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Dupilumab offers ‘clinically meaningful’ improvements in prurigo nodularis
(Dupixent), indicate results from the phase 2 LIBERTY-PN PRIME trial.
The research was presented at the annual Congress of the European Academy of Dermatology and Venereology.
More than 150 patients with severe PN whose quality of life was impaired were randomly assigned to receive dupilumab (Dupixent) or placebo for 24 weeks. Use of the monoclonal antibody was associated with significant improvements in itch scores.
The researchers also found that the percentage of patients who had no or few PN lesions increased substantially with use of dupilumab, and there were no new safety signals, confirming results from previous studies. Dupilumab, an interleukin-4 receptor alpha antagonist administered by injection, was initially approved by the U.S. Food and Drug Administration for treating atopic dermatitis in 2022.
Study presenter Gil Yosipovitch, MD, professor of dermatology at the University of Miami, emphasized that the improvements in itch and skin lesions seen in these patients were “clinically meaningful.”
In the discussion after the presentation, Dr. Yosipovitch was asked whether the presence or absence of atopy had any bearing on the results.
He replied that although there were too few patients with atopy in the current study to answer that question, other data indicate that there is no overall difference between patients with atopy and those without atopy.
Asked whether dupilumab should be used for only 24 weeks, Dr. Yosipovitch said his that “impression” is that there can be a “honeymoon period” during which the medication is stopped and the treating clinician sees “what happens.”
“It would be interesting in the future” to find out, he added, but he noted that whatever the result, patients would need treatment “for the rest of their life.”
Dr. Yosipovitch, director of the Miami Itch Center and the study’s principal investigator, began his presentation by noting that currently, no systemic therapies have been approved by the FDA or the European Medicines Agency for PN.
Although treatments such as topical medications, ultraviolet light therapy, immunosuppressive agents, and systemic neuromodulators are used off label, for many patients with moderate to severe PN, disease control is inadequate, and the patients are “miserable.”
Recently, the phase 3 LIBERTY-PN PRIME2 trial showed that dupilumab significantly reduced itch and skin lesions for patients with PN, and the safety profile was consistent with that seen in approved indications for the drug.
Dr. Yosipovitch explained that LIBERTY-PN PRIME was a phase 2 study in which, after a screening period, patients with PN were randomly assigned in a 1:1 ratio to receive dupilumab as a 600-mg loading dose followed by 300 mg twice weekly or a matched placebo. Treatment was given for 24 weeks, after which there was a post treatment 12-week follow-up period.
Participants were aged 18-80 years and had been diagnosed with PN for a period of at least 3 months. To be included in the trial, patients had to have an average Worst Itch Numerical Rating Scale (WI-NRS) score of at least 7 and at least 20 lesions, among other criteria. (Patients were allowed to continue treatment with mid- to low-potency topical steroids or topical calcineurin inhibitors if they had been taking them at baseline.)
Among 151 patients in the study, the mean age was 50.1 years, and 66.2% were women. The majority (53.0%) were White; 7.3% were Black; and 35.8% were Asian; 40.4% of patients had a history of atopy. The mean WI-NRS was 8.5, and the mean skin pain score on a 10-point scale was 7.2.
The Investigator’s Global Assessment for PN stage of disease (IGA PN-S) was also employed in the trial. That measure uses a 5-point scale to assess disease severity, with 0 indicating no lesions and 4 indicating more than 100 lesions. At baseline, 28.7% of patients had a score of 4, and the remainder had a score of 3, indicating the presence of 20-100 PN lesions.
Dr. Yosipovitch said that quality of life for these patients was “low” and that scores on the Hospital Anxiety and Depression scale indicated that the participants, many of whom had previously received topical and systemic medications for their PN, indicated they were depressed.
He showed that at week 24, the proportion of patients who had experienced an improvement in the WI-NRS score of greater than or equal to 4 (the study’s primary endpoint) was significantly greater with dupilumab, at 60.0% versus 18.4% among patients given placebo (P < .0001).
Moreover, the proportion of patients at week 24 with an IGA PN-S score of 0 or 1 (the secondary endpoint) was 48.0% in the active treatment group, versus 18.4% with placebo (P =.0004).
With regard to safety, rates of any treatment-emergent adverse events were similar between the groups, at 70.7% for dupilumab and 62.7% for placebo, as were rates for severe treatment-emergent adverse events, at 6.7% and 10.7%, respectively.
Rates of treatment-emergent adverse events of interest, such as skin infections, conjunctivitis, herpes viral infections, and injection site reactions, also suggested that there was no increased risk with active treatment.
Dupilumab is currently under review at the FDA and in Europe for the treatment of PN, according to dupilumab manufacturers Regeneron and Sanofi.
The study was sponsored by Sanofi in collaboration with Regeneron Pharmaceuticals. Dr. Yosipovitch has relationships with Arcutis Biotherapeutics, Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics.
A version of this article first appeared on Medscape.com.
(Dupixent), indicate results from the phase 2 LIBERTY-PN PRIME trial.
The research was presented at the annual Congress of the European Academy of Dermatology and Venereology.
More than 150 patients with severe PN whose quality of life was impaired were randomly assigned to receive dupilumab (Dupixent) or placebo for 24 weeks. Use of the monoclonal antibody was associated with significant improvements in itch scores.
The researchers also found that the percentage of patients who had no or few PN lesions increased substantially with use of dupilumab, and there were no new safety signals, confirming results from previous studies. Dupilumab, an interleukin-4 receptor alpha antagonist administered by injection, was initially approved by the U.S. Food and Drug Administration for treating atopic dermatitis in 2022.
Study presenter Gil Yosipovitch, MD, professor of dermatology at the University of Miami, emphasized that the improvements in itch and skin lesions seen in these patients were “clinically meaningful.”
In the discussion after the presentation, Dr. Yosipovitch was asked whether the presence or absence of atopy had any bearing on the results.
He replied that although there were too few patients with atopy in the current study to answer that question, other data indicate that there is no overall difference between patients with atopy and those without atopy.
Asked whether dupilumab should be used for only 24 weeks, Dr. Yosipovitch said his that “impression” is that there can be a “honeymoon period” during which the medication is stopped and the treating clinician sees “what happens.”
“It would be interesting in the future” to find out, he added, but he noted that whatever the result, patients would need treatment “for the rest of their life.”
Dr. Yosipovitch, director of the Miami Itch Center and the study’s principal investigator, began his presentation by noting that currently, no systemic therapies have been approved by the FDA or the European Medicines Agency for PN.
Although treatments such as topical medications, ultraviolet light therapy, immunosuppressive agents, and systemic neuromodulators are used off label, for many patients with moderate to severe PN, disease control is inadequate, and the patients are “miserable.”
Recently, the phase 3 LIBERTY-PN PRIME2 trial showed that dupilumab significantly reduced itch and skin lesions for patients with PN, and the safety profile was consistent with that seen in approved indications for the drug.
Dr. Yosipovitch explained that LIBERTY-PN PRIME was a phase 2 study in which, after a screening period, patients with PN were randomly assigned in a 1:1 ratio to receive dupilumab as a 600-mg loading dose followed by 300 mg twice weekly or a matched placebo. Treatment was given for 24 weeks, after which there was a post treatment 12-week follow-up period.
Participants were aged 18-80 years and had been diagnosed with PN for a period of at least 3 months. To be included in the trial, patients had to have an average Worst Itch Numerical Rating Scale (WI-NRS) score of at least 7 and at least 20 lesions, among other criteria. (Patients were allowed to continue treatment with mid- to low-potency topical steroids or topical calcineurin inhibitors if they had been taking them at baseline.)
Among 151 patients in the study, the mean age was 50.1 years, and 66.2% were women. The majority (53.0%) were White; 7.3% were Black; and 35.8% were Asian; 40.4% of patients had a history of atopy. The mean WI-NRS was 8.5, and the mean skin pain score on a 10-point scale was 7.2.
The Investigator’s Global Assessment for PN stage of disease (IGA PN-S) was also employed in the trial. That measure uses a 5-point scale to assess disease severity, with 0 indicating no lesions and 4 indicating more than 100 lesions. At baseline, 28.7% of patients had a score of 4, and the remainder had a score of 3, indicating the presence of 20-100 PN lesions.
Dr. Yosipovitch said that quality of life for these patients was “low” and that scores on the Hospital Anxiety and Depression scale indicated that the participants, many of whom had previously received topical and systemic medications for their PN, indicated they were depressed.
He showed that at week 24, the proportion of patients who had experienced an improvement in the WI-NRS score of greater than or equal to 4 (the study’s primary endpoint) was significantly greater with dupilumab, at 60.0% versus 18.4% among patients given placebo (P < .0001).
Moreover, the proportion of patients at week 24 with an IGA PN-S score of 0 or 1 (the secondary endpoint) was 48.0% in the active treatment group, versus 18.4% with placebo (P =.0004).
With regard to safety, rates of any treatment-emergent adverse events were similar between the groups, at 70.7% for dupilumab and 62.7% for placebo, as were rates for severe treatment-emergent adverse events, at 6.7% and 10.7%, respectively.
Rates of treatment-emergent adverse events of interest, such as skin infections, conjunctivitis, herpes viral infections, and injection site reactions, also suggested that there was no increased risk with active treatment.
Dupilumab is currently under review at the FDA and in Europe for the treatment of PN, according to dupilumab manufacturers Regeneron and Sanofi.
The study was sponsored by Sanofi in collaboration with Regeneron Pharmaceuticals. Dr. Yosipovitch has relationships with Arcutis Biotherapeutics, Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics.
A version of this article first appeared on Medscape.com.
(Dupixent), indicate results from the phase 2 LIBERTY-PN PRIME trial.
The research was presented at the annual Congress of the European Academy of Dermatology and Venereology.
More than 150 patients with severe PN whose quality of life was impaired were randomly assigned to receive dupilumab (Dupixent) or placebo for 24 weeks. Use of the monoclonal antibody was associated with significant improvements in itch scores.
The researchers also found that the percentage of patients who had no or few PN lesions increased substantially with use of dupilumab, and there were no new safety signals, confirming results from previous studies. Dupilumab, an interleukin-4 receptor alpha antagonist administered by injection, was initially approved by the U.S. Food and Drug Administration for treating atopic dermatitis in 2022.
Study presenter Gil Yosipovitch, MD, professor of dermatology at the University of Miami, emphasized that the improvements in itch and skin lesions seen in these patients were “clinically meaningful.”
In the discussion after the presentation, Dr. Yosipovitch was asked whether the presence or absence of atopy had any bearing on the results.
He replied that although there were too few patients with atopy in the current study to answer that question, other data indicate that there is no overall difference between patients with atopy and those without atopy.
Asked whether dupilumab should be used for only 24 weeks, Dr. Yosipovitch said his that “impression” is that there can be a “honeymoon period” during which the medication is stopped and the treating clinician sees “what happens.”
“It would be interesting in the future” to find out, he added, but he noted that whatever the result, patients would need treatment “for the rest of their life.”
Dr. Yosipovitch, director of the Miami Itch Center and the study’s principal investigator, began his presentation by noting that currently, no systemic therapies have been approved by the FDA or the European Medicines Agency for PN.
Although treatments such as topical medications, ultraviolet light therapy, immunosuppressive agents, and systemic neuromodulators are used off label, for many patients with moderate to severe PN, disease control is inadequate, and the patients are “miserable.”
Recently, the phase 3 LIBERTY-PN PRIME2 trial showed that dupilumab significantly reduced itch and skin lesions for patients with PN, and the safety profile was consistent with that seen in approved indications for the drug.
Dr. Yosipovitch explained that LIBERTY-PN PRIME was a phase 2 study in which, after a screening period, patients with PN were randomly assigned in a 1:1 ratio to receive dupilumab as a 600-mg loading dose followed by 300 mg twice weekly or a matched placebo. Treatment was given for 24 weeks, after which there was a post treatment 12-week follow-up period.
Participants were aged 18-80 years and had been diagnosed with PN for a period of at least 3 months. To be included in the trial, patients had to have an average Worst Itch Numerical Rating Scale (WI-NRS) score of at least 7 and at least 20 lesions, among other criteria. (Patients were allowed to continue treatment with mid- to low-potency topical steroids or topical calcineurin inhibitors if they had been taking them at baseline.)
Among 151 patients in the study, the mean age was 50.1 years, and 66.2% were women. The majority (53.0%) were White; 7.3% were Black; and 35.8% were Asian; 40.4% of patients had a history of atopy. The mean WI-NRS was 8.5, and the mean skin pain score on a 10-point scale was 7.2.
The Investigator’s Global Assessment for PN stage of disease (IGA PN-S) was also employed in the trial. That measure uses a 5-point scale to assess disease severity, with 0 indicating no lesions and 4 indicating more than 100 lesions. At baseline, 28.7% of patients had a score of 4, and the remainder had a score of 3, indicating the presence of 20-100 PN lesions.
Dr. Yosipovitch said that quality of life for these patients was “low” and that scores on the Hospital Anxiety and Depression scale indicated that the participants, many of whom had previously received topical and systemic medications for their PN, indicated they were depressed.
He showed that at week 24, the proportion of patients who had experienced an improvement in the WI-NRS score of greater than or equal to 4 (the study’s primary endpoint) was significantly greater with dupilumab, at 60.0% versus 18.4% among patients given placebo (P < .0001).
Moreover, the proportion of patients at week 24 with an IGA PN-S score of 0 or 1 (the secondary endpoint) was 48.0% in the active treatment group, versus 18.4% with placebo (P =.0004).
With regard to safety, rates of any treatment-emergent adverse events were similar between the groups, at 70.7% for dupilumab and 62.7% for placebo, as were rates for severe treatment-emergent adverse events, at 6.7% and 10.7%, respectively.
Rates of treatment-emergent adverse events of interest, such as skin infections, conjunctivitis, herpes viral infections, and injection site reactions, also suggested that there was no increased risk with active treatment.
Dupilumab is currently under review at the FDA and in Europe for the treatment of PN, according to dupilumab manufacturers Regeneron and Sanofi.
The study was sponsored by Sanofi in collaboration with Regeneron Pharmaceuticals. Dr. Yosipovitch has relationships with Arcutis Biotherapeutics, Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics.
A version of this article first appeared on Medscape.com.
FROM THE EADV CONGRESS
Dermatoses often occur in people who wear face masks
according to a recently published systematic review and meta-analysis.
“This report finds the most statistically significant risk factor for developing a facial dermatosis under a face mask is how long one wears the mask. Specifically, wearing a mask for more than 4 to 6 hours correlated most strongly with the development of a facial skin problem,” Jami L. Miller, MD, associate professor of dermatology, Vanderbilt University Medical Center, Nashville, Tenn., told this news organization. Dr. Miller was not involved in the study.
“The type of mask and the environment were of less significance,” she added.
Mask wearing for infection control has been common during the COVID-19 pandemic and will likely continue for some time, study coauthors Lim Yi Shen Justin, MBBS, and Yik Weng Yew*, MBBS, MPH, PhD, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, write in Contact Dermatitis. And cross-sectional studies have suggested a link between mask wearing and various facial dermatoses.
To evaluate this link, as well as potential risk factors for facial dermatoses, the researchers reviewed 37 studies published between 2004 and 2022 involving 29,557 adult participants self-reporting regular use of any face mask type across 17 countries in Europe and Asia. The mask types commonly studied in the papers they analyzed included surgical masks and respirators.
Facial dermatoses were self-reported in 30 studies (81.1%) and were diagnosed by trained dermatologists in seven studies (18.9%).
Dr. Justin and Dr. Yew found that:
- The overall prevalence of facial dermatoses was 55%
- Individually, facial dermatitis, itch, acne, and pressure injuries were consistently reported as facial dermatoses, with pooled prevalence rates of 24%, 30%, 31%, and 31%, respectively
- The duration of mask wearing was the most significant risk factor for facial dermatoses (P < .001)
- Respirators, including N95 masks, were not more likely than surgical masks to be linked with facial dermatoses
“Understanding risk factors of mask wearing, including situation, duration, and type of mask, may allow for targeted interventions to mitigate problems,” Dr. Yew told this news organization.
He advised taking a break from mask wearing after 4 to 6 hours to improve outcomes.
Dr. Yew acknowledged limitations, including that most of the reviewed studies relied on self-reported symptoms.
“Patient factors were not investigated in most studies; therefore, we were not able to ascertain their contributory role in the development of facial dermatoses from mask wearing,” he said. “We were also unable to prove causation between risk factors and outcome.”
Four dermatologists welcome the findings
Dr. Miller called this an “interesting, and certainly relevant” study, now that mask wearing is common and facial skin problems are fairly common complaints in medical visits.
“As the authors say, irritants or contact allergens with longer exposures can be expected to cause a more severe dermatitis than short contact,” she said. “Longer duration also can cause occlusion of pores and hair follicles, which can be expected to worsen acne and folliculitis.”
“I was surprised that the type of mask did not seem to matter significantly,” she added. “Patients wearing N95 masks may be relieved to know N95s do not cause more skin problems than lighter masks.”
Still, Dr. Miller had several questions, including if the materials and chemical finishes that vary by manufacturer may affect skin conditions.
Olga Bunimovich, MD, assistant professor, department of dermatology, University of Pittsburgh School of Medicine, Pennsylvania, called this study “an excellent step towards characterizing the role masks play in facial dermatoses.”
“The study provides a window into the prevalence of these conditions, as well as some understanding of the factors that may be contributing to it,” Dr. Bunimovich, who was not part of the study, added. But “we can also utilize this information to alter behavior in the work environment, allowing ‘mask-free’ breaks to decrease the risk of facial dermatoses.”
Elma Baron, MD, professor and director, Skin Study Center, department of dermatology, Case Western Reserve University School of Medicine, Cleveland, expected skin problems to be linked with mask wearing but didn’t expect the prevalence to be as high as 55%, which she called “very significant.”
“Mask wearing is an important means to prevent transmission of communicable infections, and the practice will most likely continue,” she said.
“Given the data, it is reasonable to advise patients who are already prone to these specific dermatoses to be proactive,” she added. “Early intervention with proper topical medications, preferably prescribed by a dermatologist or other health care provider, and changing masks frequently before they get soaked with moisture, will hopefully lessen the severity of skin rashes and minimize the negative impact on quality of life.”
Also commenting on the study, Susan Massick, MD, dermatologist and clinical associate professor of internal medicine, The Ohio State University Wexner Medical Center, Westerville, said in an interview that she urges people to wear masks, despite these risks.
“The majority of concerns are straightforward, manageable, and overall benign,” she said. “We have a multitude of treatments that can help control, address, or improve symptoms.”
“Masks are an effective and easy way to protect yourself from infection, and they remain one of the most reliable preventions we have,” Dr. Massick noted. “The findings in this article should not preclude anyone from wearing a mask, nor should facial dermatoses be a cause for people to stop wearing their masks.”
The study received no funding. The authors, as well as Dr. Baron, Dr. Miller, Dr. Bunimovich, and Dr. Massick, who were not involved in the study, reported no relevant financial relationships. All experts commented by email.
A version of this article first appeared on Medscape.com.
Correction, 9/22/22: An earlier version of this article misstated the name of Dr. Yik Weng Yew.
according to a recently published systematic review and meta-analysis.
“This report finds the most statistically significant risk factor for developing a facial dermatosis under a face mask is how long one wears the mask. Specifically, wearing a mask for more than 4 to 6 hours correlated most strongly with the development of a facial skin problem,” Jami L. Miller, MD, associate professor of dermatology, Vanderbilt University Medical Center, Nashville, Tenn., told this news organization. Dr. Miller was not involved in the study.
“The type of mask and the environment were of less significance,” she added.
Mask wearing for infection control has been common during the COVID-19 pandemic and will likely continue for some time, study coauthors Lim Yi Shen Justin, MBBS, and Yik Weng Yew*, MBBS, MPH, PhD, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, write in Contact Dermatitis. And cross-sectional studies have suggested a link between mask wearing and various facial dermatoses.
To evaluate this link, as well as potential risk factors for facial dermatoses, the researchers reviewed 37 studies published between 2004 and 2022 involving 29,557 adult participants self-reporting regular use of any face mask type across 17 countries in Europe and Asia. The mask types commonly studied in the papers they analyzed included surgical masks and respirators.
Facial dermatoses were self-reported in 30 studies (81.1%) and were diagnosed by trained dermatologists in seven studies (18.9%).
Dr. Justin and Dr. Yew found that:
- The overall prevalence of facial dermatoses was 55%
- Individually, facial dermatitis, itch, acne, and pressure injuries were consistently reported as facial dermatoses, with pooled prevalence rates of 24%, 30%, 31%, and 31%, respectively
- The duration of mask wearing was the most significant risk factor for facial dermatoses (P < .001)
- Respirators, including N95 masks, were not more likely than surgical masks to be linked with facial dermatoses
“Understanding risk factors of mask wearing, including situation, duration, and type of mask, may allow for targeted interventions to mitigate problems,” Dr. Yew told this news organization.
He advised taking a break from mask wearing after 4 to 6 hours to improve outcomes.
Dr. Yew acknowledged limitations, including that most of the reviewed studies relied on self-reported symptoms.
“Patient factors were not investigated in most studies; therefore, we were not able to ascertain their contributory role in the development of facial dermatoses from mask wearing,” he said. “We were also unable to prove causation between risk factors and outcome.”
Four dermatologists welcome the findings
Dr. Miller called this an “interesting, and certainly relevant” study, now that mask wearing is common and facial skin problems are fairly common complaints in medical visits.
“As the authors say, irritants or contact allergens with longer exposures can be expected to cause a more severe dermatitis than short contact,” she said. “Longer duration also can cause occlusion of pores and hair follicles, which can be expected to worsen acne and folliculitis.”
“I was surprised that the type of mask did not seem to matter significantly,” she added. “Patients wearing N95 masks may be relieved to know N95s do not cause more skin problems than lighter masks.”
Still, Dr. Miller had several questions, including if the materials and chemical finishes that vary by manufacturer may affect skin conditions.
Olga Bunimovich, MD, assistant professor, department of dermatology, University of Pittsburgh School of Medicine, Pennsylvania, called this study “an excellent step towards characterizing the role masks play in facial dermatoses.”
“The study provides a window into the prevalence of these conditions, as well as some understanding of the factors that may be contributing to it,” Dr. Bunimovich, who was not part of the study, added. But “we can also utilize this information to alter behavior in the work environment, allowing ‘mask-free’ breaks to decrease the risk of facial dermatoses.”
Elma Baron, MD, professor and director, Skin Study Center, department of dermatology, Case Western Reserve University School of Medicine, Cleveland, expected skin problems to be linked with mask wearing but didn’t expect the prevalence to be as high as 55%, which she called “very significant.”
“Mask wearing is an important means to prevent transmission of communicable infections, and the practice will most likely continue,” she said.
“Given the data, it is reasonable to advise patients who are already prone to these specific dermatoses to be proactive,” she added. “Early intervention with proper topical medications, preferably prescribed by a dermatologist or other health care provider, and changing masks frequently before they get soaked with moisture, will hopefully lessen the severity of skin rashes and minimize the negative impact on quality of life.”
Also commenting on the study, Susan Massick, MD, dermatologist and clinical associate professor of internal medicine, The Ohio State University Wexner Medical Center, Westerville, said in an interview that she urges people to wear masks, despite these risks.
“The majority of concerns are straightforward, manageable, and overall benign,” she said. “We have a multitude of treatments that can help control, address, or improve symptoms.”
“Masks are an effective and easy way to protect yourself from infection, and they remain one of the most reliable preventions we have,” Dr. Massick noted. “The findings in this article should not preclude anyone from wearing a mask, nor should facial dermatoses be a cause for people to stop wearing their masks.”
The study received no funding. The authors, as well as Dr. Baron, Dr. Miller, Dr. Bunimovich, and Dr. Massick, who were not involved in the study, reported no relevant financial relationships. All experts commented by email.
A version of this article first appeared on Medscape.com.
Correction, 9/22/22: An earlier version of this article misstated the name of Dr. Yik Weng Yew.
according to a recently published systematic review and meta-analysis.
“This report finds the most statistically significant risk factor for developing a facial dermatosis under a face mask is how long one wears the mask. Specifically, wearing a mask for more than 4 to 6 hours correlated most strongly with the development of a facial skin problem,” Jami L. Miller, MD, associate professor of dermatology, Vanderbilt University Medical Center, Nashville, Tenn., told this news organization. Dr. Miller was not involved in the study.
“The type of mask and the environment were of less significance,” she added.
Mask wearing for infection control has been common during the COVID-19 pandemic and will likely continue for some time, study coauthors Lim Yi Shen Justin, MBBS, and Yik Weng Yew*, MBBS, MPH, PhD, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, write in Contact Dermatitis. And cross-sectional studies have suggested a link between mask wearing and various facial dermatoses.
To evaluate this link, as well as potential risk factors for facial dermatoses, the researchers reviewed 37 studies published between 2004 and 2022 involving 29,557 adult participants self-reporting regular use of any face mask type across 17 countries in Europe and Asia. The mask types commonly studied in the papers they analyzed included surgical masks and respirators.
Facial dermatoses were self-reported in 30 studies (81.1%) and were diagnosed by trained dermatologists in seven studies (18.9%).
Dr. Justin and Dr. Yew found that:
- The overall prevalence of facial dermatoses was 55%
- Individually, facial dermatitis, itch, acne, and pressure injuries were consistently reported as facial dermatoses, with pooled prevalence rates of 24%, 30%, 31%, and 31%, respectively
- The duration of mask wearing was the most significant risk factor for facial dermatoses (P < .001)
- Respirators, including N95 masks, were not more likely than surgical masks to be linked with facial dermatoses
“Understanding risk factors of mask wearing, including situation, duration, and type of mask, may allow for targeted interventions to mitigate problems,” Dr. Yew told this news organization.
He advised taking a break from mask wearing after 4 to 6 hours to improve outcomes.
Dr. Yew acknowledged limitations, including that most of the reviewed studies relied on self-reported symptoms.
“Patient factors were not investigated in most studies; therefore, we were not able to ascertain their contributory role in the development of facial dermatoses from mask wearing,” he said. “We were also unable to prove causation between risk factors and outcome.”
Four dermatologists welcome the findings
Dr. Miller called this an “interesting, and certainly relevant” study, now that mask wearing is common and facial skin problems are fairly common complaints in medical visits.
“As the authors say, irritants or contact allergens with longer exposures can be expected to cause a more severe dermatitis than short contact,” she said. “Longer duration also can cause occlusion of pores and hair follicles, which can be expected to worsen acne and folliculitis.”
“I was surprised that the type of mask did not seem to matter significantly,” she added. “Patients wearing N95 masks may be relieved to know N95s do not cause more skin problems than lighter masks.”
Still, Dr. Miller had several questions, including if the materials and chemical finishes that vary by manufacturer may affect skin conditions.
Olga Bunimovich, MD, assistant professor, department of dermatology, University of Pittsburgh School of Medicine, Pennsylvania, called this study “an excellent step towards characterizing the role masks play in facial dermatoses.”
“The study provides a window into the prevalence of these conditions, as well as some understanding of the factors that may be contributing to it,” Dr. Bunimovich, who was not part of the study, added. But “we can also utilize this information to alter behavior in the work environment, allowing ‘mask-free’ breaks to decrease the risk of facial dermatoses.”
Elma Baron, MD, professor and director, Skin Study Center, department of dermatology, Case Western Reserve University School of Medicine, Cleveland, expected skin problems to be linked with mask wearing but didn’t expect the prevalence to be as high as 55%, which she called “very significant.”
“Mask wearing is an important means to prevent transmission of communicable infections, and the practice will most likely continue,” she said.
“Given the data, it is reasonable to advise patients who are already prone to these specific dermatoses to be proactive,” she added. “Early intervention with proper topical medications, preferably prescribed by a dermatologist or other health care provider, and changing masks frequently before they get soaked with moisture, will hopefully lessen the severity of skin rashes and minimize the negative impact on quality of life.”
Also commenting on the study, Susan Massick, MD, dermatologist and clinical associate professor of internal medicine, The Ohio State University Wexner Medical Center, Westerville, said in an interview that she urges people to wear masks, despite these risks.
“The majority of concerns are straightforward, manageable, and overall benign,” she said. “We have a multitude of treatments that can help control, address, or improve symptoms.”
“Masks are an effective and easy way to protect yourself from infection, and they remain one of the most reliable preventions we have,” Dr. Massick noted. “The findings in this article should not preclude anyone from wearing a mask, nor should facial dermatoses be a cause for people to stop wearing their masks.”
The study received no funding. The authors, as well as Dr. Baron, Dr. Miller, Dr. Bunimovich, and Dr. Massick, who were not involved in the study, reported no relevant financial relationships. All experts commented by email.
A version of this article first appeared on Medscape.com.
Correction, 9/22/22: An earlier version of this article misstated the name of Dr. Yik Weng Yew.
Risk factors linked to post–COVID vaccination death identified
The researchers have identified factors that put a person at greater risk of COVID-related death after they have completed both doses of the primary COVID vaccination schedule and a booster dose.
For their research, published in JAMA Network Open, researchers from the Office for National Statistics (ONS); Public Health Scotland; the University of Strathclyde, Glasgow; and the University of Edinburgh used data from the ONS Public linked data set combining the 2011 Census of England and covering 80% of the population of England. The study population included 19,473,570 individuals aged 18-100 years (mean age 60.8 years, 45.2% men, 92.0% White individuals) living in England who had completed both doses of their primary vaccination schedule and had received their mRNA booster 14 days or more prior to Dec. 31, 2021. The outcome of interest was time to death involving COVID-19 occurring between Jan. 1 and March 16, 2022.
Prioritization of booster doses and COVID-19 treatments
The authors highlighted how it had become “critical” to identify risk factors associated with COVID-19 death in those who had been vaccinated and pointed out that existing evidence was “based on people who have received one or two doses of a COVID-19 vaccine and were infected by the Alpha or Delta variant”. They emphasized that establishing which groups are at increased risk of COVID-19 death after receiving a booster is crucial for the “prioritization of further booster doses and access to COVID-19 therapeutics.”
During the study period the authors found that there were 4,781 (0.02%) deaths involving COVID-19 and 58,020 (0.3%) deaths from other causes. Of those who died of coronavirus, the mean age was 83.3 years, and the authors highlighted how “age was the most important characteristic” associated with the risk of postbooster COVID-19 death. They added that, compared with a 50-year-old, the HR for an 80-year-old individual was 31.3 (95% confidence interval, 26.1-37.6).
They found that women were at lower risk than men with an HR of 0.52 (95% CI, 0.49-0.55). An increased risk of COVID-19 death was also associated with living in a care home or in a socioeconomically deprived area.
Of note, they said that “there was no association between the risk of COVID-19 death and ethnicity, except for those of Indian background”, who they explained were at slightly elevated risk, compared with White individuals. However, they explained how the association with ethnicity was “unclear and differed from previous studies”, with their findings likely to be due “largely to the pronounced differences in vaccination uptake” between ethnic groups in previous studies.
Dementia concern
With regard to existing health conditions the authors commented that “most of the QCovid risk groups were associated with an increased HR of postbooster breakthrough death, except for of congenital heart disease, asthma, and prior fracture.”
Risk was particularly elevated, they said, for people with severe combined immunodeficiency (HR, 6.2; 95% CI, 3.3-11.5), and they also identified several conditions associated with HRs of greater than 3, including dementia.
In July, Alzheimer’s Research UK urged the Government to boost the development and deployment of new dementia treatments having found that a significant proportion of people who died of COVID-19 in 2020 and 2021 were living with the condition. At the time, data published by the ONS of deaths caused by coronavirus in England and Wales in 2021 showed dementia to be the second-most common pre-existing condition.
David Thomas, head of policy at Alzheimer’s Research UK, said: “We’ve known for some time that people with dementia have been hit disproportionately hard during the pandemic, but this new data serves as a stark reminder of the growing challenge we face in tackling the condition, and the urgent need to address it.”
The authors of the new research acknowledged the study’s limitations, notably that only data for the population living in England who were enumerated in the 2011 Census of England and Wales was included.
However, subpopulations “remain at increased risk of COVID-19 fatality” after receiving a booster vaccine during the Omicron wave, they pointed out.
“The subpopulations with the highest risk should be considered a priority for COVID-19 therapeutics and further booster doses,” they urged.
A version of this article first appeared on Medscape UK.
The researchers have identified factors that put a person at greater risk of COVID-related death after they have completed both doses of the primary COVID vaccination schedule and a booster dose.
For their research, published in JAMA Network Open, researchers from the Office for National Statistics (ONS); Public Health Scotland; the University of Strathclyde, Glasgow; and the University of Edinburgh used data from the ONS Public linked data set combining the 2011 Census of England and covering 80% of the population of England. The study population included 19,473,570 individuals aged 18-100 years (mean age 60.8 years, 45.2% men, 92.0% White individuals) living in England who had completed both doses of their primary vaccination schedule and had received their mRNA booster 14 days or more prior to Dec. 31, 2021. The outcome of interest was time to death involving COVID-19 occurring between Jan. 1 and March 16, 2022.
Prioritization of booster doses and COVID-19 treatments
The authors highlighted how it had become “critical” to identify risk factors associated with COVID-19 death in those who had been vaccinated and pointed out that existing evidence was “based on people who have received one or two doses of a COVID-19 vaccine and were infected by the Alpha or Delta variant”. They emphasized that establishing which groups are at increased risk of COVID-19 death after receiving a booster is crucial for the “prioritization of further booster doses and access to COVID-19 therapeutics.”
During the study period the authors found that there were 4,781 (0.02%) deaths involving COVID-19 and 58,020 (0.3%) deaths from other causes. Of those who died of coronavirus, the mean age was 83.3 years, and the authors highlighted how “age was the most important characteristic” associated with the risk of postbooster COVID-19 death. They added that, compared with a 50-year-old, the HR for an 80-year-old individual was 31.3 (95% confidence interval, 26.1-37.6).
They found that women were at lower risk than men with an HR of 0.52 (95% CI, 0.49-0.55). An increased risk of COVID-19 death was also associated with living in a care home or in a socioeconomically deprived area.
Of note, they said that “there was no association between the risk of COVID-19 death and ethnicity, except for those of Indian background”, who they explained were at slightly elevated risk, compared with White individuals. However, they explained how the association with ethnicity was “unclear and differed from previous studies”, with their findings likely to be due “largely to the pronounced differences in vaccination uptake” between ethnic groups in previous studies.
Dementia concern
With regard to existing health conditions the authors commented that “most of the QCovid risk groups were associated with an increased HR of postbooster breakthrough death, except for of congenital heart disease, asthma, and prior fracture.”
Risk was particularly elevated, they said, for people with severe combined immunodeficiency (HR, 6.2; 95% CI, 3.3-11.5), and they also identified several conditions associated with HRs of greater than 3, including dementia.
In July, Alzheimer’s Research UK urged the Government to boost the development and deployment of new dementia treatments having found that a significant proportion of people who died of COVID-19 in 2020 and 2021 were living with the condition. At the time, data published by the ONS of deaths caused by coronavirus in England and Wales in 2021 showed dementia to be the second-most common pre-existing condition.
David Thomas, head of policy at Alzheimer’s Research UK, said: “We’ve known for some time that people with dementia have been hit disproportionately hard during the pandemic, but this new data serves as a stark reminder of the growing challenge we face in tackling the condition, and the urgent need to address it.”
The authors of the new research acknowledged the study’s limitations, notably that only data for the population living in England who were enumerated in the 2011 Census of England and Wales was included.
However, subpopulations “remain at increased risk of COVID-19 fatality” after receiving a booster vaccine during the Omicron wave, they pointed out.
“The subpopulations with the highest risk should be considered a priority for COVID-19 therapeutics and further booster doses,” they urged.
A version of this article first appeared on Medscape UK.
The researchers have identified factors that put a person at greater risk of COVID-related death after they have completed both doses of the primary COVID vaccination schedule and a booster dose.
For their research, published in JAMA Network Open, researchers from the Office for National Statistics (ONS); Public Health Scotland; the University of Strathclyde, Glasgow; and the University of Edinburgh used data from the ONS Public linked data set combining the 2011 Census of England and covering 80% of the population of England. The study population included 19,473,570 individuals aged 18-100 years (mean age 60.8 years, 45.2% men, 92.0% White individuals) living in England who had completed both doses of their primary vaccination schedule and had received their mRNA booster 14 days or more prior to Dec. 31, 2021. The outcome of interest was time to death involving COVID-19 occurring between Jan. 1 and March 16, 2022.
Prioritization of booster doses and COVID-19 treatments
The authors highlighted how it had become “critical” to identify risk factors associated with COVID-19 death in those who had been vaccinated and pointed out that existing evidence was “based on people who have received one or two doses of a COVID-19 vaccine and were infected by the Alpha or Delta variant”. They emphasized that establishing which groups are at increased risk of COVID-19 death after receiving a booster is crucial for the “prioritization of further booster doses and access to COVID-19 therapeutics.”
During the study period the authors found that there were 4,781 (0.02%) deaths involving COVID-19 and 58,020 (0.3%) deaths from other causes. Of those who died of coronavirus, the mean age was 83.3 years, and the authors highlighted how “age was the most important characteristic” associated with the risk of postbooster COVID-19 death. They added that, compared with a 50-year-old, the HR for an 80-year-old individual was 31.3 (95% confidence interval, 26.1-37.6).
They found that women were at lower risk than men with an HR of 0.52 (95% CI, 0.49-0.55). An increased risk of COVID-19 death was also associated with living in a care home or in a socioeconomically deprived area.
Of note, they said that “there was no association between the risk of COVID-19 death and ethnicity, except for those of Indian background”, who they explained were at slightly elevated risk, compared with White individuals. However, they explained how the association with ethnicity was “unclear and differed from previous studies”, with their findings likely to be due “largely to the pronounced differences in vaccination uptake” between ethnic groups in previous studies.
Dementia concern
With regard to existing health conditions the authors commented that “most of the QCovid risk groups were associated with an increased HR of postbooster breakthrough death, except for of congenital heart disease, asthma, and prior fracture.”
Risk was particularly elevated, they said, for people with severe combined immunodeficiency (HR, 6.2; 95% CI, 3.3-11.5), and they also identified several conditions associated with HRs of greater than 3, including dementia.
In July, Alzheimer’s Research UK urged the Government to boost the development and deployment of new dementia treatments having found that a significant proportion of people who died of COVID-19 in 2020 and 2021 were living with the condition. At the time, data published by the ONS of deaths caused by coronavirus in England and Wales in 2021 showed dementia to be the second-most common pre-existing condition.
David Thomas, head of policy at Alzheimer’s Research UK, said: “We’ve known for some time that people with dementia have been hit disproportionately hard during the pandemic, but this new data serves as a stark reminder of the growing challenge we face in tackling the condition, and the urgent need to address it.”
The authors of the new research acknowledged the study’s limitations, notably that only data for the population living in England who were enumerated in the 2011 Census of England and Wales was included.
However, subpopulations “remain at increased risk of COVID-19 fatality” after receiving a booster vaccine during the Omicron wave, they pointed out.
“The subpopulations with the highest risk should be considered a priority for COVID-19 therapeutics and further booster doses,” they urged.
A version of this article first appeared on Medscape UK.
FROM JAMA NETWORK OPEN
‘Spectacular’ polypill results also puzzle docs
But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.
How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?
Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.
As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
A matter of adherence?
In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.
Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).
Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)
The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).
“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.
“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.
Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.
In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.
Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.
One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.
Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.
Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.
When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”
“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
Can the results be replicated?
Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”
“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.
Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.
Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.
To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”
“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.
In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.
“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”
Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.
But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.
“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”
For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.
Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.
Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.
Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.
Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.
“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.
That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.
The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.”
The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.
A version of this article first appeared on Medscape.com.
But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.
How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?
Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.
As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
A matter of adherence?
In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.
Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).
Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)
The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).
“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.
“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.
Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.
In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.
Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.
One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.
Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.
Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.
When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”
“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
Can the results be replicated?
Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”
“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.
Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.
Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.
To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”
“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.
In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.
“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”
Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.
But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.
“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”
For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.
Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.
Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.
Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.
Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.
“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.
That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.
The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.”
The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.
A version of this article first appeared on Medscape.com.
But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.
How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?
Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.
As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
A matter of adherence?
In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.
Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).
Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)
The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).
“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.
“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.
Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.
In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.
Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.
One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.
Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.
Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.
When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”
“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
Can the results be replicated?
Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”
“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.
Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.
Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.
To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”
“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.
In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.
“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”
Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.
But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.
“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”
For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.
Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.
Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.
Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.
Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.
“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.
That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.
The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.”
The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.
A version of this article first appeared on Medscape.com.
Pediatric vaccines & infectious diseases, 2022
Introduction
ICYMI articles featuring 9 important developments of the past year – and COVID is still here
By Christopher J. Harrison, MD
Table of contents
Antibiotics use and vaccine antibody levels
Commentary
Emerging tick-borne pathogen has spread to state of Georgia
Commentary
WHO, UNICEF warn about increased risk of measles outbreaks
Commentary
Babies die as congenital syphilis continues a decade-long surge across the U.S.
Commentary
Meningococcal vaccine shows moderate protective effect against gonorrhea
Commentary
Adolescents are undertested for STIs
Commentary
TB treatment can be shortened for most children: Study
Commentary
Nirsevimab protects healthy infants from RSV
Commentary
Norovirus vaccine candidates employ different approaches
Commentary
Introduction
ICYMI articles featuring 9 important developments of the past year – and COVID is still here
By Christopher J. Harrison, MD
Table of contents
Antibiotics use and vaccine antibody levels
Commentary
Emerging tick-borne pathogen has spread to state of Georgia
Commentary
WHO, UNICEF warn about increased risk of measles outbreaks
Commentary
Babies die as congenital syphilis continues a decade-long surge across the U.S.
Commentary
Meningococcal vaccine shows moderate protective effect against gonorrhea
Commentary
Adolescents are undertested for STIs
Commentary
TB treatment can be shortened for most children: Study
Commentary
Nirsevimab protects healthy infants from RSV
Commentary
Norovirus vaccine candidates employ different approaches
Commentary
Introduction
ICYMI articles featuring 9 important developments of the past year – and COVID is still here
By Christopher J. Harrison, MD
Table of contents
Antibiotics use and vaccine antibody levels
Commentary
Emerging tick-borne pathogen has spread to state of Georgia
Commentary
WHO, UNICEF warn about increased risk of measles outbreaks
Commentary
Babies die as congenital syphilis continues a decade-long surge across the U.S.
Commentary
Meningococcal vaccine shows moderate protective effect against gonorrhea
Commentary
Adolescents are undertested for STIs
Commentary
TB treatment can be shortened for most children: Study
Commentary
Nirsevimab protects healthy infants from RSV
Commentary
Norovirus vaccine candidates employ different approaches
Commentary
ICYMI articles featuring 9 important developments of the past year – and COVID is still here
We can’t affect most of the world’s big problems, but we can continue to do what pediatric providers have always done well – share the best science-based knowledge with families and be strong vaccine advocates.
You can read about some new aspects of science-based 2021-2022 data in this digital issue. For example, there are newer international data on the longer-acting and more effective anti-RSV monoclonal antibody nirsevimab, which may soon replace palivizumab. Closer to home, check out the article on lower antibody concentrations in infants related to the number and class of antibiotics that they had received. Measles outbreaks in areas of the world with the lowest measles vaccine uptake will likely produce more imported measles in the United States. If you have never heard of Lone-star virus, an article tells us it occurs mostly in Southern and Atlantic coastal regions; no specific treatment exists, but it is now in the differential diagnosis for endemic tick-borne febrile infections.
A bit of good news is the World Health Organization recommending a shorter course of treatment for pediatric tuberculosis. Pediatric TB has a long history of poor treatment adherence, so shorter, simpler regimens are certainly welcome. And finally, prospects for a norovirus vaccine are looking brighter with new approaches generating mucosal antibodies – a key in protection against gastrointestinal infections.
Again, no articles in this digital supplement feature SARS-CoV-2 this year, but a summer surge continues because of third-generation Omicron viruses BA.4/BA.5. The surge exists because the SARS-CoV-2 vaccine is being underutilized; plus BA.4/BA.5 is the most contagious variant yet.
A major reason deaths are not surging is COVID-19 vaccines. Having multiple vaccines authorized within 9 months of SARS-CoV-2 hitting U.S. shores is amazing despite the hiccups and politicization that accompanied implementation. Each vaccine more than met the original goal: greater than or equal to 50% effectiveness with an acceptable adverse effect profile. In the United States, two mRMA-vaccines (Moderna and Pfizer) are now authorized for use down to 6 months of age; Novavax’s more traditional protein-based vaccine was more recently given an emergency use authorization for those 18 years and older. Ongoing trials indicate that Omicron-based mRNA vaccines are highly immunogenic and safe even if blended with the original strain vaccine. Fall boosters will have an Omicron component. We need to immunize and boost enough folks so that SARS-CoV-2 variants arise infrequently, allowing high-risk persons to be able to go out in public without masks.
Dr. Harrison is professor, University of Missouri–Kansas City School of Medicine, department of medicine, infectious diseases section. He has no conflicts of interest.
We can’t affect most of the world’s big problems, but we can continue to do what pediatric providers have always done well – share the best science-based knowledge with families and be strong vaccine advocates.
You can read about some new aspects of science-based 2021-2022 data in this digital issue. For example, there are newer international data on the longer-acting and more effective anti-RSV monoclonal antibody nirsevimab, which may soon replace palivizumab. Closer to home, check out the article on lower antibody concentrations in infants related to the number and class of antibiotics that they had received. Measles outbreaks in areas of the world with the lowest measles vaccine uptake will likely produce more imported measles in the United States. If you have never heard of Lone-star virus, an article tells us it occurs mostly in Southern and Atlantic coastal regions; no specific treatment exists, but it is now in the differential diagnosis for endemic tick-borne febrile infections.
A bit of good news is the World Health Organization recommending a shorter course of treatment for pediatric tuberculosis. Pediatric TB has a long history of poor treatment adherence, so shorter, simpler regimens are certainly welcome. And finally, prospects for a norovirus vaccine are looking brighter with new approaches generating mucosal antibodies – a key in protection against gastrointestinal infections.
Again, no articles in this digital supplement feature SARS-CoV-2 this year, but a summer surge continues because of third-generation Omicron viruses BA.4/BA.5. The surge exists because the SARS-CoV-2 vaccine is being underutilized; plus BA.4/BA.5 is the most contagious variant yet.
A major reason deaths are not surging is COVID-19 vaccines. Having multiple vaccines authorized within 9 months of SARS-CoV-2 hitting U.S. shores is amazing despite the hiccups and politicization that accompanied implementation. Each vaccine more than met the original goal: greater than or equal to 50% effectiveness with an acceptable adverse effect profile. In the United States, two mRMA-vaccines (Moderna and Pfizer) are now authorized for use down to 6 months of age; Novavax’s more traditional protein-based vaccine was more recently given an emergency use authorization for those 18 years and older. Ongoing trials indicate that Omicron-based mRNA vaccines are highly immunogenic and safe even if blended with the original strain vaccine. Fall boosters will have an Omicron component. We need to immunize and boost enough folks so that SARS-CoV-2 variants arise infrequently, allowing high-risk persons to be able to go out in public without masks.
Dr. Harrison is professor, University of Missouri–Kansas City School of Medicine, department of medicine, infectious diseases section. He has no conflicts of interest.
We can’t affect most of the world’s big problems, but we can continue to do what pediatric providers have always done well – share the best science-based knowledge with families and be strong vaccine advocates.
You can read about some new aspects of science-based 2021-2022 data in this digital issue. For example, there are newer international data on the longer-acting and more effective anti-RSV monoclonal antibody nirsevimab, which may soon replace palivizumab. Closer to home, check out the article on lower antibody concentrations in infants related to the number and class of antibiotics that they had received. Measles outbreaks in areas of the world with the lowest measles vaccine uptake will likely produce more imported measles in the United States. If you have never heard of Lone-star virus, an article tells us it occurs mostly in Southern and Atlantic coastal regions; no specific treatment exists, but it is now in the differential diagnosis for endemic tick-borne febrile infections.
A bit of good news is the World Health Organization recommending a shorter course of treatment for pediatric tuberculosis. Pediatric TB has a long history of poor treatment adherence, so shorter, simpler regimens are certainly welcome. And finally, prospects for a norovirus vaccine are looking brighter with new approaches generating mucosal antibodies – a key in protection against gastrointestinal infections.
Again, no articles in this digital supplement feature SARS-CoV-2 this year, but a summer surge continues because of third-generation Omicron viruses BA.4/BA.5. The surge exists because the SARS-CoV-2 vaccine is being underutilized; plus BA.4/BA.5 is the most contagious variant yet.
A major reason deaths are not surging is COVID-19 vaccines. Having multiple vaccines authorized within 9 months of SARS-CoV-2 hitting U.S. shores is amazing despite the hiccups and politicization that accompanied implementation. Each vaccine more than met the original goal: greater than or equal to 50% effectiveness with an acceptable adverse effect profile. In the United States, two mRMA-vaccines (Moderna and Pfizer) are now authorized for use down to 6 months of age; Novavax’s more traditional protein-based vaccine was more recently given an emergency use authorization for those 18 years and older. Ongoing trials indicate that Omicron-based mRNA vaccines are highly immunogenic and safe even if blended with the original strain vaccine. Fall boosters will have an Omicron component. We need to immunize and boost enough folks so that SARS-CoV-2 variants arise infrequently, allowing high-risk persons to be able to go out in public without masks.
Dr. Harrison is professor, University of Missouri–Kansas City School of Medicine, department of medicine, infectious diseases section. He has no conflicts of interest.
Psychedelics may ease fear of death and dying
Psychedelics can produce positive changes in attitudes about death and dying – and may be a way to help ease anxiety and depression toward the end of life, new research suggests.
In a retrospective study of more than 3,000 participants,
“Individuals with existential anxiety and depression at end of life account for substantial suffering and significantly increased health care expenses from desperate and often futile seeking of intensive and expensive medical treatments,” co-investigator Roland Griffiths, PhD, Center for Psychedelics and Consciousness Research at Johns Hopkins Medicine, Baltimore, told this news organization.
“The present findings, which show that both psychedelic and non–drug-occasioned experiences can produce positive and enduring changes in attitudes about death, suggest the importance of future prospective experimental and clinical observational studies to better understand mechanisms of such changes as well as their potential clinical utility in ameliorating suffering related to fear of death,” Dr. Griffiths said.
The results were published online Aug. 24 in PLOS ONE.
Direct comparisons
Both psychedelic drug experiences and near-death experiences can alter perspectives on death and dying, but there have been few direct comparisons of these phenomena, the investigators note.
In the current study, they directly compared psychedelic-occasioned and nondrug experiences, which altered individuals’ beliefs about death.
The researchers surveyed 3,192 mostly White adults from the United States, including 933 who had a natural, nondrug near-death experience and 2,259 who had psychedelic near-death experiences induced with lysergic acid diethylamide, psilocybin, ayahuasca, or N,N-dimethyltryptamine.
The psychedelic group had more men than women and tended to be younger at the time of the experience than was the nondrug group.
Nearly 90% of individuals in both groups said that they were less afraid of death than they were before their experiences.
About half of both groups said they’d encountered something they might call “God” during the experience.
Three-quarters of the psychedelic group and 85% of the nondrug group rated their experiences as among the top five most personally meaningful and spiritually significant events of their life.
Individuals in both groups also reported moderate- to strong-lasting positive changes in personal well-being and life purpose and meaning after their experiences.
However, there were some differences between the groups.
More research needed
Compared with the psychedelic group, the nondrug group was more likely to report being unconscious, clinically dead, or that their life was in imminent danger.
The nonpsychedelic group was also more likely to report that their experience was very brief, lasting 5 minutes or less.
Both the psychedelic and nondrug participants showed robust increases on standardized measures of mystical and near-death experiences, but these measures were significantly greater in the psychedelic group.
The survey findings are in line with several recent clinical trials showing that a single treatment with the psychedelic psilocybin produced sustained decreases in anxiety and depression among patients with a life-threatening cancer diagnosis.
This includes a 2016 study by Dr. Griffiths and colleagues, which included 51 patients with late-stage cancer. As reported at the time, results showed a single, high dose of psilocybin had rapid, clinically significant, and lasting effects on mood and anxiety.
Limitations of the current survey cited by the researchers include the use of retrospective self-report to describe changes in death attitudes and the subjective features of the experiences. Also, respondents were a self-selected study population that may not be representative of all psychedelic or near-death experiences.
In addition, the study did not attempt to document worldview and other belief changes, such as increased belief in afterlife, that might help explain why death attitudes changed.
Looking ahead, the researchers note that future studies are needed to better understand the potential clinical use of psychedelics in ameliorating suffering related to fear of death.
Support through the Johns Hopkins Center for Psychedelic and Consciousness Research was provided by Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation. Funding was also provided by the Y.C. Ho/Helen and Michael Chiang Foundation. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Psychedelics can produce positive changes in attitudes about death and dying – and may be a way to help ease anxiety and depression toward the end of life, new research suggests.
In a retrospective study of more than 3,000 participants,
“Individuals with existential anxiety and depression at end of life account for substantial suffering and significantly increased health care expenses from desperate and often futile seeking of intensive and expensive medical treatments,” co-investigator Roland Griffiths, PhD, Center for Psychedelics and Consciousness Research at Johns Hopkins Medicine, Baltimore, told this news organization.
“The present findings, which show that both psychedelic and non–drug-occasioned experiences can produce positive and enduring changes in attitudes about death, suggest the importance of future prospective experimental and clinical observational studies to better understand mechanisms of such changes as well as their potential clinical utility in ameliorating suffering related to fear of death,” Dr. Griffiths said.
The results were published online Aug. 24 in PLOS ONE.
Direct comparisons
Both psychedelic drug experiences and near-death experiences can alter perspectives on death and dying, but there have been few direct comparisons of these phenomena, the investigators note.
In the current study, they directly compared psychedelic-occasioned and nondrug experiences, which altered individuals’ beliefs about death.
The researchers surveyed 3,192 mostly White adults from the United States, including 933 who had a natural, nondrug near-death experience and 2,259 who had psychedelic near-death experiences induced with lysergic acid diethylamide, psilocybin, ayahuasca, or N,N-dimethyltryptamine.
The psychedelic group had more men than women and tended to be younger at the time of the experience than was the nondrug group.
Nearly 90% of individuals in both groups said that they were less afraid of death than they were before their experiences.
About half of both groups said they’d encountered something they might call “God” during the experience.
Three-quarters of the psychedelic group and 85% of the nondrug group rated their experiences as among the top five most personally meaningful and spiritually significant events of their life.
Individuals in both groups also reported moderate- to strong-lasting positive changes in personal well-being and life purpose and meaning after their experiences.
However, there were some differences between the groups.
More research needed
Compared with the psychedelic group, the nondrug group was more likely to report being unconscious, clinically dead, or that their life was in imminent danger.
The nonpsychedelic group was also more likely to report that their experience was very brief, lasting 5 minutes or less.
Both the psychedelic and nondrug participants showed robust increases on standardized measures of mystical and near-death experiences, but these measures were significantly greater in the psychedelic group.
The survey findings are in line with several recent clinical trials showing that a single treatment with the psychedelic psilocybin produced sustained decreases in anxiety and depression among patients with a life-threatening cancer diagnosis.
This includes a 2016 study by Dr. Griffiths and colleagues, which included 51 patients with late-stage cancer. As reported at the time, results showed a single, high dose of psilocybin had rapid, clinically significant, and lasting effects on mood and anxiety.
Limitations of the current survey cited by the researchers include the use of retrospective self-report to describe changes in death attitudes and the subjective features of the experiences. Also, respondents were a self-selected study population that may not be representative of all psychedelic or near-death experiences.
In addition, the study did not attempt to document worldview and other belief changes, such as increased belief in afterlife, that might help explain why death attitudes changed.
Looking ahead, the researchers note that future studies are needed to better understand the potential clinical use of psychedelics in ameliorating suffering related to fear of death.
Support through the Johns Hopkins Center for Psychedelic and Consciousness Research was provided by Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation. Funding was also provided by the Y.C. Ho/Helen and Michael Chiang Foundation. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Psychedelics can produce positive changes in attitudes about death and dying – and may be a way to help ease anxiety and depression toward the end of life, new research suggests.
In a retrospective study of more than 3,000 participants,
“Individuals with existential anxiety and depression at end of life account for substantial suffering and significantly increased health care expenses from desperate and often futile seeking of intensive and expensive medical treatments,” co-investigator Roland Griffiths, PhD, Center for Psychedelics and Consciousness Research at Johns Hopkins Medicine, Baltimore, told this news organization.
“The present findings, which show that both psychedelic and non–drug-occasioned experiences can produce positive and enduring changes in attitudes about death, suggest the importance of future prospective experimental and clinical observational studies to better understand mechanisms of such changes as well as their potential clinical utility in ameliorating suffering related to fear of death,” Dr. Griffiths said.
The results were published online Aug. 24 in PLOS ONE.
Direct comparisons
Both psychedelic drug experiences and near-death experiences can alter perspectives on death and dying, but there have been few direct comparisons of these phenomena, the investigators note.
In the current study, they directly compared psychedelic-occasioned and nondrug experiences, which altered individuals’ beliefs about death.
The researchers surveyed 3,192 mostly White adults from the United States, including 933 who had a natural, nondrug near-death experience and 2,259 who had psychedelic near-death experiences induced with lysergic acid diethylamide, psilocybin, ayahuasca, or N,N-dimethyltryptamine.
The psychedelic group had more men than women and tended to be younger at the time of the experience than was the nondrug group.
Nearly 90% of individuals in both groups said that they were less afraid of death than they were before their experiences.
About half of both groups said they’d encountered something they might call “God” during the experience.
Three-quarters of the psychedelic group and 85% of the nondrug group rated their experiences as among the top five most personally meaningful and spiritually significant events of their life.
Individuals in both groups also reported moderate- to strong-lasting positive changes in personal well-being and life purpose and meaning after their experiences.
However, there were some differences between the groups.
More research needed
Compared with the psychedelic group, the nondrug group was more likely to report being unconscious, clinically dead, or that their life was in imminent danger.
The nonpsychedelic group was also more likely to report that their experience was very brief, lasting 5 minutes or less.
Both the psychedelic and nondrug participants showed robust increases on standardized measures of mystical and near-death experiences, but these measures were significantly greater in the psychedelic group.
The survey findings are in line with several recent clinical trials showing that a single treatment with the psychedelic psilocybin produced sustained decreases in anxiety and depression among patients with a life-threatening cancer diagnosis.
This includes a 2016 study by Dr. Griffiths and colleagues, which included 51 patients with late-stage cancer. As reported at the time, results showed a single, high dose of psilocybin had rapid, clinically significant, and lasting effects on mood and anxiety.
Limitations of the current survey cited by the researchers include the use of retrospective self-report to describe changes in death attitudes and the subjective features of the experiences. Also, respondents were a self-selected study population that may not be representative of all psychedelic or near-death experiences.
In addition, the study did not attempt to document worldview and other belief changes, such as increased belief in afterlife, that might help explain why death attitudes changed.
Looking ahead, the researchers note that future studies are needed to better understand the potential clinical use of psychedelics in ameliorating suffering related to fear of death.
Support through the Johns Hopkins Center for Psychedelic and Consciousness Research was provided by Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation. Funding was also provided by the Y.C. Ho/Helen and Michael Chiang Foundation. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM PLOS ONE
FDA approves oral TYK2 inhibitor deucravacitinib for treating psoriasis
the manufacturer announced on Sept. 9.
Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.
It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.
FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.
In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.
At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.
In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).
Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.
Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).
Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.
The prescribing information and patient medication guide are available online.
The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.
A version of this article first appeared on Medscape.com.
the manufacturer announced on Sept. 9.
Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.
It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.
FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.
In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.
At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.
In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).
Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.
Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).
Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.
The prescribing information and patient medication guide are available online.
The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.
A version of this article first appeared on Medscape.com.
the manufacturer announced on Sept. 9.
Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.
It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.
FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.
In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.
At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.
In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).
Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.
Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).
Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.
The prescribing information and patient medication guide are available online.
The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.
A version of this article first appeared on Medscape.com.
Blood test for multiple cancers: Many false positives
PARIS –
“As this technology develops, people must continue with their standard cancer screening, but this is a glimpse of what the future may hold,” commented study investigator Deborah Schrag, MD, MPH, chair, department of medicine, Memorial Sloan Kettering Cancer Center, New York.
For the PATHFINDER study, the Galleri blood test (developed by Grail) was used in 6,621 healthy individuals aged over 50, with or without additional cancer risk factors (such as history of smoking or genetic risk).
It found a positive cancer signal in 92 individuals (1.4%).
None of the individuals who tested positive was known to have cancer at the time of testing. Subsequent workup, which could include scans and/or biopsy, found cancer in 38% of those with a positive test.
“When the test was positive, the workups were typically done in less than 3 months,” Dr. Schrag commented, adding that “the blood test typically predicted the origin of the cancer.”
Dr. Schrag presented the findings at the annual meeting of the European Society for Medical Oncology (ESMO).
Approached for comment, Anthony J. Olszanski, MD, RPh, vice chair of research at the Fox Chase Cancer Center, Philadelphia, noted that the use of a blood test to “find” cancer has long been on the minds of patients. “It is not uncommon to hear oncology patients ask: ‘Why didn’t my doctor find my cancer earlier, on blood tests?’ ”
As this study suggests, finding a malignancy before it becomes apparent on imaging or because of symptoms is one step closer to becoming a reality. “But although this is an important study, it must be noted that only about 40% of patients with a positive test result were actually found to have cancer,” Dr. Olszanski said. “Conversely, about 60% of patients with a positive test result likely suffered from a considerable amount of anxiety that may persist even after further testing did not reveal a malignancy.”
Another important issue is that such testing may incur substantial health care cost. “Less than 2 participants per 100 had a positive test result, and those patients underwent further testing to interrogate the result,” he added. “It also remains unclear if detecting cancer early will lead to better outcomes.”
Whether or not the test will be cost-effective remains unknown, as Dr. Schrag emphasized they do not have a formal cost analysis at this time. “This technology is not ready for population-wide screening, but as the technology improves, costs will go down,” she said.
Dr. Schrag also added that this is a new concept and the trial shows it is feasible to detect cancer using a blood test. “It was not designed to determine if the test can decrease cancer mortality, which is obviously the purpose of screening, but it’s premature for that,” she said.
Details of the results
The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal across more than 50 cancer types as well as to predict cancer signal origin.
Overall, the test detected a cancer signal in 1.4% (n = 92) of participants with analyzable samples.
A total of 90 participants underwent diagnostic testing (33 true positives and 57 false positives). Of the true positives, 81.8% underwent more than one invasive diagnostic test, as did 29.8% of false positives.
Specificity was 99.1%, positive predictive value (PPV) was approximately 40%, and 73% of those who were true positives had diagnostic resolution in less than 3 months.
Of the cancers that were diagnosed, 19 were solid tumors and 17 were hematologic cancers; 7 were diagnosed in a person with a history of cancer, 26 were cancer types without standard screening, and 14 were diagnosed at an early stage.
“What is exciting about this new paradigm is that many of these were cancers for which we don’t have standard screening,” said Dr. Schrag.
Dr. Schrag noted that given the immense interest in this study, the manufacturer is working toward refining the assay and improving the test. A reanalysis was conducted on all specimens using a refined version of the test.
“Importantly, the new analysis identified fewer patients with having positive signals, from 1.4% to 0.9%,” she said. “Specificity improved to 99.5% as did PPV – from 38% to 43.1% – and more people need to be screened to find a cancer – up to 263 from 189.”
False positives concerning
Previous, and very similar, results from the PATHFINDER trial were presented last year at the annual meeting of the American Society of Clinical Oncology.
Max Diehn, MD, PhD, associate professor of radiation oncology at Stanford (Calif.) University, was an invited discussant for the study.
He pointed out that there were more false positives than true positives and noted that “there were a significant number of invasive procedures in false positives, which could cause harm to these patients who don’t have cancer.”
Dr. Diehn also explained that most true positives were for lymphoid malignancies, not solid tumors, and it is not known whether early detection of lymphoid malignancy has clinical utility.
The Galleri test is already available in the United States and is being offered by a number of U.S. health networks. However, it is not approved by the U.S. Food and Drug Administration and is not covered by medical insurance, so individuals have to pay around $950 for it out of pocket.
Although some experts are excited by its potential, describing it as a “game-changer,” others are concerned that there are no clinical pathways in place yet to deal with the results of such a blood test, and say it is not ready for prime time.
The study was funded by Grail, a subsidiary of Illumina. Dr. Shrag has reported relationships with Grail, the Journal of the American Medical Association, and Pfizer. Several coauthors also have disclosed relationships with industry. Dr. Olszanski has reported participating in advisory boards for BMS, Merck, and Instil Bio, and running trials for them.
A version of this article first appeared on Medscape.com.
PARIS –
“As this technology develops, people must continue with their standard cancer screening, but this is a glimpse of what the future may hold,” commented study investigator Deborah Schrag, MD, MPH, chair, department of medicine, Memorial Sloan Kettering Cancer Center, New York.
For the PATHFINDER study, the Galleri blood test (developed by Grail) was used in 6,621 healthy individuals aged over 50, with or without additional cancer risk factors (such as history of smoking or genetic risk).
It found a positive cancer signal in 92 individuals (1.4%).
None of the individuals who tested positive was known to have cancer at the time of testing. Subsequent workup, which could include scans and/or biopsy, found cancer in 38% of those with a positive test.
“When the test was positive, the workups were typically done in less than 3 months,” Dr. Schrag commented, adding that “the blood test typically predicted the origin of the cancer.”
Dr. Schrag presented the findings at the annual meeting of the European Society for Medical Oncology (ESMO).
Approached for comment, Anthony J. Olszanski, MD, RPh, vice chair of research at the Fox Chase Cancer Center, Philadelphia, noted that the use of a blood test to “find” cancer has long been on the minds of patients. “It is not uncommon to hear oncology patients ask: ‘Why didn’t my doctor find my cancer earlier, on blood tests?’ ”
As this study suggests, finding a malignancy before it becomes apparent on imaging or because of symptoms is one step closer to becoming a reality. “But although this is an important study, it must be noted that only about 40% of patients with a positive test result were actually found to have cancer,” Dr. Olszanski said. “Conversely, about 60% of patients with a positive test result likely suffered from a considerable amount of anxiety that may persist even after further testing did not reveal a malignancy.”
Another important issue is that such testing may incur substantial health care cost. “Less than 2 participants per 100 had a positive test result, and those patients underwent further testing to interrogate the result,” he added. “It also remains unclear if detecting cancer early will lead to better outcomes.”
Whether or not the test will be cost-effective remains unknown, as Dr. Schrag emphasized they do not have a formal cost analysis at this time. “This technology is not ready for population-wide screening, but as the technology improves, costs will go down,” she said.
Dr. Schrag also added that this is a new concept and the trial shows it is feasible to detect cancer using a blood test. “It was not designed to determine if the test can decrease cancer mortality, which is obviously the purpose of screening, but it’s premature for that,” she said.
Details of the results
The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal across more than 50 cancer types as well as to predict cancer signal origin.
Overall, the test detected a cancer signal in 1.4% (n = 92) of participants with analyzable samples.
A total of 90 participants underwent diagnostic testing (33 true positives and 57 false positives). Of the true positives, 81.8% underwent more than one invasive diagnostic test, as did 29.8% of false positives.
Specificity was 99.1%, positive predictive value (PPV) was approximately 40%, and 73% of those who were true positives had diagnostic resolution in less than 3 months.
Of the cancers that were diagnosed, 19 were solid tumors and 17 were hematologic cancers; 7 were diagnosed in a person with a history of cancer, 26 were cancer types without standard screening, and 14 were diagnosed at an early stage.
“What is exciting about this new paradigm is that many of these were cancers for which we don’t have standard screening,” said Dr. Schrag.
Dr. Schrag noted that given the immense interest in this study, the manufacturer is working toward refining the assay and improving the test. A reanalysis was conducted on all specimens using a refined version of the test.
“Importantly, the new analysis identified fewer patients with having positive signals, from 1.4% to 0.9%,” she said. “Specificity improved to 99.5% as did PPV – from 38% to 43.1% – and more people need to be screened to find a cancer – up to 263 from 189.”
False positives concerning
Previous, and very similar, results from the PATHFINDER trial were presented last year at the annual meeting of the American Society of Clinical Oncology.
Max Diehn, MD, PhD, associate professor of radiation oncology at Stanford (Calif.) University, was an invited discussant for the study.
He pointed out that there were more false positives than true positives and noted that “there were a significant number of invasive procedures in false positives, which could cause harm to these patients who don’t have cancer.”
Dr. Diehn also explained that most true positives were for lymphoid malignancies, not solid tumors, and it is not known whether early detection of lymphoid malignancy has clinical utility.
The Galleri test is already available in the United States and is being offered by a number of U.S. health networks. However, it is not approved by the U.S. Food and Drug Administration and is not covered by medical insurance, so individuals have to pay around $950 for it out of pocket.
Although some experts are excited by its potential, describing it as a “game-changer,” others are concerned that there are no clinical pathways in place yet to deal with the results of such a blood test, and say it is not ready for prime time.
The study was funded by Grail, a subsidiary of Illumina. Dr. Shrag has reported relationships with Grail, the Journal of the American Medical Association, and Pfizer. Several coauthors also have disclosed relationships with industry. Dr. Olszanski has reported participating in advisory boards for BMS, Merck, and Instil Bio, and running trials for them.
A version of this article first appeared on Medscape.com.
PARIS –
“As this technology develops, people must continue with their standard cancer screening, but this is a glimpse of what the future may hold,” commented study investigator Deborah Schrag, MD, MPH, chair, department of medicine, Memorial Sloan Kettering Cancer Center, New York.
For the PATHFINDER study, the Galleri blood test (developed by Grail) was used in 6,621 healthy individuals aged over 50, with or without additional cancer risk factors (such as history of smoking or genetic risk).
It found a positive cancer signal in 92 individuals (1.4%).
None of the individuals who tested positive was known to have cancer at the time of testing. Subsequent workup, which could include scans and/or biopsy, found cancer in 38% of those with a positive test.
“When the test was positive, the workups were typically done in less than 3 months,” Dr. Schrag commented, adding that “the blood test typically predicted the origin of the cancer.”
Dr. Schrag presented the findings at the annual meeting of the European Society for Medical Oncology (ESMO).
Approached for comment, Anthony J. Olszanski, MD, RPh, vice chair of research at the Fox Chase Cancer Center, Philadelphia, noted that the use of a blood test to “find” cancer has long been on the minds of patients. “It is not uncommon to hear oncology patients ask: ‘Why didn’t my doctor find my cancer earlier, on blood tests?’ ”
As this study suggests, finding a malignancy before it becomes apparent on imaging or because of symptoms is one step closer to becoming a reality. “But although this is an important study, it must be noted that only about 40% of patients with a positive test result were actually found to have cancer,” Dr. Olszanski said. “Conversely, about 60% of patients with a positive test result likely suffered from a considerable amount of anxiety that may persist even after further testing did not reveal a malignancy.”
Another important issue is that such testing may incur substantial health care cost. “Less than 2 participants per 100 had a positive test result, and those patients underwent further testing to interrogate the result,” he added. “It also remains unclear if detecting cancer early will lead to better outcomes.”
Whether or not the test will be cost-effective remains unknown, as Dr. Schrag emphasized they do not have a formal cost analysis at this time. “This technology is not ready for population-wide screening, but as the technology improves, costs will go down,” she said.
Dr. Schrag also added that this is a new concept and the trial shows it is feasible to detect cancer using a blood test. “It was not designed to determine if the test can decrease cancer mortality, which is obviously the purpose of screening, but it’s premature for that,” she said.
Details of the results
The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal across more than 50 cancer types as well as to predict cancer signal origin.
Overall, the test detected a cancer signal in 1.4% (n = 92) of participants with analyzable samples.
A total of 90 participants underwent diagnostic testing (33 true positives and 57 false positives). Of the true positives, 81.8% underwent more than one invasive diagnostic test, as did 29.8% of false positives.
Specificity was 99.1%, positive predictive value (PPV) was approximately 40%, and 73% of those who were true positives had diagnostic resolution in less than 3 months.
Of the cancers that were diagnosed, 19 were solid tumors and 17 were hematologic cancers; 7 were diagnosed in a person with a history of cancer, 26 were cancer types without standard screening, and 14 were diagnosed at an early stage.
“What is exciting about this new paradigm is that many of these were cancers for which we don’t have standard screening,” said Dr. Schrag.
Dr. Schrag noted that given the immense interest in this study, the manufacturer is working toward refining the assay and improving the test. A reanalysis was conducted on all specimens using a refined version of the test.
“Importantly, the new analysis identified fewer patients with having positive signals, from 1.4% to 0.9%,” she said. “Specificity improved to 99.5% as did PPV – from 38% to 43.1% – and more people need to be screened to find a cancer – up to 263 from 189.”
False positives concerning
Previous, and very similar, results from the PATHFINDER trial were presented last year at the annual meeting of the American Society of Clinical Oncology.
Max Diehn, MD, PhD, associate professor of radiation oncology at Stanford (Calif.) University, was an invited discussant for the study.
He pointed out that there were more false positives than true positives and noted that “there were a significant number of invasive procedures in false positives, which could cause harm to these patients who don’t have cancer.”
Dr. Diehn also explained that most true positives were for lymphoid malignancies, not solid tumors, and it is not known whether early detection of lymphoid malignancy has clinical utility.
The Galleri test is already available in the United States and is being offered by a number of U.S. health networks. However, it is not approved by the U.S. Food and Drug Administration and is not covered by medical insurance, so individuals have to pay around $950 for it out of pocket.
Although some experts are excited by its potential, describing it as a “game-changer,” others are concerned that there are no clinical pathways in place yet to deal with the results of such a blood test, and say it is not ready for prime time.
The study was funded by Grail, a subsidiary of Illumina. Dr. Shrag has reported relationships with Grail, the Journal of the American Medical Association, and Pfizer. Several coauthors also have disclosed relationships with industry. Dr. Olszanski has reported participating in advisory boards for BMS, Merck, and Instil Bio, and running trials for them.
A version of this article first appeared on Medscape.com.
AT ESMO 2022
ILD on the rise: Doctors offer tips for diagnosing deadly disease
“There is definitely a delay from the time of symptom onset to the time that they are even evaluated for ILD,” said Dr. Kulkarni of the department of pulmonary, allergy and critical care medicine at the University of Alabama, Birmingham. “Some patients have had a significant loss of lung function by the time they come to see us. By that point we are limited by what treatment options we can offer.”
Interstitial lung disease is an umbrella term for a group of disorders involving progressive scarring of the lungs – typically irreversible – usually caused by long-term exposure to hazardous materials or by autoimmune effects. It includes idiopathic pulmonary fibrosis (IPF), a disease that is fairly rare but which has therapy options that can be effective if caught early enough. The term pulmonary fibrosis refers to lung scarring. Another type of ILD is pulmonary sarcoidosis, in which small clumps of immune cells form in the lungs in an immune response sometimes following an environmental trigger, and can lead to lung scarring if it doesn’t resolve.
Cases of ILD appear to be on the rise, and COVID-19 has made diagnosing it more complicated. One study found the prevalence of ILD and pulmonary sarcoidosis in high-income countries was about 122 of every 100,000 people in 1990 and rose to about 198 of every 100,000 people in 2017. The data were pulled from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. Globally, the researchers found a prevalence of 62 per 100,000 in 1990, compared with 82 per 100,000 in 2017.
If all of a patient’s symptoms have appeared post COVID and a physician is seeing a patient within 4-6 weeks of COVID symptoms, it is likely that the symptoms are COVID related. But a full work-up is recommended if a patient has lung crackles, which are an indicator of lung scarring, she said.
“The patterns that are seen on CT scan for COVID pneumonia are very distinct from what we expect to see with idiopathic pulmonary fibrosis,” Dr. Kulkarni said. “Putting all this information together is what is important to differentiate it from COVID pneumonia, as well as other types of ILD.”
A study published earlier this year found similarities between COVID-19 and IPF in gene expression, their IL-15-heavy cytokine storms, and the type of damage to alveolar cells. Both might be driven by endoplasmic reticulum stress, they found.
“COVID-19 resembles IPF at a fundamental level,” they wrote.
Jeffrey Horowitz, MD, a pulmonologist and professor of medicine at the Ohio State University, said the need for early diagnosis is in part a function of the therapies available for ILD.
“They don’t make the lung function better,” he said. “So delays in diagnosis mean that there’s the possibility of underlying progression for months, or sometimes years, before the diagnosis is recognized.”
In an area in which diagnosis is delayed and the prognosis is dire – 3-5 years in untreated patients after diagnosis – “there’s a tremendous amount of nihilism out there” among patients, he said.
He said patients with long-term shortness of breath and unexplained cough are often told they have asthma and are prescribed inhalers, but then further assessment isn’t performed when those don’t work.
Diagnosing ILD in primary care
Many primary care physicians feel ill-equipped to discuss IPF. More than a dozen physicians contacted for this piece to talk about ILD either did not respond, or said they felt unqualified to respond to questions on the disease.
“Not my area of expertise” and “I don’t think I’m the right person for this discussion” were two of the responses provided to this news organization.
“For some reason, in the world of primary care, it seems like there’s an impediment to getting pulmonary function studies,” Dr. Horowitz said. “Anybody who has a persistent ongoing prolonged unexplained shortness of breath and cough should have pulmonary function studies done.”
Listening to the lungs alone might not be enough, he said. There might be no clear sign in the case of early pulmonary fibrosis, he said.
“There’s the textbook description of these Velcro-sounding crackles, but sometimes it’s very subtle,” he said. “And unless you’re listening very carefully it can easily be missed by somebody who has a busy practice, or it’s loud.”
William E. Golden, MD, professor of medicine and public health at the University of Arkansas, Little Rock, is the sole primary care physician contacted for this piece who spoke with authority on ILD.
For cases of suspected ILD, internist Dr. Golden, who also serves on the editorial advisory board of Internal Medicine News, suggested ordering a test for diffusing capacity for carbon monoxide (DLCO), which will be low in the case of IPF, along with a fine-cut lung CT scan to assess ongoing fibrotic changes.
It’s “not that difficult, but you need to have an index of suspicion for the diagnosis,” he said.
New initiative for helping diagnose ILD
Dr. Kulkarni is a committee member for a new effort under way to try to get patients with ILD diagnosed earlier.
The initiative, called Bridging Specialties: Timely Diagnosis for ILD Patients, has already produced an introductory podcast and a white paper on the effort, and its rationale is expected to be released soon, according to Dr. Kulkarni and her fellow committee members.
The American College of Chest Physicians and the Three Lakes Foundation – a foundation dedicated to pulmonary fibrosis awareness and research – are working together on this initiative. They plan to put together a suite of resources, to be gradually rolled out on the college’s website, to raise awareness about the importance of early diagnosis of ILD.
The full toolkit, expected to be rolled out over the next 12 months, will include a series of podcasts and resources on how to get patients diagnosed earlier and steps to take in cases of suspected ILD, Dr. Kulkarni said.
“The goal would be to try to increase awareness about the disease so that people start thinking more about it up front – and not after we’ve ruled out everything else,” she said. The main audience will be primary care providers, but patients and community pulmonologists would likely also benefit from the resources, the committee members said.
The urgency of the initiative stems from the way ILD treatments work. They are antifibrotic, meaning they help prevent scar tissue from forming, but they can’t reverse scar tissue that has already formed. If scarring is severe, the only option might be a lung transplant, and, since the average age at ILD diagnosis is in the 60s, many patients have comorbidities that make them ineligible for transplant. According to the Global Burden of Disease Study mentioned earlier, the death rate per 100,000 people with ILD was 1.93 in 2017.
“The longer we take to diagnose it, the more chance that inflammation will become scar tissue,” Dr. Kularni explained.
William Lago, MD, another member of the committee and a family physician, said identifying ILD early is not a straightforward matter .
“When they first present, it’s hard to pick up,” said Dr. Lago, who is also a staff physician at Cleveland Clinic’s Wooster Family Health Center and medical director of the COVID Recover Clinic there. “Many of them, even themselves, will discount the symptoms.”
Dr. Lago said that patients might resist having a work-up even when a primary care physician identifies symptoms as possible ILD. In rural settings, they might have to travel quite a distance for a CT scan or other necessary evaluations, or they might just not think the symptoms are serious enough.
“Most of the time when I’ve picked up some of my pulmonary fibrosis patients, it’s been incidentally while they’re in the office for other things,” he said. He often has to “push the issue” for further work-up, he said.
The overlap of shortness of breath and cough with other, much more common disorders, such as heart disease or chronic obstructive pulmonary disease (COPD), make ILD diagnosis a challenge, he said.
“For most of us, we’ve got sometimes 10 or 15 minutes with a patient who’s presenting with 5-6 different problems. And the shortness of breath or the occasional cough – that they think is nothing – is probably the least of those,” Dr. Lago said.
Dr. Golden said he suspected a tool like the one being developed by CHEST to be useful for some and not useful for others. He added that “no one has the time to spend on that kind of thing.”
Instead, he suggested just reinforcing what the core symptoms are and what the core testing is, “to make people think about it.”
Dr. Horowitiz seemed more optimistic about the likelihood of the CHEST tool being utilized to diagnose ILD.
Whether and how he would use the CHEST resource will depend on the final form it takes, Dr. Horowitz said. It’s encouraging that it’s being put together by a credible source, he added.
Dr. Kulkarni reported financial relationships with Boehringer Ingelheim, Aluda Pharmaceuticals and PureTech Lyt-100 Inc. Dr. Lago, Dr. Horowitz, and Dr. Golden reported no relevant disclosures.
Katie Lennon contributed to this report.
“There is definitely a delay from the time of symptom onset to the time that they are even evaluated for ILD,” said Dr. Kulkarni of the department of pulmonary, allergy and critical care medicine at the University of Alabama, Birmingham. “Some patients have had a significant loss of lung function by the time they come to see us. By that point we are limited by what treatment options we can offer.”
Interstitial lung disease is an umbrella term for a group of disorders involving progressive scarring of the lungs – typically irreversible – usually caused by long-term exposure to hazardous materials or by autoimmune effects. It includes idiopathic pulmonary fibrosis (IPF), a disease that is fairly rare but which has therapy options that can be effective if caught early enough. The term pulmonary fibrosis refers to lung scarring. Another type of ILD is pulmonary sarcoidosis, in which small clumps of immune cells form in the lungs in an immune response sometimes following an environmental trigger, and can lead to lung scarring if it doesn’t resolve.
Cases of ILD appear to be on the rise, and COVID-19 has made diagnosing it more complicated. One study found the prevalence of ILD and pulmonary sarcoidosis in high-income countries was about 122 of every 100,000 people in 1990 and rose to about 198 of every 100,000 people in 2017. The data were pulled from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. Globally, the researchers found a prevalence of 62 per 100,000 in 1990, compared with 82 per 100,000 in 2017.
If all of a patient’s symptoms have appeared post COVID and a physician is seeing a patient within 4-6 weeks of COVID symptoms, it is likely that the symptoms are COVID related. But a full work-up is recommended if a patient has lung crackles, which are an indicator of lung scarring, she said.
“The patterns that are seen on CT scan for COVID pneumonia are very distinct from what we expect to see with idiopathic pulmonary fibrosis,” Dr. Kulkarni said. “Putting all this information together is what is important to differentiate it from COVID pneumonia, as well as other types of ILD.”
A study published earlier this year found similarities between COVID-19 and IPF in gene expression, their IL-15-heavy cytokine storms, and the type of damage to alveolar cells. Both might be driven by endoplasmic reticulum stress, they found.
“COVID-19 resembles IPF at a fundamental level,” they wrote.
Jeffrey Horowitz, MD, a pulmonologist and professor of medicine at the Ohio State University, said the need for early diagnosis is in part a function of the therapies available for ILD.
“They don’t make the lung function better,” he said. “So delays in diagnosis mean that there’s the possibility of underlying progression for months, or sometimes years, before the diagnosis is recognized.”
In an area in which diagnosis is delayed and the prognosis is dire – 3-5 years in untreated patients after diagnosis – “there’s a tremendous amount of nihilism out there” among patients, he said.
He said patients with long-term shortness of breath and unexplained cough are often told they have asthma and are prescribed inhalers, but then further assessment isn’t performed when those don’t work.
Diagnosing ILD in primary care
Many primary care physicians feel ill-equipped to discuss IPF. More than a dozen physicians contacted for this piece to talk about ILD either did not respond, or said they felt unqualified to respond to questions on the disease.
“Not my area of expertise” and “I don’t think I’m the right person for this discussion” were two of the responses provided to this news organization.
“For some reason, in the world of primary care, it seems like there’s an impediment to getting pulmonary function studies,” Dr. Horowitz said. “Anybody who has a persistent ongoing prolonged unexplained shortness of breath and cough should have pulmonary function studies done.”
Listening to the lungs alone might not be enough, he said. There might be no clear sign in the case of early pulmonary fibrosis, he said.
“There’s the textbook description of these Velcro-sounding crackles, but sometimes it’s very subtle,” he said. “And unless you’re listening very carefully it can easily be missed by somebody who has a busy practice, or it’s loud.”
William E. Golden, MD, professor of medicine and public health at the University of Arkansas, Little Rock, is the sole primary care physician contacted for this piece who spoke with authority on ILD.
For cases of suspected ILD, internist Dr. Golden, who also serves on the editorial advisory board of Internal Medicine News, suggested ordering a test for diffusing capacity for carbon monoxide (DLCO), which will be low in the case of IPF, along with a fine-cut lung CT scan to assess ongoing fibrotic changes.
It’s “not that difficult, but you need to have an index of suspicion for the diagnosis,” he said.
New initiative for helping diagnose ILD
Dr. Kulkarni is a committee member for a new effort under way to try to get patients with ILD diagnosed earlier.
The initiative, called Bridging Specialties: Timely Diagnosis for ILD Patients, has already produced an introductory podcast and a white paper on the effort, and its rationale is expected to be released soon, according to Dr. Kulkarni and her fellow committee members.
The American College of Chest Physicians and the Three Lakes Foundation – a foundation dedicated to pulmonary fibrosis awareness and research – are working together on this initiative. They plan to put together a suite of resources, to be gradually rolled out on the college’s website, to raise awareness about the importance of early diagnosis of ILD.
The full toolkit, expected to be rolled out over the next 12 months, will include a series of podcasts and resources on how to get patients diagnosed earlier and steps to take in cases of suspected ILD, Dr. Kulkarni said.
“The goal would be to try to increase awareness about the disease so that people start thinking more about it up front – and not after we’ve ruled out everything else,” she said. The main audience will be primary care providers, but patients and community pulmonologists would likely also benefit from the resources, the committee members said.
The urgency of the initiative stems from the way ILD treatments work. They are antifibrotic, meaning they help prevent scar tissue from forming, but they can’t reverse scar tissue that has already formed. If scarring is severe, the only option might be a lung transplant, and, since the average age at ILD diagnosis is in the 60s, many patients have comorbidities that make them ineligible for transplant. According to the Global Burden of Disease Study mentioned earlier, the death rate per 100,000 people with ILD was 1.93 in 2017.
“The longer we take to diagnose it, the more chance that inflammation will become scar tissue,” Dr. Kularni explained.
William Lago, MD, another member of the committee and a family physician, said identifying ILD early is not a straightforward matter .
“When they first present, it’s hard to pick up,” said Dr. Lago, who is also a staff physician at Cleveland Clinic’s Wooster Family Health Center and medical director of the COVID Recover Clinic there. “Many of them, even themselves, will discount the symptoms.”
Dr. Lago said that patients might resist having a work-up even when a primary care physician identifies symptoms as possible ILD. In rural settings, they might have to travel quite a distance for a CT scan or other necessary evaluations, or they might just not think the symptoms are serious enough.
“Most of the time when I’ve picked up some of my pulmonary fibrosis patients, it’s been incidentally while they’re in the office for other things,” he said. He often has to “push the issue” for further work-up, he said.
The overlap of shortness of breath and cough with other, much more common disorders, such as heart disease or chronic obstructive pulmonary disease (COPD), make ILD diagnosis a challenge, he said.
“For most of us, we’ve got sometimes 10 or 15 minutes with a patient who’s presenting with 5-6 different problems. And the shortness of breath or the occasional cough – that they think is nothing – is probably the least of those,” Dr. Lago said.
Dr. Golden said he suspected a tool like the one being developed by CHEST to be useful for some and not useful for others. He added that “no one has the time to spend on that kind of thing.”
Instead, he suggested just reinforcing what the core symptoms are and what the core testing is, “to make people think about it.”
Dr. Horowitiz seemed more optimistic about the likelihood of the CHEST tool being utilized to diagnose ILD.
Whether and how he would use the CHEST resource will depend on the final form it takes, Dr. Horowitz said. It’s encouraging that it’s being put together by a credible source, he added.
Dr. Kulkarni reported financial relationships with Boehringer Ingelheim, Aluda Pharmaceuticals and PureTech Lyt-100 Inc. Dr. Lago, Dr. Horowitz, and Dr. Golden reported no relevant disclosures.
Katie Lennon contributed to this report.
“There is definitely a delay from the time of symptom onset to the time that they are even evaluated for ILD,” said Dr. Kulkarni of the department of pulmonary, allergy and critical care medicine at the University of Alabama, Birmingham. “Some patients have had a significant loss of lung function by the time they come to see us. By that point we are limited by what treatment options we can offer.”
Interstitial lung disease is an umbrella term for a group of disorders involving progressive scarring of the lungs – typically irreversible – usually caused by long-term exposure to hazardous materials or by autoimmune effects. It includes idiopathic pulmonary fibrosis (IPF), a disease that is fairly rare but which has therapy options that can be effective if caught early enough. The term pulmonary fibrosis refers to lung scarring. Another type of ILD is pulmonary sarcoidosis, in which small clumps of immune cells form in the lungs in an immune response sometimes following an environmental trigger, and can lead to lung scarring if it doesn’t resolve.
Cases of ILD appear to be on the rise, and COVID-19 has made diagnosing it more complicated. One study found the prevalence of ILD and pulmonary sarcoidosis in high-income countries was about 122 of every 100,000 people in 1990 and rose to about 198 of every 100,000 people in 2017. The data were pulled from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. Globally, the researchers found a prevalence of 62 per 100,000 in 1990, compared with 82 per 100,000 in 2017.
If all of a patient’s symptoms have appeared post COVID and a physician is seeing a patient within 4-6 weeks of COVID symptoms, it is likely that the symptoms are COVID related. But a full work-up is recommended if a patient has lung crackles, which are an indicator of lung scarring, she said.
“The patterns that are seen on CT scan for COVID pneumonia are very distinct from what we expect to see with idiopathic pulmonary fibrosis,” Dr. Kulkarni said. “Putting all this information together is what is important to differentiate it from COVID pneumonia, as well as other types of ILD.”
A study published earlier this year found similarities between COVID-19 and IPF in gene expression, their IL-15-heavy cytokine storms, and the type of damage to alveolar cells. Both might be driven by endoplasmic reticulum stress, they found.
“COVID-19 resembles IPF at a fundamental level,” they wrote.
Jeffrey Horowitz, MD, a pulmonologist and professor of medicine at the Ohio State University, said the need for early diagnosis is in part a function of the therapies available for ILD.
“They don’t make the lung function better,” he said. “So delays in diagnosis mean that there’s the possibility of underlying progression for months, or sometimes years, before the diagnosis is recognized.”
In an area in which diagnosis is delayed and the prognosis is dire – 3-5 years in untreated patients after diagnosis – “there’s a tremendous amount of nihilism out there” among patients, he said.
He said patients with long-term shortness of breath and unexplained cough are often told they have asthma and are prescribed inhalers, but then further assessment isn’t performed when those don’t work.
Diagnosing ILD in primary care
Many primary care physicians feel ill-equipped to discuss IPF. More than a dozen physicians contacted for this piece to talk about ILD either did not respond, or said they felt unqualified to respond to questions on the disease.
“Not my area of expertise” and “I don’t think I’m the right person for this discussion” were two of the responses provided to this news organization.
“For some reason, in the world of primary care, it seems like there’s an impediment to getting pulmonary function studies,” Dr. Horowitz said. “Anybody who has a persistent ongoing prolonged unexplained shortness of breath and cough should have pulmonary function studies done.”
Listening to the lungs alone might not be enough, he said. There might be no clear sign in the case of early pulmonary fibrosis, he said.
“There’s the textbook description of these Velcro-sounding crackles, but sometimes it’s very subtle,” he said. “And unless you’re listening very carefully it can easily be missed by somebody who has a busy practice, or it’s loud.”
William E. Golden, MD, professor of medicine and public health at the University of Arkansas, Little Rock, is the sole primary care physician contacted for this piece who spoke with authority on ILD.
For cases of suspected ILD, internist Dr. Golden, who also serves on the editorial advisory board of Internal Medicine News, suggested ordering a test for diffusing capacity for carbon monoxide (DLCO), which will be low in the case of IPF, along with a fine-cut lung CT scan to assess ongoing fibrotic changes.
It’s “not that difficult, but you need to have an index of suspicion for the diagnosis,” he said.
New initiative for helping diagnose ILD
Dr. Kulkarni is a committee member for a new effort under way to try to get patients with ILD diagnosed earlier.
The initiative, called Bridging Specialties: Timely Diagnosis for ILD Patients, has already produced an introductory podcast and a white paper on the effort, and its rationale is expected to be released soon, according to Dr. Kulkarni and her fellow committee members.
The American College of Chest Physicians and the Three Lakes Foundation – a foundation dedicated to pulmonary fibrosis awareness and research – are working together on this initiative. They plan to put together a suite of resources, to be gradually rolled out on the college’s website, to raise awareness about the importance of early diagnosis of ILD.
The full toolkit, expected to be rolled out over the next 12 months, will include a series of podcasts and resources on how to get patients diagnosed earlier and steps to take in cases of suspected ILD, Dr. Kulkarni said.
“The goal would be to try to increase awareness about the disease so that people start thinking more about it up front – and not after we’ve ruled out everything else,” she said. The main audience will be primary care providers, but patients and community pulmonologists would likely also benefit from the resources, the committee members said.
The urgency of the initiative stems from the way ILD treatments work. They are antifibrotic, meaning they help prevent scar tissue from forming, but they can’t reverse scar tissue that has already formed. If scarring is severe, the only option might be a lung transplant, and, since the average age at ILD diagnosis is in the 60s, many patients have comorbidities that make them ineligible for transplant. According to the Global Burden of Disease Study mentioned earlier, the death rate per 100,000 people with ILD was 1.93 in 2017.
“The longer we take to diagnose it, the more chance that inflammation will become scar tissue,” Dr. Kularni explained.
William Lago, MD, another member of the committee and a family physician, said identifying ILD early is not a straightforward matter .
“When they first present, it’s hard to pick up,” said Dr. Lago, who is also a staff physician at Cleveland Clinic’s Wooster Family Health Center and medical director of the COVID Recover Clinic there. “Many of them, even themselves, will discount the symptoms.”
Dr. Lago said that patients might resist having a work-up even when a primary care physician identifies symptoms as possible ILD. In rural settings, they might have to travel quite a distance for a CT scan or other necessary evaluations, or they might just not think the symptoms are serious enough.
“Most of the time when I’ve picked up some of my pulmonary fibrosis patients, it’s been incidentally while they’re in the office for other things,” he said. He often has to “push the issue” for further work-up, he said.
The overlap of shortness of breath and cough with other, much more common disorders, such as heart disease or chronic obstructive pulmonary disease (COPD), make ILD diagnosis a challenge, he said.
“For most of us, we’ve got sometimes 10 or 15 minutes with a patient who’s presenting with 5-6 different problems. And the shortness of breath or the occasional cough – that they think is nothing – is probably the least of those,” Dr. Lago said.
Dr. Golden said he suspected a tool like the one being developed by CHEST to be useful for some and not useful for others. He added that “no one has the time to spend on that kind of thing.”
Instead, he suggested just reinforcing what the core symptoms are and what the core testing is, “to make people think about it.”
Dr. Horowitiz seemed more optimistic about the likelihood of the CHEST tool being utilized to diagnose ILD.
Whether and how he would use the CHEST resource will depend on the final form it takes, Dr. Horowitz said. It’s encouraging that it’s being put together by a credible source, he added.
Dr. Kulkarni reported financial relationships with Boehringer Ingelheim, Aluda Pharmaceuticals and PureTech Lyt-100 Inc. Dr. Lago, Dr. Horowitz, and Dr. Golden reported no relevant disclosures.
Katie Lennon contributed to this report.