Efanesoctocog alfa, a first-in-class, bioengineered human factor VIII replacement therapy, shows safety and efficacy in the prevention of bleeding in children with severe hemophilia A, with benefits similar to those observed in adults, new research shows.

“In this study, once-weekly efanesoctocog alfa provided high sustained factor VIII activity and highly efficacious protection against bleeding episodes in children with severe hemophilia A, a population in which this goal has been difficult to achieve without burdensome treatment regimens,” report the authors in the study, published in The New England Journal of Medicine.

The results are from the phase 3, open-label XTEND-Kids study, in which first author Lynn Malec, MD, medical director of the Comprehensive Center for Bleeding Disorders and associate professor of medicine and pediatrics at The Medical College of Wisconsin, in Milwaukee, and colleagues enrolled 74 male pediatric patients with hemophilia A, including 38 under the age of 6 and 36 ages 6-12.

The participants received prophylaxis with once-weekly efanesoctocog alfa (50 IU per kg of body weight), for 52 weeks.

Prior to the treatment period, all patients had received factor VIII replacement therapy, with the exception of one who received the therapy on demand. Most (70%) received extended half-life products, such as doses twice a week or every 3 days, and the remaining 30% received standard half-life products, with dose regimens ranging from every 2 days to twice a week.

Over the course of the year-long study, none of the patients developed factor VIII inhibitors, neutralizing antibodies, a common complication in hemophilia A that prevents factor VIII replacement treatment from working to form clots.

In addition, no serious adverse events occurred that were determined to be related to efanesoctocog alfa.

“No inhibitors to factor VIII developed, most adverse events were not serious, and no adverse events led to discontinuation of efanesoctocog alfa,” the authors report.

In terms of efficacy, among 73 patients who were treated according to the protocol, the median annualized bleeding rate was 0.00 and the model-based mean rate was 0.61.

Overall, 47 patients (64%) experienced no treated bleeding episodes during the study, 65 (88%) had no spontaneous bleeding episodes, and 61 (82%) had no episodes of bleeding into joints.

Of 43 bleeding episodes, most (41; 95%) resolved with a single injection of efanesoctocog alfa.

Of note, “shortening the weekly administration interval was not deemed to be necessary in any patient during this study,” the authors add.

In comparison, other studies of children receiving other factor VIII products, including damoctocog alfa pegol, rurioctocog alfa pegol, and efmoroctocog alfa, show higher annualized bleeding rates of 2.9, 2.0, and 1.96, respectively, and studies showed the percentages of patients with no bleeding with those products were 23%, 38%, and 46%, respectively, compared with the 64% in the current study of efanesoctocog alfa.

“Although these clinical study results cannot be directly compared because of the differences in patient populations and study designs, the XTEND-Kids study showed favorable bleeding protection with efanesoctocog alfa prophylaxis as compared with these extended half-life factor VIII products,” the authors report.

Data on the once-weekly monoclonal antibody emicizumab, which has the important benefit of being administered subcutaneously instead of intravenously, is limited in children under age 12 with severe hemophilia A and without factor VIII inhibitors, the authors note.

However, the mean annualized bleeding rate with efanesoctocog alfa appears improved compared with that observed in a small Japanese study of 13 children who received emicizumab prophylaxis every 2 weeks or every 4 weeks, which showed annualized rates of treated bleeding episodes of 1.3 and 0.7 with the respective emicizumab regimens.
 

Results Compare With Findings in Adults

The results are similar to those reported among adults in the previous XTEND-1 phase 3 study, which was the basis for US Food and Drug Administration (FDA) approval of the drug in 2023 for routine prevention and on-demand treatment for the control of bleeding episodes, in addition to perioperative surgery for adults.

That approval was extended to children as well at the time, based on earlier interim results from the XTEND-Kids trial.

The annualized bleeding rate among adult patients treated with efanesoctocog alfa decreased from 2.96 to 0.69 over the 52 weeks, which was a significantly greater improvement compared with prestudy prophylaxis with conventional factor VIII prophylaxis (P < .001).

In children and adults alike, the decreased bleeding events were accompanied by improvements in physical health, pain, and joint health.

“Weekly prophylaxis with efanesoctocog alfa has the potential to provide long-term preservation of joint health,” the authors conclude.

Commenting in an editorial published concurrently with the study, Pratima Chowdary, MD, of the Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, England, underscored the need for a longer duration of prophylaxis, particularly in children.

“In children, the factor VIII protein has a shorter half-life than in adults, and intravenous administration of coagulation factors is particularly challenging, owing to poor venous access,” she explains.

“In this context, a notable outcome in [the study] is the achievement of once-weekly prophylaxis in children with sustained factor VIII levels through the week, which augurs well for protection in the context of delayed or missed doses.”

Dr. Chowdary adds that limitations include that “the study participants had pre-existing tolerance of factor VIII, because only those with previous exposure to factor VIII and without inhibitors were eligible for enrollment.”

“As such, immunogenicity needs to be assessed in other patients, especially those with no previous treatment with factor VIII.”

Further commenting to this news organization, Dr. Chowdary emphasized “the key takeaway for patients with hemophilia is that the notion of a single, lifelong treatment is outdated.”

“Regular reviews and adjustments to prophylaxis are necessary to ensure optimal control of hemophilia, aiming for zero bleeds each year,” Dr. Chowdary noted.

Furthermore, “the treatment regimen to achieve this must also align with the life goals of both patients and their parents,” she said.

The study was supported by Sanofi and Sobi. The authors’ and Dr. Chowdary’s disclosures are published with the study and editorial, respectively.

Efanesoctocog alfa, a first-in-class, bioengineered human factor VIII replacement therapy, shows safety and efficacy in the prevention of bleeding in children with severe hemophilia A, with benefits similar to those observed in adults, new research shows.

“In this study, once-weekly efanesoctocog alfa provided high sustained factor VIII activity and highly efficacious protection against bleeding episodes in children with severe hemophilia A, a population in which this goal has been difficult to achieve without burdensome treatment regimens,” report the authors in the study, published in The New England Journal of Medicine.

The results are from the phase 3, open-label XTEND-Kids study, in which first author Lynn Malec, MD, medical director of the Comprehensive Center for Bleeding Disorders and associate professor of medicine and pediatrics at The Medical College of Wisconsin, in Milwaukee, and colleagues enrolled 74 male pediatric patients with hemophilia A, including 38 under the age of 6 and 36 ages 6-12.

The participants received prophylaxis with once-weekly efanesoctocog alfa (50 IU per kg of body weight), for 52 weeks.

Prior to the treatment period, all patients had received factor VIII replacement therapy, with the exception of one who received the therapy on demand. Most (70%) received extended half-life products, such as doses twice a week or every 3 days, and the remaining 30% received standard half-life products, with dose regimens ranging from every 2 days to twice a week.

Over the course of the year-long study, none of the patients developed factor VIII inhibitors, neutralizing antibodies, a common complication in hemophilia A that prevents factor VIII replacement treatment from working to form clots.

In addition, no serious adverse events occurred that were determined to be related to efanesoctocog alfa.

“No inhibitors to factor VIII developed, most adverse events were not serious, and no adverse events led to discontinuation of efanesoctocog alfa,” the authors report.

In terms of efficacy, among 73 patients who were treated according to the protocol, the median annualized bleeding rate was 0.00 and the model-based mean rate was 0.61.

Overall, 47 patients (64%) experienced no treated bleeding episodes during the study, 65 (88%) had no spontaneous bleeding episodes, and 61 (82%) had no episodes of bleeding into joints.

Of 43 bleeding episodes, most (41; 95%) resolved with a single injection of efanesoctocog alfa.

Of note, “shortening the weekly administration interval was not deemed to be necessary in any patient during this study,” the authors add.

In comparison, other studies of children receiving other factor VIII products, including damoctocog alfa pegol, rurioctocog alfa pegol, and efmoroctocog alfa, show higher annualized bleeding rates of 2.9, 2.0, and 1.96, respectively, and studies showed the percentages of patients with no bleeding with those products were 23%, 38%, and 46%, respectively, compared with the 64% in the current study of efanesoctocog alfa.

“Although these clinical study results cannot be directly compared because of the differences in patient populations and study designs, the XTEND-Kids study showed favorable bleeding protection with efanesoctocog alfa prophylaxis as compared with these extended half-life factor VIII products,” the authors report.

Data on the once-weekly monoclonal antibody emicizumab, which has the important benefit of being administered subcutaneously instead of intravenously, is limited in children under age 12 with severe hemophilia A and without factor VIII inhibitors, the authors note.

However, the mean annualized bleeding rate with efanesoctocog alfa appears improved compared with that observed in a small Japanese study of 13 children who received emicizumab prophylaxis every 2 weeks or every 4 weeks, which showed annualized rates of treated bleeding episodes of 1.3 and 0.7 with the respective emicizumab regimens.
 

Results Compare With Findings in Adults

The results are similar to those reported among adults in the previous XTEND-1 phase 3 study, which was the basis for US Food and Drug Administration (FDA) approval of the drug in 2023 for routine prevention and on-demand treatment for the control of bleeding episodes, in addition to perioperative surgery for adults.

That approval was extended to children as well at the time, based on earlier interim results from the XTEND-Kids trial.

The annualized bleeding rate among adult patients treated with efanesoctocog alfa decreased from 2.96 to 0.69 over the 52 weeks, which was a significantly greater improvement compared with prestudy prophylaxis with conventional factor VIII prophylaxis (P < .001).

In children and adults alike, the decreased bleeding events were accompanied by improvements in physical health, pain, and joint health.

“Weekly prophylaxis with efanesoctocog alfa has the potential to provide long-term preservation of joint health,” the authors conclude.

Commenting in an editorial published concurrently with the study, Pratima Chowdary, MD, of the Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, England, underscored the need for a longer duration of prophylaxis, particularly in children.

“In children, the factor VIII protein has a shorter half-life than in adults, and intravenous administration of coagulation factors is particularly challenging, owing to poor venous access,” she explains.

“In this context, a notable outcome in [the study] is the achievement of once-weekly prophylaxis in children with sustained factor VIII levels through the week, which augurs well for protection in the context of delayed or missed doses.”

Dr. Chowdary adds that limitations include that “the study participants had pre-existing tolerance of factor VIII, because only those with previous exposure to factor VIII and without inhibitors were eligible for enrollment.”

“As such, immunogenicity needs to be assessed in other patients, especially those with no previous treatment with factor VIII.”

Further commenting to this news organization, Dr. Chowdary emphasized “the key takeaway for patients with hemophilia is that the notion of a single, lifelong treatment is outdated.”

“Regular reviews and adjustments to prophylaxis are necessary to ensure optimal control of hemophilia, aiming for zero bleeds each year,” Dr. Chowdary noted.

Furthermore, “the treatment regimen to achieve this must also align with the life goals of both patients and their parents,” she said.

The study was supported by Sanofi and Sobi. The authors’ and Dr. Chowdary’s disclosures are published with the study and editorial, respectively.

Efanesoctocog alfa, a first-in-class, bioengineered human factor VIII replacement therapy, shows safety and efficacy in the prevention of bleeding in children with severe hemophilia A, with benefits similar to those observed in adults, new research shows.

“In this study, once-weekly efanesoctocog alfa provided high sustained factor VIII activity and highly efficacious protection against bleeding episodes in children with severe hemophilia A, a population in which this goal has been difficult to achieve without burdensome treatment regimens,” report the authors in the study, published in The New England Journal of Medicine.

The results are from the phase 3, open-label XTEND-Kids study, in which first author Lynn Malec, MD, medical director of the Comprehensive Center for Bleeding Disorders and associate professor of medicine and pediatrics at The Medical College of Wisconsin, in Milwaukee, and colleagues enrolled 74 male pediatric patients with hemophilia A, including 38 under the age of 6 and 36 ages 6-12.

The participants received prophylaxis with once-weekly efanesoctocog alfa (50 IU per kg of body weight), for 52 weeks.

Prior to the treatment period, all patients had received factor VIII replacement therapy, with the exception of one who received the therapy on demand. Most (70%) received extended half-life products, such as doses twice a week or every 3 days, and the remaining 30% received standard half-life products, with dose regimens ranging from every 2 days to twice a week.

Over the course of the year-long study, none of the patients developed factor VIII inhibitors, neutralizing antibodies, a common complication in hemophilia A that prevents factor VIII replacement treatment from working to form clots.

In addition, no serious adverse events occurred that were determined to be related to efanesoctocog alfa.

“No inhibitors to factor VIII developed, most adverse events were not serious, and no adverse events led to discontinuation of efanesoctocog alfa,” the authors report.

In terms of efficacy, among 73 patients who were treated according to the protocol, the median annualized bleeding rate was 0.00 and the model-based mean rate was 0.61.

Overall, 47 patients (64%) experienced no treated bleeding episodes during the study, 65 (88%) had no spontaneous bleeding episodes, and 61 (82%) had no episodes of bleeding into joints.

Of 43 bleeding episodes, most (41; 95%) resolved with a single injection of efanesoctocog alfa.

Of note, “shortening the weekly administration interval was not deemed to be necessary in any patient during this study,” the authors add.

In comparison, other studies of children receiving other factor VIII products, including damoctocog alfa pegol, rurioctocog alfa pegol, and efmoroctocog alfa, show higher annualized bleeding rates of 2.9, 2.0, and 1.96, respectively, and studies showed the percentages of patients with no bleeding with those products were 23%, 38%, and 46%, respectively, compared with the 64% in the current study of efanesoctocog alfa.

“Although these clinical study results cannot be directly compared because of the differences in patient populations and study designs, the XTEND-Kids study showed favorable bleeding protection with efanesoctocog alfa prophylaxis as compared with these extended half-life factor VIII products,” the authors report.

Data on the once-weekly monoclonal antibody emicizumab, which has the important benefit of being administered subcutaneously instead of intravenously, is limited in children under age 12 with severe hemophilia A and without factor VIII inhibitors, the authors note.

However, the mean annualized bleeding rate with efanesoctocog alfa appears improved compared with that observed in a small Japanese study of 13 children who received emicizumab prophylaxis every 2 weeks or every 4 weeks, which showed annualized rates of treated bleeding episodes of 1.3 and 0.7 with the respective emicizumab regimens.
 

Results Compare With Findings in Adults

The results are similar to those reported among adults in the previous XTEND-1 phase 3 study, which was the basis for US Food and Drug Administration (FDA) approval of the drug in 2023 for routine prevention and on-demand treatment for the control of bleeding episodes, in addition to perioperative surgery for adults.

That approval was extended to children as well at the time, based on earlier interim results from the XTEND-Kids trial.

The annualized bleeding rate among adult patients treated with efanesoctocog alfa decreased from 2.96 to 0.69 over the 52 weeks, which was a significantly greater improvement compared with prestudy prophylaxis with conventional factor VIII prophylaxis (P < .001).

In children and adults alike, the decreased bleeding events were accompanied by improvements in physical health, pain, and joint health.

“Weekly prophylaxis with efanesoctocog alfa has the potential to provide long-term preservation of joint health,” the authors conclude.

Commenting in an editorial published concurrently with the study, Pratima Chowdary, MD, of the Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, England, underscored the need for a longer duration of prophylaxis, particularly in children.

“In children, the factor VIII protein has a shorter half-life than in adults, and intravenous administration of coagulation factors is particularly challenging, owing to poor venous access,” she explains.

“In this context, a notable outcome in [the study] is the achievement of once-weekly prophylaxis in children with sustained factor VIII levels through the week, which augurs well for protection in the context of delayed or missed doses.”

Dr. Chowdary adds that limitations include that “the study participants had pre-existing tolerance of factor VIII, because only those with previous exposure to factor VIII and without inhibitors were eligible for enrollment.”

“As such, immunogenicity needs to be assessed in other patients, especially those with no previous treatment with factor VIII.”

Further commenting to this news organization, Dr. Chowdary emphasized “the key takeaway for patients with hemophilia is that the notion of a single, lifelong treatment is outdated.”

“Regular reviews and adjustments to prophylaxis are necessary to ensure optimal control of hemophilia, aiming for zero bleeds each year,” Dr. Chowdary noted.

Furthermore, “the treatment regimen to achieve this must also align with the life goals of both patients and their parents,” she said.

The study was supported by Sanofi and Sobi. The authors’ and Dr. Chowdary’s disclosures are published with the study and editorial, respectively.

TOPLINE:

Increased dietary intake of vitamin B1 is associated with a lower prevalence of constipation, particularly among men and individuals without hypertension or diabetes. 

METHODOLOGY:

• Researchers conducted a cross-sectional study using National Health and Nutrition Examination Survey data from 2005-2010 involving 10,371 adults aged ≥ 20 years.
• Participants provided information on fecal characteristics and bowel movement frequency, which was documented for 30 days prior to data collection.
• Constipation was established by either frequency of bowel movements (fewer than three per week) or stool consistency (Bristol Stool Scale type 1 or 2).
• Data on vitamin B1 intake were collected through 24-hour total nutritional intake recall interviews. Patients were divided into three groups based on their level of B1 intake: 0.064-1.21 mg, 1.21-1.76 mg, and 1.76-12.61 mg.

TAKEAWAY:

• Overall, 10.8% of participants were identified as having constipation.
• Greater dietary vitamin B1 intake was associated with a 23% reduction in constipation risk (P = .034).
• Additionally, a subgroup analysis found that higher B1 intake was associated with a reduction in constipation risk of 20% in men, 16% in people without hypertension, and 14% in those without diabetes.

IN PRACTICE:

“This association suggests that enhanced intake of vitamin B1 through diet may facilitate softer stools and heightened intestinal motility, thereby potentially alleviating constipation symptoms. Consequently, healthcare professionals are advised to prioritize the promotion of a well-balanced diet as an initial therapeutic approach, preceding medical interventions,” the authors wrote.

SOURCE:

The study, led by Wenyi Du, the Affiliated Stomatological Hospital of Soochow University, Suzhou Stomatological Hospital, Suzhou, China, and Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center, Wuxi, China, was published online in BMC Gastroenterology.

LIMITATIONS:

A causal relationship could not be established between vitamin B1 intake and constipation owing to the cross-sectional nature of the study. The study relied on patient interviews and patient self-reported data. Additionally, 24-hour dietary recalls may not have accurately reflected the long-term eating habits of the participants.

DISCLOSURES:

The study had no specific funding source. The authors declared no competing interests. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Increased dietary intake of vitamin B1 is associated with a lower prevalence of constipation, particularly among men and individuals without hypertension or diabetes. 

METHODOLOGY:

• Researchers conducted a cross-sectional study using National Health and Nutrition Examination Survey data from 2005-2010 involving 10,371 adults aged ≥ 20 years.
• Participants provided information on fecal characteristics and bowel movement frequency, which was documented for 30 days prior to data collection.
• Constipation was established by either frequency of bowel movements (fewer than three per week) or stool consistency (Bristol Stool Scale type 1 or 2).
• Data on vitamin B1 intake were collected through 24-hour total nutritional intake recall interviews. Patients were divided into three groups based on their level of B1 intake: 0.064-1.21 mg, 1.21-1.76 mg, and 1.76-12.61 mg.

TAKEAWAY:

• Overall, 10.8% of participants were identified as having constipation.
• Greater dietary vitamin B1 intake was associated with a 23% reduction in constipation risk (P = .034).
• Additionally, a subgroup analysis found that higher B1 intake was associated with a reduction in constipation risk of 20% in men, 16% in people without hypertension, and 14% in those without diabetes.

IN PRACTICE:

“This association suggests that enhanced intake of vitamin B1 through diet may facilitate softer stools and heightened intestinal motility, thereby potentially alleviating constipation symptoms. Consequently, healthcare professionals are advised to prioritize the promotion of a well-balanced diet as an initial therapeutic approach, preceding medical interventions,” the authors wrote.

SOURCE:

The study, led by Wenyi Du, the Affiliated Stomatological Hospital of Soochow University, Suzhou Stomatological Hospital, Suzhou, China, and Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center, Wuxi, China, was published online in BMC Gastroenterology.

LIMITATIONS:

A causal relationship could not be established between vitamin B1 intake and constipation owing to the cross-sectional nature of the study. The study relied on patient interviews and patient self-reported data. Additionally, 24-hour dietary recalls may not have accurately reflected the long-term eating habits of the participants.

DISCLOSURES:

The study had no specific funding source. The authors declared no competing interests. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Increased dietary intake of vitamin B1 is associated with a lower prevalence of constipation, particularly among men and individuals without hypertension or diabetes. 

METHODOLOGY:

• Researchers conducted a cross-sectional study using National Health and Nutrition Examination Survey data from 2005-2010 involving 10,371 adults aged ≥ 20 years.
• Participants provided information on fecal characteristics and bowel movement frequency, which was documented for 30 days prior to data collection.
• Constipation was established by either frequency of bowel movements (fewer than three per week) or stool consistency (Bristol Stool Scale type 1 or 2).
• Data on vitamin B1 intake were collected through 24-hour total nutritional intake recall interviews. Patients were divided into three groups based on their level of B1 intake: 0.064-1.21 mg, 1.21-1.76 mg, and 1.76-12.61 mg.

TAKEAWAY:

• Overall, 10.8% of participants were identified as having constipation.
• Greater dietary vitamin B1 intake was associated with a 23% reduction in constipation risk (P = .034).
• Additionally, a subgroup analysis found that higher B1 intake was associated with a reduction in constipation risk of 20% in men, 16% in people without hypertension, and 14% in those without diabetes.

IN PRACTICE:

“This association suggests that enhanced intake of vitamin B1 through diet may facilitate softer stools and heightened intestinal motility, thereby potentially alleviating constipation symptoms. Consequently, healthcare professionals are advised to prioritize the promotion of a well-balanced diet as an initial therapeutic approach, preceding medical interventions,” the authors wrote.

SOURCE:

The study, led by Wenyi Du, the Affiliated Stomatological Hospital of Soochow University, Suzhou Stomatological Hospital, Suzhou, China, and Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center, Wuxi, China, was published online in BMC Gastroenterology.

LIMITATIONS:

A causal relationship could not be established between vitamin B1 intake and constipation owing to the cross-sectional nature of the study. The study relied on patient interviews and patient self-reported data. Additionally, 24-hour dietary recalls may not have accurately reflected the long-term eating habits of the participants.

DISCLOSURES:

The study had no specific funding source. The authors declared no competing interests. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Primary care, family medicine, and mental health clinicians should ask every adolescent and young adult they care for if they take muscle-building supplements such as protein or creatine, according to a new commentary in the Journal of Adolescent Health.

Muscle-building supplements are not tested before going to market, as are pharmaceutical drugs, and they are associated with greater rates of death and disability in adolescents than are vitamin supplements such as A, C, and folate. Even if protein shakes or creatine gummies do not seem to negatively affect a teen, in many cases the needed nutrients are obtained from food intake, and supplements are not necessary.

“For many young people, particularly boys, use of these supplements is pretty ubiquitous,” said Kyle T. Ganson, PhD, MSW, assistant professor of social work at the University of Toronto, and author of the commentary.

Other research has shown that males are more likely to have eating disorders linked to muscle-building, in addition to being the largest number of consumers of muscle-building supplements.

Dr. Ganson’s research has shown that more than 80% of adolescent boys and young men take a protein supplement, and 50% or less take a creatine boost. But health clinicians may not know about use because they do not ask, Dr. Ganson added. 

After clinicians ask about use and learn that a teenager or young adult is taking a dietary supplement, they should use a harm reduction approach that encourages curtailing or modifying supplement use rather than insisting on total abstinence, Dr. Ganson and coauthors wrote. 

For example, a clinician can assess the patient’s dietary intake of carbohydrates, proteins, fats, calories, vitamins, and minerals, and, if appropriate, advise the teen that he or she can get all the necessary nutrients at mealtime. Michele LaBotz, MD, medical director of the Master of Science in Athletic Training program at the University of New England in Biddeford, Maine, said most teen boys and young adults will not listen to a clinician telling them about the potential harms from supplements.

However, counseling these patients that the supplements are probably a waste of money — muscles will develop just fine with a healthy diet and regular exercise — is more effective at reducing use, according to Dr. LaBotz, who was a sports medicine physician for nearly 20 years.

Keeping open lines of communication about supplements may open the door for teens to share that they are also using muscle-building steroids. Dr. Ganson said the step to a more dangerous product sometimes occurs after teens no longer perceive they are benefiting from supplements. 

“It’s not one conversation and you’re done: It’s about providing support and medical monitoring,” Dr. Ganson said. 

Dr. Ganson said his colleagues hope professional societies develop formal clinical practice guidelines about muscle-building supplements in teens and young adults.
 

Contaminated and Dangerous Supplements

Although any teenage boy may want to build muscles, athletes are of particular concern. Dr. LaBotz authored an American Academy of Pediatrics recommendation that young athletes adhere to appropriate nutrition and training programs rather than turning to supplements.

Adverse outcomes from muscle-building supplements can occur when the products are labeled deceptively. For example, what is sold as creatine sometimes contains other ingredients that may be harmful, such as deterenol or oxilofrine, which are not approved for use in the United States.

Words like “proprietary,” “blend,” or “complex” on a supplement label should raise red flags, according to Pieter Cohen, MD, associate professor at Harvard Medical School, Boston, and an internist at the Cambridge Health Alliance who advises clinicians and patients about the safe use of dietary supplements.

Unlike for pharmaceuticals, the US Food and Drug Administration (FDA) is not authorized to assess the safety of dietary supplements before they are sold to consumers. Supplement manufacturers are not required to disclose the quantity of each ingredient in a proprietary blend on product labels. By one estimate, 23,000 emergency department visits annually in the United States are due to adverse effects from dietary supplements, ranging from cardiac trouble to swallowing difficulties.

In general, Dr. Cohen said, supplements with fewer than six ingredients that have been certified by a third party are more likely than others to be safe. The Department of Defense provides a scorecard for consumers to help decipher which supplements are safer to use. 

“American consumers are the lab rats for these products,” said Bryn Austin, ScD, SM, professor of social sciences at the Harvard T.H. Chan School of Public Health, Boston, and director of a program that trains health professionals how to intervene to prevent eating disorders. “This industry invests a lot of money to invent a health halo for themselves. Muscle-building supplements can be downright dangerous and will not turn anyone into the elite athlete of their dreams.” 

The commentary authors reported no financial disclosures. 
 

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

Primary care, family medicine, and mental health clinicians should ask every adolescent and young adult they care for if they take muscle-building supplements such as protein or creatine, according to a new commentary in the Journal of Adolescent Health.

Muscle-building supplements are not tested before going to market, as are pharmaceutical drugs, and they are associated with greater rates of death and disability in adolescents than are vitamin supplements such as A, C, and folate. Even if protein shakes or creatine gummies do not seem to negatively affect a teen, in many cases the needed nutrients are obtained from food intake, and supplements are not necessary.

“For many young people, particularly boys, use of these supplements is pretty ubiquitous,” said Kyle T. Ganson, PhD, MSW, assistant professor of social work at the University of Toronto, and author of the commentary.

Other research has shown that males are more likely to have eating disorders linked to muscle-building, in addition to being the largest number of consumers of muscle-building supplements.

Dr. Ganson’s research has shown that more than 80% of adolescent boys and young men take a protein supplement, and 50% or less take a creatine boost. But health clinicians may not know about use because they do not ask, Dr. Ganson added. 

After clinicians ask about use and learn that a teenager or young adult is taking a dietary supplement, they should use a harm reduction approach that encourages curtailing or modifying supplement use rather than insisting on total abstinence, Dr. Ganson and coauthors wrote. 

For example, a clinician can assess the patient’s dietary intake of carbohydrates, proteins, fats, calories, vitamins, and minerals, and, if appropriate, advise the teen that he or she can get all the necessary nutrients at mealtime. Michele LaBotz, MD, medical director of the Master of Science in Athletic Training program at the University of New England in Biddeford, Maine, said most teen boys and young adults will not listen to a clinician telling them about the potential harms from supplements.

However, counseling these patients that the supplements are probably a waste of money — muscles will develop just fine with a healthy diet and regular exercise — is more effective at reducing use, according to Dr. LaBotz, who was a sports medicine physician for nearly 20 years.

Keeping open lines of communication about supplements may open the door for teens to share that they are also using muscle-building steroids. Dr. Ganson said the step to a more dangerous product sometimes occurs after teens no longer perceive they are benefiting from supplements. 

“It’s not one conversation and you’re done: It’s about providing support and medical monitoring,” Dr. Ganson said. 

Dr. Ganson said his colleagues hope professional societies develop formal clinical practice guidelines about muscle-building supplements in teens and young adults.
 

Contaminated and Dangerous Supplements

Although any teenage boy may want to build muscles, athletes are of particular concern. Dr. LaBotz authored an American Academy of Pediatrics recommendation that young athletes adhere to appropriate nutrition and training programs rather than turning to supplements.

Adverse outcomes from muscle-building supplements can occur when the products are labeled deceptively. For example, what is sold as creatine sometimes contains other ingredients that may be harmful, such as deterenol or oxilofrine, which are not approved for use in the United States.

Words like “proprietary,” “blend,” or “complex” on a supplement label should raise red flags, according to Pieter Cohen, MD, associate professor at Harvard Medical School, Boston, and an internist at the Cambridge Health Alliance who advises clinicians and patients about the safe use of dietary supplements.

Unlike for pharmaceuticals, the US Food and Drug Administration (FDA) is not authorized to assess the safety of dietary supplements before they are sold to consumers. Supplement manufacturers are not required to disclose the quantity of each ingredient in a proprietary blend on product labels. By one estimate, 23,000 emergency department visits annually in the United States are due to adverse effects from dietary supplements, ranging from cardiac trouble to swallowing difficulties.

In general, Dr. Cohen said, supplements with fewer than six ingredients that have been certified by a third party are more likely than others to be safe. The Department of Defense provides a scorecard for consumers to help decipher which supplements are safer to use. 

“American consumers are the lab rats for these products,” said Bryn Austin, ScD, SM, professor of social sciences at the Harvard T.H. Chan School of Public Health, Boston, and director of a program that trains health professionals how to intervene to prevent eating disorders. “This industry invests a lot of money to invent a health halo for themselves. Muscle-building supplements can be downright dangerous and will not turn anyone into the elite athlete of their dreams.” 

The commentary authors reported no financial disclosures. 
 

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

Primary care, family medicine, and mental health clinicians should ask every adolescent and young adult they care for if they take muscle-building supplements such as protein or creatine, according to a new commentary in the Journal of Adolescent Health.

Muscle-building supplements are not tested before going to market, as are pharmaceutical drugs, and they are associated with greater rates of death and disability in adolescents than are vitamin supplements such as A, C, and folate. Even if protein shakes or creatine gummies do not seem to negatively affect a teen, in many cases the needed nutrients are obtained from food intake, and supplements are not necessary.

“For many young people, particularly boys, use of these supplements is pretty ubiquitous,” said Kyle T. Ganson, PhD, MSW, assistant professor of social work at the University of Toronto, and author of the commentary.

Other research has shown that males are more likely to have eating disorders linked to muscle-building, in addition to being the largest number of consumers of muscle-building supplements.

Dr. Ganson’s research has shown that more than 80% of adolescent boys and young men take a protein supplement, and 50% or less take a creatine boost. But health clinicians may not know about use because they do not ask, Dr. Ganson added. 

After clinicians ask about use and learn that a teenager or young adult is taking a dietary supplement, they should use a harm reduction approach that encourages curtailing or modifying supplement use rather than insisting on total abstinence, Dr. Ganson and coauthors wrote. 

For example, a clinician can assess the patient’s dietary intake of carbohydrates, proteins, fats, calories, vitamins, and minerals, and, if appropriate, advise the teen that he or she can get all the necessary nutrients at mealtime. Michele LaBotz, MD, medical director of the Master of Science in Athletic Training program at the University of New England in Biddeford, Maine, said most teen boys and young adults will not listen to a clinician telling them about the potential harms from supplements.

However, counseling these patients that the supplements are probably a waste of money — muscles will develop just fine with a healthy diet and regular exercise — is more effective at reducing use, according to Dr. LaBotz, who was a sports medicine physician for nearly 20 years.

Keeping open lines of communication about supplements may open the door for teens to share that they are also using muscle-building steroids. Dr. Ganson said the step to a more dangerous product sometimes occurs after teens no longer perceive they are benefiting from supplements. 

“It’s not one conversation and you’re done: It’s about providing support and medical monitoring,” Dr. Ganson said. 

Dr. Ganson said his colleagues hope professional societies develop formal clinical practice guidelines about muscle-building supplements in teens and young adults.
 

Contaminated and Dangerous Supplements

Although any teenage boy may want to build muscles, athletes are of particular concern. Dr. LaBotz authored an American Academy of Pediatrics recommendation that young athletes adhere to appropriate nutrition and training programs rather than turning to supplements.

Adverse outcomes from muscle-building supplements can occur when the products are labeled deceptively. For example, what is sold as creatine sometimes contains other ingredients that may be harmful, such as deterenol or oxilofrine, which are not approved for use in the United States.

Words like “proprietary,” “blend,” or “complex” on a supplement label should raise red flags, according to Pieter Cohen, MD, associate professor at Harvard Medical School, Boston, and an internist at the Cambridge Health Alliance who advises clinicians and patients about the safe use of dietary supplements.

Unlike for pharmaceuticals, the US Food and Drug Administration (FDA) is not authorized to assess the safety of dietary supplements before they are sold to consumers. Supplement manufacturers are not required to disclose the quantity of each ingredient in a proprietary blend on product labels. By one estimate, 23,000 emergency department visits annually in the United States are due to adverse effects from dietary supplements, ranging from cardiac trouble to swallowing difficulties.

In general, Dr. Cohen said, supplements with fewer than six ingredients that have been certified by a third party are more likely than others to be safe. The Department of Defense provides a scorecard for consumers to help decipher which supplements are safer to use. 

“American consumers are the lab rats for these products,” said Bryn Austin, ScD, SM, professor of social sciences at the Harvard T.H. Chan School of Public Health, Boston, and director of a program that trains health professionals how to intervene to prevent eating disorders. “This industry invests a lot of money to invent a health halo for themselves. Muscle-building supplements can be downright dangerous and will not turn anyone into the elite athlete of their dreams.” 

The commentary authors reported no financial disclosures. 
 

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

TOPLINE:

Over the past 20 years in Denmark, the incidence of type 2 diabetes–related outcomes and many treatment-related harms have both decreased without increased medication expenses despite an aging and more comorbid population; however, challenges remain.

METHODOLOGY:

• Analysis of data from 461,805 individuals in the Danish population with type 2 diabetes between 2002 and 2020.
• Multivariate analyses adjusted for potential confounders, including age, sex, and socioeconomic status.

TAKEAWAY:

• The population grew 2.7-fold from 2002 to 2020 (n = 113,105 to 306,962), the median age increased from 66 to 68 years, and the mean number of diseases per person increased from 5.2 to 8.8, with an increase in Charlson Comorbidity Index from 1.78 to 1.93.
• After adjustments, mortality per 1000 person-years decreased by 28% from 2002 to 2020, with the largest risk reduction, 63%, in acute myocardial infarction.
• The mean number of annually redeemed medications per person increased from 8.1 to 9.0, with statin and antihypertensive use increasing to 65% and 69%, respectively.
• Antiplatelet medication (aspirin and clopidogrel) use peaked at 48% in 2009 and dropped to 31% in 2020.
• Anticoagulant (warfarin and direct-acting oral anticoagulants) use gradually increased from 5% in 2002 to 14% in 2020.
• For glucose-lowering treatment, there was a shift away from using sulfonylureas to metformin and other medications.
• Diagnoses of hypoglycemia, falls, and gastric bleeding decreased over the study period, but incidences of volume depletion, ketoacidosis, infections, and electrolyte imbalances requiring hospitalization increased.
• Cumulative expenses for the population increased from €132,000,000 to €327,000,000 (approximately $144,406,680 to $357,734,730), corresponding to a 148% increase over the study period.
• However, the average medication cost per individual was 8% less in 2020 compared with 2002 despite increasing medication use, mainly driven by reduced costs of antiplatelets, antihypertensives, and statins, among others.
• In contrast, expenses for glucose-lowering medications have gradually increased, with the average more than doubling (138% increase) from €220 ($240) in 2002 to €524 ($573) in 2020.

IN PRACTICE:

“Although these trends suggest improvements in rational pharmacotherapy, they cannot be solely attributed to improved pharmacotherapy and appear to be multifactorial,” the authors wrote.

“Advancements in diabetes management have improved the balance between medication benefits, harms, and costs ... Remaining challenges, such as an increased risk of ketoacidosis and electrolyte imbalances as well as rising costs for glucose-lowering medications, highlight the importance of individualized treatment and continuous risk-benefits evaluations,” they added.
 

SOURCE:

This study was conducted by Karl Sebastian Johansson, of the Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues and was published online in Diabetes Care.

LIMITATIONS:

Analysis was confined to events diagnosed in hospital-based inpatient and outpatient settings, not primary healthcare. Only predefined adverse events were analyzed.

DISCLOSURES:

The study was funded by the Capital Region of Denmark. The authors reported no potential conflicts of interest relevant to this article.

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

TOPLINE:

Over the past 20 years in Denmark, the incidence of type 2 diabetes–related outcomes and many treatment-related harms have both decreased without increased medication expenses despite an aging and more comorbid population; however, challenges remain.

METHODOLOGY:

• Analysis of data from 461,805 individuals in the Danish population with type 2 diabetes between 2002 and 2020.
• Multivariate analyses adjusted for potential confounders, including age, sex, and socioeconomic status.

TAKEAWAY:

• The population grew 2.7-fold from 2002 to 2020 (n = 113,105 to 306,962), the median age increased from 66 to 68 years, and the mean number of diseases per person increased from 5.2 to 8.8, with an increase in Charlson Comorbidity Index from 1.78 to 1.93.
• After adjustments, mortality per 1000 person-years decreased by 28% from 2002 to 2020, with the largest risk reduction, 63%, in acute myocardial infarction.
• The mean number of annually redeemed medications per person increased from 8.1 to 9.0, with statin and antihypertensive use increasing to 65% and 69%, respectively.
• Antiplatelet medication (aspirin and clopidogrel) use peaked at 48% in 2009 and dropped to 31% in 2020.
• Anticoagulant (warfarin and direct-acting oral anticoagulants) use gradually increased from 5% in 2002 to 14% in 2020.
• For glucose-lowering treatment, there was a shift away from using sulfonylureas to metformin and other medications.
• Diagnoses of hypoglycemia, falls, and gastric bleeding decreased over the study period, but incidences of volume depletion, ketoacidosis, infections, and electrolyte imbalances requiring hospitalization increased.
• Cumulative expenses for the population increased from €132,000,000 to €327,000,000 (approximately $144,406,680 to $357,734,730), corresponding to a 148% increase over the study period.
• However, the average medication cost per individual was 8% less in 2020 compared with 2002 despite increasing medication use, mainly driven by reduced costs of antiplatelets, antihypertensives, and statins, among others.
• In contrast, expenses for glucose-lowering medications have gradually increased, with the average more than doubling (138% increase) from €220 ($240) in 2002 to €524 ($573) in 2020.

IN PRACTICE:

“Although these trends suggest improvements in rational pharmacotherapy, they cannot be solely attributed to improved pharmacotherapy and appear to be multifactorial,” the authors wrote.

“Advancements in diabetes management have improved the balance between medication benefits, harms, and costs ... Remaining challenges, such as an increased risk of ketoacidosis and electrolyte imbalances as well as rising costs for glucose-lowering medications, highlight the importance of individualized treatment and continuous risk-benefits evaluations,” they added.
 

SOURCE:

This study was conducted by Karl Sebastian Johansson, of the Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues and was published online in Diabetes Care.

LIMITATIONS:

Analysis was confined to events diagnosed in hospital-based inpatient and outpatient settings, not primary healthcare. Only predefined adverse events were analyzed.

DISCLOSURES:

The study was funded by the Capital Region of Denmark. The authors reported no potential conflicts of interest relevant to this article.

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

TOPLINE:

Over the past 20 years in Denmark, the incidence of type 2 diabetes–related outcomes and many treatment-related harms have both decreased without increased medication expenses despite an aging and more comorbid population; however, challenges remain.

METHODOLOGY:

• Analysis of data from 461,805 individuals in the Danish population with type 2 diabetes between 2002 and 2020.
• Multivariate analyses adjusted for potential confounders, including age, sex, and socioeconomic status.

TAKEAWAY:

• The population grew 2.7-fold from 2002 to 2020 (n = 113,105 to 306,962), the median age increased from 66 to 68 years, and the mean number of diseases per person increased from 5.2 to 8.8, with an increase in Charlson Comorbidity Index from 1.78 to 1.93.
• After adjustments, mortality per 1000 person-years decreased by 28% from 2002 to 2020, with the largest risk reduction, 63%, in acute myocardial infarction.
• The mean number of annually redeemed medications per person increased from 8.1 to 9.0, with statin and antihypertensive use increasing to 65% and 69%, respectively.
• Antiplatelet medication (aspirin and clopidogrel) use peaked at 48% in 2009 and dropped to 31% in 2020.
• Anticoagulant (warfarin and direct-acting oral anticoagulants) use gradually increased from 5% in 2002 to 14% in 2020.
• For glucose-lowering treatment, there was a shift away from using sulfonylureas to metformin and other medications.
• Diagnoses of hypoglycemia, falls, and gastric bleeding decreased over the study period, but incidences of volume depletion, ketoacidosis, infections, and electrolyte imbalances requiring hospitalization increased.
• Cumulative expenses for the population increased from €132,000,000 to €327,000,000 (approximately $144,406,680 to $357,734,730), corresponding to a 148% increase over the study period.
• However, the average medication cost per individual was 8% less in 2020 compared with 2002 despite increasing medication use, mainly driven by reduced costs of antiplatelets, antihypertensives, and statins, among others.
• In contrast, expenses for glucose-lowering medications have gradually increased, with the average more than doubling (138% increase) from €220 ($240) in 2002 to €524 ($573) in 2020.

IN PRACTICE:

“Although these trends suggest improvements in rational pharmacotherapy, they cannot be solely attributed to improved pharmacotherapy and appear to be multifactorial,” the authors wrote.

“Advancements in diabetes management have improved the balance between medication benefits, harms, and costs ... Remaining challenges, such as an increased risk of ketoacidosis and electrolyte imbalances as well as rising costs for glucose-lowering medications, highlight the importance of individualized treatment and continuous risk-benefits evaluations,” they added.
 

SOURCE:

This study was conducted by Karl Sebastian Johansson, of the Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues and was published online in Diabetes Care.

LIMITATIONS:

Analysis was confined to events diagnosed in hospital-based inpatient and outpatient settings, not primary healthcare. Only predefined adverse events were analyzed.

DISCLOSURES:

The study was funded by the Capital Region of Denmark. The authors reported no potential conflicts of interest relevant to this article.

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

TOPLINE:

The transvaginal ultrasonography triage strategy is unreliable for diagnosing endometrial cancer in high-risk Black women, with a significant risk for false-negative results at different endometrial thickness thresholds.

METHODOLOGY:

• Poor performance of transvaginal ultrasonography-measured endometrial thickness as a diagnostic triage strategy for endometrial cancer may contribute to racial disparity in stage at diagnosis between Black and White women.
• Researchers assessed the false-negative probability using transvaginal ultrasonography-measured endometrial thickness thresholds as triage for endometrial cancer in 1494 Black women (median age, 46 years) who underwent hysterectomy.
• The researchers focused on endometrial thickness measurements recorded within 24 months before hysterectomy, as well as demographic and clinical data.
• The endometrial thickness thresholds were defined as < 3 mm, < 4 mm, and < 5 mm, with the rest grouped as ≥ 5 mm, consistent with guidelines.
• A total of 210 women had endometrial cancer. The most common presenting symptoms were fibroids (78%), vaginal bleeding (71%), and pelvic pain (57%).

TAKEAWAY:

• Twenty-four cases of endometrial cancer were below the 5-mm endometrial thickness threshold that would trigger biopsy, resulting overall in 11.4% of endometrial cancer cases potentially missed.
• The false-negative probability was 9.5% (20 cases) at the < 4-mm threshold and 3.8% (8 cases) at the < 3-mm threshold.
• Classic risk factors for endometrial cancer (postmenopausal bleeding, age ≥ 50 years, and BMI > 40) did not result in improved performance of the endometrial thickness triage strategy.
• False-negative probability was also similar among those with fibroids (12%) but higher in the setting of partial endometrial thickness visibility (26%) and pelvic pain (15%).

IN PRACTICE:

This study reveals a “concerning error rate for a triage strategy that would terminate further workup and provide false reassurance to both patients and physicians.” The results contribute to “an increasing body of work questioning the wisdom of the (transvaginal ultrasonography) triage strategy. It may be the case that the (transvaginal ultrasonography) triage for endometrial biopsy is no longer a preferred strategy in the setting of increasing endometrial cancer rates for all. For Black patients with concerning symptoms, tissue biopsy is recommended to avoid misdiagnosis of endometrial cancer,” the researchers concluded.

SOURCE:

The study, with first author Kemi M. Doll, MD, Fred Hutchinson Cancer Center, University of Washington, Seattle, was published online in JAMA Oncology.

LIMITATIONS:

The study did not include cases where transvaginal ultrasonography reports omitted endometrial thickness measurements or reported nonvisible endometrial thickness, possibly underestimating the failure rate of the transvaginal ultrasonography triage strategy.

The sample did not include endometrial cancer cases that were not treated with hysterectomy, which may occur in young women with grade 1 endometrial cancer, those medically incapable of undergoing surgery, and those with disease so advanced that surgery is no longer an option. 
 

DISCLOSURES:

Funding was provided by Kuni Discovery Grants for Cancer Research: Advancing Innovation and by a grant from the National Institutes of Health. Dr. Doll reported receiving investigator-initiated research grants from the Patient Centered Outcomes Research Institute, American Association of Cancer Research, and Merck.

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

TOPLINE:

The transvaginal ultrasonography triage strategy is unreliable for diagnosing endometrial cancer in high-risk Black women, with a significant risk for false-negative results at different endometrial thickness thresholds.

METHODOLOGY:

• Poor performance of transvaginal ultrasonography-measured endometrial thickness as a diagnostic triage strategy for endometrial cancer may contribute to racial disparity in stage at diagnosis between Black and White women.
• Researchers assessed the false-negative probability using transvaginal ultrasonography-measured endometrial thickness thresholds as triage for endometrial cancer in 1494 Black women (median age, 46 years) who underwent hysterectomy.
• The researchers focused on endometrial thickness measurements recorded within 24 months before hysterectomy, as well as demographic and clinical data.
• The endometrial thickness thresholds were defined as < 3 mm, < 4 mm, and < 5 mm, with the rest grouped as ≥ 5 mm, consistent with guidelines.
• A total of 210 women had endometrial cancer. The most common presenting symptoms were fibroids (78%), vaginal bleeding (71%), and pelvic pain (57%).

TAKEAWAY:

• Twenty-four cases of endometrial cancer were below the 5-mm endometrial thickness threshold that would trigger biopsy, resulting overall in 11.4% of endometrial cancer cases potentially missed.
• The false-negative probability was 9.5% (20 cases) at the < 4-mm threshold and 3.8% (8 cases) at the < 3-mm threshold.
• Classic risk factors for endometrial cancer (postmenopausal bleeding, age ≥ 50 years, and BMI > 40) did not result in improved performance of the endometrial thickness triage strategy.
• False-negative probability was also similar among those with fibroids (12%) but higher in the setting of partial endometrial thickness visibility (26%) and pelvic pain (15%).

IN PRACTICE:

This study reveals a “concerning error rate for a triage strategy that would terminate further workup and provide false reassurance to both patients and physicians.” The results contribute to “an increasing body of work questioning the wisdom of the (transvaginal ultrasonography) triage strategy. It may be the case that the (transvaginal ultrasonography) triage for endometrial biopsy is no longer a preferred strategy in the setting of increasing endometrial cancer rates for all. For Black patients with concerning symptoms, tissue biopsy is recommended to avoid misdiagnosis of endometrial cancer,” the researchers concluded.

SOURCE:

The study, with first author Kemi M. Doll, MD, Fred Hutchinson Cancer Center, University of Washington, Seattle, was published online in JAMA Oncology.

LIMITATIONS:

The study did not include cases where transvaginal ultrasonography reports omitted endometrial thickness measurements or reported nonvisible endometrial thickness, possibly underestimating the failure rate of the transvaginal ultrasonography triage strategy.

The sample did not include endometrial cancer cases that were not treated with hysterectomy, which may occur in young women with grade 1 endometrial cancer, those medically incapable of undergoing surgery, and those with disease so advanced that surgery is no longer an option. 
 

DISCLOSURES:

Funding was provided by Kuni Discovery Grants for Cancer Research: Advancing Innovation and by a grant from the National Institutes of Health. Dr. Doll reported receiving investigator-initiated research grants from the Patient Centered Outcomes Research Institute, American Association of Cancer Research, and Merck.

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

TOPLINE:

The transvaginal ultrasonography triage strategy is unreliable for diagnosing endometrial cancer in high-risk Black women, with a significant risk for false-negative results at different endometrial thickness thresholds.

METHODOLOGY:

• Poor performance of transvaginal ultrasonography-measured endometrial thickness as a diagnostic triage strategy for endometrial cancer may contribute to racial disparity in stage at diagnosis between Black and White women.
• Researchers assessed the false-negative probability using transvaginal ultrasonography-measured endometrial thickness thresholds as triage for endometrial cancer in 1494 Black women (median age, 46 years) who underwent hysterectomy.
• The researchers focused on endometrial thickness measurements recorded within 24 months before hysterectomy, as well as demographic and clinical data.
• The endometrial thickness thresholds were defined as < 3 mm, < 4 mm, and < 5 mm, with the rest grouped as ≥ 5 mm, consistent with guidelines.
• A total of 210 women had endometrial cancer. The most common presenting symptoms were fibroids (78%), vaginal bleeding (71%), and pelvic pain (57%).

TAKEAWAY:

• Twenty-four cases of endometrial cancer were below the 5-mm endometrial thickness threshold that would trigger biopsy, resulting overall in 11.4% of endometrial cancer cases potentially missed.
• The false-negative probability was 9.5% (20 cases) at the < 4-mm threshold and 3.8% (8 cases) at the < 3-mm threshold.
• Classic risk factors for endometrial cancer (postmenopausal bleeding, age ≥ 50 years, and BMI > 40) did not result in improved performance of the endometrial thickness triage strategy.
• False-negative probability was also similar among those with fibroids (12%) but higher in the setting of partial endometrial thickness visibility (26%) and pelvic pain (15%).

IN PRACTICE:

This study reveals a “concerning error rate for a triage strategy that would terminate further workup and provide false reassurance to both patients and physicians.” The results contribute to “an increasing body of work questioning the wisdom of the (transvaginal ultrasonography) triage strategy. It may be the case that the (transvaginal ultrasonography) triage for endometrial biopsy is no longer a preferred strategy in the setting of increasing endometrial cancer rates for all. For Black patients with concerning symptoms, tissue biopsy is recommended to avoid misdiagnosis of endometrial cancer,” the researchers concluded.

SOURCE:

The study, with first author Kemi M. Doll, MD, Fred Hutchinson Cancer Center, University of Washington, Seattle, was published online in JAMA Oncology.

LIMITATIONS:

The study did not include cases where transvaginal ultrasonography reports omitted endometrial thickness measurements or reported nonvisible endometrial thickness, possibly underestimating the failure rate of the transvaginal ultrasonography triage strategy.

The sample did not include endometrial cancer cases that were not treated with hysterectomy, which may occur in young women with grade 1 endometrial cancer, those medically incapable of undergoing surgery, and those with disease so advanced that surgery is no longer an option. 
 

DISCLOSURES:

Funding was provided by Kuni Discovery Grants for Cancer Research: Advancing Innovation and by a grant from the National Institutes of Health. Dr. Doll reported receiving investigator-initiated research grants from the Patient Centered Outcomes Research Institute, American Association of Cancer Research, and Merck.

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

An accelerated schedule of intermittent theta burst transcranial magnetic stimulation (aiTBS) completed in less than a week is effective for treatment-resistant bipolar depression, the results of a small randomized controlled trial showed.

Investigators found those who received active aiTBS had a substantial decrease in depressive symptoms compared with those who received sham stimulation.

“aiTBS offers a new potential therapy for depressed patients with bipolar disorder who may not respond well to drugs or cannot tolerate their side effects while also significantly shortening the treatment window,” lead researcher Yvette Sheline, MD, director of the Center for Neuromodulation in Depression and Stress at the University of Pennsylvania, Philadelphia, said in a news release.

The study was published online in JAMA Psychiatry.
 

Remission After 5 Days

The Food and Drug Administration (FDA) cleared aiTBS to treat major depressive disorder. However, the treatment is not yet approved for bipolar depression.

The investigators assessed the effectiveness of aiTBS in 12 men and 12 women (mean age, 43 years) with treatment-resistant bipolar disorder. All participants were on mood stabilizers for at least 4 weeks and had Montgomery-Åsberg Depression Rating Scale (MADRS) scores of 20 or greater.

Of the 24 participants, 22 had a diagnosis of bipolar II disorder. Over 5 days, participants were randomized to receive, on a 1:1 basis, 10 sessions per day of imaging-guided active aiTBS or sham aiTBS over the left dorsolateral prefrontal cortex. Each session lasted for 1 hour. All 24 participants completed the assigned treatment and 1-month follow-up.

Active aiTBS was significantly more effective than sham stimulation in relieving depressive symptoms.

In the active treatment group, MADRS scores dropped from a mean of 30.4 at baseline to 10.5 after treatment. In contrast, the sham group experienced a minor change in MADRS scores, which decreased from a mean of 28.0 at baseline to 25.3 posttreatment.

After 5 days of treatment, half of the participants in the active aiTBS group were in remission, compared with none in the sham group.

The results demonstrate the “clinical efficacy and a short time to achieve improvement in this difficult-to-treat condition. The effect was seen even though the participant sample had high depression severity and treatment resistance, both associated with poor response,” the investigators noted.

Dr. Sheline said there were no differences between active and sham stimulation in the “expected adverse events of headache and dizziness. There were no incidences of manic “flip,” and the Young Mania Rating Scale scores were stable in both active and sham groups with no difference between them.”

The researchers noted that the “large effect size” of active aiTBS could be caused by several factors, including optimized stimulation targeting, accelerated time course, and high pulse number (18,000 per day, 90,000 total).

Future studies are needed to examine the relative contributions of the different protocol components to optimize and personalize treatment and evaluate the durability of the antidepressant effects of aiTBS, they added.
 

A Revolutionary Approach

For comment on the study, we reached out to Nolan Williams, MD, associate professor of psychiatry and behavioral sciences at Stanford University and director of the Stanford Brain Stimulation Lab, Stanford, California.

His laboratory pioneered the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), which was cleared by the FDA in 2022 for treatment-resistant depression.

Dr. Williams noted that the stimulation and targeting approach used in the current study “mirrors most aspects of the SAINT protocol with very similar results.”

“It’s exciting that we see this kind of pseudo-replication essentially of our work and is supportive of the general view that this approach is revolutionary in its ability to treat people quickly and have such a dramatic clinical effect,” said Dr. Williams.

In March 2024, Dr. Williams and colleagues reported the results of a pilot study of SAINT for bipolar depression, which demonstrated antidepressant efficacy akin to what was observed in the unipolar depression population.

Dr. Williams said, in his experience, the accelerated treatment protocol is convenient and well-liked by patients and, in general, is where the field of psychiatric treatment is headed.

“A general theme that we see in depression and psychiatry is that patients no longer accept long time frames for treatment as being the norm. Whether it be ketamine or this or the upcoming psychedelics, rapid-acting treatments that match the level of acuity will be the norm,” Dr. Williams said.

The study was funded by the Milken Institute and the Baszucki Brain Research Fund. The authors have disclosed no conflicts of interest. Dr. Williams is a named inventor on Stanford-owned intellectual property relating to accelerated TMS pulse pattern sequences and neuroimaging-based TMS targeting. He disclosed ties with Otsuka, NeuraWell, Magnus Medical, and Nooma.

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

An accelerated schedule of intermittent theta burst transcranial magnetic stimulation (aiTBS) completed in less than a week is effective for treatment-resistant bipolar depression, the results of a small randomized controlled trial showed.

Investigators found those who received active aiTBS had a substantial decrease in depressive symptoms compared with those who received sham stimulation.

“aiTBS offers a new potential therapy for depressed patients with bipolar disorder who may not respond well to drugs or cannot tolerate their side effects while also significantly shortening the treatment window,” lead researcher Yvette Sheline, MD, director of the Center for Neuromodulation in Depression and Stress at the University of Pennsylvania, Philadelphia, said in a news release.

The study was published online in JAMA Psychiatry.
 

Remission After 5 Days

The Food and Drug Administration (FDA) cleared aiTBS to treat major depressive disorder. However, the treatment is not yet approved for bipolar depression.

The investigators assessed the effectiveness of aiTBS in 12 men and 12 women (mean age, 43 years) with treatment-resistant bipolar disorder. All participants were on mood stabilizers for at least 4 weeks and had Montgomery-Åsberg Depression Rating Scale (MADRS) scores of 20 or greater.

Of the 24 participants, 22 had a diagnosis of bipolar II disorder. Over 5 days, participants were randomized to receive, on a 1:1 basis, 10 sessions per day of imaging-guided active aiTBS or sham aiTBS over the left dorsolateral prefrontal cortex. Each session lasted for 1 hour. All 24 participants completed the assigned treatment and 1-month follow-up.

Active aiTBS was significantly more effective than sham stimulation in relieving depressive symptoms.

In the active treatment group, MADRS scores dropped from a mean of 30.4 at baseline to 10.5 after treatment. In contrast, the sham group experienced a minor change in MADRS scores, which decreased from a mean of 28.0 at baseline to 25.3 posttreatment.

After 5 days of treatment, half of the participants in the active aiTBS group were in remission, compared with none in the sham group.

The results demonstrate the “clinical efficacy and a short time to achieve improvement in this difficult-to-treat condition. The effect was seen even though the participant sample had high depression severity and treatment resistance, both associated with poor response,” the investigators noted.

Dr. Sheline said there were no differences between active and sham stimulation in the “expected adverse events of headache and dizziness. There were no incidences of manic “flip,” and the Young Mania Rating Scale scores were stable in both active and sham groups with no difference between them.”

The researchers noted that the “large effect size” of active aiTBS could be caused by several factors, including optimized stimulation targeting, accelerated time course, and high pulse number (18,000 per day, 90,000 total).

Future studies are needed to examine the relative contributions of the different protocol components to optimize and personalize treatment and evaluate the durability of the antidepressant effects of aiTBS, they added.
 

A Revolutionary Approach

For comment on the study, we reached out to Nolan Williams, MD, associate professor of psychiatry and behavioral sciences at Stanford University and director of the Stanford Brain Stimulation Lab, Stanford, California.

His laboratory pioneered the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), which was cleared by the FDA in 2022 for treatment-resistant depression.

Dr. Williams noted that the stimulation and targeting approach used in the current study “mirrors most aspects of the SAINT protocol with very similar results.”

“It’s exciting that we see this kind of pseudo-replication essentially of our work and is supportive of the general view that this approach is revolutionary in its ability to treat people quickly and have such a dramatic clinical effect,” said Dr. Williams.

In March 2024, Dr. Williams and colleagues reported the results of a pilot study of SAINT for bipolar depression, which demonstrated antidepressant efficacy akin to what was observed in the unipolar depression population.

Dr. Williams said, in his experience, the accelerated treatment protocol is convenient and well-liked by patients and, in general, is where the field of psychiatric treatment is headed.

“A general theme that we see in depression and psychiatry is that patients no longer accept long time frames for treatment as being the norm. Whether it be ketamine or this or the upcoming psychedelics, rapid-acting treatments that match the level of acuity will be the norm,” Dr. Williams said.

The study was funded by the Milken Institute and the Baszucki Brain Research Fund. The authors have disclosed no conflicts of interest. Dr. Williams is a named inventor on Stanford-owned intellectual property relating to accelerated TMS pulse pattern sequences and neuroimaging-based TMS targeting. He disclosed ties with Otsuka, NeuraWell, Magnus Medical, and Nooma.

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

An accelerated schedule of intermittent theta burst transcranial magnetic stimulation (aiTBS) completed in less than a week is effective for treatment-resistant bipolar depression, the results of a small randomized controlled trial showed.

Investigators found those who received active aiTBS had a substantial decrease in depressive symptoms compared with those who received sham stimulation.

“aiTBS offers a new potential therapy for depressed patients with bipolar disorder who may not respond well to drugs or cannot tolerate their side effects while also significantly shortening the treatment window,” lead researcher Yvette Sheline, MD, director of the Center for Neuromodulation in Depression and Stress at the University of Pennsylvania, Philadelphia, said in a news release.

The study was published online in JAMA Psychiatry.
 

Remission After 5 Days

The Food and Drug Administration (FDA) cleared aiTBS to treat major depressive disorder. However, the treatment is not yet approved for bipolar depression.

The investigators assessed the effectiveness of aiTBS in 12 men and 12 women (mean age, 43 years) with treatment-resistant bipolar disorder. All participants were on mood stabilizers for at least 4 weeks and had Montgomery-Åsberg Depression Rating Scale (MADRS) scores of 20 or greater.

Of the 24 participants, 22 had a diagnosis of bipolar II disorder. Over 5 days, participants were randomized to receive, on a 1:1 basis, 10 sessions per day of imaging-guided active aiTBS or sham aiTBS over the left dorsolateral prefrontal cortex. Each session lasted for 1 hour. All 24 participants completed the assigned treatment and 1-month follow-up.

Active aiTBS was significantly more effective than sham stimulation in relieving depressive symptoms.

In the active treatment group, MADRS scores dropped from a mean of 30.4 at baseline to 10.5 after treatment. In contrast, the sham group experienced a minor change in MADRS scores, which decreased from a mean of 28.0 at baseline to 25.3 posttreatment.

After 5 days of treatment, half of the participants in the active aiTBS group were in remission, compared with none in the sham group.

The results demonstrate the “clinical efficacy and a short time to achieve improvement in this difficult-to-treat condition. The effect was seen even though the participant sample had high depression severity and treatment resistance, both associated with poor response,” the investigators noted.

Dr. Sheline said there were no differences between active and sham stimulation in the “expected adverse events of headache and dizziness. There were no incidences of manic “flip,” and the Young Mania Rating Scale scores were stable in both active and sham groups with no difference between them.”

The researchers noted that the “large effect size” of active aiTBS could be caused by several factors, including optimized stimulation targeting, accelerated time course, and high pulse number (18,000 per day, 90,000 total).

Future studies are needed to examine the relative contributions of the different protocol components to optimize and personalize treatment and evaluate the durability of the antidepressant effects of aiTBS, they added.
 

A Revolutionary Approach

For comment on the study, we reached out to Nolan Williams, MD, associate professor of psychiatry and behavioral sciences at Stanford University and director of the Stanford Brain Stimulation Lab, Stanford, California.

His laboratory pioneered the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), which was cleared by the FDA in 2022 for treatment-resistant depression.

Dr. Williams noted that the stimulation and targeting approach used in the current study “mirrors most aspects of the SAINT protocol with very similar results.”

“It’s exciting that we see this kind of pseudo-replication essentially of our work and is supportive of the general view that this approach is revolutionary in its ability to treat people quickly and have such a dramatic clinical effect,” said Dr. Williams.

In March 2024, Dr. Williams and colleagues reported the results of a pilot study of SAINT for bipolar depression, which demonstrated antidepressant efficacy akin to what was observed in the unipolar depression population.

Dr. Williams said, in his experience, the accelerated treatment protocol is convenient and well-liked by patients and, in general, is where the field of psychiatric treatment is headed.

“A general theme that we see in depression and psychiatry is that patients no longer accept long time frames for treatment as being the norm. Whether it be ketamine or this or the upcoming psychedelics, rapid-acting treatments that match the level of acuity will be the norm,” Dr. Williams said.

The study was funded by the Milken Institute and the Baszucki Brain Research Fund. The authors have disclosed no conflicts of interest. Dr. Williams is a named inventor on Stanford-owned intellectual property relating to accelerated TMS pulse pattern sequences and neuroimaging-based TMS targeting. He disclosed ties with Otsuka, NeuraWell, Magnus Medical, and Nooma.

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

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Moderate exercise in midlife is associated with a reduced risk for amyotrophic lateral sclerosis (ALS) later in life, but this benefit appears to be limited to men, findings from a large prospective study showed.

Men who reported moderate levels of physical activity had a 29% lower risk for ALS, whereas those with high levels of physical activity had a 41% lower risk for the disease.

The findings were published online in Neurology.
 

Conflicting Findings

Several famous athletes have died of ALS, including the baseball player Lou Gehrig (for whom the disease is named), football players Dwight Clark, Steve Gleason, and Kevin Turner, and the boxer Ezzard Charles. This has led some scientists to speculate that intense physical activity may play a role in the development of the disease.

Anders M. Vaage, MD, noted there have been conflicting findings in previous studies on the topic, with results showing both increased and reduced ALS risks with increasing levels of physical activity.

In one study, researchers followed more than 212,000 Swedish cross-country skiers and more than 500,000 Swedish individuals in the general population for 20 years and found that strenuous cross-country skiing was associated with a higher risk for ALS but only among the best skiers; recreational skiers appeared to have a reduced risk.

“Our study does not necessarily contradict previous studies with findings of an increased ALS risk with extreme or intense levels of physical activity in athletes, as this study reflects more moderate levels of physical activity and fitness in the total population,” said Dr. Vaage.

To further explore the association, the researchers followed 373,700 individuals who participated in a cardiovascular health survey for an average of 27 years. When the survey began, most participants were 40-42 years old.

Participants were followed until the date of ALS diagnosis, ALS death, death from other causes, emigration, or the end of study in August 2021.

Participants answered questions about physical activity levels, smoking status, and other issues relating to cardiovascular health, and participants’ resting heart rate was measured and divided into quartiles of 31-65 beats per minute (BPM), 66-74 BPM, 75-81 BPM, or 82-100 BPM.

Participants self-reported their physical activity over the past year, classifying it into one of four categories: Sedentary, at least 4 hours per week of walking or cycling, at least 4 hours per week of recreational sports or heavy gardening, or regular participation in intense training or sports competitions several times per week.

Only a few participants reported the highest level of physical activity, so researchers combined the third and fourth categories into a single high-activity group.

Of the total study cohort, 504 participants developed ALS. Of those who developed the disease, 59% were men.

Researchers found that of the 41,898 male participants with the highest level of physical activity, 63 developed ALS. In comparison, of the 76,769 male participants who reported an intermediate level of physical activity, 131 developed ALS. Among the 29,468 male participants who reported the lowest level of physical activity, 68 developed ALS.
 

No Link in Women?

After adjusting for smoking, body mass index, and other risk factors, investigators found that men with moderate physical activity levels had a 29% lower risk for ALS compared with those with low physical activity levels, whereas those with the highest activity levels had a 41% lower risk.

In addition, men in the lowest of the four categories of resting heart rate had a 32% reduced risk for ALS compared with men with a higher resting heart rate.

Investigators are unclear why there was a lack of association between physical activity and resting heart rate and ALS risk in women.

“There are known sex differences in ALS, which includes a sex ratio with male preponderance, and there are also sex differences in response to physical exercise. Perhaps underlying mechanisms herein can explain the difference observed between males and females in the study,” Dr. Vaage said. He noted that future research should explore this difference.

Study limitations included the absence of data on physical trauma and head trauma, which have been linked with increased ALS risk. In addition, there were no data on genotype.

In an accompanying editorial, Pamela Shaw, MD, and Johnathan Cooper-Knock, BMBCh, PhD, of the University of Sheffield, Sheffield, England, described the research as a “valuable contribution to the field and potentially provides some reassurance that mild/moderate levels of physical activity in middle age do not increase the risk for ALS but may instead have a beneficial protective effect.” 

Future research on exercise in ALS, they add, should consider sex differences, capture the most extreme physical activity levels, and identify any genetic factors that may mediate the association between intense exercise and ALS.

No targeted funding was reported. Dr. Vaage reported receiving funding from ALS Laboratory Group Norway.

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

Moderate exercise in midlife is associated with a reduced risk for amyotrophic lateral sclerosis (ALS) later in life, but this benefit appears to be limited to men, findings from a large prospective study showed.

Men who reported moderate levels of physical activity had a 29% lower risk for ALS, whereas those with high levels of physical activity had a 41% lower risk for the disease.

The findings were published online in Neurology.
 

Conflicting Findings

Several famous athletes have died of ALS, including the baseball player Lou Gehrig (for whom the disease is named), football players Dwight Clark, Steve Gleason, and Kevin Turner, and the boxer Ezzard Charles. This has led some scientists to speculate that intense physical activity may play a role in the development of the disease.

Anders M. Vaage, MD, noted there have been conflicting findings in previous studies on the topic, with results showing both increased and reduced ALS risks with increasing levels of physical activity.

In one study, researchers followed more than 212,000 Swedish cross-country skiers and more than 500,000 Swedish individuals in the general population for 20 years and found that strenuous cross-country skiing was associated with a higher risk for ALS but only among the best skiers; recreational skiers appeared to have a reduced risk.

“Our study does not necessarily contradict previous studies with findings of an increased ALS risk with extreme or intense levels of physical activity in athletes, as this study reflects more moderate levels of physical activity and fitness in the total population,” said Dr. Vaage.

To further explore the association, the researchers followed 373,700 individuals who participated in a cardiovascular health survey for an average of 27 years. When the survey began, most participants were 40-42 years old.

Participants were followed until the date of ALS diagnosis, ALS death, death from other causes, emigration, or the end of study in August 2021.

Participants answered questions about physical activity levels, smoking status, and other issues relating to cardiovascular health, and participants’ resting heart rate was measured and divided into quartiles of 31-65 beats per minute (BPM), 66-74 BPM, 75-81 BPM, or 82-100 BPM.

Participants self-reported their physical activity over the past year, classifying it into one of four categories: Sedentary, at least 4 hours per week of walking or cycling, at least 4 hours per week of recreational sports or heavy gardening, or regular participation in intense training or sports competitions several times per week.

Only a few participants reported the highest level of physical activity, so researchers combined the third and fourth categories into a single high-activity group.

Of the total study cohort, 504 participants developed ALS. Of those who developed the disease, 59% were men.

Researchers found that of the 41,898 male participants with the highest level of physical activity, 63 developed ALS. In comparison, of the 76,769 male participants who reported an intermediate level of physical activity, 131 developed ALS. Among the 29,468 male participants who reported the lowest level of physical activity, 68 developed ALS.
 

No Link in Women?

After adjusting for smoking, body mass index, and other risk factors, investigators found that men with moderate physical activity levels had a 29% lower risk for ALS compared with those with low physical activity levels, whereas those with the highest activity levels had a 41% lower risk.

In addition, men in the lowest of the four categories of resting heart rate had a 32% reduced risk for ALS compared with men with a higher resting heart rate.

Investigators are unclear why there was a lack of association between physical activity and resting heart rate and ALS risk in women.

“There are known sex differences in ALS, which includes a sex ratio with male preponderance, and there are also sex differences in response to physical exercise. Perhaps underlying mechanisms herein can explain the difference observed between males and females in the study,” Dr. Vaage said. He noted that future research should explore this difference.

Study limitations included the absence of data on physical trauma and head trauma, which have been linked with increased ALS risk. In addition, there were no data on genotype.

In an accompanying editorial, Pamela Shaw, MD, and Johnathan Cooper-Knock, BMBCh, PhD, of the University of Sheffield, Sheffield, England, described the research as a “valuable contribution to the field and potentially provides some reassurance that mild/moderate levels of physical activity in middle age do not increase the risk for ALS but may instead have a beneficial protective effect.” 

Future research on exercise in ALS, they add, should consider sex differences, capture the most extreme physical activity levels, and identify any genetic factors that may mediate the association between intense exercise and ALS.

No targeted funding was reported. Dr. Vaage reported receiving funding from ALS Laboratory Group Norway.

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

Moderate exercise in midlife is associated with a reduced risk for amyotrophic lateral sclerosis (ALS) later in life, but this benefit appears to be limited to men, findings from a large prospective study showed.

Men who reported moderate levels of physical activity had a 29% lower risk for ALS, whereas those with high levels of physical activity had a 41% lower risk for the disease.

The findings were published online in Neurology.
 

Conflicting Findings

Several famous athletes have died of ALS, including the baseball player Lou Gehrig (for whom the disease is named), football players Dwight Clark, Steve Gleason, and Kevin Turner, and the boxer Ezzard Charles. This has led some scientists to speculate that intense physical activity may play a role in the development of the disease.

Anders M. Vaage, MD, noted there have been conflicting findings in previous studies on the topic, with results showing both increased and reduced ALS risks with increasing levels of physical activity.

In one study, researchers followed more than 212,000 Swedish cross-country skiers and more than 500,000 Swedish individuals in the general population for 20 years and found that strenuous cross-country skiing was associated with a higher risk for ALS but only among the best skiers; recreational skiers appeared to have a reduced risk.

“Our study does not necessarily contradict previous studies with findings of an increased ALS risk with extreme or intense levels of physical activity in athletes, as this study reflects more moderate levels of physical activity and fitness in the total population,” said Dr. Vaage.

To further explore the association, the researchers followed 373,700 individuals who participated in a cardiovascular health survey for an average of 27 years. When the survey began, most participants were 40-42 years old.

Participants were followed until the date of ALS diagnosis, ALS death, death from other causes, emigration, or the end of study in August 2021.

Participants answered questions about physical activity levels, smoking status, and other issues relating to cardiovascular health, and participants’ resting heart rate was measured and divided into quartiles of 31-65 beats per minute (BPM), 66-74 BPM, 75-81 BPM, or 82-100 BPM.

Participants self-reported their physical activity over the past year, classifying it into one of four categories: Sedentary, at least 4 hours per week of walking or cycling, at least 4 hours per week of recreational sports or heavy gardening, or regular participation in intense training or sports competitions several times per week.

Only a few participants reported the highest level of physical activity, so researchers combined the third and fourth categories into a single high-activity group.

Of the total study cohort, 504 participants developed ALS. Of those who developed the disease, 59% were men.

Researchers found that of the 41,898 male participants with the highest level of physical activity, 63 developed ALS. In comparison, of the 76,769 male participants who reported an intermediate level of physical activity, 131 developed ALS. Among the 29,468 male participants who reported the lowest level of physical activity, 68 developed ALS.
 

No Link in Women?

After adjusting for smoking, body mass index, and other risk factors, investigators found that men with moderate physical activity levels had a 29% lower risk for ALS compared with those with low physical activity levels, whereas those with the highest activity levels had a 41% lower risk.

In addition, men in the lowest of the four categories of resting heart rate had a 32% reduced risk for ALS compared with men with a higher resting heart rate.

Investigators are unclear why there was a lack of association between physical activity and resting heart rate and ALS risk in women.

“There are known sex differences in ALS, which includes a sex ratio with male preponderance, and there are also sex differences in response to physical exercise. Perhaps underlying mechanisms herein can explain the difference observed between males and females in the study,” Dr. Vaage said. He noted that future research should explore this difference.

Study limitations included the absence of data on physical trauma and head trauma, which have been linked with increased ALS risk. In addition, there were no data on genotype.

In an accompanying editorial, Pamela Shaw, MD, and Johnathan Cooper-Knock, BMBCh, PhD, of the University of Sheffield, Sheffield, England, described the research as a “valuable contribution to the field and potentially provides some reassurance that mild/moderate levels of physical activity in middle age do not increase the risk for ALS but may instead have a beneficial protective effect.” 

Future research on exercise in ALS, they add, should consider sex differences, capture the most extreme physical activity levels, and identify any genetic factors that may mediate the association between intense exercise and ALS.

No targeted funding was reported. Dr. Vaage reported receiving funding from ALS Laboratory Group Norway.

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

TORONTO — Be suspicious if a child with a severe dermatologic condition is unresponsive to treatment, especially if their parent or caregiver exhibits deceptive behavior.

These could be red flags for Munchausen syndrome by proxy (MSBP), also known as factitious disorder.

“The No. 1 thing dermatologists can do in situations like this is be open to thinking outside the box and ask themselves the difficult question: Could this be something the parent is inflicting on the child,” Kelly Frasier, DO, a dermatology clinical trials and epidemiology research fellow at Northwell Health, Poughkeepsie, New York, said in an interview.

courtesy Pauline Anderson

She provided a review on advancing the understanding of the dermatologic manifestations of MSBP during a poster session at the annual meeting of the Society for Pediatric Dermatology (SPD). Dr. Frasier has a particular interest in psychodermatology — she was a mental health therapist before going to medical school.

MSBP is a type of abuse intentionally inflicted by a caregiver typically on their child “for some ulterior motive,” usually to seek attention or sympathy and not for material or financial gain, explained Dr. Frasier. People with MSBP seek medical help for exaggerated or fabricated symptoms in their child. They may alter medical tests, falsify medical records, or induce symptoms in their child.

To do this, these abusers may apply any number of caustic household products, including glue, directly to the child’s skin or even in formula. Dr. Frasier shared a picture of a baby whose formula had been doctored with a caustic substance that had dripped onto his neck and face, causing a rash with blisters.

In addition to blistering, cutaneous manifestations of MSBP can include severe bruising. Or the child may present with signs similar to those of granuloma annulare (a benign condition characterized by small, raised bumps) or cicatricial pemphigoid (a rare, chronic autoimmune blistering disorder) or may have recurrent nail avulsion, purpura, or coagulopathy, said Dr. Frasier.

In almost all cases of MSBP (an estimated 96%), the abuse is inflicted by the mother, who may have a preexisting mental illness. “Usually, a psychological disorder is at play, such as depression or anxiety,” said Dr. Frasier.

Some evidence suggests that, in cases of MSBP, the caregiver may have a personality disorder such as borderline or histrionic personality disorder — or may have suffered abuse or neglect as a child or is experiencing major stress, which some evidence suggests can trigger MSPB, she added.

This type of abuse is rarely seen in children older than 6 years, likely because they get wise to what’s going on and are better able to fight back or resist as they get older, Dr. Fraser noted.

High Mortality Rate

It’s critical that cases of MSBP are identified early. While a small proportion of child abuse cases involve MSBP, the mortality rate is extremely high, about 10%, research suggests, said Dr. Frasier.

Dermatologists should be skeptical if the child’s condition hasn’t improved despite trying numerous treatments that normally would have some effect. “If you’re doing everything you can to treat something that’s usually pretty simple in terms of what you normally see clinically and how you treat it, and you’re not seeing any improvement or things continue to get worse, that’s definitely a sign something else may be going on,” Dr. Frasier said.

Another suspicious sign is inflammation that continues “for weeks or months” and “doesn’t match up with actual lab markers and lab values,” said Dr. Frasier.

Other signs of possible MSBP include evidence of chemicals in the child’s blood, stool, or urine, or the child’s condition improves while in the hospital, but symptoms return after returning home.

Also be aware of the interaction between the parent and child, said Dr. Frasier. “See if you can pick up that something else might be going on, especially if the symptoms aren’t lining up very well with what you’re physically seeing and what your clinical impression is.”

And be suspicious of a parent’s inappropriate behavior; for example, they seem to be deliberately making symptoms worse or appear overly distraught. The seemingly caring parent could be overcompensating for what she’s doing at home, “and she wants to make sure it doesn’t appear that way,” said Dr. Frasier.

To help determine if some sort of trauma is occurring at home, the child would ideally be separated from the caregiver, perhaps with a nurse or other member of the interdisciplinary medical team, Dr. Frasier said.

It appears that pediatric dermatologists are already aware of the importance of protecting children from abuse. During a presentation at the meeting on child abuse and maltreatment in dermatology, not specifically on MSBP, Romy Cho, MD, assistant professor, Department of Pediatrics, University of Toronto, who is involved with the SCAN Program at The Hospital for Sick Children, Toronto, Canada, polled the audience on whether they had ever contacted child protective services (CPS). Almost 80% said they had.

That’s good news for Dr. Frasier. “We have to be willing to contact CPS if we think there’s something going on, and be more open to that because it’s better to be safe than sorry, especially in cases involving children.”

Dr. Frasier and Dr. Cho had no relevant disclosures.

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

TORONTO — Be suspicious if a child with a severe dermatologic condition is unresponsive to treatment, especially if their parent or caregiver exhibits deceptive behavior.

These could be red flags for Munchausen syndrome by proxy (MSBP), also known as factitious disorder.

“The No. 1 thing dermatologists can do in situations like this is be open to thinking outside the box and ask themselves the difficult question: Could this be something the parent is inflicting on the child,” Kelly Frasier, DO, a dermatology clinical trials and epidemiology research fellow at Northwell Health, Poughkeepsie, New York, said in an interview.

courtesy Pauline Anderson

She provided a review on advancing the understanding of the dermatologic manifestations of MSBP during a poster session at the annual meeting of the Society for Pediatric Dermatology (SPD). Dr. Frasier has a particular interest in psychodermatology — she was a mental health therapist before going to medical school.

MSBP is a type of abuse intentionally inflicted by a caregiver typically on their child “for some ulterior motive,” usually to seek attention or sympathy and not for material or financial gain, explained Dr. Frasier. People with MSBP seek medical help for exaggerated or fabricated symptoms in their child. They may alter medical tests, falsify medical records, or induce symptoms in their child.

To do this, these abusers may apply any number of caustic household products, including glue, directly to the child’s skin or even in formula. Dr. Frasier shared a picture of a baby whose formula had been doctored with a caustic substance that had dripped onto his neck and face, causing a rash with blisters.

In addition to blistering, cutaneous manifestations of MSBP can include severe bruising. Or the child may present with signs similar to those of granuloma annulare (a benign condition characterized by small, raised bumps) or cicatricial pemphigoid (a rare, chronic autoimmune blistering disorder) or may have recurrent nail avulsion, purpura, or coagulopathy, said Dr. Frasier.

In almost all cases of MSBP (an estimated 96%), the abuse is inflicted by the mother, who may have a preexisting mental illness. “Usually, a psychological disorder is at play, such as depression or anxiety,” said Dr. Frasier.

Some evidence suggests that, in cases of MSBP, the caregiver may have a personality disorder such as borderline or histrionic personality disorder — or may have suffered abuse or neglect as a child or is experiencing major stress, which some evidence suggests can trigger MSPB, she added.

This type of abuse is rarely seen in children older than 6 years, likely because they get wise to what’s going on and are better able to fight back or resist as they get older, Dr. Fraser noted.

High Mortality Rate

It’s critical that cases of MSBP are identified early. While a small proportion of child abuse cases involve MSBP, the mortality rate is extremely high, about 10%, research suggests, said Dr. Frasier.

Dermatologists should be skeptical if the child’s condition hasn’t improved despite trying numerous treatments that normally would have some effect. “If you’re doing everything you can to treat something that’s usually pretty simple in terms of what you normally see clinically and how you treat it, and you’re not seeing any improvement or things continue to get worse, that’s definitely a sign something else may be going on,” Dr. Frasier said.

Another suspicious sign is inflammation that continues “for weeks or months” and “doesn’t match up with actual lab markers and lab values,” said Dr. Frasier.

Other signs of possible MSBP include evidence of chemicals in the child’s blood, stool, or urine, or the child’s condition improves while in the hospital, but symptoms return after returning home.

Also be aware of the interaction between the parent and child, said Dr. Frasier. “See if you can pick up that something else might be going on, especially if the symptoms aren’t lining up very well with what you’re physically seeing and what your clinical impression is.”

And be suspicious of a parent’s inappropriate behavior; for example, they seem to be deliberately making symptoms worse or appear overly distraught. The seemingly caring parent could be overcompensating for what she’s doing at home, “and she wants to make sure it doesn’t appear that way,” said Dr. Frasier.

To help determine if some sort of trauma is occurring at home, the child would ideally be separated from the caregiver, perhaps with a nurse or other member of the interdisciplinary medical team, Dr. Frasier said.

It appears that pediatric dermatologists are already aware of the importance of protecting children from abuse. During a presentation at the meeting on child abuse and maltreatment in dermatology, not specifically on MSBP, Romy Cho, MD, assistant professor, Department of Pediatrics, University of Toronto, who is involved with the SCAN Program at The Hospital for Sick Children, Toronto, Canada, polled the audience on whether they had ever contacted child protective services (CPS). Almost 80% said they had.

That’s good news for Dr. Frasier. “We have to be willing to contact CPS if we think there’s something going on, and be more open to that because it’s better to be safe than sorry, especially in cases involving children.”

Dr. Frasier and Dr. Cho had no relevant disclosures.

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

TORONTO — Be suspicious if a child with a severe dermatologic condition is unresponsive to treatment, especially if their parent or caregiver exhibits deceptive behavior.

These could be red flags for Munchausen syndrome by proxy (MSBP), also known as factitious disorder.

“The No. 1 thing dermatologists can do in situations like this is be open to thinking outside the box and ask themselves the difficult question: Could this be something the parent is inflicting on the child,” Kelly Frasier, DO, a dermatology clinical trials and epidemiology research fellow at Northwell Health, Poughkeepsie, New York, said in an interview.

courtesy Pauline Anderson

She provided a review on advancing the understanding of the dermatologic manifestations of MSBP during a poster session at the annual meeting of the Society for Pediatric Dermatology (SPD). Dr. Frasier has a particular interest in psychodermatology — she was a mental health therapist before going to medical school.

MSBP is a type of abuse intentionally inflicted by a caregiver typically on their child “for some ulterior motive,” usually to seek attention or sympathy and not for material or financial gain, explained Dr. Frasier. People with MSBP seek medical help for exaggerated or fabricated symptoms in their child. They may alter medical tests, falsify medical records, or induce symptoms in their child.

To do this, these abusers may apply any number of caustic household products, including glue, directly to the child’s skin or even in formula. Dr. Frasier shared a picture of a baby whose formula had been doctored with a caustic substance that had dripped onto his neck and face, causing a rash with blisters.

In addition to blistering, cutaneous manifestations of MSBP can include severe bruising. Or the child may present with signs similar to those of granuloma annulare (a benign condition characterized by small, raised bumps) or cicatricial pemphigoid (a rare, chronic autoimmune blistering disorder) or may have recurrent nail avulsion, purpura, or coagulopathy, said Dr. Frasier.

In almost all cases of MSBP (an estimated 96%), the abuse is inflicted by the mother, who may have a preexisting mental illness. “Usually, a psychological disorder is at play, such as depression or anxiety,” said Dr. Frasier.

Some evidence suggests that, in cases of MSBP, the caregiver may have a personality disorder such as borderline or histrionic personality disorder — or may have suffered abuse or neglect as a child or is experiencing major stress, which some evidence suggests can trigger MSPB, she added.

This type of abuse is rarely seen in children older than 6 years, likely because they get wise to what’s going on and are better able to fight back or resist as they get older, Dr. Fraser noted.

High Mortality Rate

It’s critical that cases of MSBP are identified early. While a small proportion of child abuse cases involve MSBP, the mortality rate is extremely high, about 10%, research suggests, said Dr. Frasier.

Dermatologists should be skeptical if the child’s condition hasn’t improved despite trying numerous treatments that normally would have some effect. “If you’re doing everything you can to treat something that’s usually pretty simple in terms of what you normally see clinically and how you treat it, and you’re not seeing any improvement or things continue to get worse, that’s definitely a sign something else may be going on,” Dr. Frasier said.

Another suspicious sign is inflammation that continues “for weeks or months” and “doesn’t match up with actual lab markers and lab values,” said Dr. Frasier.

Other signs of possible MSBP include evidence of chemicals in the child’s blood, stool, or urine, or the child’s condition improves while in the hospital, but symptoms return after returning home.

Also be aware of the interaction between the parent and child, said Dr. Frasier. “See if you can pick up that something else might be going on, especially if the symptoms aren’t lining up very well with what you’re physically seeing and what your clinical impression is.”

And be suspicious of a parent’s inappropriate behavior; for example, they seem to be deliberately making symptoms worse or appear overly distraught. The seemingly caring parent could be overcompensating for what she’s doing at home, “and she wants to make sure it doesn’t appear that way,” said Dr. Frasier.

To help determine if some sort of trauma is occurring at home, the child would ideally be separated from the caregiver, perhaps with a nurse or other member of the interdisciplinary medical team, Dr. Frasier said.

It appears that pediatric dermatologists are already aware of the importance of protecting children from abuse. During a presentation at the meeting on child abuse and maltreatment in dermatology, not specifically on MSBP, Romy Cho, MD, assistant professor, Department of Pediatrics, University of Toronto, who is involved with the SCAN Program at The Hospital for Sick Children, Toronto, Canada, polled the audience on whether they had ever contacted child protective services (CPS). Almost 80% said they had.

That’s good news for Dr. Frasier. “We have to be willing to contact CPS if we think there’s something going on, and be more open to that because it’s better to be safe than sorry, especially in cases involving children.”

Dr. Frasier and Dr. Cho had no relevant disclosures.

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

Since the European Alliance of Associations for Rheumatology (EULAR) published its 2019 recommendations, the range of therapeutic options in the management of psoriatic arthritis (PsA) has expanded significantly. Univadis France spoke to Laure Gossec, MD, PhD, a rheumatologist at Pitié-Salpêtrière Hospital and Sorbonne University in Paris, about the updates to these recommendations. 

What is the role of nonsteroidal anti-inflammatory drugs (NSAIDs) today?

NSAIDs remain the first-line treatment, but their place as monotherapy without background treatment has been mainly limited to patients with mild peripheral disease. For them, NSAIDs are recommended as monotherapy for a short duration, 2-4 weeks, while the clinician assesses and promptly introduces background treatment. We have a window of opportunity. Inflammation must be targeted quickly, especially if the patient has a form of disease associated with poor prognosis. Such patients include those with polyarticular forms or high C-reactive protein (CRP).

The two criteria of at least four swollen joints and/or a CRP greater than 5 mg/L should prompt the physician to introduce background treatment.

When prescribing NSAIDs, clinicians must rigorously evaluate the benefit-risk ratio because patients with PsA often have comorbidities. In France, one third of them have obesity, 20% have hypertension, and 20% have diabetes.
 

What is the recommended hierarchy for other treatments?

In the second phase of treatment, synthetic conventional treatments (like methotrexate, leflunomide, or sulfasalazine) are recommended. Methotrexate is by far the most used. This choice is based on efficacy, the efficacy-safety ratio, and cost.

A biologic therapy has no place as a first-line treatment because most PsA cases are moderate. In this regard, our European recommendations differ from American recommendations, which leave the choice between conventional or targeted therapies as a first-line treatment.

We have opted for a step-up approach. Although there is no study comparing a biologic therapy vs methotrexate as a first-line treatment, we have many data showing that more than half of patients will never need a biologic therapy.

We have a lot of experience with molecules like methotrexate. The benefit-risk ratio of this treatment as a first-line option is favorable, with efficacy for the skin. However, in axial forms, methotrexate is ineffective and calls for the use of biologic therapy.
 

Are there selection criteria for second-line biologic therapies?

Five classes of molecules are authorized and reimbursed in France: anti-TNF (tumor necrosis factor), anti–IL (interleukin)-17A, anti–IL-17A, -F, and -AF (bimekizumab), anti–IL-12/23 (ustekinumab), and anti–IL-23. All these treatments are effective in about two thirds of patients.

Unfortunately, we are not yet practicing personalized medicine to choose the most appropriate treatment for each patient, because we cannot predict this response. However, there are specific cases. Anti–IL-17 and anti–IL-23 can be favored in patients with bothersome skin involvement, either because it is extensive or located on the face or genital area. If a patient also has chronic inflammatory bowel disease, anti-TNF, anti–IL-23, or Janus kinase (JAK) inhibitors should be prioritized. In axial forms, anti-TNF or anti–IL-17 is recommended. But these cases concern only a minority of our patients. 

We have kept a place for JAK inhibitors in patients for whom biologic therapies are not suitable or effective. It is important to follow the recommendations of the European Medicines Agency, avoiding the use of JAK inhibitors after age 60 years, in smokers, or in those with cardiovascular risk. Oncologic monitoring is also important for patients treated with this therapeutic class.

Let’s also remember the role of apremilast, which is an alternative to biologic therapies in patients with moderate forms of the disease.

In the next 2 or 3 years, new modes of action or new molecules should be available, such as tyrosine kinase 2 (TYK2) inhibitors; izokibep, an oral nanomolecule targeting IL-17; or a new injectable anti–IL-17 with an affinity with interleukin that is incomparable to that of previous antibodies.
 

What message should be conveyed to the general practitioner?

PsA treatments are prescribed initially in hospitals, but rheumatologists will be able to prescribe them in the coming months. The general practitioner cannot initiate targeted treatment but has the role of starting methotrexate and referring the patient to specialized follow-up.

The most important thing to know is that in France, about half of patients will be on targeted treatment. The median maintenance of such therapy is only 3 years, which means that half of the patients will have replaced it with another therapy after 3 years. This switch could indicate a loss of efficacy or escape. It is therefore important for a specialist to follow the patient and to continue biologic monitoring every 2-6 months, as well as imaging every 2-5 years to check radiographic progression.

In cases of prolonged remission of more than 6 months, a gradual and cautious decrease in background treatments can be considered in a shared medical decision. However, treatment discontinuation leads to a systemic relapse in the short or long term, and a gradual decrease results in relapse in about half of the patients.
 

And in terms of monitoring?

The management of comorbidities is crucial. It is essential to keep vaccinations up to date, especially because of the increased risk for potential infections with targeted treatments. Regular screening for infections, including dental follow-up, is also recommended.

Preventive medicine is also important, especially regarding breast and colon cancer screening. General population recommendations apply.

Cardiovascular risk, which is doubled in patients with PsA compared with the general population due to chronic inflammation, should prompt monitoring of blood pressure and metabolic diseases. It should be noted that there is an 11% higher mortality rate after 8 years of follow-up, mainly due to cardiovascular and neoplastic risks.

Dr. Gossec reported receiving research grants from AbbVie, Biogen, Lilly, Novartis, and UCB and consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Janssen, Lilly, MSD, Novartis, Pfizer, Stada, and UCB.
 

This story was translated from Univadis France, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Since the European Alliance of Associations for Rheumatology (EULAR) published its 2019 recommendations, the range of therapeutic options in the management of psoriatic arthritis (PsA) has expanded significantly. Univadis France spoke to Laure Gossec, MD, PhD, a rheumatologist at Pitié-Salpêtrière Hospital and Sorbonne University in Paris, about the updates to these recommendations. 

What is the role of nonsteroidal anti-inflammatory drugs (NSAIDs) today?

NSAIDs remain the first-line treatment, but their place as monotherapy without background treatment has been mainly limited to patients with mild peripheral disease. For them, NSAIDs are recommended as monotherapy for a short duration, 2-4 weeks, while the clinician assesses and promptly introduces background treatment. We have a window of opportunity. Inflammation must be targeted quickly, especially if the patient has a form of disease associated with poor prognosis. Such patients include those with polyarticular forms or high C-reactive protein (CRP).

The two criteria of at least four swollen joints and/or a CRP greater than 5 mg/L should prompt the physician to introduce background treatment.

When prescribing NSAIDs, clinicians must rigorously evaluate the benefit-risk ratio because patients with PsA often have comorbidities. In France, one third of them have obesity, 20% have hypertension, and 20% have diabetes.
 

What is the recommended hierarchy for other treatments?

In the second phase of treatment, synthetic conventional treatments (like methotrexate, leflunomide, or sulfasalazine) are recommended. Methotrexate is by far the most used. This choice is based on efficacy, the efficacy-safety ratio, and cost.

A biologic therapy has no place as a first-line treatment because most PsA cases are moderate. In this regard, our European recommendations differ from American recommendations, which leave the choice between conventional or targeted therapies as a first-line treatment.

We have opted for a step-up approach. Although there is no study comparing a biologic therapy vs methotrexate as a first-line treatment, we have many data showing that more than half of patients will never need a biologic therapy.

We have a lot of experience with molecules like methotrexate. The benefit-risk ratio of this treatment as a first-line option is favorable, with efficacy for the skin. However, in axial forms, methotrexate is ineffective and calls for the use of biologic therapy.
 

Are there selection criteria for second-line biologic therapies?

Five classes of molecules are authorized and reimbursed in France: anti-TNF (tumor necrosis factor), anti–IL (interleukin)-17A, anti–IL-17A, -F, and -AF (bimekizumab), anti–IL-12/23 (ustekinumab), and anti–IL-23. All these treatments are effective in about two thirds of patients.

Unfortunately, we are not yet practicing personalized medicine to choose the most appropriate treatment for each patient, because we cannot predict this response. However, there are specific cases. Anti–IL-17 and anti–IL-23 can be favored in patients with bothersome skin involvement, either because it is extensive or located on the face or genital area. If a patient also has chronic inflammatory bowel disease, anti-TNF, anti–IL-23, or Janus kinase (JAK) inhibitors should be prioritized. In axial forms, anti-TNF or anti–IL-17 is recommended. But these cases concern only a minority of our patients. 

We have kept a place for JAK inhibitors in patients for whom biologic therapies are not suitable or effective. It is important to follow the recommendations of the European Medicines Agency, avoiding the use of JAK inhibitors after age 60 years, in smokers, or in those with cardiovascular risk. Oncologic monitoring is also important for patients treated with this therapeutic class.

Let’s also remember the role of apremilast, which is an alternative to biologic therapies in patients with moderate forms of the disease.

In the next 2 or 3 years, new modes of action or new molecules should be available, such as tyrosine kinase 2 (TYK2) inhibitors; izokibep, an oral nanomolecule targeting IL-17; or a new injectable anti–IL-17 with an affinity with interleukin that is incomparable to that of previous antibodies.
 

What message should be conveyed to the general practitioner?

PsA treatments are prescribed initially in hospitals, but rheumatologists will be able to prescribe them in the coming months. The general practitioner cannot initiate targeted treatment but has the role of starting methotrexate and referring the patient to specialized follow-up.

The most important thing to know is that in France, about half of patients will be on targeted treatment. The median maintenance of such therapy is only 3 years, which means that half of the patients will have replaced it with another therapy after 3 years. This switch could indicate a loss of efficacy or escape. It is therefore important for a specialist to follow the patient and to continue biologic monitoring every 2-6 months, as well as imaging every 2-5 years to check radiographic progression.

In cases of prolonged remission of more than 6 months, a gradual and cautious decrease in background treatments can be considered in a shared medical decision. However, treatment discontinuation leads to a systemic relapse in the short or long term, and a gradual decrease results in relapse in about half of the patients.
 

And in terms of monitoring?

The management of comorbidities is crucial. It is essential to keep vaccinations up to date, especially because of the increased risk for potential infections with targeted treatments. Regular screening for infections, including dental follow-up, is also recommended.

Preventive medicine is also important, especially regarding breast and colon cancer screening. General population recommendations apply.

Cardiovascular risk, which is doubled in patients with PsA compared with the general population due to chronic inflammation, should prompt monitoring of blood pressure and metabolic diseases. It should be noted that there is an 11% higher mortality rate after 8 years of follow-up, mainly due to cardiovascular and neoplastic risks.

Dr. Gossec reported receiving research grants from AbbVie, Biogen, Lilly, Novartis, and UCB and consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Janssen, Lilly, MSD, Novartis, Pfizer, Stada, and UCB.
 

This story was translated from Univadis France, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Since the European Alliance of Associations for Rheumatology (EULAR) published its 2019 recommendations, the range of therapeutic options in the management of psoriatic arthritis (PsA) has expanded significantly. Univadis France spoke to Laure Gossec, MD, PhD, a rheumatologist at Pitié-Salpêtrière Hospital and Sorbonne University in Paris, about the updates to these recommendations. 

What is the role of nonsteroidal anti-inflammatory drugs (NSAIDs) today?

NSAIDs remain the first-line treatment, but their place as monotherapy without background treatment has been mainly limited to patients with mild peripheral disease. For them, NSAIDs are recommended as monotherapy for a short duration, 2-4 weeks, while the clinician assesses and promptly introduces background treatment. We have a window of opportunity. Inflammation must be targeted quickly, especially if the patient has a form of disease associated with poor prognosis. Such patients include those with polyarticular forms or high C-reactive protein (CRP).

The two criteria of at least four swollen joints and/or a CRP greater than 5 mg/L should prompt the physician to introduce background treatment.

When prescribing NSAIDs, clinicians must rigorously evaluate the benefit-risk ratio because patients with PsA often have comorbidities. In France, one third of them have obesity, 20% have hypertension, and 20% have diabetes.
 

What is the recommended hierarchy for other treatments?

In the second phase of treatment, synthetic conventional treatments (like methotrexate, leflunomide, or sulfasalazine) are recommended. Methotrexate is by far the most used. This choice is based on efficacy, the efficacy-safety ratio, and cost.

A biologic therapy has no place as a first-line treatment because most PsA cases are moderate. In this regard, our European recommendations differ from American recommendations, which leave the choice between conventional or targeted therapies as a first-line treatment.

We have opted for a step-up approach. Although there is no study comparing a biologic therapy vs methotrexate as a first-line treatment, we have many data showing that more than half of patients will never need a biologic therapy.

We have a lot of experience with molecules like methotrexate. The benefit-risk ratio of this treatment as a first-line option is favorable, with efficacy for the skin. However, in axial forms, methotrexate is ineffective and calls for the use of biologic therapy.
 

Are there selection criteria for second-line biologic therapies?

Five classes of molecules are authorized and reimbursed in France: anti-TNF (tumor necrosis factor), anti–IL (interleukin)-17A, anti–IL-17A, -F, and -AF (bimekizumab), anti–IL-12/23 (ustekinumab), and anti–IL-23. All these treatments are effective in about two thirds of patients.

Unfortunately, we are not yet practicing personalized medicine to choose the most appropriate treatment for each patient, because we cannot predict this response. However, there are specific cases. Anti–IL-17 and anti–IL-23 can be favored in patients with bothersome skin involvement, either because it is extensive or located on the face or genital area. If a patient also has chronic inflammatory bowel disease, anti-TNF, anti–IL-23, or Janus kinase (JAK) inhibitors should be prioritized. In axial forms, anti-TNF or anti–IL-17 is recommended. But these cases concern only a minority of our patients. 

We have kept a place for JAK inhibitors in patients for whom biologic therapies are not suitable or effective. It is important to follow the recommendations of the European Medicines Agency, avoiding the use of JAK inhibitors after age 60 years, in smokers, or in those with cardiovascular risk. Oncologic monitoring is also important for patients treated with this therapeutic class.

Let’s also remember the role of apremilast, which is an alternative to biologic therapies in patients with moderate forms of the disease.

In the next 2 or 3 years, new modes of action or new molecules should be available, such as tyrosine kinase 2 (TYK2) inhibitors; izokibep, an oral nanomolecule targeting IL-17; or a new injectable anti–IL-17 with an affinity with interleukin that is incomparable to that of previous antibodies.
 

What message should be conveyed to the general practitioner?

PsA treatments are prescribed initially in hospitals, but rheumatologists will be able to prescribe them in the coming months. The general practitioner cannot initiate targeted treatment but has the role of starting methotrexate and referring the patient to specialized follow-up.

The most important thing to know is that in France, about half of patients will be on targeted treatment. The median maintenance of such therapy is only 3 years, which means that half of the patients will have replaced it with another therapy after 3 years. This switch could indicate a loss of efficacy or escape. It is therefore important for a specialist to follow the patient and to continue biologic monitoring every 2-6 months, as well as imaging every 2-5 years to check radiographic progression.

In cases of prolonged remission of more than 6 months, a gradual and cautious decrease in background treatments can be considered in a shared medical decision. However, treatment discontinuation leads to a systemic relapse in the short or long term, and a gradual decrease results in relapse in about half of the patients.
 

And in terms of monitoring?

The management of comorbidities is crucial. It is essential to keep vaccinations up to date, especially because of the increased risk for potential infections with targeted treatments. Regular screening for infections, including dental follow-up, is also recommended.

Preventive medicine is also important, especially regarding breast and colon cancer screening. General population recommendations apply.

Cardiovascular risk, which is doubled in patients with PsA compared with the general population due to chronic inflammation, should prompt monitoring of blood pressure and metabolic diseases. It should be noted that there is an 11% higher mortality rate after 8 years of follow-up, mainly due to cardiovascular and neoplastic risks.

Dr. Gossec reported receiving research grants from AbbVie, Biogen, Lilly, Novartis, and UCB and consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Janssen, Lilly, MSD, Novartis, Pfizer, Stada, and UCB.
 

This story was translated from Univadis France, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.