one would have to look carefully” at the safety of the drug.
“If it was my money, I would certainly try to look into if this was some sort of transient thing. Even when they started talking about statins, there was also this transient increase in alanine transaminase that seems to go away after a while,” he said.
“But of course, if this was persistent and triglycerides in the liver kept accumulating, then it’s a problem,” Dr. Nordestgaard added, “and then you would need to have some sort of thinking about whether you could couple it with something that got rid of the liver fat.”
He also agreed with Dr. Marston that, even if vupanorsen does not clear all hurdles before making it to market, the approach is promising.
“The target,” Dr. Nordestgaard said, seems “fantastic, from my point of view anyway.”
Dr. Marston explained that VLDL cholesterol, remnant cholesterol, and triglycerides are “surrogates for triglyceride-rich” lipoproteins, and that they are “increasingly recognized” as cardiovascular risk factors.
He highlighted that currently available therapies achieve reductions of these compounds of between 30% and 50%.
TRANSLATE-TIMI 70 included adults on stable statin therapy who had a triglyceride level of 150 mg/dL to 500 mg/dL and a non-HDL cholesterol level of 100 mg/dL or higher.
The participants were randomly assigned to one of six 2- or 4-week dosing schedules of vupanorsen or placebo and followed up over 24 weeks for a series of primary and additional endpoints, as well as safety outcomes.
The team recruited 286 individuals, who had a median age of 64 years; 44% were female. The majority (87%) were white.
The mean body mass index was 32 kg/m2, 50% had diabetes, 13% had experienced a prior myocardial infarction, and 51% were receiving high-intensity statins.
As previously reported, vupanorsen was associated with a reduction in non-HDL cholesterol vs. placebo of 22%-28%, alongside a 6%-15% reduction in apolipoprotein B levels and an 8%-16% reduction in LDL cholesterol.
In contrast, Dr. Marston showed that the various dosing schedules of the drug were associated with reductions in levels of VLDL cholesterol of 52%-66% vs. placebo at 24 weeks.
Over the same period, remnant cholesterol levels were lowered by 42%-59% vs. placebo, and triglycerides were reduced by 44%-57% in patients given vupanorsen.
There were also reductions in ANGPTL3 levels of 70%-95%.
Subgroup analysis indicated that the effect of vupanorsen was seen regardless of age, sex, body mass index, presence of diabetes, baseline triglycerides, and intensity of statin therapy.
Dr. Marston highlighted that the reductions in triglycerides, VLDL cholesterol, and remnant cholesterol levels were directly related to those for ANGPTL3 levels, but that the reductions remained meaningful even at less than maximal reductions in ANGPTL.
For example, even when ANGPTL3 levels were reduced by 70%, there were 50% reductions in triglyceride levels, 70% reductions in VLDL cholesterol levels, and a 50% drop in remnant cholesterol levels.
This, he noted, is important given that safety signals such as increases in alanine transaminase and hepatic fat occurred in a dose-dependent manner with ANGPTL3 reductions and were “most pronounced” only at the highest level of ANGPTL3 reduction.
The TRANSLATE-TIMI 70 study was sponsored by Pfizer. Dr. Marston disclosed relationships with Pfizer, Amgen, Ionis, Novartis, and AstraZeneca. Dr. Nordestgaard disclosed relationships with AstraZeneca, Sanofi, Regeneron, Akcea, Ionis, Amgen, Kowa, Denka, Amarin, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics.
A version of this article first appeared on Medscape.com.
MILAN, Italy – The antisense oligonucleotide vupanorsen substantially reduces very-low-density-lipoprotein (VLDL) and remnant cholesterol levels in patients with raised lipids despite statin therapy, suggests a subanalysis of TRANSLATE-TIMI 70 that appears to offer more hope than the primary study findings.
Vupanorsen targets hepatic angiopoietin-like protein 3 (ANGPTL3), which inhibits enzymes involved in triglyceride and cholesterol metabolism.
Earlier this year, headline data from TRANSLATE-TIMI 70 suggested that the drug reduced triglycerides and non–high-density-lipoprotein cholesterol to a degree that was significant but not clinically meaningful for cardiovascular risk reduction.
Moreover, as reported by this news organization, there were safety concerns over increases in liver enzymes among patients taking the drug, as well as dose-related increases in hepatic fat.
As a result, Pfizer announced that it would discontinue its clinical development program for vupanorsen and return the development rights to Ionis, following the signing of a worldwide exclusive agreement in November 2019.
Now, Nicholas A. Marston, MD, MPH, cardiovascular medicine, Brigham and Women’s Hospital, Boston, has presented a post-hoc analysis of the phase 2b study, showing that the drug reduces VLDL and remnant cholesterol levels by up to 60%.
These were closely tied to reductions in ANGPTL3 levels, although substantial reductions in cholesterol levels were achieved even at less than maximal reductions in ANGPTL3, where the impact on safety outcomes was reduced.
Dr. Marston said that lower doses of vupanorsen, where the safety effects would be less, or other drugs that inhibit ANGPTL3, “may have an important role in patients with residual dyslipidemia despite current therapy.”
The results were presented at the 90th European Atherosclerosis Society Congress on May 23.
Dr. Marston told this news organization that some of the reductions they saw with the lower doses of vupanorsen were “just as good as any other therapy, and the safety profile was … much better than at the highest dose.”
They wanted to pursue the subgroup analysis, despite Pfizer’s announcement, partly to “learn something in terms of the potential efficacy of the ANGPTL3 pathway in general.”
Dr. Marston said that Ionis is now focused on ANGPTL3, and the current results suggest that it “works very well,” so if other drugs are able to achieve the same efficacy as vupanorsen “but without the effects,” then it may “get elbowed out.”
Børge G. Nordestgaard, MD, PhD, of Herlev and Gentofte Hospital, Copenhagen, who was not involved in the study, called the findings “very encouraging.”
He told this news organization that being able to reduce LDL cholesterol as well as VLDL and remnant cholesterol is “exactly what I would be dreaming about” with a drug like vupanorsen.
Dr. Nordestgaard nevertheless underlined that “one would have to look carefully” at the safety of the drug.
“If it was my money, I would certainly try to look into if this was some sort of transient thing. Even when they started talking about statins, there was also this transient increase in alanine transaminase that seems to go away after a while,” he said.
“But of course, if this was persistent and triglycerides in the liver kept accumulating, then it’s a problem,” Dr. Nordestgaard added, “and then you would need to have some sort of thinking about whether you could couple it with something that got rid of the liver fat.”
He also agreed with Dr. Marston that, even if vupanorsen does not clear all hurdles before making it to market, the approach is promising.
“The target,” Dr. Nordestgaard said, seems “fantastic, from my point of view anyway.”
Dr. Marston explained that VLDL cholesterol, remnant cholesterol, and triglycerides are “surrogates for triglyceride-rich” lipoproteins, and that they are “increasingly recognized” as cardiovascular risk factors.
He highlighted that currently available therapies achieve reductions of these compounds of between 30% and 50%.
TRANSLATE-TIMI 70 included adults on stable statin therapy who had a triglyceride level of 150 mg/dL to 500 mg/dL and a non-HDL cholesterol level of 100 mg/dL or higher.
The participants were randomly assigned to one of six 2- or 4-week dosing schedules of vupanorsen or placebo and followed up over 24 weeks for a series of primary and additional endpoints, as well as safety outcomes.
The team recruited 286 individuals, who had a median age of 64 years; 44% were female. The majority (87%) were white.
The mean body mass index was 32 kg/m2, 50% had diabetes, 13% had experienced a prior myocardial infarction, and 51% were receiving high-intensity statins.
As previously reported, vupanorsen was associated with a reduction in non-HDL cholesterol vs. placebo of 22%-28%, alongside a 6%-15% reduction in apolipoprotein B levels and an 8%-16% reduction in LDL cholesterol.
In contrast, Dr. Marston showed that the various dosing schedules of the drug were associated with reductions in levels of VLDL cholesterol of 52%-66% vs. placebo at 24 weeks.
Over the same period, remnant cholesterol levels were lowered by 42%-59% vs. placebo, and triglycerides were reduced by 44%-57% in patients given vupanorsen.
There were also reductions in ANGPTL3 levels of 70%-95%.
Subgroup analysis indicated that the effect of vupanorsen was seen regardless of age, sex, body mass index, presence of diabetes, baseline triglycerides, and intensity of statin therapy.
Dr. Marston highlighted that the reductions in triglycerides, VLDL cholesterol, and remnant cholesterol levels were directly related to those for ANGPTL3 levels, but that the reductions remained meaningful even at less than maximal reductions in ANGPTL.
For example, even when ANGPTL3 levels were reduced by 70%, there were 50% reductions in triglyceride levels, 70% reductions in VLDL cholesterol levels, and a 50% drop in remnant cholesterol levels.
This, he noted, is important given that safety signals such as increases in alanine transaminase and hepatic fat occurred in a dose-dependent manner with ANGPTL3 reductions and were “most pronounced” only at the highest level of ANGPTL3 reduction.
The TRANSLATE-TIMI 70 study was sponsored by Pfizer. Dr. Marston disclosed relationships with Pfizer, Amgen, Ionis, Novartis, and AstraZeneca. Dr. Nordestgaard disclosed relationships with AstraZeneca, Sanofi, Regeneron, Akcea, Ionis, Amgen, Kowa, Denka, Amarin, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics.
A version of this article first appeared on Medscape.com.
MILAN, Italy – The antisense oligonucleotide vupanorsen substantially reduces very-low-density-lipoprotein (VLDL) and remnant cholesterol levels in patients with raised lipids despite statin therapy, suggests a subanalysis of TRANSLATE-TIMI 70 that appears to offer more hope than the primary study findings.
Vupanorsen targets hepatic angiopoietin-like protein 3 (ANGPTL3), which inhibits enzymes involved in triglyceride and cholesterol metabolism.
Earlier this year, headline data from TRANSLATE-TIMI 70 suggested that the drug reduced triglycerides and non–high-density-lipoprotein cholesterol to a degree that was significant but not clinically meaningful for cardiovascular risk reduction.
Moreover, as reported by this news organization, there were safety concerns over increases in liver enzymes among patients taking the drug, as well as dose-related increases in hepatic fat.
As a result, Pfizer announced that it would discontinue its clinical development program for vupanorsen and return the development rights to Ionis, following the signing of a worldwide exclusive agreement in November 2019.
Now, Nicholas A. Marston, MD, MPH, cardiovascular medicine, Brigham and Women’s Hospital, Boston, has presented a post-hoc analysis of the phase 2b study, showing that the drug reduces VLDL and remnant cholesterol levels by up to 60%.
These were closely tied to reductions in ANGPTL3 levels, although substantial reductions in cholesterol levels were achieved even at less than maximal reductions in ANGPTL3, where the impact on safety outcomes was reduced.
Dr. Marston said that lower doses of vupanorsen, where the safety effects would be less, or other drugs that inhibit ANGPTL3, “may have an important role in patients with residual dyslipidemia despite current therapy.”
The results were presented at the 90th European Atherosclerosis Society Congress on May 23.
Dr. Marston told this news organization that some of the reductions they saw with the lower doses of vupanorsen were “just as good as any other therapy, and the safety profile was … much better than at the highest dose.”
They wanted to pursue the subgroup analysis, despite Pfizer’s announcement, partly to “learn something in terms of the potential efficacy of the ANGPTL3 pathway in general.”
Dr. Marston said that Ionis is now focused on ANGPTL3, and the current results suggest that it “works very well,” so if other drugs are able to achieve the same efficacy as vupanorsen “but without the effects,” then it may “get elbowed out.”
Børge G. Nordestgaard, MD, PhD, of Herlev and Gentofte Hospital, Copenhagen, who was not involved in the study, called the findings “very encouraging.”
He told this news organization that being able to reduce LDL cholesterol as well as VLDL and remnant cholesterol is “exactly what I would be dreaming about” with a drug like vupanorsen.
Dr. Nordestgaard nevertheless underlined that “one would have to look carefully” at the safety of the drug.
“If it was my money, I would certainly try to look into if this was some sort of transient thing. Even when they started talking about statins, there was also this transient increase in alanine transaminase that seems to go away after a while,” he said.
“But of course, if this was persistent and triglycerides in the liver kept accumulating, then it’s a problem,” Dr. Nordestgaard added, “and then you would need to have some sort of thinking about whether you could couple it with something that got rid of the liver fat.”
He also agreed with Dr. Marston that, even if vupanorsen does not clear all hurdles before making it to market, the approach is promising.
“The target,” Dr. Nordestgaard said, seems “fantastic, from my point of view anyway.”
Dr. Marston explained that VLDL cholesterol, remnant cholesterol, and triglycerides are “surrogates for triglyceride-rich” lipoproteins, and that they are “increasingly recognized” as cardiovascular risk factors.
He highlighted that currently available therapies achieve reductions of these compounds of between 30% and 50%.
TRANSLATE-TIMI 70 included adults on stable statin therapy who had a triglyceride level of 150 mg/dL to 500 mg/dL and a non-HDL cholesterol level of 100 mg/dL or higher.
The participants were randomly assigned to one of six 2- or 4-week dosing schedules of vupanorsen or placebo and followed up over 24 weeks for a series of primary and additional endpoints, as well as safety outcomes.
The team recruited 286 individuals, who had a median age of 64 years; 44% were female. The majority (87%) were white.
The mean body mass index was 32 kg/m2, 50% had diabetes, 13% had experienced a prior myocardial infarction, and 51% were receiving high-intensity statins.
As previously reported, vupanorsen was associated with a reduction in non-HDL cholesterol vs. placebo of 22%-28%, alongside a 6%-15% reduction in apolipoprotein B levels and an 8%-16% reduction in LDL cholesterol.
In contrast, Dr. Marston showed that the various dosing schedules of the drug were associated with reductions in levels of VLDL cholesterol of 52%-66% vs. placebo at 24 weeks.
Over the same period, remnant cholesterol levels were lowered by 42%-59% vs. placebo, and triglycerides were reduced by 44%-57% in patients given vupanorsen.
There were also reductions in ANGPTL3 levels of 70%-95%.
Subgroup analysis indicated that the effect of vupanorsen was seen regardless of age, sex, body mass index, presence of diabetes, baseline triglycerides, and intensity of statin therapy.
Dr. Marston highlighted that the reductions in triglycerides, VLDL cholesterol, and remnant cholesterol levels were directly related to those for ANGPTL3 levels, but that the reductions remained meaningful even at less than maximal reductions in ANGPTL.
For example, even when ANGPTL3 levels were reduced by 70%, there were 50% reductions in triglyceride levels, 70% reductions in VLDL cholesterol levels, and a 50% drop in remnant cholesterol levels.
This, he noted, is important given that safety signals such as increases in alanine transaminase and hepatic fat occurred in a dose-dependent manner with ANGPTL3 reductions and were “most pronounced” only at the highest level of ANGPTL3 reduction.
The TRANSLATE-TIMI 70 study was sponsored by Pfizer. Dr. Marston disclosed relationships with Pfizer, Amgen, Ionis, Novartis, and AstraZeneca. Dr. Nordestgaard disclosed relationships with AstraZeneca, Sanofi, Regeneron, Akcea, Ionis, Amgen, Kowa, Denka, Amarin, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics.
A version of this article first appeared on Medscape.com.
AT EAS 2022