The annual incidence of hip fractures declined in most countries from 2005 to 2018, but this rate is projected to roughly double by 2050, according to a new study of 19 countries/regions.

The study by Chor-Wing Sing, PhD, and colleagues was presented at the annual meeting of the American Society of Bone and Mineral Research. The predicted increase in hip fractures is being driven by the aging population, with the population of those age 85 and older projected to increase 4.5-fold from 2010 to 2050, they note.

The researchers also estimate that from 2018 to 2050 the incidence of fractures will increase by 1.9-fold overall – more in men (2.4-fold) than in women (1.7-fold).

In addition, rates of use of osteoporosis drugs 1 year after a hip fracture were less than 50%, with less treatment in men. Men were also more likely than women to die within 1 year of a hip fracture.

iStock/Thinkstock

Aging will fuel rise in hip fractures; more preventive treatment needed

“Even though there is a decreasing trend of hip fracture incidence in some countries, such a percentage decrease is insufficient to offset the percentage increase in the aging population,” senior co-author Ching-Lung Cheung, PhD, associate professor in the department of pharmacology and pharmacy at the University of Hong Kong, explained to this news organization.

The takeaways from the study are that “a greater effort on fracture prevention should be made to avoid the continuous increase in the number of hip fractures,” he said.

In addition, “although initiation of anti-osteoporosis medication after hip fracture is recommended in international guidelines, the 1-year treatment rate [was] well below 50% in most of the countries and regions studied. This indicates the treatment rate is far from optimal.”

“Our study also showed that the use of anti-osteoporosis medications following a hip fracture is lower in men than in women by 30% to 67%,” he said. “Thus, more attention should be paid to preventing and treating hip fractures in men.”

“The greater increase in the projected number of hip fractures in men than in women “could be [because] osteoporosis is commonly perceived as a ‘woman’s disease,’ ” he speculated.

Invited to comment, Juliet Compston, MD, who selected the study as one of the top clinical science highlight abstracts at the ASBMR meeting, agrees that “there is substantial room for improvement” in osteoporosis treatment rates following a hip fracture “in all the regions covered by the study.”

“In addition,” she continues, “the wide variations in treatment rates can provide important lessons about the most effective models of care for people who sustain a hip fracture: for example, fracture liaison services.”

Men suffer as osteoporosis perceived to be a ‘woman’s disease’

The even lower treatment rate in men than women is “concerning and likely reflects the mistaken perception that osteoporosis is predominantly a disease affecting women,” notes Dr. Compston, emeritus professor of bone medicine, University of Cambridge, United Kingdom.  

Also invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, said that the projected doubling of hip fractures “is likely mainly due to aging of the population, with increasing lifespan for males in particular. However, increasing urbanization and decreasing weight-bearing exercise as a result are likely to also contribute in developing countries.”

“Unfortunately, despite the advances in treatments for osteoporosis over the last 25 years, osteoporosis treatment rates remain low, and osteoporosis remains undiagnosed in postmenopausal women and older men,” added Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research.

“More targeted screening for osteoporosis would help,” he said, “as would treating patients for it following other minimal trauma fractures (vertebral, distal radius, and humerus, etc.), since if left untreated, about 50% of these patients will have hip fractures later in life.”

“Some countries may be doing better because they have health quality standards for hip fracture (for example, surgery within 24 hours, investigation, and treatment for osteoporosis). In other countries like Australia, bone density tests and treatment for osteoporosis are reimbursed, increasing their uptake.”

The public health implications of this study are “substantial” according to Dr. Compston. “People who have sustained a hip fracture are at high risk of subsequent fractures if untreated. There is a range of safe, cost-effective pharmacological therapies to reduce fracture rate, and wider use of these would have a major impact on the current and future burden imposed by hip fractures in the elderly population.”

Similarly, Dr. Ebeling noted that “prevention is important to save a huge health burden for patients and costs for society.”

“Patients with minimal trauma fractures (particularly hip or spinal fractures) should be investigated and treated for osteoporosis with care pathways established in the hospitals, reaching out to the community [fracture liaison services],” he said.

Support for these is being sought under Medicare in the United States, he noted, and bone densitometry reimbursement rates also need to be higher in the United States.
 

Projections for number of hip fractures to 2050

Previous international reviews of hip fractures have been based on heterogeneous data from more than 10 to 30 years ago, the researchers note.

They performed a retrospective cohort study using a common protocol across 19 countries/regions, as described in an article about the protocol published in BMJ Open.

They analyzed data from adults aged 50 and older who were hospitalized with a hip fracture to determine 1) the annual incidence of hip fractures in 2008-2015; 2) the uptake of drugs to treat osteoporosis at 1 year after a hip fracture; and 3) all-cause mortality at 1 year after a hip fracture.

In a second step, they estimated the number of hip fractures that would occur from 2030 to 2050, using World Bank population growth projections.

The data are from 20 health care databases from 19 countries/regions: Oceania (Australia, New Zealand), Asia (Hong Kong, Japan, Singapore, South Korea, Taiwan, and Thailand), Northern Europe (Denmark, Finland, and U.K.), Western Europe (France, Germany, Italy, The Netherlands, and Spain), and North and South America (Canada, United States, and Brazil).

The population in Japan was under age 75. U.S. data are from two databases: Medicare (age ≥ 65) and Optum.

Most databases (13) covered 90%-100% of the national population, and the rest covered 5%-70% of the population.

From 2008 to 2015, the annual incidence of hip fractures declined in 11 countries/regions (Singapore, Denmark, Hong Kong, Taiwan, Finland, U.K., Italy, Spain, United States [Medicare], Canada, and New Zealand).

“One potential reason that some countries have seen relatively large declines in hip fractures is better osteoporosis management and post-fracture care,” said Dr. Sing in a press release issued by ASBMR. “Better fall-prevention programs and clearer guidelines for clinical care have likely made a difference.”

Hip fracture incidence increased in five countries (The Netherlands, South Korea, France, Germany, and Brazil) and was stable in four countries (Australia, Japan, Thailand, and United States [Optum]).

The United Kingdom had the highest rate of osteoporosis treatment at 1-year after a hip fracture (50.3%). Rates in the other countries/regions ranged from 11.5% to 37%.

Fewer men than women were receiving drugs for osteoporosis at 1 year (range 5.1% to 38.2% versus 15.0% to 54.7%).

From 2005 to 2018, rates of osteoporosis treatment at 1 year after a hip fracture declined in six countries, increased in four countries, and were stable in five countries.

All-cause mortality within 1 year of hip fracture was higher in men than in women (range 19.2% to 35.8% versus 12.1% to 25.4%).

“Among the studied countries and regions, the U.S. ranks fifth with the highest hip fracture incidence,” Dr. Cheung replied when specifically asked about this. “The risk of hip fracture is determined by multiple factors: for example, lifestyle, diet, genetics, as well as management of osteoporosis,” he noted.

“Denmark is the only country showing no projected increase, and it is because Denmark had a continuous and remarkable decrease in the incidence of hip fractures,” he added, which “can offset the number of hip fractures contributed by the population aging.”

The study was funded by Amgen. Dr. Sing and Dr. Cheung have reported no relevant financial relationships. One of the study authors is employed by Amgen.

A version of this article first appeared on Medscape.com.

The annual incidence of hip fractures declined in most countries from 2005 to 2018, but this rate is projected to roughly double by 2050, according to a new study of 19 countries/regions.

The study by Chor-Wing Sing, PhD, and colleagues was presented at the annual meeting of the American Society of Bone and Mineral Research. The predicted increase in hip fractures is being driven by the aging population, with the population of those age 85 and older projected to increase 4.5-fold from 2010 to 2050, they note.

The researchers also estimate that from 2018 to 2050 the incidence of fractures will increase by 1.9-fold overall – more in men (2.4-fold) than in women (1.7-fold).

In addition, rates of use of osteoporosis drugs 1 year after a hip fracture were less than 50%, with less treatment in men. Men were also more likely than women to die within 1 year of a hip fracture.

iStock/Thinkstock

Aging will fuel rise in hip fractures; more preventive treatment needed

“Even though there is a decreasing trend of hip fracture incidence in some countries, such a percentage decrease is insufficient to offset the percentage increase in the aging population,” senior co-author Ching-Lung Cheung, PhD, associate professor in the department of pharmacology and pharmacy at the University of Hong Kong, explained to this news organization.

The takeaways from the study are that “a greater effort on fracture prevention should be made to avoid the continuous increase in the number of hip fractures,” he said.

In addition, “although initiation of anti-osteoporosis medication after hip fracture is recommended in international guidelines, the 1-year treatment rate [was] well below 50% in most of the countries and regions studied. This indicates the treatment rate is far from optimal.”

“Our study also showed that the use of anti-osteoporosis medications following a hip fracture is lower in men than in women by 30% to 67%,” he said. “Thus, more attention should be paid to preventing and treating hip fractures in men.”

“The greater increase in the projected number of hip fractures in men than in women “could be [because] osteoporosis is commonly perceived as a ‘woman’s disease,’ ” he speculated.

Invited to comment, Juliet Compston, MD, who selected the study as one of the top clinical science highlight abstracts at the ASBMR meeting, agrees that “there is substantial room for improvement” in osteoporosis treatment rates following a hip fracture “in all the regions covered by the study.”

“In addition,” she continues, “the wide variations in treatment rates can provide important lessons about the most effective models of care for people who sustain a hip fracture: for example, fracture liaison services.”

Men suffer as osteoporosis perceived to be a ‘woman’s disease’

The even lower treatment rate in men than women is “concerning and likely reflects the mistaken perception that osteoporosis is predominantly a disease affecting women,” notes Dr. Compston, emeritus professor of bone medicine, University of Cambridge, United Kingdom.  

Also invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, said that the projected doubling of hip fractures “is likely mainly due to aging of the population, with increasing lifespan for males in particular. However, increasing urbanization and decreasing weight-bearing exercise as a result are likely to also contribute in developing countries.”

“Unfortunately, despite the advances in treatments for osteoporosis over the last 25 years, osteoporosis treatment rates remain low, and osteoporosis remains undiagnosed in postmenopausal women and older men,” added Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research.

“More targeted screening for osteoporosis would help,” he said, “as would treating patients for it following other minimal trauma fractures (vertebral, distal radius, and humerus, etc.), since if left untreated, about 50% of these patients will have hip fractures later in life.”

“Some countries may be doing better because they have health quality standards for hip fracture (for example, surgery within 24 hours, investigation, and treatment for osteoporosis). In other countries like Australia, bone density tests and treatment for osteoporosis are reimbursed, increasing their uptake.”

The public health implications of this study are “substantial” according to Dr. Compston. “People who have sustained a hip fracture are at high risk of subsequent fractures if untreated. There is a range of safe, cost-effective pharmacological therapies to reduce fracture rate, and wider use of these would have a major impact on the current and future burden imposed by hip fractures in the elderly population.”

Similarly, Dr. Ebeling noted that “prevention is important to save a huge health burden for patients and costs for society.”

“Patients with minimal trauma fractures (particularly hip or spinal fractures) should be investigated and treated for osteoporosis with care pathways established in the hospitals, reaching out to the community [fracture liaison services],” he said.

Support for these is being sought under Medicare in the United States, he noted, and bone densitometry reimbursement rates also need to be higher in the United States.
 

Projections for number of hip fractures to 2050

Previous international reviews of hip fractures have been based on heterogeneous data from more than 10 to 30 years ago, the researchers note.

They performed a retrospective cohort study using a common protocol across 19 countries/regions, as described in an article about the protocol published in BMJ Open.

They analyzed data from adults aged 50 and older who were hospitalized with a hip fracture to determine 1) the annual incidence of hip fractures in 2008-2015; 2) the uptake of drugs to treat osteoporosis at 1 year after a hip fracture; and 3) all-cause mortality at 1 year after a hip fracture.

In a second step, they estimated the number of hip fractures that would occur from 2030 to 2050, using World Bank population growth projections.

The data are from 20 health care databases from 19 countries/regions: Oceania (Australia, New Zealand), Asia (Hong Kong, Japan, Singapore, South Korea, Taiwan, and Thailand), Northern Europe (Denmark, Finland, and U.K.), Western Europe (France, Germany, Italy, The Netherlands, and Spain), and North and South America (Canada, United States, and Brazil).

The population in Japan was under age 75. U.S. data are from two databases: Medicare (age ≥ 65) and Optum.

Most databases (13) covered 90%-100% of the national population, and the rest covered 5%-70% of the population.

From 2008 to 2015, the annual incidence of hip fractures declined in 11 countries/regions (Singapore, Denmark, Hong Kong, Taiwan, Finland, U.K., Italy, Spain, United States [Medicare], Canada, and New Zealand).

“One potential reason that some countries have seen relatively large declines in hip fractures is better osteoporosis management and post-fracture care,” said Dr. Sing in a press release issued by ASBMR. “Better fall-prevention programs and clearer guidelines for clinical care have likely made a difference.”

Hip fracture incidence increased in five countries (The Netherlands, South Korea, France, Germany, and Brazil) and was stable in four countries (Australia, Japan, Thailand, and United States [Optum]).

The United Kingdom had the highest rate of osteoporosis treatment at 1-year after a hip fracture (50.3%). Rates in the other countries/regions ranged from 11.5% to 37%.

Fewer men than women were receiving drugs for osteoporosis at 1 year (range 5.1% to 38.2% versus 15.0% to 54.7%).

From 2005 to 2018, rates of osteoporosis treatment at 1 year after a hip fracture declined in six countries, increased in four countries, and were stable in five countries.

All-cause mortality within 1 year of hip fracture was higher in men than in women (range 19.2% to 35.8% versus 12.1% to 25.4%).

“Among the studied countries and regions, the U.S. ranks fifth with the highest hip fracture incidence,” Dr. Cheung replied when specifically asked about this. “The risk of hip fracture is determined by multiple factors: for example, lifestyle, diet, genetics, as well as management of osteoporosis,” he noted.

“Denmark is the only country showing no projected increase, and it is because Denmark had a continuous and remarkable decrease in the incidence of hip fractures,” he added, which “can offset the number of hip fractures contributed by the population aging.”

The study was funded by Amgen. Dr. Sing and Dr. Cheung have reported no relevant financial relationships. One of the study authors is employed by Amgen.

A version of this article first appeared on Medscape.com.

The annual incidence of hip fractures declined in most countries from 2005 to 2018, but this rate is projected to roughly double by 2050, according to a new study of 19 countries/regions.

The study by Chor-Wing Sing, PhD, and colleagues was presented at the annual meeting of the American Society of Bone and Mineral Research. The predicted increase in hip fractures is being driven by the aging population, with the population of those age 85 and older projected to increase 4.5-fold from 2010 to 2050, they note.

The researchers also estimate that from 2018 to 2050 the incidence of fractures will increase by 1.9-fold overall – more in men (2.4-fold) than in women (1.7-fold).

In addition, rates of use of osteoporosis drugs 1 year after a hip fracture were less than 50%, with less treatment in men. Men were also more likely than women to die within 1 year of a hip fracture.

iStock/Thinkstock

Aging will fuel rise in hip fractures; more preventive treatment needed

“Even though there is a decreasing trend of hip fracture incidence in some countries, such a percentage decrease is insufficient to offset the percentage increase in the aging population,” senior co-author Ching-Lung Cheung, PhD, associate professor in the department of pharmacology and pharmacy at the University of Hong Kong, explained to this news organization.

The takeaways from the study are that “a greater effort on fracture prevention should be made to avoid the continuous increase in the number of hip fractures,” he said.

In addition, “although initiation of anti-osteoporosis medication after hip fracture is recommended in international guidelines, the 1-year treatment rate [was] well below 50% in most of the countries and regions studied. This indicates the treatment rate is far from optimal.”

“Our study also showed that the use of anti-osteoporosis medications following a hip fracture is lower in men than in women by 30% to 67%,” he said. “Thus, more attention should be paid to preventing and treating hip fractures in men.”

“The greater increase in the projected number of hip fractures in men than in women “could be [because] osteoporosis is commonly perceived as a ‘woman’s disease,’ ” he speculated.

Invited to comment, Juliet Compston, MD, who selected the study as one of the top clinical science highlight abstracts at the ASBMR meeting, agrees that “there is substantial room for improvement” in osteoporosis treatment rates following a hip fracture “in all the regions covered by the study.”

“In addition,” she continues, “the wide variations in treatment rates can provide important lessons about the most effective models of care for people who sustain a hip fracture: for example, fracture liaison services.”

Men suffer as osteoporosis perceived to be a ‘woman’s disease’

The even lower treatment rate in men than women is “concerning and likely reflects the mistaken perception that osteoporosis is predominantly a disease affecting women,” notes Dr. Compston, emeritus professor of bone medicine, University of Cambridge, United Kingdom.  

Also invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, said that the projected doubling of hip fractures “is likely mainly due to aging of the population, with increasing lifespan for males in particular. However, increasing urbanization and decreasing weight-bearing exercise as a result are likely to also contribute in developing countries.”

“Unfortunately, despite the advances in treatments for osteoporosis over the last 25 years, osteoporosis treatment rates remain low, and osteoporosis remains undiagnosed in postmenopausal women and older men,” added Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research.

“More targeted screening for osteoporosis would help,” he said, “as would treating patients for it following other minimal trauma fractures (vertebral, distal radius, and humerus, etc.), since if left untreated, about 50% of these patients will have hip fractures later in life.”

“Some countries may be doing better because they have health quality standards for hip fracture (for example, surgery within 24 hours, investigation, and treatment for osteoporosis). In other countries like Australia, bone density tests and treatment for osteoporosis are reimbursed, increasing their uptake.”

The public health implications of this study are “substantial” according to Dr. Compston. “People who have sustained a hip fracture are at high risk of subsequent fractures if untreated. There is a range of safe, cost-effective pharmacological therapies to reduce fracture rate, and wider use of these would have a major impact on the current and future burden imposed by hip fractures in the elderly population.”

Similarly, Dr. Ebeling noted that “prevention is important to save a huge health burden for patients and costs for society.”

“Patients with minimal trauma fractures (particularly hip or spinal fractures) should be investigated and treated for osteoporosis with care pathways established in the hospitals, reaching out to the community [fracture liaison services],” he said.

Support for these is being sought under Medicare in the United States, he noted, and bone densitometry reimbursement rates also need to be higher in the United States.
 

Projections for number of hip fractures to 2050

Previous international reviews of hip fractures have been based on heterogeneous data from more than 10 to 30 years ago, the researchers note.

They performed a retrospective cohort study using a common protocol across 19 countries/regions, as described in an article about the protocol published in BMJ Open.

They analyzed data from adults aged 50 and older who were hospitalized with a hip fracture to determine 1) the annual incidence of hip fractures in 2008-2015; 2) the uptake of drugs to treat osteoporosis at 1 year after a hip fracture; and 3) all-cause mortality at 1 year after a hip fracture.

In a second step, they estimated the number of hip fractures that would occur from 2030 to 2050, using World Bank population growth projections.

The data are from 20 health care databases from 19 countries/regions: Oceania (Australia, New Zealand), Asia (Hong Kong, Japan, Singapore, South Korea, Taiwan, and Thailand), Northern Europe (Denmark, Finland, and U.K.), Western Europe (France, Germany, Italy, The Netherlands, and Spain), and North and South America (Canada, United States, and Brazil).

The population in Japan was under age 75. U.S. data are from two databases: Medicare (age ≥ 65) and Optum.

Most databases (13) covered 90%-100% of the national population, and the rest covered 5%-70% of the population.

From 2008 to 2015, the annual incidence of hip fractures declined in 11 countries/regions (Singapore, Denmark, Hong Kong, Taiwan, Finland, U.K., Italy, Spain, United States [Medicare], Canada, and New Zealand).

“One potential reason that some countries have seen relatively large declines in hip fractures is better osteoporosis management and post-fracture care,” said Dr. Sing in a press release issued by ASBMR. “Better fall-prevention programs and clearer guidelines for clinical care have likely made a difference.”

Hip fracture incidence increased in five countries (The Netherlands, South Korea, France, Germany, and Brazil) and was stable in four countries (Australia, Japan, Thailand, and United States [Optum]).

The United Kingdom had the highest rate of osteoporosis treatment at 1-year after a hip fracture (50.3%). Rates in the other countries/regions ranged from 11.5% to 37%.

Fewer men than women were receiving drugs for osteoporosis at 1 year (range 5.1% to 38.2% versus 15.0% to 54.7%).

From 2005 to 2018, rates of osteoporosis treatment at 1 year after a hip fracture declined in six countries, increased in four countries, and were stable in five countries.

All-cause mortality within 1 year of hip fracture was higher in men than in women (range 19.2% to 35.8% versus 12.1% to 25.4%).

“Among the studied countries and regions, the U.S. ranks fifth with the highest hip fracture incidence,” Dr. Cheung replied when specifically asked about this. “The risk of hip fracture is determined by multiple factors: for example, lifestyle, diet, genetics, as well as management of osteoporosis,” he noted.

“Denmark is the only country showing no projected increase, and it is because Denmark had a continuous and remarkable decrease in the incidence of hip fractures,” he added, which “can offset the number of hip fractures contributed by the population aging.”

The study was funded by Amgen. Dr. Sing and Dr. Cheung have reported no relevant financial relationships. One of the study authors is employed by Amgen.

A version of this article first appeared on Medscape.com.

GHENT, BELGIUM – Filgotinib (Jyseleca), a Janus kinase (JAK) inhibitor, reduced the risk of flare after withdrawal of glucocorticoids in patients with vision-threatening, noninfectious intermediate, posterior, or pan uveitis, data from a phase 2 study show.

Robin Besuyen, MD, clinical development leader in inflammatory diseases at Galapagos BV, Leiden, the Netherlands, presented the phase 2 results of the placebo-controlled HUMBOLDT trial at the 13th International Congress on Spondyloarthritides.

Treatment with filgotinib was well tolerated, with no new safety concerns for the immunosuppressed uveitis population.

Uveitis involves intraocular inflammation of the eye, accounts for 5%-20% of cases of blindness, and frequently requires long-term use of systemic therapy, mostly glucocorticoids or adalimumab (Humira).

Uveitis is documented to occur in 25%-40% of patients with spondyloarthritis, and its management is essential to prevent morbidity caused by vision loss and secondary complications. The majority of patients in HUMBOLDT had idiopathic uveitis (57%). One patient with spondyloarthritis was included.

Filgotinib is being investigated in the treatment of uveitis because Janus kinases have been found to play a role in the complex cytokine-signaling pathways implicated in immune-mediated diseases, including uveitis. “A preferential inhibitor of JAK 1 could play a role in managing this condition,” Dr. Besuyen said.

Session moderator Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany), reflected on what he said was an “important study,” which, to his knowledge, was the first study of its kind in uveitis.

“The fact that they showed a significant decrease in uveitis in such a short period of time is very positive, especially for the uveitis we know of in spondyloarthritides,” he said in an interview. “The posterior uveitis was significantly impacted, and this is a very positive signal to move forward with further JAK studies in uveitis and apply them in patients with active uveitis and spondyloarthritis.”

With respect to patients with spondyloarthritis, he pointed out that, “if uveitis is fluctuating [in patients with spondyloarthritis] then patients can lose their vision. Uveitis is one of the most frequent extraskeletal manifestations of spondyloarthritis.”

However, he noted that the researchers did not show any correlation to HLA-B27 [human leukocyte antigen B27], which is “something we consider when we discuss uveitis in spondyloarthritides, but these data are convincing.”

 

Phase 2, randomized, double-blind trial – one of very few in uveitis

Participants in the randomized, double-blind trial were at least 18 years old and had intermediate, posterior, or pan uveitis that was active despite 2 weeks of treatment with glucocorticoids (oral prednisolone 10-60 mg/day). They were randomized 1:1 to filgotinib (200 mg once daily) or placebo and were assessed for evidence of treatment failure from week 6 onwards. Glucocorticoids in all participants were tapered off over 15 weeks.

The primary endpoint was the proportion of participants with treatment failure by week 24, defined as new, active, inflammatory chorioretinal and/or retinal vascular lesions at week 6 or later; worsening of best corrected visual acuity by 15 or more letters; or inability to achieve an anterior chamber cell or vitreous haze grade less than or equal to 0.5+ at week 6 or a 2-step grade increase after week 6. These effects had to be present in at least one eye.

Patients were stratified by the presence of sarcoidosis-related uveitis, baseline use of immunosuppressants, and prior use of anti–tumor necrosis factor (TNF) therapy. The mean patient age was 46 years, and around 60% were female, 57% had pan uveitis, and 22% had posterior uveitis. The mean number of uveitis flares in the previous 12 months was two.

A total of 37 patients received filgotinib and 35 received placebo, and together they composed the safety analysis set. Of these, 32 on filgotinib and 34 on placebo continued treatment to week 6, so 66 patients entered the efficacy analysis. 

The study sponsor, Gilead, decided to stop the trial early for business reasons after the U.S. Food and Drug Administration rejected its application for filgotinib in the treatment of rheumatoid arthritis, and only 74 patients of the originally planned 248 participants were randomized. “Therefore, the conclusions that have been drawn from the study are limited, and results should be interpreted with caution,” Dr. Besuyen noted.
 

Primary endpoint of treatment failure favored filgotinib

The primary endpoint of treatment failure was met by 12 (38%) of 32 patients taking filgotinib and 23 (67%) of 34 patients taking placebo, generating an odds ratio of 0.23 favoring filgotinib, which was statistically significant (P = .008), Dr. Besuyen reported.

The median time to treatment failure on or after week 6, one of the trial’s secondary endpoints, was 22 weeks for placebo but could not be calculated for filgotinib because fewer than half of these patients failed treatment with filgotinib.

Filgotinib was safe and well tolerated, and the safety profile emerging from this study was similar to that seen in the indications for which it is marketed in the European Union, United Kingdom, and Japan (rheumatoid arthritis and ulcerative colitis). There were no deaths, no major adverse cardiovascular events, no malignancies, and no opportunistic infections. Treatment-emergent serious adverse events were seen in 13.5% with filgotinib and 5.7% with placebo.

Gilead Sciences and Galapagos NV sponsored and collaborated on the trial. Dr. Besuyen is an employee of Galapagos NV. Dr. Baraliakos has declared no relevant financial conflicts of interest.
 

GHENT, BELGIUM – Filgotinib (Jyseleca), a Janus kinase (JAK) inhibitor, reduced the risk of flare after withdrawal of glucocorticoids in patients with vision-threatening, noninfectious intermediate, posterior, or pan uveitis, data from a phase 2 study show.

Robin Besuyen, MD, clinical development leader in inflammatory diseases at Galapagos BV, Leiden, the Netherlands, presented the phase 2 results of the placebo-controlled HUMBOLDT trial at the 13th International Congress on Spondyloarthritides.

Treatment with filgotinib was well tolerated, with no new safety concerns for the immunosuppressed uveitis population.

Uveitis involves intraocular inflammation of the eye, accounts for 5%-20% of cases of blindness, and frequently requires long-term use of systemic therapy, mostly glucocorticoids or adalimumab (Humira).

Uveitis is documented to occur in 25%-40% of patients with spondyloarthritis, and its management is essential to prevent morbidity caused by vision loss and secondary complications. The majority of patients in HUMBOLDT had idiopathic uveitis (57%). One patient with spondyloarthritis was included.

Filgotinib is being investigated in the treatment of uveitis because Janus kinases have been found to play a role in the complex cytokine-signaling pathways implicated in immune-mediated diseases, including uveitis. “A preferential inhibitor of JAK 1 could play a role in managing this condition,” Dr. Besuyen said.

Session moderator Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany), reflected on what he said was an “important study,” which, to his knowledge, was the first study of its kind in uveitis.

“The fact that they showed a significant decrease in uveitis in such a short period of time is very positive, especially for the uveitis we know of in spondyloarthritides,” he said in an interview. “The posterior uveitis was significantly impacted, and this is a very positive signal to move forward with further JAK studies in uveitis and apply them in patients with active uveitis and spondyloarthritis.”

With respect to patients with spondyloarthritis, he pointed out that, “if uveitis is fluctuating [in patients with spondyloarthritis] then patients can lose their vision. Uveitis is one of the most frequent extraskeletal manifestations of spondyloarthritis.”

However, he noted that the researchers did not show any correlation to HLA-B27 [human leukocyte antigen B27], which is “something we consider when we discuss uveitis in spondyloarthritides, but these data are convincing.”

 

Phase 2, randomized, double-blind trial – one of very few in uveitis

Participants in the randomized, double-blind trial were at least 18 years old and had intermediate, posterior, or pan uveitis that was active despite 2 weeks of treatment with glucocorticoids (oral prednisolone 10-60 mg/day). They were randomized 1:1 to filgotinib (200 mg once daily) or placebo and were assessed for evidence of treatment failure from week 6 onwards. Glucocorticoids in all participants were tapered off over 15 weeks.

The primary endpoint was the proportion of participants with treatment failure by week 24, defined as new, active, inflammatory chorioretinal and/or retinal vascular lesions at week 6 or later; worsening of best corrected visual acuity by 15 or more letters; or inability to achieve an anterior chamber cell or vitreous haze grade less than or equal to 0.5+ at week 6 or a 2-step grade increase after week 6. These effects had to be present in at least one eye.

Patients were stratified by the presence of sarcoidosis-related uveitis, baseline use of immunosuppressants, and prior use of anti–tumor necrosis factor (TNF) therapy. The mean patient age was 46 years, and around 60% were female, 57% had pan uveitis, and 22% had posterior uveitis. The mean number of uveitis flares in the previous 12 months was two.

A total of 37 patients received filgotinib and 35 received placebo, and together they composed the safety analysis set. Of these, 32 on filgotinib and 34 on placebo continued treatment to week 6, so 66 patients entered the efficacy analysis. 

The study sponsor, Gilead, decided to stop the trial early for business reasons after the U.S. Food and Drug Administration rejected its application for filgotinib in the treatment of rheumatoid arthritis, and only 74 patients of the originally planned 248 participants were randomized. “Therefore, the conclusions that have been drawn from the study are limited, and results should be interpreted with caution,” Dr. Besuyen noted.
 

Primary endpoint of treatment failure favored filgotinib

The primary endpoint of treatment failure was met by 12 (38%) of 32 patients taking filgotinib and 23 (67%) of 34 patients taking placebo, generating an odds ratio of 0.23 favoring filgotinib, which was statistically significant (P = .008), Dr. Besuyen reported.

The median time to treatment failure on or after week 6, one of the trial’s secondary endpoints, was 22 weeks for placebo but could not be calculated for filgotinib because fewer than half of these patients failed treatment with filgotinib.

Filgotinib was safe and well tolerated, and the safety profile emerging from this study was similar to that seen in the indications for which it is marketed in the European Union, United Kingdom, and Japan (rheumatoid arthritis and ulcerative colitis). There were no deaths, no major adverse cardiovascular events, no malignancies, and no opportunistic infections. Treatment-emergent serious adverse events were seen in 13.5% with filgotinib and 5.7% with placebo.

Gilead Sciences and Galapagos NV sponsored and collaborated on the trial. Dr. Besuyen is an employee of Galapagos NV. Dr. Baraliakos has declared no relevant financial conflicts of interest.
 

GHENT, BELGIUM – Filgotinib (Jyseleca), a Janus kinase (JAK) inhibitor, reduced the risk of flare after withdrawal of glucocorticoids in patients with vision-threatening, noninfectious intermediate, posterior, or pan uveitis, data from a phase 2 study show.

Robin Besuyen, MD, clinical development leader in inflammatory diseases at Galapagos BV, Leiden, the Netherlands, presented the phase 2 results of the placebo-controlled HUMBOLDT trial at the 13th International Congress on Spondyloarthritides.

Treatment with filgotinib was well tolerated, with no new safety concerns for the immunosuppressed uveitis population.

Uveitis involves intraocular inflammation of the eye, accounts for 5%-20% of cases of blindness, and frequently requires long-term use of systemic therapy, mostly glucocorticoids or adalimumab (Humira).

Uveitis is documented to occur in 25%-40% of patients with spondyloarthritis, and its management is essential to prevent morbidity caused by vision loss and secondary complications. The majority of patients in HUMBOLDT had idiopathic uveitis (57%). One patient with spondyloarthritis was included.

Filgotinib is being investigated in the treatment of uveitis because Janus kinases have been found to play a role in the complex cytokine-signaling pathways implicated in immune-mediated diseases, including uveitis. “A preferential inhibitor of JAK 1 could play a role in managing this condition,” Dr. Besuyen said.

Session moderator Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany), reflected on what he said was an “important study,” which, to his knowledge, was the first study of its kind in uveitis.

“The fact that they showed a significant decrease in uveitis in such a short period of time is very positive, especially for the uveitis we know of in spondyloarthritides,” he said in an interview. “The posterior uveitis was significantly impacted, and this is a very positive signal to move forward with further JAK studies in uveitis and apply them in patients with active uveitis and spondyloarthritis.”

With respect to patients with spondyloarthritis, he pointed out that, “if uveitis is fluctuating [in patients with spondyloarthritis] then patients can lose their vision. Uveitis is one of the most frequent extraskeletal manifestations of spondyloarthritis.”

However, he noted that the researchers did not show any correlation to HLA-B27 [human leukocyte antigen B27], which is “something we consider when we discuss uveitis in spondyloarthritides, but these data are convincing.”

 

Phase 2, randomized, double-blind trial – one of very few in uveitis

Participants in the randomized, double-blind trial were at least 18 years old and had intermediate, posterior, or pan uveitis that was active despite 2 weeks of treatment with glucocorticoids (oral prednisolone 10-60 mg/day). They were randomized 1:1 to filgotinib (200 mg once daily) or placebo and were assessed for evidence of treatment failure from week 6 onwards. Glucocorticoids in all participants were tapered off over 15 weeks.

The primary endpoint was the proportion of participants with treatment failure by week 24, defined as new, active, inflammatory chorioretinal and/or retinal vascular lesions at week 6 or later; worsening of best corrected visual acuity by 15 or more letters; or inability to achieve an anterior chamber cell or vitreous haze grade less than or equal to 0.5+ at week 6 or a 2-step grade increase after week 6. These effects had to be present in at least one eye.

Patients were stratified by the presence of sarcoidosis-related uveitis, baseline use of immunosuppressants, and prior use of anti–tumor necrosis factor (TNF) therapy. The mean patient age was 46 years, and around 60% were female, 57% had pan uveitis, and 22% had posterior uveitis. The mean number of uveitis flares in the previous 12 months was two.

A total of 37 patients received filgotinib and 35 received placebo, and together they composed the safety analysis set. Of these, 32 on filgotinib and 34 on placebo continued treatment to week 6, so 66 patients entered the efficacy analysis. 

The study sponsor, Gilead, decided to stop the trial early for business reasons after the U.S. Food and Drug Administration rejected its application for filgotinib in the treatment of rheumatoid arthritis, and only 74 patients of the originally planned 248 participants were randomized. “Therefore, the conclusions that have been drawn from the study are limited, and results should be interpreted with caution,” Dr. Besuyen noted.
 

Primary endpoint of treatment failure favored filgotinib

The primary endpoint of treatment failure was met by 12 (38%) of 32 patients taking filgotinib and 23 (67%) of 34 patients taking placebo, generating an odds ratio of 0.23 favoring filgotinib, which was statistically significant (P = .008), Dr. Besuyen reported.

The median time to treatment failure on or after week 6, one of the trial’s secondary endpoints, was 22 weeks for placebo but could not be calculated for filgotinib because fewer than half of these patients failed treatment with filgotinib.

Filgotinib was safe and well tolerated, and the safety profile emerging from this study was similar to that seen in the indications for which it is marketed in the European Union, United Kingdom, and Japan (rheumatoid arthritis and ulcerative colitis). There were no deaths, no major adverse cardiovascular events, no malignancies, and no opportunistic infections. Treatment-emergent serious adverse events were seen in 13.5% with filgotinib and 5.7% with placebo.

Gilead Sciences and Galapagos NV sponsored and collaborated on the trial. Dr. Besuyen is an employee of Galapagos NV. Dr. Baraliakos has declared no relevant financial conflicts of interest.
 

Starting January 1, 2023, current President-Elect Doreen J. Addrizzo-Harris, MD, FCCP, will become the new President of the American College of Chest Physicians. Dr. Addrizzo-Harris is a pulmonary/critical care physician with an extensive background in bronchiectasis and nontuberculous mycobacterial infection and medical education working as a Professor of Medicine at the NYU Grossman School of Medicine.

Before she steps into the role of President, we spoke with Dr. Addrizzo-Harris for a glimpse into what she looks to bring to the CHEST organization.

What would you like to accomplish as President of CHEST?

For my presidency, I want to continue the great trajectory CHEST is on by focusing on increasing membership, expanding our educational offerings and advancing our communication strategies, and continuing the initiatives that strive to make diversity seamless and a part of everything we do.

As many know, I have a very strong passion for the work of the CHEST Foundation, and, throughout my presidency, I will focus on how CHEST can support and integrate with the Foundation’s goal of improving patient care – whether it’s through supporting clinical research grants, expanding patient education and advocacy events, or through funding programs like the First 5 Minutes™, which touches on strengthening the rapport and trust between clinician and patient and enhances cultural competency by building an understanding of barriers to care. I can also see increasing patient involvement in CHEST to lend a unique perspective to upcoming initiatives.

Another key focus will be to strengthen and expand our membership through many venues.

We will focus on increasing physician membership of both new members and lapsed members but will also focus on increasing membership of those other providers who help us care for our patients, including advanced practice providers, respiratory therapists and more. CHEST is already an inclusive organization to a variety of health care providers, but we can do more.

My presidency will also focus on increasing collaborations with our sister societies to find new ways to reach fellows-in-training, as well as residents and medical students who are interested in pulmonary, critical care, or sleep medicine.

Along those lines, I’m also planning a dedicated focus on providing more opportunities to fellows and early career members. The goal is to enhance communications between trainees and key thought-leaders in a way that is simple, seamless, and welcoming. CHEST already does this better than anyone else, but an expanded offering, particularly in the area of career development, can help reach even more individuals – both on a national and on an international level. One such event was our successful Young Professionals Event at the Belmont event in New York City this past June.
 

What do you consider to be the greatest strength of CHEST, and how will you build upon this during your presidency?

CHEST has many strengths, but I think our greatest is the strength of our team – our members, our faculty, our volunteer leaders, and our staff.

To build on this, my presidency will include a strong communications strategy to reach, educate, and share the variety of opportunities with our members. I want to build on some of the excellent initiatives Dr. David Schulman started this year to continue engaging and showing our newer members, or soon-to-be members how to get involved with CHEST.
 

What are some challenges facing CHEST, and how will you address these challenges?

A challenge for all associations, CHEST included, will be redefining what associations look like in the wake of a global pandemic now that virtual and hybrid learning has become a part of what we do on a day-to-day basis. What will the CHEST Annual Meeting look like 3 years from now? What will keep learners coming to a physical meeting when so much is accessible on the internet? What will keep members engaged in settings where we no longer get together in-person – like the board review that is now virtual?

This all will take a lot of strategy, which is already being worked on. It will include ideas like enhancing the networking opportunities to extend beyond the annual meeting, strengthening our international strategy, and continuing to innovate in the area of medical education.
 

And finally, what do you ask of the members and Fellows of CHEST to support you during your presidency?

I ask that everyone get involved. Please reach out if you have questions. I am (and all our leaders are) very accessible and we can connect you with the right people to get you engaged. Also, please spread the word. Tell your colleagues, trainees, etc., how great CHEST is and get them involved with CHEST too. We have so much to offer.#

Starting January 1, 2023, current President-Elect Doreen J. Addrizzo-Harris, MD, FCCP, will become the new President of the American College of Chest Physicians. Dr. Addrizzo-Harris is a pulmonary/critical care physician with an extensive background in bronchiectasis and nontuberculous mycobacterial infection and medical education working as a Professor of Medicine at the NYU Grossman School of Medicine.

Before she steps into the role of President, we spoke with Dr. Addrizzo-Harris for a glimpse into what she looks to bring to the CHEST organization.

What would you like to accomplish as President of CHEST?

For my presidency, I want to continue the great trajectory CHEST is on by focusing on increasing membership, expanding our educational offerings and advancing our communication strategies, and continuing the initiatives that strive to make diversity seamless and a part of everything we do.

As many know, I have a very strong passion for the work of the CHEST Foundation, and, throughout my presidency, I will focus on how CHEST can support and integrate with the Foundation’s goal of improving patient care – whether it’s through supporting clinical research grants, expanding patient education and advocacy events, or through funding programs like the First 5 Minutes™, which touches on strengthening the rapport and trust between clinician and patient and enhances cultural competency by building an understanding of barriers to care. I can also see increasing patient involvement in CHEST to lend a unique perspective to upcoming initiatives.

Another key focus will be to strengthen and expand our membership through many venues.

We will focus on increasing physician membership of both new members and lapsed members but will also focus on increasing membership of those other providers who help us care for our patients, including advanced practice providers, respiratory therapists and more. CHEST is already an inclusive organization to a variety of health care providers, but we can do more.

My presidency will also focus on increasing collaborations with our sister societies to find new ways to reach fellows-in-training, as well as residents and medical students who are interested in pulmonary, critical care, or sleep medicine.

Along those lines, I’m also planning a dedicated focus on providing more opportunities to fellows and early career members. The goal is to enhance communications between trainees and key thought-leaders in a way that is simple, seamless, and welcoming. CHEST already does this better than anyone else, but an expanded offering, particularly in the area of career development, can help reach even more individuals – both on a national and on an international level. One such event was our successful Young Professionals Event at the Belmont event in New York City this past June.
 

What do you consider to be the greatest strength of CHEST, and how will you build upon this during your presidency?

CHEST has many strengths, but I think our greatest is the strength of our team – our members, our faculty, our volunteer leaders, and our staff.

To build on this, my presidency will include a strong communications strategy to reach, educate, and share the variety of opportunities with our members. I want to build on some of the excellent initiatives Dr. David Schulman started this year to continue engaging and showing our newer members, or soon-to-be members how to get involved with CHEST.
 

What are some challenges facing CHEST, and how will you address these challenges?

A challenge for all associations, CHEST included, will be redefining what associations look like in the wake of a global pandemic now that virtual and hybrid learning has become a part of what we do on a day-to-day basis. What will the CHEST Annual Meeting look like 3 years from now? What will keep learners coming to a physical meeting when so much is accessible on the internet? What will keep members engaged in settings where we no longer get together in-person – like the board review that is now virtual?

This all will take a lot of strategy, which is already being worked on. It will include ideas like enhancing the networking opportunities to extend beyond the annual meeting, strengthening our international strategy, and continuing to innovate in the area of medical education.
 

And finally, what do you ask of the members and Fellows of CHEST to support you during your presidency?

I ask that everyone get involved. Please reach out if you have questions. I am (and all our leaders are) very accessible and we can connect you with the right people to get you engaged. Also, please spread the word. Tell your colleagues, trainees, etc., how great CHEST is and get them involved with CHEST too. We have so much to offer.#

Starting January 1, 2023, current President-Elect Doreen J. Addrizzo-Harris, MD, FCCP, will become the new President of the American College of Chest Physicians. Dr. Addrizzo-Harris is a pulmonary/critical care physician with an extensive background in bronchiectasis and nontuberculous mycobacterial infection and medical education working as a Professor of Medicine at the NYU Grossman School of Medicine.

Before she steps into the role of President, we spoke with Dr. Addrizzo-Harris for a glimpse into what she looks to bring to the CHEST organization.

What would you like to accomplish as President of CHEST?

For my presidency, I want to continue the great trajectory CHEST is on by focusing on increasing membership, expanding our educational offerings and advancing our communication strategies, and continuing the initiatives that strive to make diversity seamless and a part of everything we do.

As many know, I have a very strong passion for the work of the CHEST Foundation, and, throughout my presidency, I will focus on how CHEST can support and integrate with the Foundation’s goal of improving patient care – whether it’s through supporting clinical research grants, expanding patient education and advocacy events, or through funding programs like the First 5 Minutes™, which touches on strengthening the rapport and trust between clinician and patient and enhances cultural competency by building an understanding of barriers to care. I can also see increasing patient involvement in CHEST to lend a unique perspective to upcoming initiatives.

Another key focus will be to strengthen and expand our membership through many venues.

We will focus on increasing physician membership of both new members and lapsed members but will also focus on increasing membership of those other providers who help us care for our patients, including advanced practice providers, respiratory therapists and more. CHEST is already an inclusive organization to a variety of health care providers, but we can do more.

My presidency will also focus on increasing collaborations with our sister societies to find new ways to reach fellows-in-training, as well as residents and medical students who are interested in pulmonary, critical care, or sleep medicine.

Along those lines, I’m also planning a dedicated focus on providing more opportunities to fellows and early career members. The goal is to enhance communications between trainees and key thought-leaders in a way that is simple, seamless, and welcoming. CHEST already does this better than anyone else, but an expanded offering, particularly in the area of career development, can help reach even more individuals – both on a national and on an international level. One such event was our successful Young Professionals Event at the Belmont event in New York City this past June.
 

What do you consider to be the greatest strength of CHEST, and how will you build upon this during your presidency?

CHEST has many strengths, but I think our greatest is the strength of our team – our members, our faculty, our volunteer leaders, and our staff.

To build on this, my presidency will include a strong communications strategy to reach, educate, and share the variety of opportunities with our members. I want to build on some of the excellent initiatives Dr. David Schulman started this year to continue engaging and showing our newer members, or soon-to-be members how to get involved with CHEST.
 

What are some challenges facing CHEST, and how will you address these challenges?

A challenge for all associations, CHEST included, will be redefining what associations look like in the wake of a global pandemic now that virtual and hybrid learning has become a part of what we do on a day-to-day basis. What will the CHEST Annual Meeting look like 3 years from now? What will keep learners coming to a physical meeting when so much is accessible on the internet? What will keep members engaged in settings where we no longer get together in-person – like the board review that is now virtual?

This all will take a lot of strategy, which is already being worked on. It will include ideas like enhancing the networking opportunities to extend beyond the annual meeting, strengthening our international strategy, and continuing to innovate in the area of medical education.
 

And finally, what do you ask of the members and Fellows of CHEST to support you during your presidency?

I ask that everyone get involved. Please reach out if you have questions. I am (and all our leaders are) very accessible and we can connect you with the right people to get you engaged. Also, please spread the word. Tell your colleagues, trainees, etc., how great CHEST is and get them involved with CHEST too. We have so much to offer.#

PARIS – Desmoid tumors are rare, locally aggressive, soft-tissue tumors for which there is no approved systemic therapy – but a novel drug may become the first.

Nirogacestat, under development by Connecticut-based SpringWorks Therapeutics, is an oral, selective, small-molecule gamma secretase inhibitor that targets the Notch signaling pathway, which is involved in cell differentiation. Desmoid tumors express high levels of Notch, so there is a “clear mechanistic rationale” for using such drugs in these patients.

Now, nirogacestat has shown a significant improvement in progression-free survival (PFS) and also a reduction in symptoms and better quality of life, when compared with placebo in the phase 3 DeFi trial.

The company has said that, by the end of this year, it will file these data for U.S. Food and Drug Administration approval of the drug for use in desmoid tumors.

Trial results were presented at the annual meeting of the European Society for Medical Oncology.

Overall, nirogacestat demonstrated “rapid, sustained, and statistically significant improvements in all primary and secondary endpoints,” study presenter Bernd Kasper, MD, PhD, sarcoma unit, Mannheim (Germany) Cancer Center, told a press conference.

There were “really impressive” reductions in pain scores and symptom burden, as well as improvements in health-related quality of life.

Dr. Kasper highlighted that this is the “first phase 3 trial … to demonstrate a clinical benefit with a gamma secretase inhibitor in any indication.”

With the drug showing a “manageable safety profile,” despite a high rate of ovarian dysfunction, Dr. Kasper believes it “has the potential to become the standard of care for patients with desmoid tumors requiring systemic treatment.”

Asked how long patients could take the drug, he replied, “Usually you take a drug as long as the patient benefits” from it.

“That means as long as there is no progression,” Dr. Kasper said, noting that there are patients from the earlier phase trials of nirogacestat who have been taking the drug “for years.”

However, there is a “very important question that is not answered” by the current study: “How long should we treat our patients?”

Dr. Kasper said to answer that question will require further trials, including those focused on treatment discontinuation.
 

Large trial in rare cancer

DeFi is a “unique study” and “very important in many aspects,” commented Jean-Yves Blay, MD, PhD, professor of medicine at the University Claude Bernard in Lyon, France, in an ESMO press release. Dr. Blay was not involved with the DeFi research.

“The results show benefit for the first time with a novel treatment with a new mode of action in patients where treatment options are currently limited,” he said, adding that the findings are “practice changing.”

Dr. Blay also praised the study for being “smart,” as it showed that large, placebo-controlled trials can be conducted in a rare cancer, and demonstrated the “importance of targeting the right patients with right drug.”

“The success of this study puts even more emphasis on the concept of having patients with rare cancers referred into reference centers, where clinical studies can be accomplished in record times, with the potential to deliver new treatments to patients with orphan diseases,” he said.

Discussing the results following their presentation, Dr. Blay said there are nevertheless a number of different treatment options for desmoid tumors, including sorafenib (Nexavar), and it is not clear whether patients with nonprogressive disease would experience any symptomatic benefit with nirogacestat.

Biomarkers of treatment efficacy and resistance are also required, he continued, and the drug’s long-term toxicity profile needs to be understood. In addition, its impact on ovarian dysfunction, as well as on future pregnancies, is currently unclear.
 

Details of the results

Presenting the study, Dr. Kasper explained that desmoid tumors have a variable presentation and an “unpredictable disease course,” and this together with the lack of approved therapies means they are “challenging to manage.”

Moreover, “due to local and aggressive growth, desmoid tumors can cause pain, disfigurement, and functional problems that can be a real burden for patients,” Dr. Kasper stressed.

Treatment should therefore be individualized to each patient to “optimize tumor control and improve the symptom burden,” he told the audience, including the impact on pain, physical function, and overall quality of life.

Indeed, a recent global consensus-based guideline for the management of desmoid tumors recommended a five-step model for treatment selection based on the level of evidence, overall response rate, PFS rate, ease of administration, and expected toxicity.

The DeFi trial enrolled patients with progressive desmoid tumors, stratified by target tumor location (intra-/extra-abdominal), who either were treatment-naive and not amenable to surgery, or were treatment refractory, or had recurrent disease after one prior line of therapy.

Dr. Kasper said in an interview that they required the patient to have at least 20% disease progression at the tumor sites so that they would include only those “who are in need of treatment.”

He explained that requirement was “quite strict” to ensure they excluded patients with “smaller-scale disease” and those with spontaneous regression, which can occur in desmoid tumors.

In all, 142 patients from 37 sites worldwide were randomly assigned to receive either nirogacestat 150 mg or placebo twice daily in 28-day cycles until radiographic progression, at which point patients were moved into an open-label phase and placebo patients could switch to nirogacestat.

The median age of the patients was 34 years, and two-thirds were female. Dr. Kasper underlined that there was a “rather high” prevalence of multifocal disease, at around 40%.

At the data cutoff for the primary analysis on April 7, nirogacestat was associated with a significant reduction in disease progression, at a median PFS that was not reached vs. 15.1 months for placebo, or a hazard ratio of 0.29 (P < .001).

This effect was seen across all subgroups included in the analysis, including when stratifying patients by age, gender, tumor characteristics, and prior treatment.

The objective response rate was also significantly higher with nirogacestat, at 41% vs. 8% in patients assigned to placebo (P < .001). A complete response was seen in 7% of patients given active treatment vs. 0% of those in the placebo group.

The median time to response was 5.6 months with nirogacestat and 11.1 months for patients given placebo.

Dr. Kasper also showed that nirogacestat was associated with significant reductions in pain severity, compared with placebo at treatment cycle 10, as measured on the Brief Pain Index-Short Form of –1.5 (P < .001).

There were also significant improvements with nirogacestat over placebo in the DT Symptom and DT Impact Scales (P < .001 for both), and on the global health status/quality of life scale (P = .007), physical functioning scale (P < .001), and role functioning scale (P < .001) of the EORTC Quality of Life Questionnaire-Core 30.

After a median exposure of 20.6 months, grade 3 or higher treatment-emergent adverse events were observed in 57% of patients treated with nirogacestat vs. 17% of those given placebo, who had a median treatment exposure of 11.4 months.

The most commonly reported adverse events of any grade with the active drug were diarrhea (84%), nausea (54%), fatigue (51%), and hypophosphatemia (42%), but Dr. Kasper noted that 95% of treatment-emergent adverse events were grade 1 or 2, with the first onset typically during cycle 1.

Ovarian dysfunction was observed in 75% of women of childbearing age, at a median onset at 9 weeks and a median duration of 21 weeks. However, the dysfunction resolved in 74% of patients, including those who continued active therapy.

The study was funded by SpringWorks Therapeutics. Dr. Kasper declares relationships with Bayer, Blueprint, Boehringer Ingelheim, SpringWorks, GSK, PharmaMar, and Ayala.

A version of this article first appeared on Medscape.com.

PARIS – Desmoid tumors are rare, locally aggressive, soft-tissue tumors for which there is no approved systemic therapy – but a novel drug may become the first.

Nirogacestat, under development by Connecticut-based SpringWorks Therapeutics, is an oral, selective, small-molecule gamma secretase inhibitor that targets the Notch signaling pathway, which is involved in cell differentiation. Desmoid tumors express high levels of Notch, so there is a “clear mechanistic rationale” for using such drugs in these patients.

Now, nirogacestat has shown a significant improvement in progression-free survival (PFS) and also a reduction in symptoms and better quality of life, when compared with placebo in the phase 3 DeFi trial.

The company has said that, by the end of this year, it will file these data for U.S. Food and Drug Administration approval of the drug for use in desmoid tumors.

Trial results were presented at the annual meeting of the European Society for Medical Oncology.

Overall, nirogacestat demonstrated “rapid, sustained, and statistically significant improvements in all primary and secondary endpoints,” study presenter Bernd Kasper, MD, PhD, sarcoma unit, Mannheim (Germany) Cancer Center, told a press conference.

There were “really impressive” reductions in pain scores and symptom burden, as well as improvements in health-related quality of life.

Dr. Kasper highlighted that this is the “first phase 3 trial … to demonstrate a clinical benefit with a gamma secretase inhibitor in any indication.”

With the drug showing a “manageable safety profile,” despite a high rate of ovarian dysfunction, Dr. Kasper believes it “has the potential to become the standard of care for patients with desmoid tumors requiring systemic treatment.”

Asked how long patients could take the drug, he replied, “Usually you take a drug as long as the patient benefits” from it.

“That means as long as there is no progression,” Dr. Kasper said, noting that there are patients from the earlier phase trials of nirogacestat who have been taking the drug “for years.”

However, there is a “very important question that is not answered” by the current study: “How long should we treat our patients?”

Dr. Kasper said to answer that question will require further trials, including those focused on treatment discontinuation.
 

Large trial in rare cancer

DeFi is a “unique study” and “very important in many aspects,” commented Jean-Yves Blay, MD, PhD, professor of medicine at the University Claude Bernard in Lyon, France, in an ESMO press release. Dr. Blay was not involved with the DeFi research.

“The results show benefit for the first time with a novel treatment with a new mode of action in patients where treatment options are currently limited,” he said, adding that the findings are “practice changing.”

Dr. Blay also praised the study for being “smart,” as it showed that large, placebo-controlled trials can be conducted in a rare cancer, and demonstrated the “importance of targeting the right patients with right drug.”

“The success of this study puts even more emphasis on the concept of having patients with rare cancers referred into reference centers, where clinical studies can be accomplished in record times, with the potential to deliver new treatments to patients with orphan diseases,” he said.

Discussing the results following their presentation, Dr. Blay said there are nevertheless a number of different treatment options for desmoid tumors, including sorafenib (Nexavar), and it is not clear whether patients with nonprogressive disease would experience any symptomatic benefit with nirogacestat.

Biomarkers of treatment efficacy and resistance are also required, he continued, and the drug’s long-term toxicity profile needs to be understood. In addition, its impact on ovarian dysfunction, as well as on future pregnancies, is currently unclear.
 

Details of the results

Presenting the study, Dr. Kasper explained that desmoid tumors have a variable presentation and an “unpredictable disease course,” and this together with the lack of approved therapies means they are “challenging to manage.”

Moreover, “due to local and aggressive growth, desmoid tumors can cause pain, disfigurement, and functional problems that can be a real burden for patients,” Dr. Kasper stressed.

Treatment should therefore be individualized to each patient to “optimize tumor control and improve the symptom burden,” he told the audience, including the impact on pain, physical function, and overall quality of life.

Indeed, a recent global consensus-based guideline for the management of desmoid tumors recommended a five-step model for treatment selection based on the level of evidence, overall response rate, PFS rate, ease of administration, and expected toxicity.

The DeFi trial enrolled patients with progressive desmoid tumors, stratified by target tumor location (intra-/extra-abdominal), who either were treatment-naive and not amenable to surgery, or were treatment refractory, or had recurrent disease after one prior line of therapy.

Dr. Kasper said in an interview that they required the patient to have at least 20% disease progression at the tumor sites so that they would include only those “who are in need of treatment.”

He explained that requirement was “quite strict” to ensure they excluded patients with “smaller-scale disease” and those with spontaneous regression, which can occur in desmoid tumors.

In all, 142 patients from 37 sites worldwide were randomly assigned to receive either nirogacestat 150 mg or placebo twice daily in 28-day cycles until radiographic progression, at which point patients were moved into an open-label phase and placebo patients could switch to nirogacestat.

The median age of the patients was 34 years, and two-thirds were female. Dr. Kasper underlined that there was a “rather high” prevalence of multifocal disease, at around 40%.

At the data cutoff for the primary analysis on April 7, nirogacestat was associated with a significant reduction in disease progression, at a median PFS that was not reached vs. 15.1 months for placebo, or a hazard ratio of 0.29 (P < .001).

This effect was seen across all subgroups included in the analysis, including when stratifying patients by age, gender, tumor characteristics, and prior treatment.

The objective response rate was also significantly higher with nirogacestat, at 41% vs. 8% in patients assigned to placebo (P < .001). A complete response was seen in 7% of patients given active treatment vs. 0% of those in the placebo group.

The median time to response was 5.6 months with nirogacestat and 11.1 months for patients given placebo.

Dr. Kasper also showed that nirogacestat was associated with significant reductions in pain severity, compared with placebo at treatment cycle 10, as measured on the Brief Pain Index-Short Form of –1.5 (P < .001).

There were also significant improvements with nirogacestat over placebo in the DT Symptom and DT Impact Scales (P < .001 for both), and on the global health status/quality of life scale (P = .007), physical functioning scale (P < .001), and role functioning scale (P < .001) of the EORTC Quality of Life Questionnaire-Core 30.

After a median exposure of 20.6 months, grade 3 or higher treatment-emergent adverse events were observed in 57% of patients treated with nirogacestat vs. 17% of those given placebo, who had a median treatment exposure of 11.4 months.

The most commonly reported adverse events of any grade with the active drug were diarrhea (84%), nausea (54%), fatigue (51%), and hypophosphatemia (42%), but Dr. Kasper noted that 95% of treatment-emergent adverse events were grade 1 or 2, with the first onset typically during cycle 1.

Ovarian dysfunction was observed in 75% of women of childbearing age, at a median onset at 9 weeks and a median duration of 21 weeks. However, the dysfunction resolved in 74% of patients, including those who continued active therapy.

The study was funded by SpringWorks Therapeutics. Dr. Kasper declares relationships with Bayer, Blueprint, Boehringer Ingelheim, SpringWorks, GSK, PharmaMar, and Ayala.

A version of this article first appeared on Medscape.com.

PARIS – Desmoid tumors are rare, locally aggressive, soft-tissue tumors for which there is no approved systemic therapy – but a novel drug may become the first.

Nirogacestat, under development by Connecticut-based SpringWorks Therapeutics, is an oral, selective, small-molecule gamma secretase inhibitor that targets the Notch signaling pathway, which is involved in cell differentiation. Desmoid tumors express high levels of Notch, so there is a “clear mechanistic rationale” for using such drugs in these patients.

Now, nirogacestat has shown a significant improvement in progression-free survival (PFS) and also a reduction in symptoms and better quality of life, when compared with placebo in the phase 3 DeFi trial.

The company has said that, by the end of this year, it will file these data for U.S. Food and Drug Administration approval of the drug for use in desmoid tumors.

Trial results were presented at the annual meeting of the European Society for Medical Oncology.

Overall, nirogacestat demonstrated “rapid, sustained, and statistically significant improvements in all primary and secondary endpoints,” study presenter Bernd Kasper, MD, PhD, sarcoma unit, Mannheim (Germany) Cancer Center, told a press conference.

There were “really impressive” reductions in pain scores and symptom burden, as well as improvements in health-related quality of life.

Dr. Kasper highlighted that this is the “first phase 3 trial … to demonstrate a clinical benefit with a gamma secretase inhibitor in any indication.”

With the drug showing a “manageable safety profile,” despite a high rate of ovarian dysfunction, Dr. Kasper believes it “has the potential to become the standard of care for patients with desmoid tumors requiring systemic treatment.”

Asked how long patients could take the drug, he replied, “Usually you take a drug as long as the patient benefits” from it.

“That means as long as there is no progression,” Dr. Kasper said, noting that there are patients from the earlier phase trials of nirogacestat who have been taking the drug “for years.”

However, there is a “very important question that is not answered” by the current study: “How long should we treat our patients?”

Dr. Kasper said to answer that question will require further trials, including those focused on treatment discontinuation.
 

Large trial in rare cancer

DeFi is a “unique study” and “very important in many aspects,” commented Jean-Yves Blay, MD, PhD, professor of medicine at the University Claude Bernard in Lyon, France, in an ESMO press release. Dr. Blay was not involved with the DeFi research.

“The results show benefit for the first time with a novel treatment with a new mode of action in patients where treatment options are currently limited,” he said, adding that the findings are “practice changing.”

Dr. Blay also praised the study for being “smart,” as it showed that large, placebo-controlled trials can be conducted in a rare cancer, and demonstrated the “importance of targeting the right patients with right drug.”

“The success of this study puts even more emphasis on the concept of having patients with rare cancers referred into reference centers, where clinical studies can be accomplished in record times, with the potential to deliver new treatments to patients with orphan diseases,” he said.

Discussing the results following their presentation, Dr. Blay said there are nevertheless a number of different treatment options for desmoid tumors, including sorafenib (Nexavar), and it is not clear whether patients with nonprogressive disease would experience any symptomatic benefit with nirogacestat.

Biomarkers of treatment efficacy and resistance are also required, he continued, and the drug’s long-term toxicity profile needs to be understood. In addition, its impact on ovarian dysfunction, as well as on future pregnancies, is currently unclear.
 

Details of the results

Presenting the study, Dr. Kasper explained that desmoid tumors have a variable presentation and an “unpredictable disease course,” and this together with the lack of approved therapies means they are “challenging to manage.”

Moreover, “due to local and aggressive growth, desmoid tumors can cause pain, disfigurement, and functional problems that can be a real burden for patients,” Dr. Kasper stressed.

Treatment should therefore be individualized to each patient to “optimize tumor control and improve the symptom burden,” he told the audience, including the impact on pain, physical function, and overall quality of life.

Indeed, a recent global consensus-based guideline for the management of desmoid tumors recommended a five-step model for treatment selection based on the level of evidence, overall response rate, PFS rate, ease of administration, and expected toxicity.

The DeFi trial enrolled patients with progressive desmoid tumors, stratified by target tumor location (intra-/extra-abdominal), who either were treatment-naive and not amenable to surgery, or were treatment refractory, or had recurrent disease after one prior line of therapy.

Dr. Kasper said in an interview that they required the patient to have at least 20% disease progression at the tumor sites so that they would include only those “who are in need of treatment.”

He explained that requirement was “quite strict” to ensure they excluded patients with “smaller-scale disease” and those with spontaneous regression, which can occur in desmoid tumors.

In all, 142 patients from 37 sites worldwide were randomly assigned to receive either nirogacestat 150 mg or placebo twice daily in 28-day cycles until radiographic progression, at which point patients were moved into an open-label phase and placebo patients could switch to nirogacestat.

The median age of the patients was 34 years, and two-thirds were female. Dr. Kasper underlined that there was a “rather high” prevalence of multifocal disease, at around 40%.

At the data cutoff for the primary analysis on April 7, nirogacestat was associated with a significant reduction in disease progression, at a median PFS that was not reached vs. 15.1 months for placebo, or a hazard ratio of 0.29 (P < .001).

This effect was seen across all subgroups included in the analysis, including when stratifying patients by age, gender, tumor characteristics, and prior treatment.

The objective response rate was also significantly higher with nirogacestat, at 41% vs. 8% in patients assigned to placebo (P < .001). A complete response was seen in 7% of patients given active treatment vs. 0% of those in the placebo group.

The median time to response was 5.6 months with nirogacestat and 11.1 months for patients given placebo.

Dr. Kasper also showed that nirogacestat was associated with significant reductions in pain severity, compared with placebo at treatment cycle 10, as measured on the Brief Pain Index-Short Form of –1.5 (P < .001).

There were also significant improvements with nirogacestat over placebo in the DT Symptom and DT Impact Scales (P < .001 for both), and on the global health status/quality of life scale (P = .007), physical functioning scale (P < .001), and role functioning scale (P < .001) of the EORTC Quality of Life Questionnaire-Core 30.

After a median exposure of 20.6 months, grade 3 or higher treatment-emergent adverse events were observed in 57% of patients treated with nirogacestat vs. 17% of those given placebo, who had a median treatment exposure of 11.4 months.

The most commonly reported adverse events of any grade with the active drug were diarrhea (84%), nausea (54%), fatigue (51%), and hypophosphatemia (42%), but Dr. Kasper noted that 95% of treatment-emergent adverse events were grade 1 or 2, with the first onset typically during cycle 1.

Ovarian dysfunction was observed in 75% of women of childbearing age, at a median onset at 9 weeks and a median duration of 21 weeks. However, the dysfunction resolved in 74% of patients, including those who continued active therapy.

The study was funded by SpringWorks Therapeutics. Dr. Kasper declares relationships with Bayer, Blueprint, Boehringer Ingelheim, SpringWorks, GSK, PharmaMar, and Ayala.

A version of this article first appeared on Medscape.com.

New York Governor Kathy Hochul declared a state disaster emergency on Sept. 9 after the polio virus has been detected in another county. The order allows EMS workers, midwives, and pharmacists to administer the vaccine and permits physicians and nurse practitioners to issue standing orders for polio vaccines.

“On polio, we simply cannot roll the dice,” New York State Health Commissioner Dr. Mary T. Bassett said in a news release. “If you or your child are unvaccinated or not up to date with vaccinations, the risk of paralytic disease is real. I urge New Yorkers to not accept any risk at all.”

In July, an unvaccinated adult man in Rockland County, which is north of New York City, was diagnosed with polio virus. It was the first confirmed case of the virus in the United States since 2013.

New York state health officials have not announced any additional polio cases. Since as early as April, polio has also been detected in wastewater samples in New York City and in Rockland, Orange, and Sullivan counties. In August, the virus was detected in wastewater from Nassau County on Long Island.

New York’s statewide polio vaccination rate is 79%, and the New York State Department of Health is aiming for a rate over 90%, the announcement said. In some counties, vaccination rates are far below the state average, including Rockland County (60%), Orange County (59%), and Sullivan County (62%). Nassau County’s polio vaccination rate is similar to the state average.

“Polio immunization is safe and effective – protecting nearly all people against disease who receive the recommended doses,” Dr. Basset said; “Do not wait to vaccinate.”

A version of this article first appeared on Medscape.com.

New York Governor Kathy Hochul declared a state disaster emergency on Sept. 9 after the polio virus has been detected in another county. The order allows EMS workers, midwives, and pharmacists to administer the vaccine and permits physicians and nurse practitioners to issue standing orders for polio vaccines.

“On polio, we simply cannot roll the dice,” New York State Health Commissioner Dr. Mary T. Bassett said in a news release. “If you or your child are unvaccinated or not up to date with vaccinations, the risk of paralytic disease is real. I urge New Yorkers to not accept any risk at all.”

In July, an unvaccinated adult man in Rockland County, which is north of New York City, was diagnosed with polio virus. It was the first confirmed case of the virus in the United States since 2013.

New York state health officials have not announced any additional polio cases. Since as early as April, polio has also been detected in wastewater samples in New York City and in Rockland, Orange, and Sullivan counties. In August, the virus was detected in wastewater from Nassau County on Long Island.

New York’s statewide polio vaccination rate is 79%, and the New York State Department of Health is aiming for a rate over 90%, the announcement said. In some counties, vaccination rates are far below the state average, including Rockland County (60%), Orange County (59%), and Sullivan County (62%). Nassau County’s polio vaccination rate is similar to the state average.

“Polio immunization is safe and effective – protecting nearly all people against disease who receive the recommended doses,” Dr. Basset said; “Do not wait to vaccinate.”

A version of this article first appeared on Medscape.com.

New York Governor Kathy Hochul declared a state disaster emergency on Sept. 9 after the polio virus has been detected in another county. The order allows EMS workers, midwives, and pharmacists to administer the vaccine and permits physicians and nurse practitioners to issue standing orders for polio vaccines.

“On polio, we simply cannot roll the dice,” New York State Health Commissioner Dr. Mary T. Bassett said in a news release. “If you or your child are unvaccinated or not up to date with vaccinations, the risk of paralytic disease is real. I urge New Yorkers to not accept any risk at all.”

In July, an unvaccinated adult man in Rockland County, which is north of New York City, was diagnosed with polio virus. It was the first confirmed case of the virus in the United States since 2013.

New York state health officials have not announced any additional polio cases. Since as early as April, polio has also been detected in wastewater samples in New York City and in Rockland, Orange, and Sullivan counties. In August, the virus was detected in wastewater from Nassau County on Long Island.

New York’s statewide polio vaccination rate is 79%, and the New York State Department of Health is aiming for a rate over 90%, the announcement said. In some counties, vaccination rates are far below the state average, including Rockland County (60%), Orange County (59%), and Sullivan County (62%). Nassau County’s polio vaccination rate is similar to the state average.

“Polio immunization is safe and effective – protecting nearly all people against disease who receive the recommended doses,” Dr. Basset said; “Do not wait to vaccinate.”

A version of this article first appeared on Medscape.com.

After 8 weeks, eight out of ten people with seborrheic dermatitis saw their symptoms cleared or improved with once-daily treatment with roflumilast 0.3% foam, according to the results of the phase 3 STRATUM trial.

More than half experienced clearance of their symptoms, and three out of five achieved a significant improvement in pruritus, it was revealed during a late-breaking session at the annual congress of the European Academy of Dermatology and Venereology.
 

Common condition led to rapid recruitment

“Seborrheic dermatitis is a disease that’s very common, yet in my opinion, undertreated in dermatology,” said Andrew Blauvelt, MD, MBA, who presented the findings.

“It’s so common that when we did this trial, I was very surprised to see how easy it was to recruit,” said Dr. Blauvelt, a dermatologist who is president of the Oregon Medical Research Center, Portland. “Patients came in rapidly, out of the woodwork – they were desperate.”

While there are several tried and tested treatments for the condition, such as topical steroids and antifungal agents, he noted that they have their limitations: “Sometimes efficacy, sometimes the ability to be used on hair-bearing areas.”

Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor that is available for topical use in a 0.3% cream formulation (Zoryve). This formulation gained FDA approval for plaque psoriasis for patients ages 12 and older this summer and is also under investigation as a treatment for atopic dermatitis.

It’s the same product in both preparations, Dr. Blauvelt said during the discussion period. “The only major difference between the cream and the foam is the propellant used to make it into a foam. Otherwise, they have the exact same list of ingredients.”

Dr. Blauvelt reported that just over 450 patients had been recruited at 53 U.S. centers into the 8-week, double-blind, placebo-controlled trial.  

For inclusion, patients had to have moderate seborrheic dermatitis, defined as an Investigator’s Global Assessment (IGA) score of three or more. Dr. Blauvelt noted that patients as young as 9 years old could be recruited, and there was no upper age limit. The average age of participating patients, however, was around 42 years. 

Multiple improvements seen in ‘happy trial’

The primary endpoint was an IGA score of 0 or 1 with at least a 2-grade improvement (IGA success) after 8 weeks of treatment. This was achieved by 80% of patients who were treated with roflumilast 0.3% foam, compared with 60% of those who were treated with the vehicle (P less than .0001).

Dr. Blauvelt pointed out that significant improvements had also been seen after 2 weeks (about 42% vs. about 26%; P = .0003) and 4 weeks (about 72% vs. about 49%; P less than .0001) of treatment.

“Now if we raise the bar a little higher” and ask how many patients were completely clear of their seborrheic dermatitis, Dr. Blauvelt said, it was 50% at 8 weeks, more than a third at 4 weeks, over 15% at 2 weeks with the foam, and significantly lower at just under 30%, 15%, and 7% in the vehicle group.

A 4-point or more improvement in the Worst Itch Numeric Rating Scale (WI-NRS) – accepted as the minimally clinically important difference – was achieved by more than 60% of patients treated with the foam at week 8, just under 50% at week 4, and just over 30% at week 2. Corresponding rates in the vehicle group were around 40%, 30%, and 15%.

“Many patients responded in this trial. So much so that when I was doing it, I called it the ‘happy trial.’ Every time I saw patients in this trial, they seemed to be happy,” Dr. Blauvelt said anecdotally.

“In terms of adverse events, the drug turned out to be very safe, and there didn’t seem to be any issues with any things that we see with, for example, oral phosphodiesterase inhibitors,” he added.

The tolerability findings suggest that the foam vehicle “was an excellent vehicle to be used for this particular drug,” with no signs of skin irritation, as rated by patients or investigators.
 

Lesson for practice: Advise patients to moisturize?

“It seems like the vehicle would be a good skincare product for patients,” observed the session’s cochair, Jo Lambert, MD, PhD, professor and academic head of the department of dermatology at Ghent University Hospital, Belgium.

It was “a pretty dramatic vehicle response, right?” Dr. Blauvelt responded. “We normally don’t think of telling seborrheic dermatitis patients to moisturize,” he added.

“I think one of the interesting findings is perhaps we should be telling them to moisturize their scalp or moisturize their face, or it could be something unique to this particular foam.”

The study was funded by Arcutis Biotherapeutics. Dr. Blauvelt disclosed that he was an investigator for the trial and acted as consultant to the company, receiving grants/research funding and/or honoraria. Several of the study’s co-investigators are employees of Arcutis. Dr. Lambert was not involved in the study and cochaired the late-breaking session during which the STRATUM trial findings were reported.

A version of this article first appeared on Medscape.com.

After 8 weeks, eight out of ten people with seborrheic dermatitis saw their symptoms cleared or improved with once-daily treatment with roflumilast 0.3% foam, according to the results of the phase 3 STRATUM trial.

More than half experienced clearance of their symptoms, and three out of five achieved a significant improvement in pruritus, it was revealed during a late-breaking session at the annual congress of the European Academy of Dermatology and Venereology.
 

Common condition led to rapid recruitment

“Seborrheic dermatitis is a disease that’s very common, yet in my opinion, undertreated in dermatology,” said Andrew Blauvelt, MD, MBA, who presented the findings.

“It’s so common that when we did this trial, I was very surprised to see how easy it was to recruit,” said Dr. Blauvelt, a dermatologist who is president of the Oregon Medical Research Center, Portland. “Patients came in rapidly, out of the woodwork – they were desperate.”

While there are several tried and tested treatments for the condition, such as topical steroids and antifungal agents, he noted that they have their limitations: “Sometimes efficacy, sometimes the ability to be used on hair-bearing areas.”

Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor that is available for topical use in a 0.3% cream formulation (Zoryve). This formulation gained FDA approval for plaque psoriasis for patients ages 12 and older this summer and is also under investigation as a treatment for atopic dermatitis.

It’s the same product in both preparations, Dr. Blauvelt said during the discussion period. “The only major difference between the cream and the foam is the propellant used to make it into a foam. Otherwise, they have the exact same list of ingredients.”

Dr. Blauvelt reported that just over 450 patients had been recruited at 53 U.S. centers into the 8-week, double-blind, placebo-controlled trial.  

For inclusion, patients had to have moderate seborrheic dermatitis, defined as an Investigator’s Global Assessment (IGA) score of three or more. Dr. Blauvelt noted that patients as young as 9 years old could be recruited, and there was no upper age limit. The average age of participating patients, however, was around 42 years. 

Multiple improvements seen in ‘happy trial’

The primary endpoint was an IGA score of 0 or 1 with at least a 2-grade improvement (IGA success) after 8 weeks of treatment. This was achieved by 80% of patients who were treated with roflumilast 0.3% foam, compared with 60% of those who were treated with the vehicle (P less than .0001).

Dr. Blauvelt pointed out that significant improvements had also been seen after 2 weeks (about 42% vs. about 26%; P = .0003) and 4 weeks (about 72% vs. about 49%; P less than .0001) of treatment.

“Now if we raise the bar a little higher” and ask how many patients were completely clear of their seborrheic dermatitis, Dr. Blauvelt said, it was 50% at 8 weeks, more than a third at 4 weeks, over 15% at 2 weeks with the foam, and significantly lower at just under 30%, 15%, and 7% in the vehicle group.

A 4-point or more improvement in the Worst Itch Numeric Rating Scale (WI-NRS) – accepted as the minimally clinically important difference – was achieved by more than 60% of patients treated with the foam at week 8, just under 50% at week 4, and just over 30% at week 2. Corresponding rates in the vehicle group were around 40%, 30%, and 15%.

“Many patients responded in this trial. So much so that when I was doing it, I called it the ‘happy trial.’ Every time I saw patients in this trial, they seemed to be happy,” Dr. Blauvelt said anecdotally.

“In terms of adverse events, the drug turned out to be very safe, and there didn’t seem to be any issues with any things that we see with, for example, oral phosphodiesterase inhibitors,” he added.

The tolerability findings suggest that the foam vehicle “was an excellent vehicle to be used for this particular drug,” with no signs of skin irritation, as rated by patients or investigators.
 

Lesson for practice: Advise patients to moisturize?

“It seems like the vehicle would be a good skincare product for patients,” observed the session’s cochair, Jo Lambert, MD, PhD, professor and academic head of the department of dermatology at Ghent University Hospital, Belgium.

It was “a pretty dramatic vehicle response, right?” Dr. Blauvelt responded. “We normally don’t think of telling seborrheic dermatitis patients to moisturize,” he added.

“I think one of the interesting findings is perhaps we should be telling them to moisturize their scalp or moisturize their face, or it could be something unique to this particular foam.”

The study was funded by Arcutis Biotherapeutics. Dr. Blauvelt disclosed that he was an investigator for the trial and acted as consultant to the company, receiving grants/research funding and/or honoraria. Several of the study’s co-investigators are employees of Arcutis. Dr. Lambert was not involved in the study and cochaired the late-breaking session during which the STRATUM trial findings were reported.

A version of this article first appeared on Medscape.com.

After 8 weeks, eight out of ten people with seborrheic dermatitis saw their symptoms cleared or improved with once-daily treatment with roflumilast 0.3% foam, according to the results of the phase 3 STRATUM trial.

More than half experienced clearance of their symptoms, and three out of five achieved a significant improvement in pruritus, it was revealed during a late-breaking session at the annual congress of the European Academy of Dermatology and Venereology.
 

Common condition led to rapid recruitment

“Seborrheic dermatitis is a disease that’s very common, yet in my opinion, undertreated in dermatology,” said Andrew Blauvelt, MD, MBA, who presented the findings.

“It’s so common that when we did this trial, I was very surprised to see how easy it was to recruit,” said Dr. Blauvelt, a dermatologist who is president of the Oregon Medical Research Center, Portland. “Patients came in rapidly, out of the woodwork – they were desperate.”

While there are several tried and tested treatments for the condition, such as topical steroids and antifungal agents, he noted that they have their limitations: “Sometimes efficacy, sometimes the ability to be used on hair-bearing areas.”

Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor that is available for topical use in a 0.3% cream formulation (Zoryve). This formulation gained FDA approval for plaque psoriasis for patients ages 12 and older this summer and is also under investigation as a treatment for atopic dermatitis.

It’s the same product in both preparations, Dr. Blauvelt said during the discussion period. “The only major difference between the cream and the foam is the propellant used to make it into a foam. Otherwise, they have the exact same list of ingredients.”

Dr. Blauvelt reported that just over 450 patients had been recruited at 53 U.S. centers into the 8-week, double-blind, placebo-controlled trial.  

For inclusion, patients had to have moderate seborrheic dermatitis, defined as an Investigator’s Global Assessment (IGA) score of three or more. Dr. Blauvelt noted that patients as young as 9 years old could be recruited, and there was no upper age limit. The average age of participating patients, however, was around 42 years. 

Multiple improvements seen in ‘happy trial’

The primary endpoint was an IGA score of 0 or 1 with at least a 2-grade improvement (IGA success) after 8 weeks of treatment. This was achieved by 80% of patients who were treated with roflumilast 0.3% foam, compared with 60% of those who were treated with the vehicle (P less than .0001).

Dr. Blauvelt pointed out that significant improvements had also been seen after 2 weeks (about 42% vs. about 26%; P = .0003) and 4 weeks (about 72% vs. about 49%; P less than .0001) of treatment.

“Now if we raise the bar a little higher” and ask how many patients were completely clear of their seborrheic dermatitis, Dr. Blauvelt said, it was 50% at 8 weeks, more than a third at 4 weeks, over 15% at 2 weeks with the foam, and significantly lower at just under 30%, 15%, and 7% in the vehicle group.

A 4-point or more improvement in the Worst Itch Numeric Rating Scale (WI-NRS) – accepted as the minimally clinically important difference – was achieved by more than 60% of patients treated with the foam at week 8, just under 50% at week 4, and just over 30% at week 2. Corresponding rates in the vehicle group were around 40%, 30%, and 15%.

“Many patients responded in this trial. So much so that when I was doing it, I called it the ‘happy trial.’ Every time I saw patients in this trial, they seemed to be happy,” Dr. Blauvelt said anecdotally.

“In terms of adverse events, the drug turned out to be very safe, and there didn’t seem to be any issues with any things that we see with, for example, oral phosphodiesterase inhibitors,” he added.

The tolerability findings suggest that the foam vehicle “was an excellent vehicle to be used for this particular drug,” with no signs of skin irritation, as rated by patients or investigators.
 

Lesson for practice: Advise patients to moisturize?

“It seems like the vehicle would be a good skincare product for patients,” observed the session’s cochair, Jo Lambert, MD, PhD, professor and academic head of the department of dermatology at Ghent University Hospital, Belgium.

It was “a pretty dramatic vehicle response, right?” Dr. Blauvelt responded. “We normally don’t think of telling seborrheic dermatitis patients to moisturize,” he added.

“I think one of the interesting findings is perhaps we should be telling them to moisturize their scalp or moisturize their face, or it could be something unique to this particular foam.”

The study was funded by Arcutis Biotherapeutics. Dr. Blauvelt disclosed that he was an investigator for the trial and acted as consultant to the company, receiving grants/research funding and/or honoraria. Several of the study’s co-investigators are employees of Arcutis. Dr. Lambert was not involved in the study and cochaired the late-breaking session during which the STRATUM trial findings were reported.

A version of this article first appeared on Medscape.com.

Patients with inflammatory bowel disease (IBD) taking ustekinumab (Stelara) are less likely to have infections as a side effect than those taking tofacitinib (Xeljanz) or anti–tumor necrosis factor-alpha (anti-TNF), researchers say.

Although the risk of infections is not large for any of these drugs, clinicians should nonetheless take it into account, given their similar efficacy, said Ashwin Ananthakrishnan, MD, associate professor of medicine at Massachusetts General Hospital, Boston.

“These findings may not dramatically change prescribing patterns, but in those who may be particularly vulnerable for infection, they could point toward the safer biologic being Stelara,” he told this news organization.

The study by Dr. Ananthakrishnan and his colleagues was published in Clinical Gastroenterology and Hepatology.

Biologic and small-molecule immunosuppressive therapies have emerged as effective treatments for Crohn’s disease and ulcerative colitis, the two conditions that comprise IBD.

But the recent proliferation of drugs in these classes with different mechanisms of action has made prescribing decisions complicated. And because the drugs suppress the immune system, they can make patients vulnerable to infection.

Randomized controlled trials, even those comparing the drugs head to head, have not been large enough to compare safety outcomes with statistical accuracy, Dr. Ananthakrishnan and his colleagues found.
 

Accessing a large, real-world cohort

To help fill this gap, they analyzed data on 89,972,617 people enrolled in Aetna, the nationwide U.S. health insurance plan, from 2008-2019.

They identified 19,096 patients whose IBD was treated with anti-TNF agents, 2,420 with ustekinumab, and 305 with tofacitinib. The number of patients taking tofacitinib is small because it is a newer drug, Dr. Ananthakrishnan said.

They found a higher rate of infection and rate of infection-related hospitalization for the patients taking anti-TNF agents (44% and 7%, respectively), compared with those taking ustekinumab (32% and 4%, respectively) over the course of up to a year.

The researchers adjusted for age, sex, IBD duration, prior corticosteroid use, prior immunomodulator use, prior IBD hospitalization, and comorbidities, after which they then compared the risks of infection.

They found that patients taking ustekinumab were 7% less likely to have any infection than patients taking anti-TNF agents (hazard ratio, 0.93), a statistically significant difference (95% confidence interval, 0.86-0.99; P = .041). The reduction in the risk of infection-related hospitalizations was similar but not statistically significant.

The advantage with ustekinumab over anti-TNF agents was larger for patients with comorbidities. There was a 25% reduction in the risk of infections for patients taking ustekinumab who had a Charlson comorbidity index score of at least 2 and who were younger than 65 years (HRm 0.71; 95% CI, 0.58-0.87; P < .001).

For patients taking tofacitinib, there were no significant differences in the rate of infection (HR, 0.97; 95% CI, 0.75-1.24) or infection-related hospitalizations (HR, 0.59; 95% CI, 0.27-1.05), compared with TNF-antagonists.

The respiratory system and the urinary tract were the most common sites of infections. Bacterial, viral, and fungal infections were similarly distributed in the three groups.
 

Remaining questions

Further research is needed, said Dr. Ananthakrishnan, as “to understand the comparative safety may be particularly important for vulnerable populations, like those who are older or have other underlying comorbidity, where safety is increasingly an important issue.”

The findings are similar to those of other studies comparing infections in association with ustekinumab to anti-TNF medications for related conditions, such as psoriatic arthritis and psoriasis, he said.

Clinicians have seen similar differences among the drugs in clinical practice, said Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at Cleveland Clinic, Ohio, who was not involved in the study.

“It aligns well with what we’ve thought, but it’s nice to see in a publication,” he said in an interview.

The implications of the study are limited, because it was not a prospective randomized trial and because the number of patients taking tofacitinib was so small, Dr. Regueiro added.

Another limitation is that the patients who were admitted to the hospital in this database were not necessarily admitted because of their infections, said Stephen Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who also was not involved in the study.

Dr. Hanauer told this news organization that comparisons with other agents would be helpful.

“They didn’t look at vedolizumab (Entyvio) in this database,” he said. “Entyvio is generally considered to be safer than TNF inhibitors or tofacitinib with fairly comparable safety to ustekinumab.”

Dr. Ananthakrishnan reported financial relationships with Gilead, Ikena Therapeutics, and Sun Pharma. Dr. Regueiro reported financial relationships with AbbVie, BMS, Janssen, UCB, Pfizer, Takeda, Celgene, Genentech, Gilead, UCB, Miraca Labs, Amgen, Celgene, Seres, Allergan, Salix, Prometheus, Lilly, TARGET Pharma Solutions, Alfasigigma, and BMS. Dr. Hanauer reported financial relationships with Janssen Pharmaceuticals, AbbVie, Takeda Pharmaceutical, and Pfizer.

A version of this article first appeared on Medscape.com.

Patients with inflammatory bowel disease (IBD) taking ustekinumab (Stelara) are less likely to have infections as a side effect than those taking tofacitinib (Xeljanz) or anti–tumor necrosis factor-alpha (anti-TNF), researchers say.

Although the risk of infections is not large for any of these drugs, clinicians should nonetheless take it into account, given their similar efficacy, said Ashwin Ananthakrishnan, MD, associate professor of medicine at Massachusetts General Hospital, Boston.

“These findings may not dramatically change prescribing patterns, but in those who may be particularly vulnerable for infection, they could point toward the safer biologic being Stelara,” he told this news organization.

The study by Dr. Ananthakrishnan and his colleagues was published in Clinical Gastroenterology and Hepatology.

Biologic and small-molecule immunosuppressive therapies have emerged as effective treatments for Crohn’s disease and ulcerative colitis, the two conditions that comprise IBD.

But the recent proliferation of drugs in these classes with different mechanisms of action has made prescribing decisions complicated. And because the drugs suppress the immune system, they can make patients vulnerable to infection.

Randomized controlled trials, even those comparing the drugs head to head, have not been large enough to compare safety outcomes with statistical accuracy, Dr. Ananthakrishnan and his colleagues found.
 

Accessing a large, real-world cohort

To help fill this gap, they analyzed data on 89,972,617 people enrolled in Aetna, the nationwide U.S. health insurance plan, from 2008-2019.

They identified 19,096 patients whose IBD was treated with anti-TNF agents, 2,420 with ustekinumab, and 305 with tofacitinib. The number of patients taking tofacitinib is small because it is a newer drug, Dr. Ananthakrishnan said.

They found a higher rate of infection and rate of infection-related hospitalization for the patients taking anti-TNF agents (44% and 7%, respectively), compared with those taking ustekinumab (32% and 4%, respectively) over the course of up to a year.

The researchers adjusted for age, sex, IBD duration, prior corticosteroid use, prior immunomodulator use, prior IBD hospitalization, and comorbidities, after which they then compared the risks of infection.

They found that patients taking ustekinumab were 7% less likely to have any infection than patients taking anti-TNF agents (hazard ratio, 0.93), a statistically significant difference (95% confidence interval, 0.86-0.99; P = .041). The reduction in the risk of infection-related hospitalizations was similar but not statistically significant.

The advantage with ustekinumab over anti-TNF agents was larger for patients with comorbidities. There was a 25% reduction in the risk of infections for patients taking ustekinumab who had a Charlson comorbidity index score of at least 2 and who were younger than 65 years (HRm 0.71; 95% CI, 0.58-0.87; P < .001).

For patients taking tofacitinib, there were no significant differences in the rate of infection (HR, 0.97; 95% CI, 0.75-1.24) or infection-related hospitalizations (HR, 0.59; 95% CI, 0.27-1.05), compared with TNF-antagonists.

The respiratory system and the urinary tract were the most common sites of infections. Bacterial, viral, and fungal infections were similarly distributed in the three groups.
 

Remaining questions

Further research is needed, said Dr. Ananthakrishnan, as “to understand the comparative safety may be particularly important for vulnerable populations, like those who are older or have other underlying comorbidity, where safety is increasingly an important issue.”

The findings are similar to those of other studies comparing infections in association with ustekinumab to anti-TNF medications for related conditions, such as psoriatic arthritis and psoriasis, he said.

Clinicians have seen similar differences among the drugs in clinical practice, said Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at Cleveland Clinic, Ohio, who was not involved in the study.

“It aligns well with what we’ve thought, but it’s nice to see in a publication,” he said in an interview.

The implications of the study are limited, because it was not a prospective randomized trial and because the number of patients taking tofacitinib was so small, Dr. Regueiro added.

Another limitation is that the patients who were admitted to the hospital in this database were not necessarily admitted because of their infections, said Stephen Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who also was not involved in the study.

Dr. Hanauer told this news organization that comparisons with other agents would be helpful.

“They didn’t look at vedolizumab (Entyvio) in this database,” he said. “Entyvio is generally considered to be safer than TNF inhibitors or tofacitinib with fairly comparable safety to ustekinumab.”

Dr. Ananthakrishnan reported financial relationships with Gilead, Ikena Therapeutics, and Sun Pharma. Dr. Regueiro reported financial relationships with AbbVie, BMS, Janssen, UCB, Pfizer, Takeda, Celgene, Genentech, Gilead, UCB, Miraca Labs, Amgen, Celgene, Seres, Allergan, Salix, Prometheus, Lilly, TARGET Pharma Solutions, Alfasigigma, and BMS. Dr. Hanauer reported financial relationships with Janssen Pharmaceuticals, AbbVie, Takeda Pharmaceutical, and Pfizer.

A version of this article first appeared on Medscape.com.

Patients with inflammatory bowel disease (IBD) taking ustekinumab (Stelara) are less likely to have infections as a side effect than those taking tofacitinib (Xeljanz) or anti–tumor necrosis factor-alpha (anti-TNF), researchers say.

Although the risk of infections is not large for any of these drugs, clinicians should nonetheless take it into account, given their similar efficacy, said Ashwin Ananthakrishnan, MD, associate professor of medicine at Massachusetts General Hospital, Boston.

“These findings may not dramatically change prescribing patterns, but in those who may be particularly vulnerable for infection, they could point toward the safer biologic being Stelara,” he told this news organization.

The study by Dr. Ananthakrishnan and his colleagues was published in Clinical Gastroenterology and Hepatology.

Biologic and small-molecule immunosuppressive therapies have emerged as effective treatments for Crohn’s disease and ulcerative colitis, the two conditions that comprise IBD.

But the recent proliferation of drugs in these classes with different mechanisms of action has made prescribing decisions complicated. And because the drugs suppress the immune system, they can make patients vulnerable to infection.

Randomized controlled trials, even those comparing the drugs head to head, have not been large enough to compare safety outcomes with statistical accuracy, Dr. Ananthakrishnan and his colleagues found.
 

Accessing a large, real-world cohort

To help fill this gap, they analyzed data on 89,972,617 people enrolled in Aetna, the nationwide U.S. health insurance plan, from 2008-2019.

They identified 19,096 patients whose IBD was treated with anti-TNF agents, 2,420 with ustekinumab, and 305 with tofacitinib. The number of patients taking tofacitinib is small because it is a newer drug, Dr. Ananthakrishnan said.

They found a higher rate of infection and rate of infection-related hospitalization for the patients taking anti-TNF agents (44% and 7%, respectively), compared with those taking ustekinumab (32% and 4%, respectively) over the course of up to a year.

The researchers adjusted for age, sex, IBD duration, prior corticosteroid use, prior immunomodulator use, prior IBD hospitalization, and comorbidities, after which they then compared the risks of infection.

They found that patients taking ustekinumab were 7% less likely to have any infection than patients taking anti-TNF agents (hazard ratio, 0.93), a statistically significant difference (95% confidence interval, 0.86-0.99; P = .041). The reduction in the risk of infection-related hospitalizations was similar but not statistically significant.

The advantage with ustekinumab over anti-TNF agents was larger for patients with comorbidities. There was a 25% reduction in the risk of infections for patients taking ustekinumab who had a Charlson comorbidity index score of at least 2 and who were younger than 65 years (HRm 0.71; 95% CI, 0.58-0.87; P < .001).

For patients taking tofacitinib, there were no significant differences in the rate of infection (HR, 0.97; 95% CI, 0.75-1.24) or infection-related hospitalizations (HR, 0.59; 95% CI, 0.27-1.05), compared with TNF-antagonists.

The respiratory system and the urinary tract were the most common sites of infections. Bacterial, viral, and fungal infections were similarly distributed in the three groups.
 

Remaining questions

Further research is needed, said Dr. Ananthakrishnan, as “to understand the comparative safety may be particularly important for vulnerable populations, like those who are older or have other underlying comorbidity, where safety is increasingly an important issue.”

The findings are similar to those of other studies comparing infections in association with ustekinumab to anti-TNF medications for related conditions, such as psoriatic arthritis and psoriasis, he said.

Clinicians have seen similar differences among the drugs in clinical practice, said Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at Cleveland Clinic, Ohio, who was not involved in the study.

“It aligns well with what we’ve thought, but it’s nice to see in a publication,” he said in an interview.

The implications of the study are limited, because it was not a prospective randomized trial and because the number of patients taking tofacitinib was so small, Dr. Regueiro added.

Another limitation is that the patients who were admitted to the hospital in this database were not necessarily admitted because of their infections, said Stephen Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who also was not involved in the study.

Dr. Hanauer told this news organization that comparisons with other agents would be helpful.

“They didn’t look at vedolizumab (Entyvio) in this database,” he said. “Entyvio is generally considered to be safer than TNF inhibitors or tofacitinib with fairly comparable safety to ustekinumab.”

Dr. Ananthakrishnan reported financial relationships with Gilead, Ikena Therapeutics, and Sun Pharma. Dr. Regueiro reported financial relationships with AbbVie, BMS, Janssen, UCB, Pfizer, Takeda, Celgene, Genentech, Gilead, UCB, Miraca Labs, Amgen, Celgene, Seres, Allergan, Salix, Prometheus, Lilly, TARGET Pharma Solutions, Alfasigigma, and BMS. Dr. Hanauer reported financial relationships with Janssen Pharmaceuticals, AbbVie, Takeda Pharmaceutical, and Pfizer.

A version of this article first appeared on Medscape.com.

An Italian study of women diagnosed with breast cancer reported that around 50% experienced body image disturbance and 20% noted a negative impact on their sex life. And while meeting with a specialist in psycho-oncology was universally viewed as an acceptable option, only one out of four patients considered consulting a sexologist. All these women should be encouraged to face and address issues related to sexuality so that they can truly regain a good quality of life, the study suggests.

The study, which was conducted at the breast unit of Santa Maria Goretti Hospital in Latina, Italy, enrolled 141 patients who had undergone breast cancer surgery. Participants were asked to complete a questionnaire that included questions regarding self-image, sexual activity, and sexual satisfaction, and it analyzed these aspects before and after treatment. The participants were then asked whether they felt that they needed to see a sexologist or a specialist in psycho-oncology.

The findings clearly showed a worsening in terms of body image perception. When the women were asked about the relationship they had with their body, femininity, and beauty prior to being diagnosed, 37.4% characterized it as very good and 58.9% as “normal,” with ups and downs but nothing that they would term “conflictual.” After diagnosis, 48.9% noted that the disease had an impact on their body image with a partial conditioning about their femininity and beauty. However, 7.2% had difficulty when it came to recognizing their own body, and their relationship with femininity also became difficult.

On the topic of sexuality, 71.2% of patients were completely satisfied with their sex life before they were diagnosed with breast cancer, 23.7% were partially satisfied, and 5.0% were unsatisfied. As for their sex life after diagnosis and surgery, 20.1% stated that it continued to be fulfilling and 55.4% said that it had gotten worse; 18.8% reported significant sexual dissatisfaction.

The participants were asked whether consulting a professional would be warranted, and whether that would provide useful support for overcoming the difficulties and challenges arising from the disease and the related treatments. In response, 97.1% said they would go to a specialist in psycho-oncology, but only 27.3% would seek help from a sexologist.

“Despite the negative impact on body image and on sexuality, few patients would seek the help of a sexologist; nearly all of the patients, however, would seek the help of a specialist in psycho-oncology. This was very surprising to us,” write the authors. They went on to note that they are carrying out another project to understand the reason for this disparity.

In addition, they advised clinicians to encourage communication about sexuality – a topic that is regularly overlooked and not included in discussions with patients, mostly because of cultural barriers. Often, physicians aren’t comfortable talking about sexuality, as they don’t feel they have the proper training to do so. Patients who are experiencing issues related to sexuality also often have difficulty asking for help. And so, in their conclusion, the authors point out that “collaborating together in the right direction is the basis of change and good communication.”

This article was translated from Univadis Italy and appeared on Medscape.com.

An Italian study of women diagnosed with breast cancer reported that around 50% experienced body image disturbance and 20% noted a negative impact on their sex life. And while meeting with a specialist in psycho-oncology was universally viewed as an acceptable option, only one out of four patients considered consulting a sexologist. All these women should be encouraged to face and address issues related to sexuality so that they can truly regain a good quality of life, the study suggests.

The study, which was conducted at the breast unit of Santa Maria Goretti Hospital in Latina, Italy, enrolled 141 patients who had undergone breast cancer surgery. Participants were asked to complete a questionnaire that included questions regarding self-image, sexual activity, and sexual satisfaction, and it analyzed these aspects before and after treatment. The participants were then asked whether they felt that they needed to see a sexologist or a specialist in psycho-oncology.

The findings clearly showed a worsening in terms of body image perception. When the women were asked about the relationship they had with their body, femininity, and beauty prior to being diagnosed, 37.4% characterized it as very good and 58.9% as “normal,” with ups and downs but nothing that they would term “conflictual.” After diagnosis, 48.9% noted that the disease had an impact on their body image with a partial conditioning about their femininity and beauty. However, 7.2% had difficulty when it came to recognizing their own body, and their relationship with femininity also became difficult.

On the topic of sexuality, 71.2% of patients were completely satisfied with their sex life before they were diagnosed with breast cancer, 23.7% were partially satisfied, and 5.0% were unsatisfied. As for their sex life after diagnosis and surgery, 20.1% stated that it continued to be fulfilling and 55.4% said that it had gotten worse; 18.8% reported significant sexual dissatisfaction.

The participants were asked whether consulting a professional would be warranted, and whether that would provide useful support for overcoming the difficulties and challenges arising from the disease and the related treatments. In response, 97.1% said they would go to a specialist in psycho-oncology, but only 27.3% would seek help from a sexologist.

“Despite the negative impact on body image and on sexuality, few patients would seek the help of a sexologist; nearly all of the patients, however, would seek the help of a specialist in psycho-oncology. This was very surprising to us,” write the authors. They went on to note that they are carrying out another project to understand the reason for this disparity.

In addition, they advised clinicians to encourage communication about sexuality – a topic that is regularly overlooked and not included in discussions with patients, mostly because of cultural barriers. Often, physicians aren’t comfortable talking about sexuality, as they don’t feel they have the proper training to do so. Patients who are experiencing issues related to sexuality also often have difficulty asking for help. And so, in their conclusion, the authors point out that “collaborating together in the right direction is the basis of change and good communication.”

This article was translated from Univadis Italy and appeared on Medscape.com.

An Italian study of women diagnosed with breast cancer reported that around 50% experienced body image disturbance and 20% noted a negative impact on their sex life. And while meeting with a specialist in psycho-oncology was universally viewed as an acceptable option, only one out of four patients considered consulting a sexologist. All these women should be encouraged to face and address issues related to sexuality so that they can truly regain a good quality of life, the study suggests.

The study, which was conducted at the breast unit of Santa Maria Goretti Hospital in Latina, Italy, enrolled 141 patients who had undergone breast cancer surgery. Participants were asked to complete a questionnaire that included questions regarding self-image, sexual activity, and sexual satisfaction, and it analyzed these aspects before and after treatment. The participants were then asked whether they felt that they needed to see a sexologist or a specialist in psycho-oncology.

The findings clearly showed a worsening in terms of body image perception. When the women were asked about the relationship they had with their body, femininity, and beauty prior to being diagnosed, 37.4% characterized it as very good and 58.9% as “normal,” with ups and downs but nothing that they would term “conflictual.” After diagnosis, 48.9% noted that the disease had an impact on their body image with a partial conditioning about their femininity and beauty. However, 7.2% had difficulty when it came to recognizing their own body, and their relationship with femininity also became difficult.

On the topic of sexuality, 71.2% of patients were completely satisfied with their sex life before they were diagnosed with breast cancer, 23.7% were partially satisfied, and 5.0% were unsatisfied. As for their sex life after diagnosis and surgery, 20.1% stated that it continued to be fulfilling and 55.4% said that it had gotten worse; 18.8% reported significant sexual dissatisfaction.

The participants were asked whether consulting a professional would be warranted, and whether that would provide useful support for overcoming the difficulties and challenges arising from the disease and the related treatments. In response, 97.1% said they would go to a specialist in psycho-oncology, but only 27.3% would seek help from a sexologist.

“Despite the negative impact on body image and on sexuality, few patients would seek the help of a sexologist; nearly all of the patients, however, would seek the help of a specialist in psycho-oncology. This was very surprising to us,” write the authors. They went on to note that they are carrying out another project to understand the reason for this disparity.

In addition, they advised clinicians to encourage communication about sexuality – a topic that is regularly overlooked and not included in discussions with patients, mostly because of cultural barriers. Often, physicians aren’t comfortable talking about sexuality, as they don’t feel they have the proper training to do so. Patients who are experiencing issues related to sexuality also often have difficulty asking for help. And so, in their conclusion, the authors point out that “collaborating together in the right direction is the basis of change and good communication.”

This article was translated from Univadis Italy and appeared on Medscape.com.

The health benefits of maintaining a physically active lifestyle are vast and irrefutable.¹ Physical activity is an important modifiable behavior demonstrated to reduce the risk for many chronic diseases while improving physical function (TABLE 1²).³ Physical inactivity increases with age, making older adults (ages ≥ 65 years) the least active age group and the group at greatest risk for inactivity-­related health consequences.^4-6 Engaging in a physically active lifestyle is especially important for older adults to maintain independence,⁷ quality of life,⁸ and the ability to perform activities of daily living.^3,9

Prescribe physical activity for older adults

The 2018 Physical Activity Guidelines for Americans recommend that all healthy adults (including healthy older adults) ideally should perform muscle-strengthening activities of moderate or greater intensity that involve all major muscle groups on 2 or more days per week and either (a) 150 to 300 minutes per week of moderate-intensity aerobic physical activity, (b) 75 to 150 minutes per week of vigorous-intensity aerobic physical activity, or (c) an equivalent combination, if possible (TABLE 2²).³ It is recommended that older adults specifically follow a multicomponent physical activity program that includes balance training, as well as aerobic and muscle-strengthening activities.³ Unfortunately, nearly 80% of older adults do not meet the recommended guidelines for aerobic or muscle-strengthening exercise.³

Identify barriers to exercise

Older adults report several barriers that limit physical activity. Some of the most commonly reported barriers include a lack of motivation, low self-efficacy for being active, physical limitations due to health conditions, inconvenient physical activity locations, boredom with physical activity, and lack of guidance from professionals.^10-12 Physical activity programs designed for older adults should specifically target these barriers for maximum effectiveness.

Clinicians also face potential barriers for promoting physical activity among older adults. Screening patients for physical inactivity can be a challenge, given the robust number of clinical preventive services and conversations that are already recommended for older adults. Additionally, screening for physical activity is not a reimbursable service. In July, the US Preventive Services Task Force (USPSTF) reaffirmed its 2017 recommendation to individualize the decision to offer or refer adults without obesity, hypertension, dyslipidemia, or abnormal blood glucose levels or diabetes to behavioral counseling to promote a healthy diet and physical activity (Grade C rating).¹³

Treat physical activity as a vital sign

The Exercise is Medicine (EIM) model is based on the principle that physical activity should be treated as a vital sign and discussed during all health care visits. Health care professionals have a unique opportunity to promote physical activity, since more than 80% of US adults see a physician annually. Evidence also suggests clinician advice is associated with patients’ healthy lifestyle behaviors.^14,15

EIM is a global health initiative that was established in 2007 and is managed by the American College of Sports Medicine (ACSM). The primary objective of the EIM model is to treat physical activity behavior as a vital sign and include physical activity promotion as a standard of clinical care. In order to achieve this objective, the EIM model recommends health care systems follow 3 simple rules: (1) treat physical activity as a vital sign by measuring physical activity of every patient at every visit, (2) prescribe exercise to those patients who report not meeting the physical activity guidelines, and/or (3) refer inactive patients to evidence-based physical activity resources to receive exercise counseling.^16,17

Screen for physical activity using this 2-question self-report

Clinicians may employ multiple tactics to screen patients for their current levels of physical activity. Physical Activity Vital Sign (PAVS) is a 2-item self-report measure developed to briefly assess a patient’s level of physical activity; results can be entered into the patient’s electronic medical record and used to begin a process of referring inactive patients for behavioral counseling.^17,18 The PAVS can be administered in less than 1 minute by a medical assistant and/or nursing staff during rooming or intake of patients. The PAVS questions include, “On average, how many days per week do you engage in moderate-to-vigorous physical activity?” and “On average, how many minutes do you engage in physical activity at this level?” The clinician can then multiply the 2 numbers to calculate the patient’s total minutes of ­moderate-to-vigorous physical activity per week to determine whether a patient is meeting the recommended physical activity guidelines.¹⁶ (For more on the PAVS and other resources, see TABLE 3.)

Continue to: The PAVS has been established...

Approximately 80% of older adults do not meet the recommended guidelines for aerobic or muscle-strengthening exercise.

The PAVS has been established as a valid instrument for detecting patients who may need counseling on physical activity for chronic disease recognition, management, and prevention.¹⁷ Furthermore, there is a strong association between PAVS, elevated body mass index, and chronic disease burden.¹⁹ Therefore, we recommend that primary care physicians screen their patients for physical activity levels. It has been demonstrated, however, that many primary care visits for older individuals include discussions of diet and physical activity but do not provide recommendations for lifestyle change.¹⁹ Thus, exploring ways to counsel patients on lifestyle change in an efficient manner is recommended. It has been demonstrated that counseling and referral from primary care centers can promote increased adherence to physical activity practices.^20,21

Determine physical activity readiness

Prior to recommending a physical activity regimen, it is important to evaluate the patient’s readiness to make a change. Various questionnaires—such as the Physical Activity Readiness Questionnaire—have been developed to determine a patient’s level of readiness, evaluating both psychological and physical factors (www.nasm.org/docs/pdf/parqplus-2020.pdf?sfvrsn=401bf1af_24). Questionnaires also help you to determine whether further medical evaluation prior to beginning an exercise regimen is necessary. It’s important to note that, as is true with any office intervention, patients may be in a precontemplation or contemplation phase and may not be prepared to immediately make changes.

Evaluate risk level

Assess cardiovascular risk. Physicians and patients are often concerned about cardiovascular risk or injury risk during physical activity counseling, which may lead to fewer exercise prescriptions. As a physician, it is important to remember that for most adults, the benefits of exercise will outweigh any potential risks,³ and there is generally a low risk of cardiovascular events related to light to moderate–intensity exercise regimens.² Additionally, it has been demonstrated that exercise and cardiovascular rehabilitation are highly beneficial for primary and secondary prevention of cardiovascular disease.²² Given that cardiovascular comorbidities are relatively common in older adults, some older adults will need to undergo risk stratification evaluation prior to initiating an exercise regimen.

Review preparticipation screening guidelines and recommendations

Guidelines can be contradictory regarding the ideal pre-exercise evaluation. In general, the USPSTF recommends against screening with resting or exercise electrocardiography (EKG) to prevent cardiovascular disease events in asymptomatic adults who are at low risk. It also finds insufficient evidence to assess the balance of benefits and harms of screening with resting or exercise EKG to prevent cardiovascular disease events in asymptomatic adults who are at intermediate or high risk.²²

Similarly, the 2020 ACSM Guidelines for Exercise Testing and Prescription reflect that routine exercise testing is not recommended for all older adult patients prior to starting an exercise regimen.¹⁷ However, the ACSM does recommend all patients with signs or symptoms of a cardiovascular, renal, or metabolic disease consult with a clinician for medical risk stratification and potential subsequent testing prior to starting an exercise regimen. If an individual already exercises and is having new/worsening signs or symptoms of a cardiovascular, renal, or metabolic disease, that patient should cease exercise until medical evaluation is performed. Additionally, ACSM recommends that asymptomatic patients who do not exercise but who have known cardiovascular, renal, or metabolic disease receive medical evaluation prior to starting an exercise regimen.¹⁷

Continue to: Is there evidence of cardiovascular, renal, or metabolic disease?

 

 

Is there evidence of cardiovascular, renal, or metabolic disease?

Initial screening can be completed by obtaining the patient’s history and conducting a physical examination. Patients reporting chest pain or discomfort (or any anginal equivalent), dyspnea, syncope, orthopnea, lower extremity edema, signs of tachyarrhythmia/bradyarrhythmia, intermittent claudication, exertional fatigue, or new exertional symptoms should all be considered for cardiovascular stress testing. Patients with a diagnosis of renal disease or either type 1 or type 2 diabetes should also be considered for cardiovascular stress testing.

Ready to prescribe exercise? Cover these 4 points

When prescribing any exercise plan for older adults, it is important for clinicians to specify 4 key components: frequency, intensity, time, and type (this can be remembered using the acronym “FITT”).²³ A sedentary adult should be encouraged to engage in moderate-­intensity exercise, such as walking, for 15 minutes 3 times per week. The key with a sedentary adult is appropriate follow-up to monitor progression and modify activity to help ensure the patient can achieve the goal number of minutes per week. It can be helpful to share the “next step” with the patient, as well (eg, increase to 4 times per week after 2 weeks, or increase by 5 minutes every week). For the intermittent exerciser, a program of moderate exercise, such as using an elliptical, for 30 to 40 minutes 5 times per week is a recommended prescription. FITT components can be tailored to meet individual patient physical readiness.²³

Frequency. While the 2018 Physical Activity Guidelines for Americans recommend a specific frequency of physical activity throughout the week, it is important to remember that some older adults will be unable to meet these recommendations, particularly in the setting of frailty and comorbidities (TABLE 2²). In these cases, the guidelines simply recommend that older adults should be as physically active as their abilities and comorbidities allow. Some exercise is better than none, and generally moving more and sitting less will yield health benefits for older adult patients.

Intensity is a description of how hard an individual is working during physical activity. An older adult’s individual capacity for exercise intensity will depend on many factors, including their comorbidities. An activity’s intensity will be relative to a person’s unique level of fitness. Given this heterogeneity, exercise prescriptions should be tailored to the individual. Light-intensity exercise generally causes a slight increase in pulse and respiratory rate, moderate-intensity exercise causes a noticeable increase in pulse and respiratory rate, and vigorous-intensity exercise causes a significant increase in pulse and respiratory rate (TABLE 4^2,16,17,24).²

The “talk test” is a simple, practical, and validated test that can help one determine an individual’s capacity for moderate- or ­vigorous-intensity exercise.²³ In general, a person performing vigorous-intensity exercise will be unable to talk comfortably during activity for more than a few words without pausing for breath. Similarly, a person will be able to talk but not sing comfortably during moderate-intensity exercise.^3,23

Continue to: Time

Time. The 2018 Physical Activity Guidelines for Americans recommend a specific duration of physical activity throughout the week; however, as with frequency, it is important to remember that duration of exercise is individualized (TABLE 2²). Older adults should be as physically active as their abilities and comorbidities allow, and in the setting of frailty, numerous comorbidities, and/or a sedentary lifestyle, it is reasonable to initiate exercise recommendations with shorter durations.

The PAVS is a 2-item self-report measure used to quickly assess a patient’s level of physical activity.

Type of exercise. As noted in the 2018 Physical Activity Guidelines for Americans, recommendations for older adults include multiple types of exercise. In addition to these general exercise recommendations, exercise prescriptions can be individualized to target specific comorbidities (TABLE 2²). Weight-bearing, bone-strengthening exercises can benefit patients with disorders of low bone density and possibly those with osteoarthritis.^3,23 Patients at increased risk for falls should focus on balance-training options that strengthen the muscles of the back, abdomen, and legs, such as tai chi.^3,23 Patients with cardiovascular risk can benefit from moderate- to high-intensity aerobic exercise (although exercise should be performed below anginal threshold in patients with known cardiovascular disease). Patients with type 2 diabetes achieve improved glycemic control when engaging in combined moderate-intensity aerobic exercise and resistance training.^7,23

Referral to a physical therapist or sport and exercise medicine specialist can always be considered, particularly for patients with significant neurologic disorders, disability secondary to traumatic injury, or health conditions.³

An improved quality of life. Incorporating physical activity into older adults’ lives can enhance their quality of life. Family physicians are well positioned to counsel older adults on the importance and benefits of exercise and to help them overcome the barriers or resistance to undertaking a change in behavior. Guidelines, recommendations, patient history, and resources provide the support needed to prescribe individualized exercise plans for this distinct population. 

CORRESPONDENCE
Scott T. Larson, MD, 200 Hawkins Drive, Iowa City, IA, 52242; scott-larson@uiowa.edu

The health benefits of maintaining a physically active lifestyle are vast and irrefutable.¹ Physical activity is an important modifiable behavior demonstrated to reduce the risk for many chronic diseases while improving physical function (TABLE 1²).³ Physical inactivity increases with age, making older adults (ages ≥ 65 years) the least active age group and the group at greatest risk for inactivity-­related health consequences.^4-6 Engaging in a physically active lifestyle is especially important for older adults to maintain independence,⁷ quality of life,⁸ and the ability to perform activities of daily living.^3,9

Prescribe physical activity for older adults

The 2018 Physical Activity Guidelines for Americans recommend that all healthy adults (including healthy older adults) ideally should perform muscle-strengthening activities of moderate or greater intensity that involve all major muscle groups on 2 or more days per week and either (a) 150 to 300 minutes per week of moderate-intensity aerobic physical activity, (b) 75 to 150 minutes per week of vigorous-intensity aerobic physical activity, or (c) an equivalent combination, if possible (TABLE 2²).³ It is recommended that older adults specifically follow a multicomponent physical activity program that includes balance training, as well as aerobic and muscle-strengthening activities.³ Unfortunately, nearly 80% of older adults do not meet the recommended guidelines for aerobic or muscle-strengthening exercise.³

Identify barriers to exercise

Older adults report several barriers that limit physical activity. Some of the most commonly reported barriers include a lack of motivation, low self-efficacy for being active, physical limitations due to health conditions, inconvenient physical activity locations, boredom with physical activity, and lack of guidance from professionals.^10-12 Physical activity programs designed for older adults should specifically target these barriers for maximum effectiveness.

Clinicians also face potential barriers for promoting physical activity among older adults. Screening patients for physical inactivity can be a challenge, given the robust number of clinical preventive services and conversations that are already recommended for older adults. Additionally, screening for physical activity is not a reimbursable service. In July, the US Preventive Services Task Force (USPSTF) reaffirmed its 2017 recommendation to individualize the decision to offer or refer adults without obesity, hypertension, dyslipidemia, or abnormal blood glucose levels or diabetes to behavioral counseling to promote a healthy diet and physical activity (Grade C rating).¹³

Treat physical activity as a vital sign

The Exercise is Medicine (EIM) model is based on the principle that physical activity should be treated as a vital sign and discussed during all health care visits. Health care professionals have a unique opportunity to promote physical activity, since more than 80% of US adults see a physician annually. Evidence also suggests clinician advice is associated with patients’ healthy lifestyle behaviors.^14,15

EIM is a global health initiative that was established in 2007 and is managed by the American College of Sports Medicine (ACSM). The primary objective of the EIM model is to treat physical activity behavior as a vital sign and include physical activity promotion as a standard of clinical care. In order to achieve this objective, the EIM model recommends health care systems follow 3 simple rules: (1) treat physical activity as a vital sign by measuring physical activity of every patient at every visit, (2) prescribe exercise to those patients who report not meeting the physical activity guidelines, and/or (3) refer inactive patients to evidence-based physical activity resources to receive exercise counseling.^16,17

Screen for physical activity using this 2-question self-report

Clinicians may employ multiple tactics to screen patients for their current levels of physical activity. Physical Activity Vital Sign (PAVS) is a 2-item self-report measure developed to briefly assess a patient’s level of physical activity; results can be entered into the patient’s electronic medical record and used to begin a process of referring inactive patients for behavioral counseling.^17,18 The PAVS can be administered in less than 1 minute by a medical assistant and/or nursing staff during rooming or intake of patients. The PAVS questions include, “On average, how many days per week do you engage in moderate-to-vigorous physical activity?” and “On average, how many minutes do you engage in physical activity at this level?” The clinician can then multiply the 2 numbers to calculate the patient’s total minutes of ­moderate-to-vigorous physical activity per week to determine whether a patient is meeting the recommended physical activity guidelines.¹⁶ (For more on the PAVS and other resources, see TABLE 3.)

Continue to: The PAVS has been established...

Approximately 80% of older adults do not meet the recommended guidelines for aerobic or muscle-strengthening exercise.

The PAVS has been established as a valid instrument for detecting patients who may need counseling on physical activity for chronic disease recognition, management, and prevention.¹⁷ Furthermore, there is a strong association between PAVS, elevated body mass index, and chronic disease burden.¹⁹ Therefore, we recommend that primary care physicians screen their patients for physical activity levels. It has been demonstrated, however, that many primary care visits for older individuals include discussions of diet and physical activity but do not provide recommendations for lifestyle change.¹⁹ Thus, exploring ways to counsel patients on lifestyle change in an efficient manner is recommended. It has been demonstrated that counseling and referral from primary care centers can promote increased adherence to physical activity practices.^20,21

Determine physical activity readiness

Prior to recommending a physical activity regimen, it is important to evaluate the patient’s readiness to make a change. Various questionnaires—such as the Physical Activity Readiness Questionnaire—have been developed to determine a patient’s level of readiness, evaluating both psychological and physical factors (www.nasm.org/docs/pdf/parqplus-2020.pdf?sfvrsn=401bf1af_24). Questionnaires also help you to determine whether further medical evaluation prior to beginning an exercise regimen is necessary. It’s important to note that, as is true with any office intervention, patients may be in a precontemplation or contemplation phase and may not be prepared to immediately make changes.

Evaluate risk level

Assess cardiovascular risk. Physicians and patients are often concerned about cardiovascular risk or injury risk during physical activity counseling, which may lead to fewer exercise prescriptions. As a physician, it is important to remember that for most adults, the benefits of exercise will outweigh any potential risks,³ and there is generally a low risk of cardiovascular events related to light to moderate–intensity exercise regimens.² Additionally, it has been demonstrated that exercise and cardiovascular rehabilitation are highly beneficial for primary and secondary prevention of cardiovascular disease.²² Given that cardiovascular comorbidities are relatively common in older adults, some older adults will need to undergo risk stratification evaluation prior to initiating an exercise regimen.

Review preparticipation screening guidelines and recommendations

Guidelines can be contradictory regarding the ideal pre-exercise evaluation. In general, the USPSTF recommends against screening with resting or exercise electrocardiography (EKG) to prevent cardiovascular disease events in asymptomatic adults who are at low risk. It also finds insufficient evidence to assess the balance of benefits and harms of screening with resting or exercise EKG to prevent cardiovascular disease events in asymptomatic adults who are at intermediate or high risk.²²

Similarly, the 2020 ACSM Guidelines for Exercise Testing and Prescription reflect that routine exercise testing is not recommended for all older adult patients prior to starting an exercise regimen.¹⁷ However, the ACSM does recommend all patients with signs or symptoms of a cardiovascular, renal, or metabolic disease consult with a clinician for medical risk stratification and potential subsequent testing prior to starting an exercise regimen. If an individual already exercises and is having new/worsening signs or symptoms of a cardiovascular, renal, or metabolic disease, that patient should cease exercise until medical evaluation is performed. Additionally, ACSM recommends that asymptomatic patients who do not exercise but who have known cardiovascular, renal, or metabolic disease receive medical evaluation prior to starting an exercise regimen.¹⁷

Continue to: Is there evidence of cardiovascular, renal, or metabolic disease?

 

 

Is there evidence of cardiovascular, renal, or metabolic disease?

Initial screening can be completed by obtaining the patient’s history and conducting a physical examination. Patients reporting chest pain or discomfort (or any anginal equivalent), dyspnea, syncope, orthopnea, lower extremity edema, signs of tachyarrhythmia/bradyarrhythmia, intermittent claudication, exertional fatigue, or new exertional symptoms should all be considered for cardiovascular stress testing. Patients with a diagnosis of renal disease or either type 1 or type 2 diabetes should also be considered for cardiovascular stress testing.

Ready to prescribe exercise? Cover these 4 points

When prescribing any exercise plan for older adults, it is important for clinicians to specify 4 key components: frequency, intensity, time, and type (this can be remembered using the acronym “FITT”).²³ A sedentary adult should be encouraged to engage in moderate-­intensity exercise, such as walking, for 15 minutes 3 times per week. The key with a sedentary adult is appropriate follow-up to monitor progression and modify activity to help ensure the patient can achieve the goal number of minutes per week. It can be helpful to share the “next step” with the patient, as well (eg, increase to 4 times per week after 2 weeks, or increase by 5 minutes every week). For the intermittent exerciser, a program of moderate exercise, such as using an elliptical, for 30 to 40 minutes 5 times per week is a recommended prescription. FITT components can be tailored to meet individual patient physical readiness.²³

Frequency. While the 2018 Physical Activity Guidelines for Americans recommend a specific frequency of physical activity throughout the week, it is important to remember that some older adults will be unable to meet these recommendations, particularly in the setting of frailty and comorbidities (TABLE 2²). In these cases, the guidelines simply recommend that older adults should be as physically active as their abilities and comorbidities allow. Some exercise is better than none, and generally moving more and sitting less will yield health benefits for older adult patients.

Intensity is a description of how hard an individual is working during physical activity. An older adult’s individual capacity for exercise intensity will depend on many factors, including their comorbidities. An activity’s intensity will be relative to a person’s unique level of fitness. Given this heterogeneity, exercise prescriptions should be tailored to the individual. Light-intensity exercise generally causes a slight increase in pulse and respiratory rate, moderate-intensity exercise causes a noticeable increase in pulse and respiratory rate, and vigorous-intensity exercise causes a significant increase in pulse and respiratory rate (TABLE 4^2,16,17,24).²

The “talk test” is a simple, practical, and validated test that can help one determine an individual’s capacity for moderate- or ­vigorous-intensity exercise.²³ In general, a person performing vigorous-intensity exercise will be unable to talk comfortably during activity for more than a few words without pausing for breath. Similarly, a person will be able to talk but not sing comfortably during moderate-intensity exercise.^3,23

Continue to: Time

Time. The 2018 Physical Activity Guidelines for Americans recommend a specific duration of physical activity throughout the week; however, as with frequency, it is important to remember that duration of exercise is individualized (TABLE 2²). Older adults should be as physically active as their abilities and comorbidities allow, and in the setting of frailty, numerous comorbidities, and/or a sedentary lifestyle, it is reasonable to initiate exercise recommendations with shorter durations.

The PAVS is a 2-item self-report measure used to quickly assess a patient’s level of physical activity.

Type of exercise. As noted in the 2018 Physical Activity Guidelines for Americans, recommendations for older adults include multiple types of exercise. In addition to these general exercise recommendations, exercise prescriptions can be individualized to target specific comorbidities (TABLE 2²). Weight-bearing, bone-strengthening exercises can benefit patients with disorders of low bone density and possibly those with osteoarthritis.^3,23 Patients at increased risk for falls should focus on balance-training options that strengthen the muscles of the back, abdomen, and legs, such as tai chi.^3,23 Patients with cardiovascular risk can benefit from moderate- to high-intensity aerobic exercise (although exercise should be performed below anginal threshold in patients with known cardiovascular disease). Patients with type 2 diabetes achieve improved glycemic control when engaging in combined moderate-intensity aerobic exercise and resistance training.^7,23

Referral to a physical therapist or sport and exercise medicine specialist can always be considered, particularly for patients with significant neurologic disorders, disability secondary to traumatic injury, or health conditions.³

An improved quality of life. Incorporating physical activity into older adults’ lives can enhance their quality of life. Family physicians are well positioned to counsel older adults on the importance and benefits of exercise and to help them overcome the barriers or resistance to undertaking a change in behavior. Guidelines, recommendations, patient history, and resources provide the support needed to prescribe individualized exercise plans for this distinct population. 

CORRESPONDENCE
Scott T. Larson, MD, 200 Hawkins Drive, Iowa City, IA, 52242; scott-larson@uiowa.edu

The health benefits of maintaining a physically active lifestyle are vast and irrefutable.¹ Physical activity is an important modifiable behavior demonstrated to reduce the risk for many chronic diseases while improving physical function (TABLE 1²).³ Physical inactivity increases with age, making older adults (ages ≥ 65 years) the least active age group and the group at greatest risk for inactivity-­related health consequences.^4-6 Engaging in a physically active lifestyle is especially important for older adults to maintain independence,⁷ quality of life,⁸ and the ability to perform activities of daily living.^3,9

Prescribe physical activity for older adults

The 2018 Physical Activity Guidelines for Americans recommend that all healthy adults (including healthy older adults) ideally should perform muscle-strengthening activities of moderate or greater intensity that involve all major muscle groups on 2 or more days per week and either (a) 150 to 300 minutes per week of moderate-intensity aerobic physical activity, (b) 75 to 150 minutes per week of vigorous-intensity aerobic physical activity, or (c) an equivalent combination, if possible (TABLE 2²).³ It is recommended that older adults specifically follow a multicomponent physical activity program that includes balance training, as well as aerobic and muscle-strengthening activities.³ Unfortunately, nearly 80% of older adults do not meet the recommended guidelines for aerobic or muscle-strengthening exercise.³

Identify barriers to exercise

Older adults report several barriers that limit physical activity. Some of the most commonly reported barriers include a lack of motivation, low self-efficacy for being active, physical limitations due to health conditions, inconvenient physical activity locations, boredom with physical activity, and lack of guidance from professionals.^10-12 Physical activity programs designed for older adults should specifically target these barriers for maximum effectiveness.

Clinicians also face potential barriers for promoting physical activity among older adults. Screening patients for physical inactivity can be a challenge, given the robust number of clinical preventive services and conversations that are already recommended for older adults. Additionally, screening for physical activity is not a reimbursable service. In July, the US Preventive Services Task Force (USPSTF) reaffirmed its 2017 recommendation to individualize the decision to offer or refer adults without obesity, hypertension, dyslipidemia, or abnormal blood glucose levels or diabetes to behavioral counseling to promote a healthy diet and physical activity (Grade C rating).¹³

Treat physical activity as a vital sign

The Exercise is Medicine (EIM) model is based on the principle that physical activity should be treated as a vital sign and discussed during all health care visits. Health care professionals have a unique opportunity to promote physical activity, since more than 80% of US adults see a physician annually. Evidence also suggests clinician advice is associated with patients’ healthy lifestyle behaviors.^14,15

EIM is a global health initiative that was established in 2007 and is managed by the American College of Sports Medicine (ACSM). The primary objective of the EIM model is to treat physical activity behavior as a vital sign and include physical activity promotion as a standard of clinical care. In order to achieve this objective, the EIM model recommends health care systems follow 3 simple rules: (1) treat physical activity as a vital sign by measuring physical activity of every patient at every visit, (2) prescribe exercise to those patients who report not meeting the physical activity guidelines, and/or (3) refer inactive patients to evidence-based physical activity resources to receive exercise counseling.^16,17

Screen for physical activity using this 2-question self-report

Clinicians may employ multiple tactics to screen patients for their current levels of physical activity. Physical Activity Vital Sign (PAVS) is a 2-item self-report measure developed to briefly assess a patient’s level of physical activity; results can be entered into the patient’s electronic medical record and used to begin a process of referring inactive patients for behavioral counseling.^17,18 The PAVS can be administered in less than 1 minute by a medical assistant and/or nursing staff during rooming or intake of patients. The PAVS questions include, “On average, how many days per week do you engage in moderate-to-vigorous physical activity?” and “On average, how many minutes do you engage in physical activity at this level?” The clinician can then multiply the 2 numbers to calculate the patient’s total minutes of ­moderate-to-vigorous physical activity per week to determine whether a patient is meeting the recommended physical activity guidelines.¹⁶ (For more on the PAVS and other resources, see TABLE 3.)

Continue to: The PAVS has been established...

Approximately 80% of older adults do not meet the recommended guidelines for aerobic or muscle-strengthening exercise.

The PAVS has been established as a valid instrument for detecting patients who may need counseling on physical activity for chronic disease recognition, management, and prevention.¹⁷ Furthermore, there is a strong association between PAVS, elevated body mass index, and chronic disease burden.¹⁹ Therefore, we recommend that primary care physicians screen their patients for physical activity levels. It has been demonstrated, however, that many primary care visits for older individuals include discussions of diet and physical activity but do not provide recommendations for lifestyle change.¹⁹ Thus, exploring ways to counsel patients on lifestyle change in an efficient manner is recommended. It has been demonstrated that counseling and referral from primary care centers can promote increased adherence to physical activity practices.^20,21

Determine physical activity readiness

Prior to recommending a physical activity regimen, it is important to evaluate the patient’s readiness to make a change. Various questionnaires—such as the Physical Activity Readiness Questionnaire—have been developed to determine a patient’s level of readiness, evaluating both psychological and physical factors (www.nasm.org/docs/pdf/parqplus-2020.pdf?sfvrsn=401bf1af_24). Questionnaires also help you to determine whether further medical evaluation prior to beginning an exercise regimen is necessary. It’s important to note that, as is true with any office intervention, patients may be in a precontemplation or contemplation phase and may not be prepared to immediately make changes.

Evaluate risk level

Assess cardiovascular risk. Physicians and patients are often concerned about cardiovascular risk or injury risk during physical activity counseling, which may lead to fewer exercise prescriptions. As a physician, it is important to remember that for most adults, the benefits of exercise will outweigh any potential risks,³ and there is generally a low risk of cardiovascular events related to light to moderate–intensity exercise regimens.² Additionally, it has been demonstrated that exercise and cardiovascular rehabilitation are highly beneficial for primary and secondary prevention of cardiovascular disease.²² Given that cardiovascular comorbidities are relatively common in older adults, some older adults will need to undergo risk stratification evaluation prior to initiating an exercise regimen.

Review preparticipation screening guidelines and recommendations

Guidelines can be contradictory regarding the ideal pre-exercise evaluation. In general, the USPSTF recommends against screening with resting or exercise electrocardiography (EKG) to prevent cardiovascular disease events in asymptomatic adults who are at low risk. It also finds insufficient evidence to assess the balance of benefits and harms of screening with resting or exercise EKG to prevent cardiovascular disease events in asymptomatic adults who are at intermediate or high risk.²²

Similarly, the 2020 ACSM Guidelines for Exercise Testing and Prescription reflect that routine exercise testing is not recommended for all older adult patients prior to starting an exercise regimen.¹⁷ However, the ACSM does recommend all patients with signs or symptoms of a cardiovascular, renal, or metabolic disease consult with a clinician for medical risk stratification and potential subsequent testing prior to starting an exercise regimen. If an individual already exercises and is having new/worsening signs or symptoms of a cardiovascular, renal, or metabolic disease, that patient should cease exercise until medical evaluation is performed. Additionally, ACSM recommends that asymptomatic patients who do not exercise but who have known cardiovascular, renal, or metabolic disease receive medical evaluation prior to starting an exercise regimen.¹⁷

Continue to: Is there evidence of cardiovascular, renal, or metabolic disease?

 

 

Is there evidence of cardiovascular, renal, or metabolic disease?

Initial screening can be completed by obtaining the patient’s history and conducting a physical examination. Patients reporting chest pain or discomfort (or any anginal equivalent), dyspnea, syncope, orthopnea, lower extremity edema, signs of tachyarrhythmia/bradyarrhythmia, intermittent claudication, exertional fatigue, or new exertional symptoms should all be considered for cardiovascular stress testing. Patients with a diagnosis of renal disease or either type 1 or type 2 diabetes should also be considered for cardiovascular stress testing.

Ready to prescribe exercise? Cover these 4 points

When prescribing any exercise plan for older adults, it is important for clinicians to specify 4 key components: frequency, intensity, time, and type (this can be remembered using the acronym “FITT”).²³ A sedentary adult should be encouraged to engage in moderate-­intensity exercise, such as walking, for 15 minutes 3 times per week. The key with a sedentary adult is appropriate follow-up to monitor progression and modify activity to help ensure the patient can achieve the goal number of minutes per week. It can be helpful to share the “next step” with the patient, as well (eg, increase to 4 times per week after 2 weeks, or increase by 5 minutes every week). For the intermittent exerciser, a program of moderate exercise, such as using an elliptical, for 30 to 40 minutes 5 times per week is a recommended prescription. FITT components can be tailored to meet individual patient physical readiness.²³

Frequency. While the 2018 Physical Activity Guidelines for Americans recommend a specific frequency of physical activity throughout the week, it is important to remember that some older adults will be unable to meet these recommendations, particularly in the setting of frailty and comorbidities (TABLE 2²). In these cases, the guidelines simply recommend that older adults should be as physically active as their abilities and comorbidities allow. Some exercise is better than none, and generally moving more and sitting less will yield health benefits for older adult patients.

Intensity is a description of how hard an individual is working during physical activity. An older adult’s individual capacity for exercise intensity will depend on many factors, including their comorbidities. An activity’s intensity will be relative to a person’s unique level of fitness. Given this heterogeneity, exercise prescriptions should be tailored to the individual. Light-intensity exercise generally causes a slight increase in pulse and respiratory rate, moderate-intensity exercise causes a noticeable increase in pulse and respiratory rate, and vigorous-intensity exercise causes a significant increase in pulse and respiratory rate (TABLE 4^2,16,17,24).²

The “talk test” is a simple, practical, and validated test that can help one determine an individual’s capacity for moderate- or ­vigorous-intensity exercise.²³ In general, a person performing vigorous-intensity exercise will be unable to talk comfortably during activity for more than a few words without pausing for breath. Similarly, a person will be able to talk but not sing comfortably during moderate-intensity exercise.^3,23

Continue to: Time

Time. The 2018 Physical Activity Guidelines for Americans recommend a specific duration of physical activity throughout the week; however, as with frequency, it is important to remember that duration of exercise is individualized (TABLE 2²). Older adults should be as physically active as their abilities and comorbidities allow, and in the setting of frailty, numerous comorbidities, and/or a sedentary lifestyle, it is reasonable to initiate exercise recommendations with shorter durations.

The PAVS is a 2-item self-report measure used to quickly assess a patient’s level of physical activity.

Type of exercise. As noted in the 2018 Physical Activity Guidelines for Americans, recommendations for older adults include multiple types of exercise. In addition to these general exercise recommendations, exercise prescriptions can be individualized to target specific comorbidities (TABLE 2²). Weight-bearing, bone-strengthening exercises can benefit patients with disorders of low bone density and possibly those with osteoarthritis.^3,23 Patients at increased risk for falls should focus on balance-training options that strengthen the muscles of the back, abdomen, and legs, such as tai chi.^3,23 Patients with cardiovascular risk can benefit from moderate- to high-intensity aerobic exercise (although exercise should be performed below anginal threshold in patients with known cardiovascular disease). Patients with type 2 diabetes achieve improved glycemic control when engaging in combined moderate-intensity aerobic exercise and resistance training.^7,23

Referral to a physical therapist or sport and exercise medicine specialist can always be considered, particularly for patients with significant neurologic disorders, disability secondary to traumatic injury, or health conditions.³

An improved quality of life. Incorporating physical activity into older adults’ lives can enhance their quality of life. Family physicians are well positioned to counsel older adults on the importance and benefits of exercise and to help them overcome the barriers or resistance to undertaking a change in behavior. Guidelines, recommendations, patient history, and resources provide the support needed to prescribe individualized exercise plans for this distinct population. 

CORRESPONDENCE
Scott T. Larson, MD, 200 Hawkins Drive, Iowa City, IA, 52242; scott-larson@uiowa.edu

Congenital cytomegalovirus cases declined significantly during the COVID-19 pandemic, compared with a period before the pandemic, based on data from nearly 20,000 newborns.

A study originated to explore racial and ethnic differences in congenital cytomegalovirus (cCMV) began in 2016, but was halted in April 2020 because of the COVID-19 pandemic, wrote Mark R. Schleiss, MD, of the University of Minnesota, Minneapolis, and colleagues. The study resumed for a period from August 2020 to December 2021, and the researchers compared data on cCMV before and during the pandemic. The prepandemic period included data from April 2016 to March 2020.

“We have been screening for congenital CMV infection in Minnesota for 6 years as a part of a multicenter collaborative study that I lead as the primary investigator,” Dr. Schleiss said in an interview. “Our efforts have contributed to the decision, vetted through the Minnesota Legislature and signed into law in 2021 (the “Vivian Act”), to begin universal screening for all newborns in Minnesota in 2023. In the context of this ongoing screening/surveillance study, it was important and scientifically very interesting to examine the impact of the COVID-19 pandemic on the risk of congenital CMV infection,” he explained.

The findings were published in a research letter in JAMA Network Open. A total of 15,697 newborns were screened before the pandemic and 4,222 were screened during the pandemic period at six hospitals. The majority of the mothers participating during the prepandemic and pandemic periods were non-Hispanic White (71% and 60%, respectively).

Overall, the percentage screened prevalence for cCMV was 79% in the prepandemic period and 21% during the pandemic, with rates of 4.5 per 1,000 and 1.4 per 1,000, respectively.

Although the highest percentage of cCMV cases occurred in newborns of mothers aged 25 years and older (86%), the prevalence was highest among newborns of mothers aged 24 years and younger (6.0 per 1,000). The prevalence of cCMV overall was higher in infants of non-Hispanic Black mothers vs. non-Hispanic White mothers, but not significantly different (5.1 per 1,000 vs. 4.6 per 1,000) and among second newborns vs. first newborns (6.0 vs. 3.2 per 1,000, respectively).

Factors related to COVID-19, including reduced day care attendance, behavioral changes, and mitigation measures at childcare facilities such as smaller classes and increased hand hygiene and disinfection may have contributed to this decrease in cCMV in the pandemic period, the researchers wrote in their discussion.

The comparable prevalence in newborns of non-Hispanic Black and White mothers contrasts with previous studies showing a higher prevalence in children of non-Hispanic Black mothers, the researchers noted in their discussion.

The study was limited by several factors, including the variation in time points for enrollment at different sites and the exclusion of families in the newborn nursery with positive COVID-19 results during the pandemic, they wrote. More research is needed on the potential effects of behavioral interventions to reduce CMV risk during pregnancy, as well as future CMV vaccination for childbearing-aged women and young children, they concluded.

However, the researchers were surprised by the impact of COVID-19 on the prevalence of cCMV, Dr. Schleiss said in an interview. “We have had the knowledge for many years that CMV infections in young women are commonly acquired through interactions with their toddlers. These interactions – sharing food, wiping drool and nasal discharge from the toddler’s nose, changing diapers, kissing the child on the mouth – can transmit CMV,” he said. In addition, toddlers may acquire CMV from group day care; the child then sheds CMV and transmits the virus to their pregnant mother, who then transmits the virus across the placenta, leading to cCMV infection in the newborn, Dr. Schleiss explained.

Although the researchers expected a decrease in CMV in the wake of closures of group day care, increased home schooling, decreased interactions among children, hygienic precautions, and social isolation, the decrease exceeded their expectations, said Dr. Schleiss. “Our previous work showed that in the 5-year period leading up to the pandemic, about one baby in every 200 births was born with CMV. Between August 2020 and December 2021, the number decreased to one baby in every 1,000 births,” a difference he and his team found striking.

The message from the study is that CMV can be prevented, said Dr. Schleiss. “Hygienic precautions during pregnancy had a big impact. Since congenital CMV infection is the most common congenital infection in the United States, and probably globally, that causes disabilities in children, the implications are highly significant,” he said. “The hygienic precautions we all have engaged in during the pandemic, such as masking, handwashing, and infection prevention behaviors, were almost certainly responsible for the reduction in CMV transmission, which in turn protected mothers and newborns from the potentially devastating effects of the CMV virus,” he noted.

Looking ahead, “Vaccines are moving forward in clinical trials that aim to confer immunity on young women of childbearing age to protect future pregnancies against transmission of CMV to the newborn infant; it would be very important to examine in future studies whether hygienic precautions would have the same impact as a potential vaccine,” Dr. Schleiss said. More research is needed to examine the effect of education of women about CMV transmission, he added. “We think it is very important to share this knowledge from our study with the pediatric community, since pediatricians can be important in counseling women about future pregnancies and the risks of CMV acquisition and transmission,” he noted.

Implications for other viruses

Although CMV poses minimal risk for healthy populations, irreversible complications for infants born with congenital CMV, especially hearing loss, are very concerning, said Catherine Haut, DNP, CPNP-AC/PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview.

“The study of viral transmission during a time of isolation, masking, and other mitigation procedures for COVID-19 assists in awareness that other viruses may also be limited with the use of these measures,” she said.

Dr. Haut was not surprised by the findings, given that CMV is transmitted primarily through direct contact with body fluids and that more than 50% of American adults have been infected by age 40, according to the Centers for Disease Control and Prevention, she said.

The take-home message for pediatricians, Dr. Haut said, is measures to prevent transmission of viral infection can yield significant positive health outcomes for the pediatric population; however, the effect of isolation, which has been associated with a higher rate of mental health problems, should not be ignored.

“Despite appropriate statistical analyses and presentation of findings in this study, the population sampled during the pandemic was less than 30% of the pre-COVID sampling, representing a study limitation,” and conducting research in a single state limits generalizability, Dr. Haut noted. “I agree with the authors that additional study is necessary to better understand prevention measures and apply these methods to reduce CMV transmission. Pursuit of CMV immunization opportunities is also needed,” she said.

The study was supported by the Centers for Disease Control and Prevention, the National Vaccine Program Office, the Minnesota Department of Health Newborn Screening Program, and the University of South Carolina Disability Research and Dissemination Center. Lead author Dr. Schleiss disclosed grants from the CDC, the National Institutes of Health, and the DRDC during the conduct of the study; he also disclosed receiving personal fees from Moderna, Sanofi, GlaxoSmithKline, and Merck unrelated to the study. Dr. Haut had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.

Congenital cytomegalovirus cases declined significantly during the COVID-19 pandemic, compared with a period before the pandemic, based on data from nearly 20,000 newborns.

A study originated to explore racial and ethnic differences in congenital cytomegalovirus (cCMV) began in 2016, but was halted in April 2020 because of the COVID-19 pandemic, wrote Mark R. Schleiss, MD, of the University of Minnesota, Minneapolis, and colleagues. The study resumed for a period from August 2020 to December 2021, and the researchers compared data on cCMV before and during the pandemic. The prepandemic period included data from April 2016 to March 2020.

“We have been screening for congenital CMV infection in Minnesota for 6 years as a part of a multicenter collaborative study that I lead as the primary investigator,” Dr. Schleiss said in an interview. “Our efforts have contributed to the decision, vetted through the Minnesota Legislature and signed into law in 2021 (the “Vivian Act”), to begin universal screening for all newborns in Minnesota in 2023. In the context of this ongoing screening/surveillance study, it was important and scientifically very interesting to examine the impact of the COVID-19 pandemic on the risk of congenital CMV infection,” he explained.

The findings were published in a research letter in JAMA Network Open. A total of 15,697 newborns were screened before the pandemic and 4,222 were screened during the pandemic period at six hospitals. The majority of the mothers participating during the prepandemic and pandemic periods were non-Hispanic White (71% and 60%, respectively).

Overall, the percentage screened prevalence for cCMV was 79% in the prepandemic period and 21% during the pandemic, with rates of 4.5 per 1,000 and 1.4 per 1,000, respectively.

Although the highest percentage of cCMV cases occurred in newborns of mothers aged 25 years and older (86%), the prevalence was highest among newborns of mothers aged 24 years and younger (6.0 per 1,000). The prevalence of cCMV overall was higher in infants of non-Hispanic Black mothers vs. non-Hispanic White mothers, but not significantly different (5.1 per 1,000 vs. 4.6 per 1,000) and among second newborns vs. first newborns (6.0 vs. 3.2 per 1,000, respectively).

Factors related to COVID-19, including reduced day care attendance, behavioral changes, and mitigation measures at childcare facilities such as smaller classes and increased hand hygiene and disinfection may have contributed to this decrease in cCMV in the pandemic period, the researchers wrote in their discussion.

The comparable prevalence in newborns of non-Hispanic Black and White mothers contrasts with previous studies showing a higher prevalence in children of non-Hispanic Black mothers, the researchers noted in their discussion.

The study was limited by several factors, including the variation in time points for enrollment at different sites and the exclusion of families in the newborn nursery with positive COVID-19 results during the pandemic, they wrote. More research is needed on the potential effects of behavioral interventions to reduce CMV risk during pregnancy, as well as future CMV vaccination for childbearing-aged women and young children, they concluded.

However, the researchers were surprised by the impact of COVID-19 on the prevalence of cCMV, Dr. Schleiss said in an interview. “We have had the knowledge for many years that CMV infections in young women are commonly acquired through interactions with their toddlers. These interactions – sharing food, wiping drool and nasal discharge from the toddler’s nose, changing diapers, kissing the child on the mouth – can transmit CMV,” he said. In addition, toddlers may acquire CMV from group day care; the child then sheds CMV and transmits the virus to their pregnant mother, who then transmits the virus across the placenta, leading to cCMV infection in the newborn, Dr. Schleiss explained.

Although the researchers expected a decrease in CMV in the wake of closures of group day care, increased home schooling, decreased interactions among children, hygienic precautions, and social isolation, the decrease exceeded their expectations, said Dr. Schleiss. “Our previous work showed that in the 5-year period leading up to the pandemic, about one baby in every 200 births was born with CMV. Between August 2020 and December 2021, the number decreased to one baby in every 1,000 births,” a difference he and his team found striking.

The message from the study is that CMV can be prevented, said Dr. Schleiss. “Hygienic precautions during pregnancy had a big impact. Since congenital CMV infection is the most common congenital infection in the United States, and probably globally, that causes disabilities in children, the implications are highly significant,” he said. “The hygienic precautions we all have engaged in during the pandemic, such as masking, handwashing, and infection prevention behaviors, were almost certainly responsible for the reduction in CMV transmission, which in turn protected mothers and newborns from the potentially devastating effects of the CMV virus,” he noted.

Looking ahead, “Vaccines are moving forward in clinical trials that aim to confer immunity on young women of childbearing age to protect future pregnancies against transmission of CMV to the newborn infant; it would be very important to examine in future studies whether hygienic precautions would have the same impact as a potential vaccine,” Dr. Schleiss said. More research is needed to examine the effect of education of women about CMV transmission, he added. “We think it is very important to share this knowledge from our study with the pediatric community, since pediatricians can be important in counseling women about future pregnancies and the risks of CMV acquisition and transmission,” he noted.

Implications for other viruses

Although CMV poses minimal risk for healthy populations, irreversible complications for infants born with congenital CMV, especially hearing loss, are very concerning, said Catherine Haut, DNP, CPNP-AC/PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview.

“The study of viral transmission during a time of isolation, masking, and other mitigation procedures for COVID-19 assists in awareness that other viruses may also be limited with the use of these measures,” she said.

Dr. Haut was not surprised by the findings, given that CMV is transmitted primarily through direct contact with body fluids and that more than 50% of American adults have been infected by age 40, according to the Centers for Disease Control and Prevention, she said.

The take-home message for pediatricians, Dr. Haut said, is measures to prevent transmission of viral infection can yield significant positive health outcomes for the pediatric population; however, the effect of isolation, which has been associated with a higher rate of mental health problems, should not be ignored.

“Despite appropriate statistical analyses and presentation of findings in this study, the population sampled during the pandemic was less than 30% of the pre-COVID sampling, representing a study limitation,” and conducting research in a single state limits generalizability, Dr. Haut noted. “I agree with the authors that additional study is necessary to better understand prevention measures and apply these methods to reduce CMV transmission. Pursuit of CMV immunization opportunities is also needed,” she said.

The study was supported by the Centers for Disease Control and Prevention, the National Vaccine Program Office, the Minnesota Department of Health Newborn Screening Program, and the University of South Carolina Disability Research and Dissemination Center. Lead author Dr. Schleiss disclosed grants from the CDC, the National Institutes of Health, and the DRDC during the conduct of the study; he also disclosed receiving personal fees from Moderna, Sanofi, GlaxoSmithKline, and Merck unrelated to the study. Dr. Haut had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.

Congenital cytomegalovirus cases declined significantly during the COVID-19 pandemic, compared with a period before the pandemic, based on data from nearly 20,000 newborns.

A study originated to explore racial and ethnic differences in congenital cytomegalovirus (cCMV) began in 2016, but was halted in April 2020 because of the COVID-19 pandemic, wrote Mark R. Schleiss, MD, of the University of Minnesota, Minneapolis, and colleagues. The study resumed for a period from August 2020 to December 2021, and the researchers compared data on cCMV before and during the pandemic. The prepandemic period included data from April 2016 to March 2020.

“We have been screening for congenital CMV infection in Minnesota for 6 years as a part of a multicenter collaborative study that I lead as the primary investigator,” Dr. Schleiss said in an interview. “Our efforts have contributed to the decision, vetted through the Minnesota Legislature and signed into law in 2021 (the “Vivian Act”), to begin universal screening for all newborns in Minnesota in 2023. In the context of this ongoing screening/surveillance study, it was important and scientifically very interesting to examine the impact of the COVID-19 pandemic on the risk of congenital CMV infection,” he explained.

The findings were published in a research letter in JAMA Network Open. A total of 15,697 newborns were screened before the pandemic and 4,222 were screened during the pandemic period at six hospitals. The majority of the mothers participating during the prepandemic and pandemic periods were non-Hispanic White (71% and 60%, respectively).

Overall, the percentage screened prevalence for cCMV was 79% in the prepandemic period and 21% during the pandemic, with rates of 4.5 per 1,000 and 1.4 per 1,000, respectively.

Although the highest percentage of cCMV cases occurred in newborns of mothers aged 25 years and older (86%), the prevalence was highest among newborns of mothers aged 24 years and younger (6.0 per 1,000). The prevalence of cCMV overall was higher in infants of non-Hispanic Black mothers vs. non-Hispanic White mothers, but not significantly different (5.1 per 1,000 vs. 4.6 per 1,000) and among second newborns vs. first newborns (6.0 vs. 3.2 per 1,000, respectively).

Factors related to COVID-19, including reduced day care attendance, behavioral changes, and mitigation measures at childcare facilities such as smaller classes and increased hand hygiene and disinfection may have contributed to this decrease in cCMV in the pandemic period, the researchers wrote in their discussion.

The comparable prevalence in newborns of non-Hispanic Black and White mothers contrasts with previous studies showing a higher prevalence in children of non-Hispanic Black mothers, the researchers noted in their discussion.

The study was limited by several factors, including the variation in time points for enrollment at different sites and the exclusion of families in the newborn nursery with positive COVID-19 results during the pandemic, they wrote. More research is needed on the potential effects of behavioral interventions to reduce CMV risk during pregnancy, as well as future CMV vaccination for childbearing-aged women and young children, they concluded.

However, the researchers were surprised by the impact of COVID-19 on the prevalence of cCMV, Dr. Schleiss said in an interview. “We have had the knowledge for many years that CMV infections in young women are commonly acquired through interactions with their toddlers. These interactions – sharing food, wiping drool and nasal discharge from the toddler’s nose, changing diapers, kissing the child on the mouth – can transmit CMV,” he said. In addition, toddlers may acquire CMV from group day care; the child then sheds CMV and transmits the virus to their pregnant mother, who then transmits the virus across the placenta, leading to cCMV infection in the newborn, Dr. Schleiss explained.

Although the researchers expected a decrease in CMV in the wake of closures of group day care, increased home schooling, decreased interactions among children, hygienic precautions, and social isolation, the decrease exceeded their expectations, said Dr. Schleiss. “Our previous work showed that in the 5-year period leading up to the pandemic, about one baby in every 200 births was born with CMV. Between August 2020 and December 2021, the number decreased to one baby in every 1,000 births,” a difference he and his team found striking.

The message from the study is that CMV can be prevented, said Dr. Schleiss. “Hygienic precautions during pregnancy had a big impact. Since congenital CMV infection is the most common congenital infection in the United States, and probably globally, that causes disabilities in children, the implications are highly significant,” he said. “The hygienic precautions we all have engaged in during the pandemic, such as masking, handwashing, and infection prevention behaviors, were almost certainly responsible for the reduction in CMV transmission, which in turn protected mothers and newborns from the potentially devastating effects of the CMV virus,” he noted.

Looking ahead, “Vaccines are moving forward in clinical trials that aim to confer immunity on young women of childbearing age to protect future pregnancies against transmission of CMV to the newborn infant; it would be very important to examine in future studies whether hygienic precautions would have the same impact as a potential vaccine,” Dr. Schleiss said. More research is needed to examine the effect of education of women about CMV transmission, he added. “We think it is very important to share this knowledge from our study with the pediatric community, since pediatricians can be important in counseling women about future pregnancies and the risks of CMV acquisition and transmission,” he noted.

Implications for other viruses

Although CMV poses minimal risk for healthy populations, irreversible complications for infants born with congenital CMV, especially hearing loss, are very concerning, said Catherine Haut, DNP, CPNP-AC/PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview.

“The study of viral transmission during a time of isolation, masking, and other mitigation procedures for COVID-19 assists in awareness that other viruses may also be limited with the use of these measures,” she said.

Dr. Haut was not surprised by the findings, given that CMV is transmitted primarily through direct contact with body fluids and that more than 50% of American adults have been infected by age 40, according to the Centers for Disease Control and Prevention, she said.

The take-home message for pediatricians, Dr. Haut said, is measures to prevent transmission of viral infection can yield significant positive health outcomes for the pediatric population; however, the effect of isolation, which has been associated with a higher rate of mental health problems, should not be ignored.

“Despite appropriate statistical analyses and presentation of findings in this study, the population sampled during the pandemic was less than 30% of the pre-COVID sampling, representing a study limitation,” and conducting research in a single state limits generalizability, Dr. Haut noted. “I agree with the authors that additional study is necessary to better understand prevention measures and apply these methods to reduce CMV transmission. Pursuit of CMV immunization opportunities is also needed,” she said.

The study was supported by the Centers for Disease Control and Prevention, the National Vaccine Program Office, the Minnesota Department of Health Newborn Screening Program, and the University of South Carolina Disability Research and Dissemination Center. Lead author Dr. Schleiss disclosed grants from the CDC, the National Institutes of Health, and the DRDC during the conduct of the study; he also disclosed receiving personal fees from Moderna, Sanofi, GlaxoSmithKline, and Merck unrelated to the study. Dr. Haut had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.