News

Real-world data accumulated in Europe outside of a clinical trial support both the safety and the benefit of two transcatheter edge-to-edge (TEER) devices designed specifically for the treatment of tricuspid regurgitation (TR).

For the TriClip system (Abbott), the data were drawn from a prospective postmarketing registry, and for the EVOQUE system (Edwards Lifesciences), data were generated by a compassionate use program.

The TriClip system is approved and available in Europe, but neither system has regulatory approval in the United States.

The two sets of data, each presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, are consistent with controlled trials. Each system was associated with high rates of procedural success, low rates of adverse events, and sustained improvements in quality of life.
 

Real-world backup for TRILUMINATE

Presented just days before the pivotal multinational TRILUMINATE trial was published in the New England Journal of Medicine, the bRIGHT postmarketing study of the TriClip device demonstrated a procedural rate of success and a subsequent reduction in TR that was at least as good but in a substantially sicker patient population.

“To appreciate these results, you have to put into perspective the baseline TR in our population,” reported Philipp Lurz, MD, PhD, of the Heart Center Leipzig, University of Leipzig, Germany. Whereas only 70% of those randomized in TRILUMINATE had grade 4 (massive) or 5 (torrential) TR, the proportion was 90% in bRIGHT.

The proportion with TR of moderate or less severity was 77% when assessed at 30 days in bRIGHT versus 72%, however, when assessed at 1 year in TRILUMINATE. In addition, procedural success was 99% in both studies even though patients in bRIGHT were on average older and had more comorbidities. At baseline, 80% of bRIGHT patients were in New York Heart Association (NYHA) class III or IV heart failure versus 59% of those in TRILUMINATE.

TRILUMINATE data, presented prior to publication at the annual meeting of the American College of Cardiology earlier this year, did not associate the transcatheter TR repair with a reduction in mortality or a reduction in hospitalization for heart failure, which were the first two of three hierarchical endpoints, but it did show benefit on the third, which was quality of life. As measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), patients in the transcatheter repair group gained 12.3 points versus 0.6 points (P < .001) on medical therapy.

In the bRIGHT registry, patients gained 19 points in the KCCQ score after treatment. By 30 days, the proportion of patients in NHYA class III/IV had fallen from 80% to 20%. The major adverse event rate of 2.5% at 30 days was only modestly higher than the 1.7% rate at 30 days in TRILUMINATE.

“The safety profile remained strong despite the sicker population treated in the registry,” reported Dr. Lurz, whose results were simultaneously published in the Journal of the American College of Cardiology (JACC).

The bRIGHT registry analysis was based on 511 patients treated at 26 sites in Europe. Dr. Lurz characterized it as “the first prospective, single-arm, open-label, multicenter, postmarket registry to evaluate the safety and performance of any transcatheter tricuspid valve repair system.”

In a panel discussion following the presentation, Nicole Karam, MD, PhD, codirector of the heart valve unit, Hospital Georges Pompidou, Paris, praised a study of TEER tricuspid valve device in the real world, but she pointed out that the question of who to treat remains unanswered. Although symptom relief has value for a condition that can impose large deficits in quality of life, she called for more data to identify optimal candidates, particularly in the persistent absence of a major effect on hard endpoints.

Dr. Lurz agreed. In bRIGHT, predictors of a moderate or less TR at discharge included a smaller tethering distance, a smaller right ventricular end diastolic dimension, a smaller right atrial volume, and a smaller tricuspid annular diameter.

Each of these predictors argues for earlier treatment, he said, even if later treatment in a clinical trial provides a greater likelihood of eventually demonstrating benefits on hard endpoints.

‘Remarkable reduction’

The data from the much smaller compassionate use evaluation of the EVOQUE system generated similar evidence of safety and benefit while also making the point that earlier intervention offers a greater opportunity for preventing irreversible progression. With much longer follow up, the compassionate-use analysis, which involved patients even sicker than those included in bRIGHT, suggested these repairs are durable.

In this retrospective analysis of 38 patients treated at eight centers in Europe, the United States, and Canada, the mortality climbed steadily over 2 years of follow-up, reaching 29% at 2 years despite the fact that TR was reduced to < 1% after the procedure and remained durably suppressed at a median follow-up of 520 days.

The tricuspid valve repair with the EVOQUE system “was associated with a remarkable reduction in heart failure symptoms and significant improvement in NYHA functional class up to a maximum of 1,074 days after the intervention,” reported Lukas Stolz, MD, an interventional cardiologist at Ludwig-Maximilians-University, Munich.

In the data he presented at EuroPCR, which was published simultaneously as a letter in JACC, he said that favorable reverse remodeling of the right ventricle, which was observed as early as 30 days after the procedure, was maintained at long-term follow up.

The uncontrolled data from the compassionate analysis, like the bRIGHT registry, could not confirm that tricuspid valve repair changes the trajectory of progressive heart disease, but the favorable effects Dr. Stolz reported on cardiovascular function, not just symptoms, support this idea.

Dr. Lutz has financial relationships with Edwards Lifesciences, ReCor, and Abbott, which funded the bRIGHT registry. Dr. Karam reports financial relationships with Abbott, Edwards Lifesciences, and Medtronic. Dr. Stolz reports no potential conflicts of interest, but other coinvestigators of the retrospective analysis have financial relationships with Edwards Lifesciences, which is developing the EVOQUE system.

Real-world data accumulated in Europe outside of a clinical trial support both the safety and the benefit of two transcatheter edge-to-edge (TEER) devices designed specifically for the treatment of tricuspid regurgitation (TR).

For the TriClip system (Abbott), the data were drawn from a prospective postmarketing registry, and for the EVOQUE system (Edwards Lifesciences), data were generated by a compassionate use program.

The TriClip system is approved and available in Europe, but neither system has regulatory approval in the United States.

The two sets of data, each presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, are consistent with controlled trials. Each system was associated with high rates of procedural success, low rates of adverse events, and sustained improvements in quality of life.
 

Real-world backup for TRILUMINATE

Presented just days before the pivotal multinational TRILUMINATE trial was published in the New England Journal of Medicine, the bRIGHT postmarketing study of the TriClip device demonstrated a procedural rate of success and a subsequent reduction in TR that was at least as good but in a substantially sicker patient population.

“To appreciate these results, you have to put into perspective the baseline TR in our population,” reported Philipp Lurz, MD, PhD, of the Heart Center Leipzig, University of Leipzig, Germany. Whereas only 70% of those randomized in TRILUMINATE had grade 4 (massive) or 5 (torrential) TR, the proportion was 90% in bRIGHT.

The proportion with TR of moderate or less severity was 77% when assessed at 30 days in bRIGHT versus 72%, however, when assessed at 1 year in TRILUMINATE. In addition, procedural success was 99% in both studies even though patients in bRIGHT were on average older and had more comorbidities. At baseline, 80% of bRIGHT patients were in New York Heart Association (NYHA) class III or IV heart failure versus 59% of those in TRILUMINATE.

TRILUMINATE data, presented prior to publication at the annual meeting of the American College of Cardiology earlier this year, did not associate the transcatheter TR repair with a reduction in mortality or a reduction in hospitalization for heart failure, which were the first two of three hierarchical endpoints, but it did show benefit on the third, which was quality of life. As measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), patients in the transcatheter repair group gained 12.3 points versus 0.6 points (P < .001) on medical therapy.

In the bRIGHT registry, patients gained 19 points in the KCCQ score after treatment. By 30 days, the proportion of patients in NHYA class III/IV had fallen from 80% to 20%. The major adverse event rate of 2.5% at 30 days was only modestly higher than the 1.7% rate at 30 days in TRILUMINATE.

“The safety profile remained strong despite the sicker population treated in the registry,” reported Dr. Lurz, whose results were simultaneously published in the Journal of the American College of Cardiology (JACC).

The bRIGHT registry analysis was based on 511 patients treated at 26 sites in Europe. Dr. Lurz characterized it as “the first prospective, single-arm, open-label, multicenter, postmarket registry to evaluate the safety and performance of any transcatheter tricuspid valve repair system.”

In a panel discussion following the presentation, Nicole Karam, MD, PhD, codirector of the heart valve unit, Hospital Georges Pompidou, Paris, praised a study of TEER tricuspid valve device in the real world, but she pointed out that the question of who to treat remains unanswered. Although symptom relief has value for a condition that can impose large deficits in quality of life, she called for more data to identify optimal candidates, particularly in the persistent absence of a major effect on hard endpoints.

Dr. Lurz agreed. In bRIGHT, predictors of a moderate or less TR at discharge included a smaller tethering distance, a smaller right ventricular end diastolic dimension, a smaller right atrial volume, and a smaller tricuspid annular diameter.

Each of these predictors argues for earlier treatment, he said, even if later treatment in a clinical trial provides a greater likelihood of eventually demonstrating benefits on hard endpoints.

‘Remarkable reduction’

The data from the much smaller compassionate use evaluation of the EVOQUE system generated similar evidence of safety and benefit while also making the point that earlier intervention offers a greater opportunity for preventing irreversible progression. With much longer follow up, the compassionate-use analysis, which involved patients even sicker than those included in bRIGHT, suggested these repairs are durable.

In this retrospective analysis of 38 patients treated at eight centers in Europe, the United States, and Canada, the mortality climbed steadily over 2 years of follow-up, reaching 29% at 2 years despite the fact that TR was reduced to < 1% after the procedure and remained durably suppressed at a median follow-up of 520 days.

The tricuspid valve repair with the EVOQUE system “was associated with a remarkable reduction in heart failure symptoms and significant improvement in NYHA functional class up to a maximum of 1,074 days after the intervention,” reported Lukas Stolz, MD, an interventional cardiologist at Ludwig-Maximilians-University, Munich.

In the data he presented at EuroPCR, which was published simultaneously as a letter in JACC, he said that favorable reverse remodeling of the right ventricle, which was observed as early as 30 days after the procedure, was maintained at long-term follow up.

The uncontrolled data from the compassionate analysis, like the bRIGHT registry, could not confirm that tricuspid valve repair changes the trajectory of progressive heart disease, but the favorable effects Dr. Stolz reported on cardiovascular function, not just symptoms, support this idea.

Dr. Lutz has financial relationships with Edwards Lifesciences, ReCor, and Abbott, which funded the bRIGHT registry. Dr. Karam reports financial relationships with Abbott, Edwards Lifesciences, and Medtronic. Dr. Stolz reports no potential conflicts of interest, but other coinvestigators of the retrospective analysis have financial relationships with Edwards Lifesciences, which is developing the EVOQUE system.

Real-world data accumulated in Europe outside of a clinical trial support both the safety and the benefit of two transcatheter edge-to-edge (TEER) devices designed specifically for the treatment of tricuspid regurgitation (TR).

For the TriClip system (Abbott), the data were drawn from a prospective postmarketing registry, and for the EVOQUE system (Edwards Lifesciences), data were generated by a compassionate use program.

The TriClip system is approved and available in Europe, but neither system has regulatory approval in the United States.

The two sets of data, each presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, are consistent with controlled trials. Each system was associated with high rates of procedural success, low rates of adverse events, and sustained improvements in quality of life.
 

Real-world backup for TRILUMINATE

Presented just days before the pivotal multinational TRILUMINATE trial was published in the New England Journal of Medicine, the bRIGHT postmarketing study of the TriClip device demonstrated a procedural rate of success and a subsequent reduction in TR that was at least as good but in a substantially sicker patient population.

“To appreciate these results, you have to put into perspective the baseline TR in our population,” reported Philipp Lurz, MD, PhD, of the Heart Center Leipzig, University of Leipzig, Germany. Whereas only 70% of those randomized in TRILUMINATE had grade 4 (massive) or 5 (torrential) TR, the proportion was 90% in bRIGHT.

The proportion with TR of moderate or less severity was 77% when assessed at 30 days in bRIGHT versus 72%, however, when assessed at 1 year in TRILUMINATE. In addition, procedural success was 99% in both studies even though patients in bRIGHT were on average older and had more comorbidities. At baseline, 80% of bRIGHT patients were in New York Heart Association (NYHA) class III or IV heart failure versus 59% of those in TRILUMINATE.

TRILUMINATE data, presented prior to publication at the annual meeting of the American College of Cardiology earlier this year, did not associate the transcatheter TR repair with a reduction in mortality or a reduction in hospitalization for heart failure, which were the first two of three hierarchical endpoints, but it did show benefit on the third, which was quality of life. As measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), patients in the transcatheter repair group gained 12.3 points versus 0.6 points (P < .001) on medical therapy.

In the bRIGHT registry, patients gained 19 points in the KCCQ score after treatment. By 30 days, the proportion of patients in NHYA class III/IV had fallen from 80% to 20%. The major adverse event rate of 2.5% at 30 days was only modestly higher than the 1.7% rate at 30 days in TRILUMINATE.

“The safety profile remained strong despite the sicker population treated in the registry,” reported Dr. Lurz, whose results were simultaneously published in the Journal of the American College of Cardiology (JACC).

The bRIGHT registry analysis was based on 511 patients treated at 26 sites in Europe. Dr. Lurz characterized it as “the first prospective, single-arm, open-label, multicenter, postmarket registry to evaluate the safety and performance of any transcatheter tricuspid valve repair system.”

In a panel discussion following the presentation, Nicole Karam, MD, PhD, codirector of the heart valve unit, Hospital Georges Pompidou, Paris, praised a study of TEER tricuspid valve device in the real world, but she pointed out that the question of who to treat remains unanswered. Although symptom relief has value for a condition that can impose large deficits in quality of life, she called for more data to identify optimal candidates, particularly in the persistent absence of a major effect on hard endpoints.

Dr. Lurz agreed. In bRIGHT, predictors of a moderate or less TR at discharge included a smaller tethering distance, a smaller right ventricular end diastolic dimension, a smaller right atrial volume, and a smaller tricuspid annular diameter.

Each of these predictors argues for earlier treatment, he said, even if later treatment in a clinical trial provides a greater likelihood of eventually demonstrating benefits on hard endpoints.

‘Remarkable reduction’

The data from the much smaller compassionate use evaluation of the EVOQUE system generated similar evidence of safety and benefit while also making the point that earlier intervention offers a greater opportunity for preventing irreversible progression. With much longer follow up, the compassionate-use analysis, which involved patients even sicker than those included in bRIGHT, suggested these repairs are durable.

In this retrospective analysis of 38 patients treated at eight centers in Europe, the United States, and Canada, the mortality climbed steadily over 2 years of follow-up, reaching 29% at 2 years despite the fact that TR was reduced to < 1% after the procedure and remained durably suppressed at a median follow-up of 520 days.

The tricuspid valve repair with the EVOQUE system “was associated with a remarkable reduction in heart failure symptoms and significant improvement in NYHA functional class up to a maximum of 1,074 days after the intervention,” reported Lukas Stolz, MD, an interventional cardiologist at Ludwig-Maximilians-University, Munich.

In the data he presented at EuroPCR, which was published simultaneously as a letter in JACC, he said that favorable reverse remodeling of the right ventricle, which was observed as early as 30 days after the procedure, was maintained at long-term follow up.

The uncontrolled data from the compassionate analysis, like the bRIGHT registry, could not confirm that tricuspid valve repair changes the trajectory of progressive heart disease, but the favorable effects Dr. Stolz reported on cardiovascular function, not just symptoms, support this idea.

Dr. Lutz has financial relationships with Edwards Lifesciences, ReCor, and Abbott, which funded the bRIGHT registry. Dr. Karam reports financial relationships with Abbott, Edwards Lifesciences, and Medtronic. Dr. Stolz reports no potential conflicts of interest, but other coinvestigators of the retrospective analysis have financial relationships with Edwards Lifesciences, which is developing the EVOQUE system.

DUBLIN – Substantial reductions in body weight across body mass index categories, as well as improved body composition, were achieved with tirzepatide (Mounjaro) in adults for chronic weight management, according to the latest results of the SURMOUNT-1 study.

The new analysis showed that up to 63% of participants achieved a reduction in body weight of at least 20%, and all three tirzepatide doses (5 mg, 10 mg, and 15 mg) led to substantial, clinically meaningful, and sustained body-weight reduction, compared with placebo at 72 weeks of follow-up.

Mean weight loss was –16.0%, –21.4%, and –22.5% with tirzepatide 5 mg, 10 mg, and 15 mg, compared with –2.4% for placebo (all P < .001 vs. placebo). And among participants taking the highest 15-mg dose of tirzepatide, 96%, 90%, and 78% of patients achieved weight reductions of at least 5%, 10%, and 15%.

Tirzepatide is approved in the United States and the European Union for the treatment of type 2 diabetes but is not yet approved for obesity in any country. The manufacturer of tirzepatide, Eli Lilly, intends to seek approval for the drug as an obesity treatment from the U.S. Food and Drug Administration, European Medicines Agency, and in other territories beginning in 2023.

Regardless of baseline BMI category, 9 out of 10 people achieved the greater than or equal to 5% body weight reduction threshold across all doses of tirzepatide, and at the higher doses, over one-third achieved weight loss of 25% or more.

“Similar to lifestyle and surgical treatments, participants on tirzepatide had around a threefold greater percent reduction in fat mass, compared with lean mass, resulting in an overall improvement in body composition,” reported SURMOUNT-1 co-investigator Louis Aronne, MD, Comprehensive Weight Control Center, Weill Cornell Medicine, New York.

Weight loss and body composition explored

Tirzepatide is a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that works to activate the GIP and GLP-1 receptors, respectively, found in areas of the brain important for appetite regulation, decreasing food intake, and modulating fat utilization. 

The phase 3, double-blind, randomized, controlled trial included data from 2,539 adults with a BMI greater than or equal to 30 kg/m² (class I, II, III obesity) or greater than or equal to 27 kg/m² (overweight) with one or more weight-related complications, excluding diabetes. At baseline, mean body weight was 104.8 kg, mean BMI was 38.0 kg/m², and 94.5% of participants had BMI greater than or equal to 30 kg/m².

Patients were randomized to once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks. The primary objective was to show that tirzepatide was superior to placebo in terms of percentage change in body weight and proportion of participants with body-weight reduction of greater than or equal to 5%. The percentage change from baseline body weight and proportion of participants with body weight reduction greater than or equal to 5% were also assessed across BMI categories of greater than or equal to 27 to less than 30 kg/m², greater than or equal to 30 to less than 35 kg/m² (class 1 obesity), greater than or equal to 35 to less than 40 kg/m² (class 2 obesity), and greater than or equal to 40 kg/m² (class 3 obesity).

In addition, in a retrospective subanalysis, body composition was evaluated in a subpopulation that underwent dual-energy x-ray absorptiometry, assessing change from baseline body composition within age subgroups less than 50 years (n = 99), 50-64.9 years (n = 41), and greater than or equal to 65 years (n = 20).

The average weight reduction over the 72 weeks of follow-up was –16.0%, –21.4%, and –22.5% with tirzepatide 5 mg, 10 mg, and 15 mg, compared with –2.4% for participants taking placebo (all P < .001 vs. placebo).

The percentages of participants reaching target weight reductions of greater than or equal to 5%, greater than or equal to 10%, greater than or equal to 15%, greater than or equal to 20%, and greater than or equal to 25% were recorded. Over 90% achieved greater than or equal to 5% weight loss, irrespective of BMI and tirzepatide dose, while 55.5% and 62.9% in the 10-mg and 15-mg groups achieved greater than or equal to 20% weight loss, and 35.0% and 39.7% in the 10-mg and 15-mg groups achieved greater than or equal to 25% weight loss, respectively.

By increasing BMI category, in the 10-mg group, weight loss was –18.2 kg, –21.9 kg, –22.0, and –20.7 kg; and in the 15-mg group, weight loss was –18.1kg, –21.2 kg, –24.5 kg, and –22.8 kg. Weight loss in the 5-mg group ranged from –16.6 kg to –15.9 kg from lowest to highest BMI category. 

“In the lower-weight categories, there is less weight to lose, so we see a flattening of the curve [with a] maximum of around 18%, so it may be that as we learn more about a drug that is so potent, we recognize that we don’t need to use such a high dose in people with BMI 27-30 kg/m²,” he explained. “It’s the higher BMI categories where we need the higher dose.”

As with lifestyle and surgical treatments, participants taking tirzepatide had around a three times greater percentage reduction in fat mass than lean mass, resulting in an overall improvement in body composition, reported Dr. Aronne.

“We want loss of fat, not lean mass, and we know that we lose around one part lean to three parts fat mass when on a diet and exercise regimen,” he went on to explain. “We see exactly this [balance of lean-to-fat-mass loss] here with 33.9% total fat mass reduction in the treatment group, compared with 8.2% in the placebo group.”

Visceral fat mass reduction was 40% in the treatment group, compared with 7.3% with placebo. “It’s good to see there’s more loss of visceral fat,” said Dr. Aronne. Lean mass loss was 10.9%. “So around three times greater reduction in fat over lean mass loss, resulting in overall improvement of body composition,” he reported. 

Also, in older people (≥ 65 years) there was approximately no difference in fat versus lean mass loss, compared with younger people, despite older people being more likely to lose more lean mass.

With respect to patient-reported outcomes based on the 36-item Short-Form Health Survey (SF-36), Dr. Aronne said that physical functioning scores significantly improved at 72 weeks, compared with placebo, particularly in participants with physical function limitations at baseline.

“In an interesting subanalysis, those with physical limitations at baseline showed a significant improvement versus placebo of over 5% difference [considered significant],” he added.

Safety and tolerability were previously reported in the NEJM article. The most common adverse events with tirzepatide were gastrointestinal, and adverse events causing treatment discontinuation occurred in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg doses or placebo, respectively.

“A revolution is coming in the treatment of obesity and cardiometabolic disease, and most physicians cannot grasp this. We’re finally getting the efficacy we’ve been looking for that will produce benefits in every realm,” concluded Dr. Aronne. “These data show that we are now hitting all the secondary endpoints and making our patients better.”

“I think this bodes well. I always envisioned a time when the treatment of obesity would come first before the treatment of cardiometabolic complications of obesity, and I think we’re on the verge of that era with semaglutide, tirzepatide, and the very exciting treatments to come.”

The SURMOUNT-1 trial was sponsored by Lilly. Dr. Aronne is cofounder, chief scientific advisor, and a member of the board of directors for Intellihealth. He is also a paid scientific advisory board member for Eli Lilly.

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

DUBLIN – Substantial reductions in body weight across body mass index categories, as well as improved body composition, were achieved with tirzepatide (Mounjaro) in adults for chronic weight management, according to the latest results of the SURMOUNT-1 study.

The new analysis showed that up to 63% of participants achieved a reduction in body weight of at least 20%, and all three tirzepatide doses (5 mg, 10 mg, and 15 mg) led to substantial, clinically meaningful, and sustained body-weight reduction, compared with placebo at 72 weeks of follow-up.

Mean weight loss was –16.0%, –21.4%, and –22.5% with tirzepatide 5 mg, 10 mg, and 15 mg, compared with –2.4% for placebo (all P < .001 vs. placebo). And among participants taking the highest 15-mg dose of tirzepatide, 96%, 90%, and 78% of patients achieved weight reductions of at least 5%, 10%, and 15%.

Tirzepatide is approved in the United States and the European Union for the treatment of type 2 diabetes but is not yet approved for obesity in any country. The manufacturer of tirzepatide, Eli Lilly, intends to seek approval for the drug as an obesity treatment from the U.S. Food and Drug Administration, European Medicines Agency, and in other territories beginning in 2023.

Regardless of baseline BMI category, 9 out of 10 people achieved the greater than or equal to 5% body weight reduction threshold across all doses of tirzepatide, and at the higher doses, over one-third achieved weight loss of 25% or more.

“Similar to lifestyle and surgical treatments, participants on tirzepatide had around a threefold greater percent reduction in fat mass, compared with lean mass, resulting in an overall improvement in body composition,” reported SURMOUNT-1 co-investigator Louis Aronne, MD, Comprehensive Weight Control Center, Weill Cornell Medicine, New York.

Weight loss and body composition explored

Tirzepatide is a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that works to activate the GIP and GLP-1 receptors, respectively, found in areas of the brain important for appetite regulation, decreasing food intake, and modulating fat utilization. 

The phase 3, double-blind, randomized, controlled trial included data from 2,539 adults with a BMI greater than or equal to 30 kg/m² (class I, II, III obesity) or greater than or equal to 27 kg/m² (overweight) with one or more weight-related complications, excluding diabetes. At baseline, mean body weight was 104.8 kg, mean BMI was 38.0 kg/m², and 94.5% of participants had BMI greater than or equal to 30 kg/m².

Patients were randomized to once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks. The primary objective was to show that tirzepatide was superior to placebo in terms of percentage change in body weight and proportion of participants with body-weight reduction of greater than or equal to 5%. The percentage change from baseline body weight and proportion of participants with body weight reduction greater than or equal to 5% were also assessed across BMI categories of greater than or equal to 27 to less than 30 kg/m², greater than or equal to 30 to less than 35 kg/m² (class 1 obesity), greater than or equal to 35 to less than 40 kg/m² (class 2 obesity), and greater than or equal to 40 kg/m² (class 3 obesity).

In addition, in a retrospective subanalysis, body composition was evaluated in a subpopulation that underwent dual-energy x-ray absorptiometry, assessing change from baseline body composition within age subgroups less than 50 years (n = 99), 50-64.9 years (n = 41), and greater than or equal to 65 years (n = 20).

The average weight reduction over the 72 weeks of follow-up was –16.0%, –21.4%, and –22.5% with tirzepatide 5 mg, 10 mg, and 15 mg, compared with –2.4% for participants taking placebo (all P < .001 vs. placebo).

The percentages of participants reaching target weight reductions of greater than or equal to 5%, greater than or equal to 10%, greater than or equal to 15%, greater than or equal to 20%, and greater than or equal to 25% were recorded. Over 90% achieved greater than or equal to 5% weight loss, irrespective of BMI and tirzepatide dose, while 55.5% and 62.9% in the 10-mg and 15-mg groups achieved greater than or equal to 20% weight loss, and 35.0% and 39.7% in the 10-mg and 15-mg groups achieved greater than or equal to 25% weight loss, respectively.

By increasing BMI category, in the 10-mg group, weight loss was –18.2 kg, –21.9 kg, –22.0, and –20.7 kg; and in the 15-mg group, weight loss was –18.1kg, –21.2 kg, –24.5 kg, and –22.8 kg. Weight loss in the 5-mg group ranged from –16.6 kg to –15.9 kg from lowest to highest BMI category. 

“In the lower-weight categories, there is less weight to lose, so we see a flattening of the curve [with a] maximum of around 18%, so it may be that as we learn more about a drug that is so potent, we recognize that we don’t need to use such a high dose in people with BMI 27-30 kg/m²,” he explained. “It’s the higher BMI categories where we need the higher dose.”

As with lifestyle and surgical treatments, participants taking tirzepatide had around a three times greater percentage reduction in fat mass than lean mass, resulting in an overall improvement in body composition, reported Dr. Aronne.

“We want loss of fat, not lean mass, and we know that we lose around one part lean to three parts fat mass when on a diet and exercise regimen,” he went on to explain. “We see exactly this [balance of lean-to-fat-mass loss] here with 33.9% total fat mass reduction in the treatment group, compared with 8.2% in the placebo group.”

Visceral fat mass reduction was 40% in the treatment group, compared with 7.3% with placebo. “It’s good to see there’s more loss of visceral fat,” said Dr. Aronne. Lean mass loss was 10.9%. “So around three times greater reduction in fat over lean mass loss, resulting in overall improvement of body composition,” he reported. 

Also, in older people (≥ 65 years) there was approximately no difference in fat versus lean mass loss, compared with younger people, despite older people being more likely to lose more lean mass.

With respect to patient-reported outcomes based on the 36-item Short-Form Health Survey (SF-36), Dr. Aronne said that physical functioning scores significantly improved at 72 weeks, compared with placebo, particularly in participants with physical function limitations at baseline.

“In an interesting subanalysis, those with physical limitations at baseline showed a significant improvement versus placebo of over 5% difference [considered significant],” he added.

Safety and tolerability were previously reported in the NEJM article. The most common adverse events with tirzepatide were gastrointestinal, and adverse events causing treatment discontinuation occurred in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg doses or placebo, respectively.

“A revolution is coming in the treatment of obesity and cardiometabolic disease, and most physicians cannot grasp this. We’re finally getting the efficacy we’ve been looking for that will produce benefits in every realm,” concluded Dr. Aronne. “These data show that we are now hitting all the secondary endpoints and making our patients better.”

“I think this bodes well. I always envisioned a time when the treatment of obesity would come first before the treatment of cardiometabolic complications of obesity, and I think we’re on the verge of that era with semaglutide, tirzepatide, and the very exciting treatments to come.”

The SURMOUNT-1 trial was sponsored by Lilly. Dr. Aronne is cofounder, chief scientific advisor, and a member of the board of directors for Intellihealth. He is also a paid scientific advisory board member for Eli Lilly.

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

DUBLIN – Substantial reductions in body weight across body mass index categories, as well as improved body composition, were achieved with tirzepatide (Mounjaro) in adults for chronic weight management, according to the latest results of the SURMOUNT-1 study.

The new analysis showed that up to 63% of participants achieved a reduction in body weight of at least 20%, and all three tirzepatide doses (5 mg, 10 mg, and 15 mg) led to substantial, clinically meaningful, and sustained body-weight reduction, compared with placebo at 72 weeks of follow-up.

Mean weight loss was –16.0%, –21.4%, and –22.5% with tirzepatide 5 mg, 10 mg, and 15 mg, compared with –2.4% for placebo (all P < .001 vs. placebo). And among participants taking the highest 15-mg dose of tirzepatide, 96%, 90%, and 78% of patients achieved weight reductions of at least 5%, 10%, and 15%.

Tirzepatide is approved in the United States and the European Union for the treatment of type 2 diabetes but is not yet approved for obesity in any country. The manufacturer of tirzepatide, Eli Lilly, intends to seek approval for the drug as an obesity treatment from the U.S. Food and Drug Administration, European Medicines Agency, and in other territories beginning in 2023.

Regardless of baseline BMI category, 9 out of 10 people achieved the greater than or equal to 5% body weight reduction threshold across all doses of tirzepatide, and at the higher doses, over one-third achieved weight loss of 25% or more.

“Similar to lifestyle and surgical treatments, participants on tirzepatide had around a threefold greater percent reduction in fat mass, compared with lean mass, resulting in an overall improvement in body composition,” reported SURMOUNT-1 co-investigator Louis Aronne, MD, Comprehensive Weight Control Center, Weill Cornell Medicine, New York.

Weight loss and body composition explored

Tirzepatide is a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that works to activate the GIP and GLP-1 receptors, respectively, found in areas of the brain important for appetite regulation, decreasing food intake, and modulating fat utilization. 

The phase 3, double-blind, randomized, controlled trial included data from 2,539 adults with a BMI greater than or equal to 30 kg/m² (class I, II, III obesity) or greater than or equal to 27 kg/m² (overweight) with one or more weight-related complications, excluding diabetes. At baseline, mean body weight was 104.8 kg, mean BMI was 38.0 kg/m², and 94.5% of participants had BMI greater than or equal to 30 kg/m².

Patients were randomized to once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks. The primary objective was to show that tirzepatide was superior to placebo in terms of percentage change in body weight and proportion of participants with body-weight reduction of greater than or equal to 5%. The percentage change from baseline body weight and proportion of participants with body weight reduction greater than or equal to 5% were also assessed across BMI categories of greater than or equal to 27 to less than 30 kg/m², greater than or equal to 30 to less than 35 kg/m² (class 1 obesity), greater than or equal to 35 to less than 40 kg/m² (class 2 obesity), and greater than or equal to 40 kg/m² (class 3 obesity).

In addition, in a retrospective subanalysis, body composition was evaluated in a subpopulation that underwent dual-energy x-ray absorptiometry, assessing change from baseline body composition within age subgroups less than 50 years (n = 99), 50-64.9 years (n = 41), and greater than or equal to 65 years (n = 20).

The average weight reduction over the 72 weeks of follow-up was –16.0%, –21.4%, and –22.5% with tirzepatide 5 mg, 10 mg, and 15 mg, compared with –2.4% for participants taking placebo (all P < .001 vs. placebo).

The percentages of participants reaching target weight reductions of greater than or equal to 5%, greater than or equal to 10%, greater than or equal to 15%, greater than or equal to 20%, and greater than or equal to 25% were recorded. Over 90% achieved greater than or equal to 5% weight loss, irrespective of BMI and tirzepatide dose, while 55.5% and 62.9% in the 10-mg and 15-mg groups achieved greater than or equal to 20% weight loss, and 35.0% and 39.7% in the 10-mg and 15-mg groups achieved greater than or equal to 25% weight loss, respectively.

By increasing BMI category, in the 10-mg group, weight loss was –18.2 kg, –21.9 kg, –22.0, and –20.7 kg; and in the 15-mg group, weight loss was –18.1kg, –21.2 kg, –24.5 kg, and –22.8 kg. Weight loss in the 5-mg group ranged from –16.6 kg to –15.9 kg from lowest to highest BMI category. 

“In the lower-weight categories, there is less weight to lose, so we see a flattening of the curve [with a] maximum of around 18%, so it may be that as we learn more about a drug that is so potent, we recognize that we don’t need to use such a high dose in people with BMI 27-30 kg/m²,” he explained. “It’s the higher BMI categories where we need the higher dose.”

As with lifestyle and surgical treatments, participants taking tirzepatide had around a three times greater percentage reduction in fat mass than lean mass, resulting in an overall improvement in body composition, reported Dr. Aronne.

“We want loss of fat, not lean mass, and we know that we lose around one part lean to three parts fat mass when on a diet and exercise regimen,” he went on to explain. “We see exactly this [balance of lean-to-fat-mass loss] here with 33.9% total fat mass reduction in the treatment group, compared with 8.2% in the placebo group.”

Visceral fat mass reduction was 40% in the treatment group, compared with 7.3% with placebo. “It’s good to see there’s more loss of visceral fat,” said Dr. Aronne. Lean mass loss was 10.9%. “So around three times greater reduction in fat over lean mass loss, resulting in overall improvement of body composition,” he reported. 

Also, in older people (≥ 65 years) there was approximately no difference in fat versus lean mass loss, compared with younger people, despite older people being more likely to lose more lean mass.

With respect to patient-reported outcomes based on the 36-item Short-Form Health Survey (SF-36), Dr. Aronne said that physical functioning scores significantly improved at 72 weeks, compared with placebo, particularly in participants with physical function limitations at baseline.

“In an interesting subanalysis, those with physical limitations at baseline showed a significant improvement versus placebo of over 5% difference [considered significant],” he added.

Safety and tolerability were previously reported in the NEJM article. The most common adverse events with tirzepatide were gastrointestinal, and adverse events causing treatment discontinuation occurred in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg doses or placebo, respectively.

“A revolution is coming in the treatment of obesity and cardiometabolic disease, and most physicians cannot grasp this. We’re finally getting the efficacy we’ve been looking for that will produce benefits in every realm,” concluded Dr. Aronne. “These data show that we are now hitting all the secondary endpoints and making our patients better.”

“I think this bodes well. I always envisioned a time when the treatment of obesity would come first before the treatment of cardiometabolic complications of obesity, and I think we’re on the verge of that era with semaglutide, tirzepatide, and the very exciting treatments to come.”

The SURMOUNT-1 trial was sponsored by Lilly. Dr. Aronne is cofounder, chief scientific advisor, and a member of the board of directors for Intellihealth. He is also a paid scientific advisory board member for Eli Lilly.

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

DUBLIN – Ear acupuncture with stimulation beads leads to weight loss and a reduction in both waist circumference and body fat percentage, when combined with restricted food intake, in men with high levels of visceral fat and overweight/obesity.

Edward Olive/Dreamstime.com

Three months of auricular acupuncture stimulation and dietary restriction led to a mean weight loss of nearly 9 kg plus a drop in waist circumference of more than 10 cm.

According to the researchers, acupuncture beads, used in Japan to augment weight loss for more than 30 years, are thought to stimulate nerves and organs that regulate appetite, satiety, hunger, and food cravings.

Findings of the observational study were presented by Takahiro Fujimoto, MD, PhD, Clinic F, Tokyo, at this year’s European Congress on Obesity.

Together with a prior study using the same intervention in women, Dr. Fujimoto and colleagues have now gathered data in more than 1,000 individuals, he said. “We wanted a method that was simple and noninvasive that would serve as a support to exercise and dietary therapy,” Dr. Fujimoto said in an interview.

“We believe there is an effect,” he asserted. “Acupuncture’s effect lies in stimulating the satiety center with benefits in helping individuals to control their food cravings and intake when reducing meals,” he said, pointing out that similar techniques have been used in patients undergoing withdrawal from drug addiction and in smoking cessation. He explained that acupuncture beads are believed to help individuals change their lifestyle habits, and added that “the relapse rate after 6 months is addressed in another paper, and it is very low.”

Professor Jason C.G. Halford, PhD, head of school at the University of Leeds, England, and president of the European Association for the Study of Obesity, commented on the findings. “There is no control group here receiving everything but the acupuncture,” he noted. “As such, it could be other elements of the intervention driving this [effect] including the act of keeping a food diary increasing awareness of one’s diet. A randomized controlled trial would be the next step.”

In women, the technique led to significantly more weight loss than in those who were untreated, and weight loss was maintained for 6 months after the end of treatment.

The researchers added that acupuncture stimulation with beads was a simpler method than traditional use of intradermal needles requiring expert acupuncturists. The stimulation is applied with 1.5-mm metal ear beads on 6 points of the outer ear (shen men, food pipe, upper stomach opening, stomach, lungs, and endocrine system) that correspond to meridian lines, and as such, restores the flow of qi by resolving any blockages or disruption. This may help with a variety of health conditions, according to the researchers. Placed on both ears, surgical tape was used to keep the beads in place to ensure participants continuously received uniform pressure on each of the six acupuncture points.

Dietary guidance was provided to participants to help reduce food intake by half, and nutritional supplements were given to compensate for any deficiencies. Participants attended twice-weekly clinic visits for bead sticking and diet progress monitoring. Body weight, body fat percentage, fat mass, lean mass, muscle mass, body mass index (BMI), and abdominal fat were assessed at the start and end of the study period.

“Since these tiny metal beads are attached to six points on the outer ear that stimulate nerves and organs which regulate appetite, satiety, and hunger, this type of acupuncture does not require complex knowledge or skill,” explained Dr. Fujimoto.

The results of the latest study, in men only, build on a prior study of more than 1,300 women who also received auricular acupuncture stimulation with beads as well as a halving of their food intake. In women, the weight loss program led to total body weight loss of 11.2% over 3 months.

At baseline, the 81 male participants, ages 21-78 years, had a mean BMI of 28.4 kg/m² and mean waist circumference of 98.4 cm. Body fat percentage was 28.2%.

After 3 months, participants lost a mean of 8.6 kg (P < .001), decreased waist circumference by a mean of 10.4 cm (P < .001), and lost a mean of 4.0% of total body fat (P < .001). Visceral fat levels also fell by 2.2 points (P < .001), from 15.2 points at baseline to 13.0 points after 3 months. (A healthy visceral fat rating is between 1 and 12 points.) BMI decreased by almost 3 kg/m² (from 28.4 at baseline to 25.5 at 3 months; P < .001).

Improvement in muscle-to-fat ratio was greater in men than women, whereas women had a greater decrease in percentage body fat than men.

“Whilst receiving ear acupuncture, the investigators asked participants to cut their food intake by half. It’s not unreasonable to expect that this major dietary change was the main reason participants lost weight,” remarked Graham Wheeler, PhD, statistical ambassador at the Royal Statistical Society, United Kingdom.

He also commented on the lack of a control group: “This study does not show us the impact of ear acupuncture on weight loss.”

Dr. Fujimoto and Dr. Halford have reported no relevant financial relationships. Dr. Wheeler is a statistical ambassador for the Royal Statistical Society, is employed by GSK, and holds an honorary senior lecturer post at Imperial College London.

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

DUBLIN – Ear acupuncture with stimulation beads leads to weight loss and a reduction in both waist circumference and body fat percentage, when combined with restricted food intake, in men with high levels of visceral fat and overweight/obesity.

Edward Olive/Dreamstime.com

Three months of auricular acupuncture stimulation and dietary restriction led to a mean weight loss of nearly 9 kg plus a drop in waist circumference of more than 10 cm.

According to the researchers, acupuncture beads, used in Japan to augment weight loss for more than 30 years, are thought to stimulate nerves and organs that regulate appetite, satiety, hunger, and food cravings.

Findings of the observational study were presented by Takahiro Fujimoto, MD, PhD, Clinic F, Tokyo, at this year’s European Congress on Obesity.

Together with a prior study using the same intervention in women, Dr. Fujimoto and colleagues have now gathered data in more than 1,000 individuals, he said. “We wanted a method that was simple and noninvasive that would serve as a support to exercise and dietary therapy,” Dr. Fujimoto said in an interview.

“We believe there is an effect,” he asserted. “Acupuncture’s effect lies in stimulating the satiety center with benefits in helping individuals to control their food cravings and intake when reducing meals,” he said, pointing out that similar techniques have been used in patients undergoing withdrawal from drug addiction and in smoking cessation. He explained that acupuncture beads are believed to help individuals change their lifestyle habits, and added that “the relapse rate after 6 months is addressed in another paper, and it is very low.”

Professor Jason C.G. Halford, PhD, head of school at the University of Leeds, England, and president of the European Association for the Study of Obesity, commented on the findings. “There is no control group here receiving everything but the acupuncture,” he noted. “As such, it could be other elements of the intervention driving this [effect] including the act of keeping a food diary increasing awareness of one’s diet. A randomized controlled trial would be the next step.”

In women, the technique led to significantly more weight loss than in those who were untreated, and weight loss was maintained for 6 months after the end of treatment.

The researchers added that acupuncture stimulation with beads was a simpler method than traditional use of intradermal needles requiring expert acupuncturists. The stimulation is applied with 1.5-mm metal ear beads on 6 points of the outer ear (shen men, food pipe, upper stomach opening, stomach, lungs, and endocrine system) that correspond to meridian lines, and as such, restores the flow of qi by resolving any blockages or disruption. This may help with a variety of health conditions, according to the researchers. Placed on both ears, surgical tape was used to keep the beads in place to ensure participants continuously received uniform pressure on each of the six acupuncture points.

Dietary guidance was provided to participants to help reduce food intake by half, and nutritional supplements were given to compensate for any deficiencies. Participants attended twice-weekly clinic visits for bead sticking and diet progress monitoring. Body weight, body fat percentage, fat mass, lean mass, muscle mass, body mass index (BMI), and abdominal fat were assessed at the start and end of the study period.

“Since these tiny metal beads are attached to six points on the outer ear that stimulate nerves and organs which regulate appetite, satiety, and hunger, this type of acupuncture does not require complex knowledge or skill,” explained Dr. Fujimoto.

The results of the latest study, in men only, build on a prior study of more than 1,300 women who also received auricular acupuncture stimulation with beads as well as a halving of their food intake. In women, the weight loss program led to total body weight loss of 11.2% over 3 months.

At baseline, the 81 male participants, ages 21-78 years, had a mean BMI of 28.4 kg/m² and mean waist circumference of 98.4 cm. Body fat percentage was 28.2%.

After 3 months, participants lost a mean of 8.6 kg (P < .001), decreased waist circumference by a mean of 10.4 cm (P < .001), and lost a mean of 4.0% of total body fat (P < .001). Visceral fat levels also fell by 2.2 points (P < .001), from 15.2 points at baseline to 13.0 points after 3 months. (A healthy visceral fat rating is between 1 and 12 points.) BMI decreased by almost 3 kg/m² (from 28.4 at baseline to 25.5 at 3 months; P < .001).

Improvement in muscle-to-fat ratio was greater in men than women, whereas women had a greater decrease in percentage body fat than men.

“Whilst receiving ear acupuncture, the investigators asked participants to cut their food intake by half. It’s not unreasonable to expect that this major dietary change was the main reason participants lost weight,” remarked Graham Wheeler, PhD, statistical ambassador at the Royal Statistical Society, United Kingdom.

He also commented on the lack of a control group: “This study does not show us the impact of ear acupuncture on weight loss.”

Dr. Fujimoto and Dr. Halford have reported no relevant financial relationships. Dr. Wheeler is a statistical ambassador for the Royal Statistical Society, is employed by GSK, and holds an honorary senior lecturer post at Imperial College London.

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

DUBLIN – Ear acupuncture with stimulation beads leads to weight loss and a reduction in both waist circumference and body fat percentage, when combined with restricted food intake, in men with high levels of visceral fat and overweight/obesity.

Edward Olive/Dreamstime.com

Three months of auricular acupuncture stimulation and dietary restriction led to a mean weight loss of nearly 9 kg plus a drop in waist circumference of more than 10 cm.

According to the researchers, acupuncture beads, used in Japan to augment weight loss for more than 30 years, are thought to stimulate nerves and organs that regulate appetite, satiety, hunger, and food cravings.

Findings of the observational study were presented by Takahiro Fujimoto, MD, PhD, Clinic F, Tokyo, at this year’s European Congress on Obesity.

Together with a prior study using the same intervention in women, Dr. Fujimoto and colleagues have now gathered data in more than 1,000 individuals, he said. “We wanted a method that was simple and noninvasive that would serve as a support to exercise and dietary therapy,” Dr. Fujimoto said in an interview.

“We believe there is an effect,” he asserted. “Acupuncture’s effect lies in stimulating the satiety center with benefits in helping individuals to control their food cravings and intake when reducing meals,” he said, pointing out that similar techniques have been used in patients undergoing withdrawal from drug addiction and in smoking cessation. He explained that acupuncture beads are believed to help individuals change their lifestyle habits, and added that “the relapse rate after 6 months is addressed in another paper, and it is very low.”

Professor Jason C.G. Halford, PhD, head of school at the University of Leeds, England, and president of the European Association for the Study of Obesity, commented on the findings. “There is no control group here receiving everything but the acupuncture,” he noted. “As such, it could be other elements of the intervention driving this [effect] including the act of keeping a food diary increasing awareness of one’s diet. A randomized controlled trial would be the next step.”

In women, the technique led to significantly more weight loss than in those who were untreated, and weight loss was maintained for 6 months after the end of treatment.

The researchers added that acupuncture stimulation with beads was a simpler method than traditional use of intradermal needles requiring expert acupuncturists. The stimulation is applied with 1.5-mm metal ear beads on 6 points of the outer ear (shen men, food pipe, upper stomach opening, stomach, lungs, and endocrine system) that correspond to meridian lines, and as such, restores the flow of qi by resolving any blockages or disruption. This may help with a variety of health conditions, according to the researchers. Placed on both ears, surgical tape was used to keep the beads in place to ensure participants continuously received uniform pressure on each of the six acupuncture points.

Dietary guidance was provided to participants to help reduce food intake by half, and nutritional supplements were given to compensate for any deficiencies. Participants attended twice-weekly clinic visits for bead sticking and diet progress monitoring. Body weight, body fat percentage, fat mass, lean mass, muscle mass, body mass index (BMI), and abdominal fat were assessed at the start and end of the study period.

“Since these tiny metal beads are attached to six points on the outer ear that stimulate nerves and organs which regulate appetite, satiety, and hunger, this type of acupuncture does not require complex knowledge or skill,” explained Dr. Fujimoto.

The results of the latest study, in men only, build on a prior study of more than 1,300 women who also received auricular acupuncture stimulation with beads as well as a halving of their food intake. In women, the weight loss program led to total body weight loss of 11.2% over 3 months.

At baseline, the 81 male participants, ages 21-78 years, had a mean BMI of 28.4 kg/m² and mean waist circumference of 98.4 cm. Body fat percentage was 28.2%.

After 3 months, participants lost a mean of 8.6 kg (P < .001), decreased waist circumference by a mean of 10.4 cm (P < .001), and lost a mean of 4.0% of total body fat (P < .001). Visceral fat levels also fell by 2.2 points (P < .001), from 15.2 points at baseline to 13.0 points after 3 months. (A healthy visceral fat rating is between 1 and 12 points.) BMI decreased by almost 3 kg/m² (from 28.4 at baseline to 25.5 at 3 months; P < .001).

Improvement in muscle-to-fat ratio was greater in men than women, whereas women had a greater decrease in percentage body fat than men.

“Whilst receiving ear acupuncture, the investigators asked participants to cut their food intake by half. It’s not unreasonable to expect that this major dietary change was the main reason participants lost weight,” remarked Graham Wheeler, PhD, statistical ambassador at the Royal Statistical Society, United Kingdom.

He also commented on the lack of a control group: “This study does not show us the impact of ear acupuncture on weight loss.”

Dr. Fujimoto and Dr. Halford have reported no relevant financial relationships. Dr. Wheeler is a statistical ambassador for the Royal Statistical Society, is employed by GSK, and holds an honorary senior lecturer post at Imperial College London.

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

SEOUL, SOUTH KOREA – A panel of urinary biomarkers may do better than measuring proteinuria in predicting which patients with lupus nephritis are going to respond to treatment, according to a presentation at an international congress on systemic lupus erythematosus.

Physician-scientist Andrea Fava, MD, of the division of rheumatology at Johns Hopkins University, Baltimore, presented data from a study using urine proteomics to identify biomarkers present in the urine of patients with lupus nephritis at 3 months after starting treatment that were linked to better outcomes from that treatment at 1 year.

While proteinuria is the standard measure used to guide decisions about whether to do a kidney biopsy and how to treat lupus nephritis, it doesn’t always correlate with what’s actually going on inside the kidney in terms of histology and inflammation, Dr. Fava said.

Bianca Nogrady/MDedge News

He pointed to an earlier study in which researchers did kidney biopsies 6 months after patients with lupus nephritis started treatment with mycophenolate. This suggested that around half of patients who showed a clinical response to treatment – defined as proteinuria below 500 mg/day – still had significant histologic disease activity. Another study suggested that this elevated histologic disease activity is associated with a risk of flare, which can result in significant nephron loss. On the flip side, nearly two-thirds of patients in complete histologic remission still had elevated proteinuria.

Unfortunately, it’s not possible or practical to biopsy patients on a regular basis, Dr. Fava said. “So we need better biomarkers, and to do so, we need better knowledge of the pathophysiology because if we have biomarkers that reflect tissue biology in real-time, that may surely guide personalized treatments,” he said at the congress.

Dr. Fava and colleagues enrolled 225 patients with SLE who were undergoing kidney biopsy and 10 healthy controls and used proteomics to quantify the urinary levels of around 1,200 proteins at baseline, 3, 6, and 12 months after initiating treatment.

The team then analyzed these data to look for protein signatures that correlated with histologic phenotypes – particularly the amount of inflammation in the kidney – and clinical features such as response to treatment.

They found several protein biomarkers that appeared to be linked to histologic activity in the kidney, including interleukin (IL)-16, CD163, and neutrophil granule proteins.

Initially, the team looked at baseline levels of these proteins to see if they predicted who responded to treatment, but found no difference between responders and nonresponders.

However, when they looked at levels at 3 months after treatment, a pattern emerged. “We found that in patients who were not responding, there were no changes after 3 months of treatment in the urine proteome,” Dr. Fava said. Among those who did respond to treatment, the levels of these proteins – IL-16, CD163, galectin-1, and CD206 – decreased significantly.

“So the proteins that are linked to renal activity decrease only in responders, suggesting that effective immunosuppression is effective in reducing intrarenal inflammation, which eventually results in low proteinuria at 1 year.”

The decline in these biomarkers persisted at 1 year, and the study suggested it was a better predictor of which patients would respond to treatment at 1 year than proteinuria.

Dr. Fava said in an interview that better biomarkers could revolutionize the treatment and management of lupus nephritis.

“First of all, it can shift the management strategy from treatment to prevention, because at the very beginning we can nip it in the bud maybe with very gentle treatment,” he said. Different panels of urine biomarkers could identify patients at risk of treatment failure, and also help patients to taper off their immunosuppressive therapy without an increased risk of flare. “If we have a way to tell us there’s still inflammation that needs treatment, that could change the way we do it,” he said.

He acknowledged there are significant challenges to developing these biomarkers for clinical use; one is the decision of how to define disease activity without relying on proteinuria as a measure. “Why do I want a biomarker that can predict another biomarker?” he said.

Another presentation during the same session, by Huihua Ding, MD, of Shanghai Jiao Tong University in Shanghai, China, reported on the use of urinary L-selectin to assess renal disease activity and response to treatment in a multiethnic cohort.

This study, involving 474 patients with SLE with or without renal involvement in the United States and China, found levels of urinary L-selectin were elevated only in patients with active lupus nephritis and showed patterns that correlated with renal histologic characteristics.

Clinical rheumatologist Eric F. Morand, MD, PhD, and head of the School of Clinical Sciences at Monash University in Melbourne said one challenge with using urinary biomarkers was that it was not yet clear what these biomarkers reveal about the kidney. “It will be important to see whether this proteomic data actually link to renal outcomes,” Dr. Morand said in an interview. “I think predicting the response to treatment should be based around GFR [glomerular filtration rate] preservation, and I don’t think I’ve seen data yet that the urine biomarkers are going to tell us how to do that better.”

Dr. Morand is optimistic that urine biomarkers will one day be able to achieve that, but he stressed the importance of having urine biomarker tests available in the field at low cost. “You’re going to be doing the tests repeatedly, so therefore, you’re probably going to need to come down to a smaller list of proteins that you measure.”

Dr. Fava reported receiving support from Sanofi and Annexion Bio.

SEOUL, SOUTH KOREA – A panel of urinary biomarkers may do better than measuring proteinuria in predicting which patients with lupus nephritis are going to respond to treatment, according to a presentation at an international congress on systemic lupus erythematosus.

Physician-scientist Andrea Fava, MD, of the division of rheumatology at Johns Hopkins University, Baltimore, presented data from a study using urine proteomics to identify biomarkers present in the urine of patients with lupus nephritis at 3 months after starting treatment that were linked to better outcomes from that treatment at 1 year.

While proteinuria is the standard measure used to guide decisions about whether to do a kidney biopsy and how to treat lupus nephritis, it doesn’t always correlate with what’s actually going on inside the kidney in terms of histology and inflammation, Dr. Fava said.

Bianca Nogrady/MDedge News

He pointed to an earlier study in which researchers did kidney biopsies 6 months after patients with lupus nephritis started treatment with mycophenolate. This suggested that around half of patients who showed a clinical response to treatment – defined as proteinuria below 500 mg/day – still had significant histologic disease activity. Another study suggested that this elevated histologic disease activity is associated with a risk of flare, which can result in significant nephron loss. On the flip side, nearly two-thirds of patients in complete histologic remission still had elevated proteinuria.

Unfortunately, it’s not possible or practical to biopsy patients on a regular basis, Dr. Fava said. “So we need better biomarkers, and to do so, we need better knowledge of the pathophysiology because if we have biomarkers that reflect tissue biology in real-time, that may surely guide personalized treatments,” he said at the congress.

Dr. Fava and colleagues enrolled 225 patients with SLE who were undergoing kidney biopsy and 10 healthy controls and used proteomics to quantify the urinary levels of around 1,200 proteins at baseline, 3, 6, and 12 months after initiating treatment.

The team then analyzed these data to look for protein signatures that correlated with histologic phenotypes – particularly the amount of inflammation in the kidney – and clinical features such as response to treatment.

They found several protein biomarkers that appeared to be linked to histologic activity in the kidney, including interleukin (IL)-16, CD163, and neutrophil granule proteins.

Initially, the team looked at baseline levels of these proteins to see if they predicted who responded to treatment, but found no difference between responders and nonresponders.

However, when they looked at levels at 3 months after treatment, a pattern emerged. “We found that in patients who were not responding, there were no changes after 3 months of treatment in the urine proteome,” Dr. Fava said. Among those who did respond to treatment, the levels of these proteins – IL-16, CD163, galectin-1, and CD206 – decreased significantly.

“So the proteins that are linked to renal activity decrease only in responders, suggesting that effective immunosuppression is effective in reducing intrarenal inflammation, which eventually results in low proteinuria at 1 year.”

The decline in these biomarkers persisted at 1 year, and the study suggested it was a better predictor of which patients would respond to treatment at 1 year than proteinuria.

Dr. Fava said in an interview that better biomarkers could revolutionize the treatment and management of lupus nephritis.

“First of all, it can shift the management strategy from treatment to prevention, because at the very beginning we can nip it in the bud maybe with very gentle treatment,” he said. Different panels of urine biomarkers could identify patients at risk of treatment failure, and also help patients to taper off their immunosuppressive therapy without an increased risk of flare. “If we have a way to tell us there’s still inflammation that needs treatment, that could change the way we do it,” he said.

He acknowledged there are significant challenges to developing these biomarkers for clinical use; one is the decision of how to define disease activity without relying on proteinuria as a measure. “Why do I want a biomarker that can predict another biomarker?” he said.

Another presentation during the same session, by Huihua Ding, MD, of Shanghai Jiao Tong University in Shanghai, China, reported on the use of urinary L-selectin to assess renal disease activity and response to treatment in a multiethnic cohort.

This study, involving 474 patients with SLE with or without renal involvement in the United States and China, found levels of urinary L-selectin were elevated only in patients with active lupus nephritis and showed patterns that correlated with renal histologic characteristics.

Clinical rheumatologist Eric F. Morand, MD, PhD, and head of the School of Clinical Sciences at Monash University in Melbourne said one challenge with using urinary biomarkers was that it was not yet clear what these biomarkers reveal about the kidney. “It will be important to see whether this proteomic data actually link to renal outcomes,” Dr. Morand said in an interview. “I think predicting the response to treatment should be based around GFR [glomerular filtration rate] preservation, and I don’t think I’ve seen data yet that the urine biomarkers are going to tell us how to do that better.”

Dr. Morand is optimistic that urine biomarkers will one day be able to achieve that, but he stressed the importance of having urine biomarker tests available in the field at low cost. “You’re going to be doing the tests repeatedly, so therefore, you’re probably going to need to come down to a smaller list of proteins that you measure.”

Dr. Fava reported receiving support from Sanofi and Annexion Bio.

SEOUL, SOUTH KOREA – A panel of urinary biomarkers may do better than measuring proteinuria in predicting which patients with lupus nephritis are going to respond to treatment, according to a presentation at an international congress on systemic lupus erythematosus.

Physician-scientist Andrea Fava, MD, of the division of rheumatology at Johns Hopkins University, Baltimore, presented data from a study using urine proteomics to identify biomarkers present in the urine of patients with lupus nephritis at 3 months after starting treatment that were linked to better outcomes from that treatment at 1 year.

While proteinuria is the standard measure used to guide decisions about whether to do a kidney biopsy and how to treat lupus nephritis, it doesn’t always correlate with what’s actually going on inside the kidney in terms of histology and inflammation, Dr. Fava said.

Bianca Nogrady/MDedge News

He pointed to an earlier study in which researchers did kidney biopsies 6 months after patients with lupus nephritis started treatment with mycophenolate. This suggested that around half of patients who showed a clinical response to treatment – defined as proteinuria below 500 mg/day – still had significant histologic disease activity. Another study suggested that this elevated histologic disease activity is associated with a risk of flare, which can result in significant nephron loss. On the flip side, nearly two-thirds of patients in complete histologic remission still had elevated proteinuria.

Unfortunately, it’s not possible or practical to biopsy patients on a regular basis, Dr. Fava said. “So we need better biomarkers, and to do so, we need better knowledge of the pathophysiology because if we have biomarkers that reflect tissue biology in real-time, that may surely guide personalized treatments,” he said at the congress.

Dr. Fava and colleagues enrolled 225 patients with SLE who were undergoing kidney biopsy and 10 healthy controls and used proteomics to quantify the urinary levels of around 1,200 proteins at baseline, 3, 6, and 12 months after initiating treatment.

The team then analyzed these data to look for protein signatures that correlated with histologic phenotypes – particularly the amount of inflammation in the kidney – and clinical features such as response to treatment.

They found several protein biomarkers that appeared to be linked to histologic activity in the kidney, including interleukin (IL)-16, CD163, and neutrophil granule proteins.

Initially, the team looked at baseline levels of these proteins to see if they predicted who responded to treatment, but found no difference between responders and nonresponders.

However, when they looked at levels at 3 months after treatment, a pattern emerged. “We found that in patients who were not responding, there were no changes after 3 months of treatment in the urine proteome,” Dr. Fava said. Among those who did respond to treatment, the levels of these proteins – IL-16, CD163, galectin-1, and CD206 – decreased significantly.

“So the proteins that are linked to renal activity decrease only in responders, suggesting that effective immunosuppression is effective in reducing intrarenal inflammation, which eventually results in low proteinuria at 1 year.”

The decline in these biomarkers persisted at 1 year, and the study suggested it was a better predictor of which patients would respond to treatment at 1 year than proteinuria.

Dr. Fava said in an interview that better biomarkers could revolutionize the treatment and management of lupus nephritis.

“First of all, it can shift the management strategy from treatment to prevention, because at the very beginning we can nip it in the bud maybe with very gentle treatment,” he said. Different panels of urine biomarkers could identify patients at risk of treatment failure, and also help patients to taper off their immunosuppressive therapy without an increased risk of flare. “If we have a way to tell us there’s still inflammation that needs treatment, that could change the way we do it,” he said.

He acknowledged there are significant challenges to developing these biomarkers for clinical use; one is the decision of how to define disease activity without relying on proteinuria as a measure. “Why do I want a biomarker that can predict another biomarker?” he said.

Another presentation during the same session, by Huihua Ding, MD, of Shanghai Jiao Tong University in Shanghai, China, reported on the use of urinary L-selectin to assess renal disease activity and response to treatment in a multiethnic cohort.

This study, involving 474 patients with SLE with or without renal involvement in the United States and China, found levels of urinary L-selectin were elevated only in patients with active lupus nephritis and showed patterns that correlated with renal histologic characteristics.

Clinical rheumatologist Eric F. Morand, MD, PhD, and head of the School of Clinical Sciences at Monash University in Melbourne said one challenge with using urinary biomarkers was that it was not yet clear what these biomarkers reveal about the kidney. “It will be important to see whether this proteomic data actually link to renal outcomes,” Dr. Morand said in an interview. “I think predicting the response to treatment should be based around GFR [glomerular filtration rate] preservation, and I don’t think I’ve seen data yet that the urine biomarkers are going to tell us how to do that better.”

Dr. Morand is optimistic that urine biomarkers will one day be able to achieve that, but he stressed the importance of having urine biomarker tests available in the field at low cost. “You’re going to be doing the tests repeatedly, so therefore, you’re probably going to need to come down to a smaller list of proteins that you measure.”

Dr. Fava reported receiving support from Sanofi and Annexion Bio.

CLEVELAND – Patients with axial spondyloarthritis or psoriatic arthritis who used Janus kinase (JAK) inhibitors did not have higher risk of myocardial infarction, stroke, or venous thromboembolism (VTE), compared with those who used tumor necrosis factor inhibitors (TNFi), according to new research.

The information was presented in a poster at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

Patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) have increased cardiovascular risk compared with the general population. Emerging evidence has suggested that TNFi may protect the cardiovascular system and that there are cardiovascular and thrombotic concerns with JAK inhibitors.

Sali Merjanah, MD, a rheumatology fellow at Boston University, and colleagues, compared how drugs in the two treatment classes affected the likelihood of major adverse cardiovascular events (MACE) or VTE. MACE in this study were myocardial infarction and stroke.

In a search of the Marketscan Database during 2006-2021, the researchers identified 1,621 TNFi and 47 JAK inhibitor users with 273 and 8 cases of MACE, respectively. They identified 2,507 TNFi and 96 JAK users with 452 and 26 cases of VTE, respectively. Patients were aged 18-65 years and had at least one inpatient or two outpatient axSpA or PsA ICD-9 or ICD-10 diagnosis codes separated by at least 7 days.

The likelihood of MACE was 14% lower among JAK inhibitor users than TNFi users (the reference group), whereas the likelihood of VTE was 39% higher for JAK inhibitor users, but neither comparison was statistically significant. JAK/TNFi nonusers had a statistically significant 27% greater likelihood of MACE than did TNFi users. The likelihood for VTE was 12% higher for JAK/TNFi nonusers, compared with TNFi users, but this finding was not statistically significant. The researchers adjusted comparisons for age, medications, and comorbidities.
 

Small numbers complicate the research

Lianne Gensler, MD, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco, who was not part of the study, said the limitations the authors list are important to note. The researchers said that the study’s small number of JAK inhibitor users, short duration of exposure, and low event rate limit its precision, and there is potential misclassification of TNF/JAK inhibitor exposure, as well as confounding by indication.

Dr. Gensler noted that these same limitations apply to studies of patients with RA as well that try to answer the question of risk for MACE and malignancy when using these drugs,

“MACE is a rare event, malignancy is a rare event. So it’s like finding a needle in a haystack, and the haystack is really big. You either have to enrich the haystack with more needles or you have to make a smaller haystack,” Dr. Gensler said.

Nevertheless, she said, she credits the researchers for bringing the available information to light.

“I think we have to do this many different ways to try to get at the answer in a partial way,” she said.

The data were drawn from 2006 to 2021, but JAK inhibitors have only been approved for axSpA in the last one and a half years and for PsA at the end of 2017.

Additionally, the people taking JAK inhibitors would have likely already failed TNFis, she said, adding that this can make it hard to tell whether an event was linked with the JAK or the TNFi.
 

Nonusers may have other risk factors

She pointed out that in this study patients who were not using TNF or JAK inhibitors had slightly higher risk numerically for both MACE and VTE than did those using TNFis.

“There, the assumption is always that this is confounding by indication, meaning it is likely that the people who are nonusers have other risk factors for MACE, which is why we’re not giving them these drugs.”

Having heart failure, for instance, is a contraindication for using a TNF inhibitor, she noted. “So it’s not that these are protective compared to nonusers. It’s probably that the nonuser has higher risk and is not getting treated with these drugs to begin with.”

The authors properly concluded from the data that patients using JAK inhibitors did not have higher risk of MACE or VTE, compared with those who used TNFis, she said, but larger studies with more follow-up are needed.

“No evidence doesn’t mean no effect,” she said. “Part of it depends on the [statistical] power and the population you’re studying.”

Dr. Gensler is a consultant for AbbVie, Acceleron, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and has received grant support from Novartis and UCB. The authors’ financial relationships were not available.

CLEVELAND – Patients with axial spondyloarthritis or psoriatic arthritis who used Janus kinase (JAK) inhibitors did not have higher risk of myocardial infarction, stroke, or venous thromboembolism (VTE), compared with those who used tumor necrosis factor inhibitors (TNFi), according to new research.

The information was presented in a poster at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

Patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) have increased cardiovascular risk compared with the general population. Emerging evidence has suggested that TNFi may protect the cardiovascular system and that there are cardiovascular and thrombotic concerns with JAK inhibitors.

Sali Merjanah, MD, a rheumatology fellow at Boston University, and colleagues, compared how drugs in the two treatment classes affected the likelihood of major adverse cardiovascular events (MACE) or VTE. MACE in this study were myocardial infarction and stroke.

In a search of the Marketscan Database during 2006-2021, the researchers identified 1,621 TNFi and 47 JAK inhibitor users with 273 and 8 cases of MACE, respectively. They identified 2,507 TNFi and 96 JAK users with 452 and 26 cases of VTE, respectively. Patients were aged 18-65 years and had at least one inpatient or two outpatient axSpA or PsA ICD-9 or ICD-10 diagnosis codes separated by at least 7 days.

The likelihood of MACE was 14% lower among JAK inhibitor users than TNFi users (the reference group), whereas the likelihood of VTE was 39% higher for JAK inhibitor users, but neither comparison was statistically significant. JAK/TNFi nonusers had a statistically significant 27% greater likelihood of MACE than did TNFi users. The likelihood for VTE was 12% higher for JAK/TNFi nonusers, compared with TNFi users, but this finding was not statistically significant. The researchers adjusted comparisons for age, medications, and comorbidities.
 

Small numbers complicate the research

Lianne Gensler, MD, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco, who was not part of the study, said the limitations the authors list are important to note. The researchers said that the study’s small number of JAK inhibitor users, short duration of exposure, and low event rate limit its precision, and there is potential misclassification of TNF/JAK inhibitor exposure, as well as confounding by indication.

Dr. Gensler noted that these same limitations apply to studies of patients with RA as well that try to answer the question of risk for MACE and malignancy when using these drugs,

“MACE is a rare event, malignancy is a rare event. So it’s like finding a needle in a haystack, and the haystack is really big. You either have to enrich the haystack with more needles or you have to make a smaller haystack,” Dr. Gensler said.

Nevertheless, she said, she credits the researchers for bringing the available information to light.

“I think we have to do this many different ways to try to get at the answer in a partial way,” she said.

The data were drawn from 2006 to 2021, but JAK inhibitors have only been approved for axSpA in the last one and a half years and for PsA at the end of 2017.

Additionally, the people taking JAK inhibitors would have likely already failed TNFis, she said, adding that this can make it hard to tell whether an event was linked with the JAK or the TNFi.
 

Nonusers may have other risk factors

She pointed out that in this study patients who were not using TNF or JAK inhibitors had slightly higher risk numerically for both MACE and VTE than did those using TNFis.

“There, the assumption is always that this is confounding by indication, meaning it is likely that the people who are nonusers have other risk factors for MACE, which is why we’re not giving them these drugs.”

Having heart failure, for instance, is a contraindication for using a TNF inhibitor, she noted. “So it’s not that these are protective compared to nonusers. It’s probably that the nonuser has higher risk and is not getting treated with these drugs to begin with.”

The authors properly concluded from the data that patients using JAK inhibitors did not have higher risk of MACE or VTE, compared with those who used TNFis, she said, but larger studies with more follow-up are needed.

“No evidence doesn’t mean no effect,” she said. “Part of it depends on the [statistical] power and the population you’re studying.”

Dr. Gensler is a consultant for AbbVie, Acceleron, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and has received grant support from Novartis and UCB. The authors’ financial relationships were not available.

CLEVELAND – Patients with axial spondyloarthritis or psoriatic arthritis who used Janus kinase (JAK) inhibitors did not have higher risk of myocardial infarction, stroke, or venous thromboembolism (VTE), compared with those who used tumor necrosis factor inhibitors (TNFi), according to new research.

The information was presented in a poster at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

Patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) have increased cardiovascular risk compared with the general population. Emerging evidence has suggested that TNFi may protect the cardiovascular system and that there are cardiovascular and thrombotic concerns with JAK inhibitors.

Sali Merjanah, MD, a rheumatology fellow at Boston University, and colleagues, compared how drugs in the two treatment classes affected the likelihood of major adverse cardiovascular events (MACE) or VTE. MACE in this study were myocardial infarction and stroke.

In a search of the Marketscan Database during 2006-2021, the researchers identified 1,621 TNFi and 47 JAK inhibitor users with 273 and 8 cases of MACE, respectively. They identified 2,507 TNFi and 96 JAK users with 452 and 26 cases of VTE, respectively. Patients were aged 18-65 years and had at least one inpatient or two outpatient axSpA or PsA ICD-9 or ICD-10 diagnosis codes separated by at least 7 days.

The likelihood of MACE was 14% lower among JAK inhibitor users than TNFi users (the reference group), whereas the likelihood of VTE was 39% higher for JAK inhibitor users, but neither comparison was statistically significant. JAK/TNFi nonusers had a statistically significant 27% greater likelihood of MACE than did TNFi users. The likelihood for VTE was 12% higher for JAK/TNFi nonusers, compared with TNFi users, but this finding was not statistically significant. The researchers adjusted comparisons for age, medications, and comorbidities.
 

Small numbers complicate the research

Lianne Gensler, MD, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco, who was not part of the study, said the limitations the authors list are important to note. The researchers said that the study’s small number of JAK inhibitor users, short duration of exposure, and low event rate limit its precision, and there is potential misclassification of TNF/JAK inhibitor exposure, as well as confounding by indication.

Dr. Gensler noted that these same limitations apply to studies of patients with RA as well that try to answer the question of risk for MACE and malignancy when using these drugs,

“MACE is a rare event, malignancy is a rare event. So it’s like finding a needle in a haystack, and the haystack is really big. You either have to enrich the haystack with more needles or you have to make a smaller haystack,” Dr. Gensler said.

Nevertheless, she said, she credits the researchers for bringing the available information to light.

“I think we have to do this many different ways to try to get at the answer in a partial way,” she said.

The data were drawn from 2006 to 2021, but JAK inhibitors have only been approved for axSpA in the last one and a half years and for PsA at the end of 2017.

Additionally, the people taking JAK inhibitors would have likely already failed TNFis, she said, adding that this can make it hard to tell whether an event was linked with the JAK or the TNFi.
 

Nonusers may have other risk factors

She pointed out that in this study patients who were not using TNF or JAK inhibitors had slightly higher risk numerically for both MACE and VTE than did those using TNFis.

“There, the assumption is always that this is confounding by indication, meaning it is likely that the people who are nonusers have other risk factors for MACE, which is why we’re not giving them these drugs.”

Having heart failure, for instance, is a contraindication for using a TNF inhibitor, she noted. “So it’s not that these are protective compared to nonusers. It’s probably that the nonuser has higher risk and is not getting treated with these drugs to begin with.”

The authors properly concluded from the data that patients using JAK inhibitors did not have higher risk of MACE or VTE, compared with those who used TNFis, she said, but larger studies with more follow-up are needed.

“No evidence doesn’t mean no effect,” she said. “Part of it depends on the [statistical] power and the population you’re studying.”

Dr. Gensler is a consultant for AbbVie, Acceleron, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and has received grant support from Novartis and UCB. The authors’ financial relationships were not available.

The Food and Drug Administration has approved the oral Janus kinase (JAK) inhibitor upadacitinib for adults with moderately to severely active Crohn’s disease whose condition failed to respond adequately or who can’t tolerate one or more tumor necrosis factor (TNF) inhibitors, the company has announced.

Upadacitinib (Rinvoq, AbbVie) is the first oral small molecule approved by the FDA for Crohn’s disease, which is noteworthy, said Kristin E. Burke, MD, MPH, medical director of clinical operations for the Massachusetts General Hospital Crohn’s and Colitis Center, Boston.

Massachusetts General Hospital

“Crohn’s disease is a complex immune-mediated disease for which more effective and fast-acting treatment options are needed. The approval of upadacitinib for anti-TNF refractory Crohn’s disease represents an important milestone in the expansion of treatment options for this disease as the first oral small molecule available,” she said.

The approval for Crohn’s disease was supported by data from two induction studies (U-EXCEED and U-EXCEL) and one maintenance study (U-ENDURE).

In the two induction studies, 857 patients were randomly assigned to receive upadacitinib 45 mg or placebo once daily for 12 weeks. At week 12, a greater proportion of patients who received upadacitinib (vs. those who received placebo) achieved clinical remission, as determined on the basis of the Crohn’s Disease Activity Index (CDAI), and improvement in intestinal inflammation as assessed by colonoscopy.

In the maintenance study, 343 patients who responded to induction therapy with upadacitinib were randomly assigned to receive either a maintenance regimen of 15 or 30 mg once daily or placebo for 52 weeks.

At week 52, a greater proportion of patients who were treated with upadacitinib 15 mg or 30 mg, compared with those who received placebo, achieved clinical remission.

Data from the trials of upadacitinib in Crohn’s disease were presented at the European Crohn’s and Colitis Organisation (ECCO) 2023 Congress in March.

“Symptoms of moderately to severely active Crohn’s disease can be disruptive and uncomfortable for patients, so relief as early as possible is key. Given the progressive nature of the disease, endoscopic response is just as important,” U-EXCEL study investigator Edward V. Loftus Jr., MD, professor of medicine in the division of gastroenterology and hepatology at Mayo Clinic in Rochester, Minn., said in a news release.

“Based on the clinical trial results, treatment with Rinvoq shows both early and long-term symptom relief along with evidence of a visible reduction of damage to the intestinal lining caused by excess inflammation,” he said.

Patients should initially be given 45 mg of upadacitinib once daily for 12 weeks. After 12 weeks, the recommended maintenance dosage is 15 mg once a day. A maintenance dose of 30 mg once daily can be considered for patients with refractory, severe, or extensive Crohn’s disease, the FDA said in a statement announcing approval.

The most common side effects of upadacitinib in patients with Crohn’s disease are upper respiratory tract infection, anemia, fever, acne, herpes zoster, and headache.

Upadacitinib is not recommended for use in combination with other JAK inhibitors, biological therapies for Crohn’s disease, or with strong immunosuppressants, such as azathioprine and cyclosporine.

Serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis have occurred with JAK inhibitors such as upadacitinib.

The indication in Crohn’s disease marks the seventh in the United States for the JAK inhibitor. Other indications include rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

Full prescribing information is available online.

Dr. Burke disclosed no conflicts. Dr. Loftus is a consultant and adviser for AbbVie.
 

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

The Food and Drug Administration has approved the oral Janus kinase (JAK) inhibitor upadacitinib for adults with moderately to severely active Crohn’s disease whose condition failed to respond adequately or who can’t tolerate one or more tumor necrosis factor (TNF) inhibitors, the company has announced.

Upadacitinib (Rinvoq, AbbVie) is the first oral small molecule approved by the FDA for Crohn’s disease, which is noteworthy, said Kristin E. Burke, MD, MPH, medical director of clinical operations for the Massachusetts General Hospital Crohn’s and Colitis Center, Boston.

Massachusetts General Hospital

“Crohn’s disease is a complex immune-mediated disease for which more effective and fast-acting treatment options are needed. The approval of upadacitinib for anti-TNF refractory Crohn’s disease represents an important milestone in the expansion of treatment options for this disease as the first oral small molecule available,” she said.

The approval for Crohn’s disease was supported by data from two induction studies (U-EXCEED and U-EXCEL) and one maintenance study (U-ENDURE).

In the two induction studies, 857 patients were randomly assigned to receive upadacitinib 45 mg or placebo once daily for 12 weeks. At week 12, a greater proportion of patients who received upadacitinib (vs. those who received placebo) achieved clinical remission, as determined on the basis of the Crohn’s Disease Activity Index (CDAI), and improvement in intestinal inflammation as assessed by colonoscopy.

In the maintenance study, 343 patients who responded to induction therapy with upadacitinib were randomly assigned to receive either a maintenance regimen of 15 or 30 mg once daily or placebo for 52 weeks.

At week 52, a greater proportion of patients who were treated with upadacitinib 15 mg or 30 mg, compared with those who received placebo, achieved clinical remission.

Data from the trials of upadacitinib in Crohn’s disease were presented at the European Crohn’s and Colitis Organisation (ECCO) 2023 Congress in March.

“Symptoms of moderately to severely active Crohn’s disease can be disruptive and uncomfortable for patients, so relief as early as possible is key. Given the progressive nature of the disease, endoscopic response is just as important,” U-EXCEL study investigator Edward V. Loftus Jr., MD, professor of medicine in the division of gastroenterology and hepatology at Mayo Clinic in Rochester, Minn., said in a news release.

“Based on the clinical trial results, treatment with Rinvoq shows both early and long-term symptom relief along with evidence of a visible reduction of damage to the intestinal lining caused by excess inflammation,” he said.

Patients should initially be given 45 mg of upadacitinib once daily for 12 weeks. After 12 weeks, the recommended maintenance dosage is 15 mg once a day. A maintenance dose of 30 mg once daily can be considered for patients with refractory, severe, or extensive Crohn’s disease, the FDA said in a statement announcing approval.

The most common side effects of upadacitinib in patients with Crohn’s disease are upper respiratory tract infection, anemia, fever, acne, herpes zoster, and headache.

Upadacitinib is not recommended for use in combination with other JAK inhibitors, biological therapies for Crohn’s disease, or with strong immunosuppressants, such as azathioprine and cyclosporine.

Serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis have occurred with JAK inhibitors such as upadacitinib.

The indication in Crohn’s disease marks the seventh in the United States for the JAK inhibitor. Other indications include rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

Full prescribing information is available online.

Dr. Burke disclosed no conflicts. Dr. Loftus is a consultant and adviser for AbbVie.
 

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

The Food and Drug Administration has approved the oral Janus kinase (JAK) inhibitor upadacitinib for adults with moderately to severely active Crohn’s disease whose condition failed to respond adequately or who can’t tolerate one or more tumor necrosis factor (TNF) inhibitors, the company has announced.

Upadacitinib (Rinvoq, AbbVie) is the first oral small molecule approved by the FDA for Crohn’s disease, which is noteworthy, said Kristin E. Burke, MD, MPH, medical director of clinical operations for the Massachusetts General Hospital Crohn’s and Colitis Center, Boston.

Massachusetts General Hospital

“Crohn’s disease is a complex immune-mediated disease for which more effective and fast-acting treatment options are needed. The approval of upadacitinib for anti-TNF refractory Crohn’s disease represents an important milestone in the expansion of treatment options for this disease as the first oral small molecule available,” she said.

The approval for Crohn’s disease was supported by data from two induction studies (U-EXCEED and U-EXCEL) and one maintenance study (U-ENDURE).

In the two induction studies, 857 patients were randomly assigned to receive upadacitinib 45 mg or placebo once daily for 12 weeks. At week 12, a greater proportion of patients who received upadacitinib (vs. those who received placebo) achieved clinical remission, as determined on the basis of the Crohn’s Disease Activity Index (CDAI), and improvement in intestinal inflammation as assessed by colonoscopy.

In the maintenance study, 343 patients who responded to induction therapy with upadacitinib were randomly assigned to receive either a maintenance regimen of 15 or 30 mg once daily or placebo for 52 weeks.

At week 52, a greater proportion of patients who were treated with upadacitinib 15 mg or 30 mg, compared with those who received placebo, achieved clinical remission.

Data from the trials of upadacitinib in Crohn’s disease were presented at the European Crohn’s and Colitis Organisation (ECCO) 2023 Congress in March.

“Symptoms of moderately to severely active Crohn’s disease can be disruptive and uncomfortable for patients, so relief as early as possible is key. Given the progressive nature of the disease, endoscopic response is just as important,” U-EXCEL study investigator Edward V. Loftus Jr., MD, professor of medicine in the division of gastroenterology and hepatology at Mayo Clinic in Rochester, Minn., said in a news release.

“Based on the clinical trial results, treatment with Rinvoq shows both early and long-term symptom relief along with evidence of a visible reduction of damage to the intestinal lining caused by excess inflammation,” he said.

Patients should initially be given 45 mg of upadacitinib once daily for 12 weeks. After 12 weeks, the recommended maintenance dosage is 15 mg once a day. A maintenance dose of 30 mg once daily can be considered for patients with refractory, severe, or extensive Crohn’s disease, the FDA said in a statement announcing approval.

The most common side effects of upadacitinib in patients with Crohn’s disease are upper respiratory tract infection, anemia, fever, acne, herpes zoster, and headache.

Upadacitinib is not recommended for use in combination with other JAK inhibitors, biological therapies for Crohn’s disease, or with strong immunosuppressants, such as azathioprine and cyclosporine.

Serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis have occurred with JAK inhibitors such as upadacitinib.

The indication in Crohn’s disease marks the seventh in the United States for the JAK inhibitor. Other indications include rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

Full prescribing information is available online.

Dr. Burke disclosed no conflicts. Dr. Loftus is a consultant and adviser for AbbVie.
 

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

A new strategy proposed by an international team of experts would limit the use of the prostate-specific antigen (PSA) test for screening tor prostate cancer to men who are younger than 70 years and who are at high risk or symptomatic.

This would reduce potential harms from overdiagnosis and overtreatment, the risk for which is high with the on-demand screening that is the current standard of care in most wealthy nations.

In a paper published online in The BMJ, the panel recommends instead a comprehensive nationwide program that would base PSA testing on individual patient risk and direct those with abnormal results to a managed system of imaging, targeted biopsy only if indicated, and subsequent active monitoring or treatment for those with more aggressive disease features.

Alternatively, government health programs could actively discourage widespread PSA testing and implement policies that would effectively limit PSA-based screening only to men with urologic symptoms warranting further exploration, said the authors, led by Andrew Vickers, PhD, a research epidemiologist at Memorial Sloan Kettering Cancer Center in New York.

“Although we believe that early detection of prostate cancer should involve shared decision making, the current approach of determining testing by shared decision making has resulted in the worst possible practical outcome of high levels of PSA testing and medical harm, with minimal benefit and inequity,” they wrote.

“To make better use of PSA testing, policy makers should choose between a comprehensive, risk adapted approach that is specifically designed to reduce overdiagnosis and overtreatment, or restricting PSA testing to people referred to urologists with symptoms. That choice will need to take into account wider patient and public perspective, as well as health economic concerns,” they continued.
 

Inappropriate testing

Since the Food and Drug Administration approved the first PSA screen in 1986 as a means for monitoring disease progression in patients being treated for prostate cancer, the test has remained controversial, embraced by some for its presumed ability to spot early prostate cancer but scorned by others for its equivocal results in patients with benign prostate pathology and for its potential to lead to overdiagnosis and overtreatment of low-grade disease in men who would otherwise be likely to die of other causes.

Currently, only Lithuania and Kazakhstan have government-supported population-based screening programs for prostate cancer. In contrast, the United States, United Kingdom, and other high-income countries have opted not to implement nationwide prostate cancer screening but allow so-called “informed choice testing,” in which men can receiving PSA screening after discussion with a primary care physician, urologist, or other specialist.

The U.S. Preventive Services Task Force recommends that for men aged 55-69 years, the decision to undergo PSA testing should be an individual one, based on an understanding of the risks and benefits. For men aged 70 or older, the task force flatly states, “Do not screen for prostate cancer.”

But as Dr. Vickers and colleagues noted, “high income countries that have made PSA testing available to men who request it after shared decision making with their physician now have a high prevalence of PSA testing with an inappropriate age distribution.”

For example, they pointed out that in the United Kingdom, men in their 80s are twice as likely as are men in their 50s to get a PSA test, even though men in the older age group are far less likely to have benefit and far more likely to experience harm from treatment. Similarly, in France, nearly one-third of men over 40 get an annual PSA test, with the highest incidence of PSA testing in men over age 70. There are also high rates of PSA testing in men over 70 in Italy, Germany, and Ireland.

“A key problem is that, in current routine care – and despite guidelines to the contrary – most men with an abnormal PSA result have prostate biopsy, even though only a minority will have aggressive prostate cancer,” Dr. Vickers and colleagues wrote. “Furthermore, most men with biopsy-detected cancers have either surgery or radiotherapy (with or without androgen deprivation therapy) even if they have low-risk tumors that are unlikely to cause cancer related morbidity or mortality.”

In addition, informed-choice PSA testing may lead to health inequities, the team noted, citing data from the United States, Canada, and Switzerland showing an inverse association between income and education and the likelihood of PSA testing. Also, in the United States and Canada, men from ethnic minority groups are less likely to have PSA testing.
 

Comprehensive risk-based program

Dr. Vickers and colleagues proposed that a “comprehensive, risk-based prostate cancer detection program based on best evidence on how to use PSA testing and manage subsequent diagnostic follow-up and treatment could reduce overdiagnosis and overtreatment.

“Such a program would restrict testing to men (and those not identifying as male but who have a prostate) aged 50-70, define testing intervals by PSA levels, stop testing early for those with lower PSA, offer biopsy only to those identified as at high risk of aggressive disease after a secondary test (such as magnetic resonance imaging [MRI] or blood markers), and limit treatment to those with high Gleason grade tumors,” they wrote.
 

‘Sound analysis’

Two experts who were not involved with the BMJ paper applaud the suggestions made in comments posted on the U.K. Science Media Centre.

Benjamin W. Lamb, MBBS, MA, PhD, a consultant urologist and surgeon at Barts Health NHS Trust in London, said the analysis conducted by the panel “is sound as there are known benefits from risk-adapted comprehensive screening trials in men aged 50-70, but discordance with current practice, meaning benefits and harms are not those seen in trials.”

However, he also said that the strategies proposed by the authors would be unlikely to prevent older, well-informed men from requesting and getting a PSA test.

“In my view, the emphasis should be on engaging younger and at-risk men rather than restricting access for older men,” he said, noting that the alternative proposal of restricting PSA testing “in my view, is not feasible.”

Nick James, MBBS, PhD, professor of prostate and bladder cancer research at the Institute of Cancer Research, London, and consultant oncologist at the Royal Marsden NHS Foundation Trust, said, “I agree with the authors and strongly support the implementation of a risk-based approach to PSA testing at a national level.

“There is an urgent need for a more equitable and targeted screening strategy, which could help address existing health disparities,” Dr. James said. “Currently, individuals from economically disadvantaged backgrounds are less likely to undergo PSA testing. Men in their 50s or younger, who may stand to benefit more from these tests, are also less likely to receive PSA tests compared to older men who benefit less. Linked to better diagnostic pathways with MRI, already standard in the UK, potential harms from overdiagnosis and overtreatment can be mitigated.”

The analysis was supported in part by the U.S. National Institutes of Health/National Cancer Institute with a Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center, and NIH grants to coauthors. Dr. Vickers is a coinventor of the 4Kscore, a commercial test for predicting prostate biopsy outcome. He receives royalties from sales of the test and owns stock options in OPKO, which offers the test. Coauthor James W.F. Catto, PhD, disclosed ties to Astellas, AstraZeneca, BMS, Ferring, Gilead, Janssen, MSD, Nucleix, Photocure, QED Therapeutics, and Roche.

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

A new strategy proposed by an international team of experts would limit the use of the prostate-specific antigen (PSA) test for screening tor prostate cancer to men who are younger than 70 years and who are at high risk or symptomatic.

This would reduce potential harms from overdiagnosis and overtreatment, the risk for which is high with the on-demand screening that is the current standard of care in most wealthy nations.

In a paper published online in The BMJ, the panel recommends instead a comprehensive nationwide program that would base PSA testing on individual patient risk and direct those with abnormal results to a managed system of imaging, targeted biopsy only if indicated, and subsequent active monitoring or treatment for those with more aggressive disease features.

Alternatively, government health programs could actively discourage widespread PSA testing and implement policies that would effectively limit PSA-based screening only to men with urologic symptoms warranting further exploration, said the authors, led by Andrew Vickers, PhD, a research epidemiologist at Memorial Sloan Kettering Cancer Center in New York.

“Although we believe that early detection of prostate cancer should involve shared decision making, the current approach of determining testing by shared decision making has resulted in the worst possible practical outcome of high levels of PSA testing and medical harm, with minimal benefit and inequity,” they wrote.

“To make better use of PSA testing, policy makers should choose between a comprehensive, risk adapted approach that is specifically designed to reduce overdiagnosis and overtreatment, or restricting PSA testing to people referred to urologists with symptoms. That choice will need to take into account wider patient and public perspective, as well as health economic concerns,” they continued.
 

Inappropriate testing

Since the Food and Drug Administration approved the first PSA screen in 1986 as a means for monitoring disease progression in patients being treated for prostate cancer, the test has remained controversial, embraced by some for its presumed ability to spot early prostate cancer but scorned by others for its equivocal results in patients with benign prostate pathology and for its potential to lead to overdiagnosis and overtreatment of low-grade disease in men who would otherwise be likely to die of other causes.

Currently, only Lithuania and Kazakhstan have government-supported population-based screening programs for prostate cancer. In contrast, the United States, United Kingdom, and other high-income countries have opted not to implement nationwide prostate cancer screening but allow so-called “informed choice testing,” in which men can receiving PSA screening after discussion with a primary care physician, urologist, or other specialist.

The U.S. Preventive Services Task Force recommends that for men aged 55-69 years, the decision to undergo PSA testing should be an individual one, based on an understanding of the risks and benefits. For men aged 70 or older, the task force flatly states, “Do not screen for prostate cancer.”

But as Dr. Vickers and colleagues noted, “high income countries that have made PSA testing available to men who request it after shared decision making with their physician now have a high prevalence of PSA testing with an inappropriate age distribution.”

For example, they pointed out that in the United Kingdom, men in their 80s are twice as likely as are men in their 50s to get a PSA test, even though men in the older age group are far less likely to have benefit and far more likely to experience harm from treatment. Similarly, in France, nearly one-third of men over 40 get an annual PSA test, with the highest incidence of PSA testing in men over age 70. There are also high rates of PSA testing in men over 70 in Italy, Germany, and Ireland.

“A key problem is that, in current routine care – and despite guidelines to the contrary – most men with an abnormal PSA result have prostate biopsy, even though only a minority will have aggressive prostate cancer,” Dr. Vickers and colleagues wrote. “Furthermore, most men with biopsy-detected cancers have either surgery or radiotherapy (with or without androgen deprivation therapy) even if they have low-risk tumors that are unlikely to cause cancer related morbidity or mortality.”

In addition, informed-choice PSA testing may lead to health inequities, the team noted, citing data from the United States, Canada, and Switzerland showing an inverse association between income and education and the likelihood of PSA testing. Also, in the United States and Canada, men from ethnic minority groups are less likely to have PSA testing.
 

Comprehensive risk-based program

Dr. Vickers and colleagues proposed that a “comprehensive, risk-based prostate cancer detection program based on best evidence on how to use PSA testing and manage subsequent diagnostic follow-up and treatment could reduce overdiagnosis and overtreatment.

“Such a program would restrict testing to men (and those not identifying as male but who have a prostate) aged 50-70, define testing intervals by PSA levels, stop testing early for those with lower PSA, offer biopsy only to those identified as at high risk of aggressive disease after a secondary test (such as magnetic resonance imaging [MRI] or blood markers), and limit treatment to those with high Gleason grade tumors,” they wrote.
 

‘Sound analysis’

Two experts who were not involved with the BMJ paper applaud the suggestions made in comments posted on the U.K. Science Media Centre.

Benjamin W. Lamb, MBBS, MA, PhD, a consultant urologist and surgeon at Barts Health NHS Trust in London, said the analysis conducted by the panel “is sound as there are known benefits from risk-adapted comprehensive screening trials in men aged 50-70, but discordance with current practice, meaning benefits and harms are not those seen in trials.”

However, he also said that the strategies proposed by the authors would be unlikely to prevent older, well-informed men from requesting and getting a PSA test.

“In my view, the emphasis should be on engaging younger and at-risk men rather than restricting access for older men,” he said, noting that the alternative proposal of restricting PSA testing “in my view, is not feasible.”

Nick James, MBBS, PhD, professor of prostate and bladder cancer research at the Institute of Cancer Research, London, and consultant oncologist at the Royal Marsden NHS Foundation Trust, said, “I agree with the authors and strongly support the implementation of a risk-based approach to PSA testing at a national level.

“There is an urgent need for a more equitable and targeted screening strategy, which could help address existing health disparities,” Dr. James said. “Currently, individuals from economically disadvantaged backgrounds are less likely to undergo PSA testing. Men in their 50s or younger, who may stand to benefit more from these tests, are also less likely to receive PSA tests compared to older men who benefit less. Linked to better diagnostic pathways with MRI, already standard in the UK, potential harms from overdiagnosis and overtreatment can be mitigated.”

The analysis was supported in part by the U.S. National Institutes of Health/National Cancer Institute with a Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center, and NIH grants to coauthors. Dr. Vickers is a coinventor of the 4Kscore, a commercial test for predicting prostate biopsy outcome. He receives royalties from sales of the test and owns stock options in OPKO, which offers the test. Coauthor James W.F. Catto, PhD, disclosed ties to Astellas, AstraZeneca, BMS, Ferring, Gilead, Janssen, MSD, Nucleix, Photocure, QED Therapeutics, and Roche.

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

A new strategy proposed by an international team of experts would limit the use of the prostate-specific antigen (PSA) test for screening tor prostate cancer to men who are younger than 70 years and who are at high risk or symptomatic.

This would reduce potential harms from overdiagnosis and overtreatment, the risk for which is high with the on-demand screening that is the current standard of care in most wealthy nations.

In a paper published online in The BMJ, the panel recommends instead a comprehensive nationwide program that would base PSA testing on individual patient risk and direct those with abnormal results to a managed system of imaging, targeted biopsy only if indicated, and subsequent active monitoring or treatment for those with more aggressive disease features.

Alternatively, government health programs could actively discourage widespread PSA testing and implement policies that would effectively limit PSA-based screening only to men with urologic symptoms warranting further exploration, said the authors, led by Andrew Vickers, PhD, a research epidemiologist at Memorial Sloan Kettering Cancer Center in New York.

“Although we believe that early detection of prostate cancer should involve shared decision making, the current approach of determining testing by shared decision making has resulted in the worst possible practical outcome of high levels of PSA testing and medical harm, with minimal benefit and inequity,” they wrote.

“To make better use of PSA testing, policy makers should choose between a comprehensive, risk adapted approach that is specifically designed to reduce overdiagnosis and overtreatment, or restricting PSA testing to people referred to urologists with symptoms. That choice will need to take into account wider patient and public perspective, as well as health economic concerns,” they continued.
 

Inappropriate testing

Since the Food and Drug Administration approved the first PSA screen in 1986 as a means for monitoring disease progression in patients being treated for prostate cancer, the test has remained controversial, embraced by some for its presumed ability to spot early prostate cancer but scorned by others for its equivocal results in patients with benign prostate pathology and for its potential to lead to overdiagnosis and overtreatment of low-grade disease in men who would otherwise be likely to die of other causes.

Currently, only Lithuania and Kazakhstan have government-supported population-based screening programs for prostate cancer. In contrast, the United States, United Kingdom, and other high-income countries have opted not to implement nationwide prostate cancer screening but allow so-called “informed choice testing,” in which men can receiving PSA screening after discussion with a primary care physician, urologist, or other specialist.

The U.S. Preventive Services Task Force recommends that for men aged 55-69 years, the decision to undergo PSA testing should be an individual one, based on an understanding of the risks and benefits. For men aged 70 or older, the task force flatly states, “Do not screen for prostate cancer.”

But as Dr. Vickers and colleagues noted, “high income countries that have made PSA testing available to men who request it after shared decision making with their physician now have a high prevalence of PSA testing with an inappropriate age distribution.”

For example, they pointed out that in the United Kingdom, men in their 80s are twice as likely as are men in their 50s to get a PSA test, even though men in the older age group are far less likely to have benefit and far more likely to experience harm from treatment. Similarly, in France, nearly one-third of men over 40 get an annual PSA test, with the highest incidence of PSA testing in men over age 70. There are also high rates of PSA testing in men over 70 in Italy, Germany, and Ireland.

“A key problem is that, in current routine care – and despite guidelines to the contrary – most men with an abnormal PSA result have prostate biopsy, even though only a minority will have aggressive prostate cancer,” Dr. Vickers and colleagues wrote. “Furthermore, most men with biopsy-detected cancers have either surgery or radiotherapy (with or without androgen deprivation therapy) even if they have low-risk tumors that are unlikely to cause cancer related morbidity or mortality.”

In addition, informed-choice PSA testing may lead to health inequities, the team noted, citing data from the United States, Canada, and Switzerland showing an inverse association between income and education and the likelihood of PSA testing. Also, in the United States and Canada, men from ethnic minority groups are less likely to have PSA testing.
 

Comprehensive risk-based program

Dr. Vickers and colleagues proposed that a “comprehensive, risk-based prostate cancer detection program based on best evidence on how to use PSA testing and manage subsequent diagnostic follow-up and treatment could reduce overdiagnosis and overtreatment.

“Such a program would restrict testing to men (and those not identifying as male but who have a prostate) aged 50-70, define testing intervals by PSA levels, stop testing early for those with lower PSA, offer biopsy only to those identified as at high risk of aggressive disease after a secondary test (such as magnetic resonance imaging [MRI] or blood markers), and limit treatment to those with high Gleason grade tumors,” they wrote.
 

‘Sound analysis’

Two experts who were not involved with the BMJ paper applaud the suggestions made in comments posted on the U.K. Science Media Centre.

Benjamin W. Lamb, MBBS, MA, PhD, a consultant urologist and surgeon at Barts Health NHS Trust in London, said the analysis conducted by the panel “is sound as there are known benefits from risk-adapted comprehensive screening trials in men aged 50-70, but discordance with current practice, meaning benefits and harms are not those seen in trials.”

However, he also said that the strategies proposed by the authors would be unlikely to prevent older, well-informed men from requesting and getting a PSA test.

“In my view, the emphasis should be on engaging younger and at-risk men rather than restricting access for older men,” he said, noting that the alternative proposal of restricting PSA testing “in my view, is not feasible.”

Nick James, MBBS, PhD, professor of prostate and bladder cancer research at the Institute of Cancer Research, London, and consultant oncologist at the Royal Marsden NHS Foundation Trust, said, “I agree with the authors and strongly support the implementation of a risk-based approach to PSA testing at a national level.

“There is an urgent need for a more equitable and targeted screening strategy, which could help address existing health disparities,” Dr. James said. “Currently, individuals from economically disadvantaged backgrounds are less likely to undergo PSA testing. Men in their 50s or younger, who may stand to benefit more from these tests, are also less likely to receive PSA tests compared to older men who benefit less. Linked to better diagnostic pathways with MRI, already standard in the UK, potential harms from overdiagnosis and overtreatment can be mitigated.”

The analysis was supported in part by the U.S. National Institutes of Health/National Cancer Institute with a Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center, and NIH grants to coauthors. Dr. Vickers is a coinventor of the 4Kscore, a commercial test for predicting prostate biopsy outcome. He receives royalties from sales of the test and owns stock options in OPKO, which offers the test. Coauthor James W.F. Catto, PhD, disclosed ties to Astellas, AstraZeneca, BMS, Ferring, Gilead, Janssen, MSD, Nucleix, Photocure, QED Therapeutics, and Roche.

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

AURORA, COLO. – Do you ask your patients about their sexual health? Many providers do not broach the topic – whether because they lack the time, feel awkward, or their patients have other, more pressing concerns to discuss.

Yet nearly half of women experience some form of sexual dysfunction, such as low sex drive, pain during sex (dyspareunia), or trouble reaching orgasm. When dysfunction is paired with significant distress, the condition is called hypoactive sexual desire disorder (HSDD).

At the annual meeting of the Society of General Internal Medicine, experts said patients want to talk about these problems, but they need their physicians to be ready for the conversation.

Hannah Abumusa, MD, clinical instructor of medicine at the University of Pittsburgh Medical Center, recommended implementing the “5As” framework.

• Ask. Start by asking patients if they would be comfortable with you posing a few questions about their sexual health.
• Advise. Make sure your patient knows many women struggle with the problem they have raised.
• Assess. Ask a set of standardized assessment questions.
• Assist. Tell your patient about treatment options.
• Arrange. Arrange a follow-up visit to see if treatment has been effective.

Kathryn Leyens, MD, admitted she does not discuss sexual health enough with her patients, although she believes the topic is important.

“If it’s brought up, I’m comfortable talking about it,” said Dr. Leyens, a clinical assistant professor of medicine at the University of Pittsburgh. “But I think it’s something that I could initiate more often.”

The 5As framework offers a helpful way to initiate those conversations, she said.
 

Medications might be to blame

Holly Thomas, MD, an assistant professor of medicine at the University of Pittsburgh, first conducts a medication review when discussing low sexual desire with her patients.

“There are definitely medications that we commonly use in primary care that can have negative effects on sexual function,” Dr. Thomas said. “But we’re not always the best at talking with patients about these things, and I think sometimes patients get the message that they should deprioritize their sex lives to their medication needs.”

For example, sexual dysfunction is a common side effect of antidepressants, with paroxetine, fluvoxamine, sertraline, and fluoxetine carrying the highest frequency of this reported effect. Beta-blockers are also known to cause sexual dysfunction in women. 
 

Pharmacologic options

Once clinicians conduct a medication review, they can discuss treatment options with patients, which can range from prescription drugs to therapy. 

Several medications have been shown in clinical trials to increase sexual desire in women. Flibanserin (Addyi), a once-daily pill, boosted libido in about half of women who used the drug in studies leading to its approvalby the Food and Drug Administration in 2015. 

The most common adverse effects reported in clinical trials included dizziness, syncope, and somnolence, which occurred in roughly 12% of users. The FDA recommends people avoid alcohol 2 hours before and after taking the drug.

Bremelanotide (Vyleesi) is an on-demand medication, like sildenafil for men, which in trials led to modest increases in desire among 25% of women who took the drug. About 40% of users reported experiencing nausea. Hyperpigmentation can also be a side effect, which in rare cases can be permanent, Dr. Thomas said. Patients can use a maximum of eight doses per month of the drug.

Testosterone serves as an off-label treatment, as the FDA has not approved the hormone for women. Adverse effects can include acne and weight gain. Data on the safety of its use past 2 years are scarce. 

“But up until then, there’s pretty strong evidence for the efficacy and safety of testosterone for treatment of hypoactive sexual desire disorder in women,” Dr. Thomas said.

Hormone replacement therapy is another potential treatment option, which could include estrogen plus progesterone.

“It’s not FDA approved for HSDD, but if you’re using it for other menopausal symptoms, it’s likely to improve sexual function with small- to moderate-effect sizes,” she said.

Bupropion (multiple brands) is a cost-effective option also prescribed for depression, Dr. Thomas said. A recently published systematic review provided further data to support the efficacy of the drug. 

“That’s something that a lot of us are very familiar with and maybe more comfortable prescribing if we’re less familiar with some of the newer options,” she said.
 

Nonpharmacologic interventions

Dr. Thomas encouraged clinicians to consider nonpharmacologic approaches, too, such as referring patients to sex therapists.

“There’s something called ‘sensate focus,’ which is a type of sex therapy that’s been around for decades, but it’s still very effective,” Dr. Thomas said.

Cognitive-behavioral therapy (CBT) is another option, she said. A systematic review published in 2022 showed CBT was an effective tool for treating HSDD, although Dr. Thomas noted the evidence is limited.

A newer treatment gaining traction is mindfulness meditation, often provided by therapists, which focuses on present moment and nonjudgmental bodily awareness. Dr. Thomas recommended referring patients to educational literature such as “Better Sex Through Mindfulness: How Women Can Cultivate Desire” by Lori Brotto (Vancouver: Greystone Books, 2018). The book also comes with a workbook.

“This has actually been shown in multiple trials to be effective for the treatment of low sexual desire with moderate to large effect sizes,” she said.

Dr. Abumusa, Dr. Leyens, and Dr. Thomas reported no relevant financial relationships.

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

AURORA, COLO. – Do you ask your patients about their sexual health? Many providers do not broach the topic – whether because they lack the time, feel awkward, or their patients have other, more pressing concerns to discuss.

Yet nearly half of women experience some form of sexual dysfunction, such as low sex drive, pain during sex (dyspareunia), or trouble reaching orgasm. When dysfunction is paired with significant distress, the condition is called hypoactive sexual desire disorder (HSDD).

At the annual meeting of the Society of General Internal Medicine, experts said patients want to talk about these problems, but they need their physicians to be ready for the conversation.

Hannah Abumusa, MD, clinical instructor of medicine at the University of Pittsburgh Medical Center, recommended implementing the “5As” framework.

• Ask. Start by asking patients if they would be comfortable with you posing a few questions about their sexual health.
• Advise. Make sure your patient knows many women struggle with the problem they have raised.
• Assess. Ask a set of standardized assessment questions.
• Assist. Tell your patient about treatment options.
• Arrange. Arrange a follow-up visit to see if treatment has been effective.

Kathryn Leyens, MD, admitted she does not discuss sexual health enough with her patients, although she believes the topic is important.

“If it’s brought up, I’m comfortable talking about it,” said Dr. Leyens, a clinical assistant professor of medicine at the University of Pittsburgh. “But I think it’s something that I could initiate more often.”

The 5As framework offers a helpful way to initiate those conversations, she said.
 

Medications might be to blame

Holly Thomas, MD, an assistant professor of medicine at the University of Pittsburgh, first conducts a medication review when discussing low sexual desire with her patients.

“There are definitely medications that we commonly use in primary care that can have negative effects on sexual function,” Dr. Thomas said. “But we’re not always the best at talking with patients about these things, and I think sometimes patients get the message that they should deprioritize their sex lives to their medication needs.”

For example, sexual dysfunction is a common side effect of antidepressants, with paroxetine, fluvoxamine, sertraline, and fluoxetine carrying the highest frequency of this reported effect. Beta-blockers are also known to cause sexual dysfunction in women. 
 

Pharmacologic options

Once clinicians conduct a medication review, they can discuss treatment options with patients, which can range from prescription drugs to therapy. 

Several medications have been shown in clinical trials to increase sexual desire in women. Flibanserin (Addyi), a once-daily pill, boosted libido in about half of women who used the drug in studies leading to its approvalby the Food and Drug Administration in 2015. 

The most common adverse effects reported in clinical trials included dizziness, syncope, and somnolence, which occurred in roughly 12% of users. The FDA recommends people avoid alcohol 2 hours before and after taking the drug.

Bremelanotide (Vyleesi) is an on-demand medication, like sildenafil for men, which in trials led to modest increases in desire among 25% of women who took the drug. About 40% of users reported experiencing nausea. Hyperpigmentation can also be a side effect, which in rare cases can be permanent, Dr. Thomas said. Patients can use a maximum of eight doses per month of the drug.

Testosterone serves as an off-label treatment, as the FDA has not approved the hormone for women. Adverse effects can include acne and weight gain. Data on the safety of its use past 2 years are scarce. 

“But up until then, there’s pretty strong evidence for the efficacy and safety of testosterone for treatment of hypoactive sexual desire disorder in women,” Dr. Thomas said.

Hormone replacement therapy is another potential treatment option, which could include estrogen plus progesterone.

“It’s not FDA approved for HSDD, but if you’re using it for other menopausal symptoms, it’s likely to improve sexual function with small- to moderate-effect sizes,” she said.

Bupropion (multiple brands) is a cost-effective option also prescribed for depression, Dr. Thomas said. A recently published systematic review provided further data to support the efficacy of the drug. 

“That’s something that a lot of us are very familiar with and maybe more comfortable prescribing if we’re less familiar with some of the newer options,” she said.
 

Nonpharmacologic interventions

Dr. Thomas encouraged clinicians to consider nonpharmacologic approaches, too, such as referring patients to sex therapists.

“There’s something called ‘sensate focus,’ which is a type of sex therapy that’s been around for decades, but it’s still very effective,” Dr. Thomas said.

Cognitive-behavioral therapy (CBT) is another option, she said. A systematic review published in 2022 showed CBT was an effective tool for treating HSDD, although Dr. Thomas noted the evidence is limited.

A newer treatment gaining traction is mindfulness meditation, often provided by therapists, which focuses on present moment and nonjudgmental bodily awareness. Dr. Thomas recommended referring patients to educational literature such as “Better Sex Through Mindfulness: How Women Can Cultivate Desire” by Lori Brotto (Vancouver: Greystone Books, 2018). The book also comes with a workbook.

“This has actually been shown in multiple trials to be effective for the treatment of low sexual desire with moderate to large effect sizes,” she said.

Dr. Abumusa, Dr. Leyens, and Dr. Thomas reported no relevant financial relationships.

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

AURORA, COLO. – Do you ask your patients about their sexual health? Many providers do not broach the topic – whether because they lack the time, feel awkward, or their patients have other, more pressing concerns to discuss.

Yet nearly half of women experience some form of sexual dysfunction, such as low sex drive, pain during sex (dyspareunia), or trouble reaching orgasm. When dysfunction is paired with significant distress, the condition is called hypoactive sexual desire disorder (HSDD).

At the annual meeting of the Society of General Internal Medicine, experts said patients want to talk about these problems, but they need their physicians to be ready for the conversation.

Hannah Abumusa, MD, clinical instructor of medicine at the University of Pittsburgh Medical Center, recommended implementing the “5As” framework.

• Ask. Start by asking patients if they would be comfortable with you posing a few questions about their sexual health.
• Advise. Make sure your patient knows many women struggle with the problem they have raised.
• Assess. Ask a set of standardized assessment questions.
• Assist. Tell your patient about treatment options.
• Arrange. Arrange a follow-up visit to see if treatment has been effective.

Kathryn Leyens, MD, admitted she does not discuss sexual health enough with her patients, although she believes the topic is important.

“If it’s brought up, I’m comfortable talking about it,” said Dr. Leyens, a clinical assistant professor of medicine at the University of Pittsburgh. “But I think it’s something that I could initiate more often.”

The 5As framework offers a helpful way to initiate those conversations, she said.
 

Medications might be to blame

Holly Thomas, MD, an assistant professor of medicine at the University of Pittsburgh, first conducts a medication review when discussing low sexual desire with her patients.

“There are definitely medications that we commonly use in primary care that can have negative effects on sexual function,” Dr. Thomas said. “But we’re not always the best at talking with patients about these things, and I think sometimes patients get the message that they should deprioritize their sex lives to their medication needs.”

For example, sexual dysfunction is a common side effect of antidepressants, with paroxetine, fluvoxamine, sertraline, and fluoxetine carrying the highest frequency of this reported effect. Beta-blockers are also known to cause sexual dysfunction in women. 
 

Pharmacologic options

Once clinicians conduct a medication review, they can discuss treatment options with patients, which can range from prescription drugs to therapy. 

Several medications have been shown in clinical trials to increase sexual desire in women. Flibanserin (Addyi), a once-daily pill, boosted libido in about half of women who used the drug in studies leading to its approvalby the Food and Drug Administration in 2015. 

The most common adverse effects reported in clinical trials included dizziness, syncope, and somnolence, which occurred in roughly 12% of users. The FDA recommends people avoid alcohol 2 hours before and after taking the drug.

Bremelanotide (Vyleesi) is an on-demand medication, like sildenafil for men, which in trials led to modest increases in desire among 25% of women who took the drug. About 40% of users reported experiencing nausea. Hyperpigmentation can also be a side effect, which in rare cases can be permanent, Dr. Thomas said. Patients can use a maximum of eight doses per month of the drug.

Testosterone serves as an off-label treatment, as the FDA has not approved the hormone for women. Adverse effects can include acne and weight gain. Data on the safety of its use past 2 years are scarce. 

“But up until then, there’s pretty strong evidence for the efficacy and safety of testosterone for treatment of hypoactive sexual desire disorder in women,” Dr. Thomas said.

Hormone replacement therapy is another potential treatment option, which could include estrogen plus progesterone.

“It’s not FDA approved for HSDD, but if you’re using it for other menopausal symptoms, it’s likely to improve sexual function with small- to moderate-effect sizes,” she said.

Bupropion (multiple brands) is a cost-effective option also prescribed for depression, Dr. Thomas said. A recently published systematic review provided further data to support the efficacy of the drug. 

“That’s something that a lot of us are very familiar with and maybe more comfortable prescribing if we’re less familiar with some of the newer options,” she said.
 

Nonpharmacologic interventions

Dr. Thomas encouraged clinicians to consider nonpharmacologic approaches, too, such as referring patients to sex therapists.

“There’s something called ‘sensate focus,’ which is a type of sex therapy that’s been around for decades, but it’s still very effective,” Dr. Thomas said.

Cognitive-behavioral therapy (CBT) is another option, she said. A systematic review published in 2022 showed CBT was an effective tool for treating HSDD, although Dr. Thomas noted the evidence is limited.

A newer treatment gaining traction is mindfulness meditation, often provided by therapists, which focuses on present moment and nonjudgmental bodily awareness. Dr. Thomas recommended referring patients to educational literature such as “Better Sex Through Mindfulness: How Women Can Cultivate Desire” by Lori Brotto (Vancouver: Greystone Books, 2018). The book also comes with a workbook.

“This has actually been shown in multiple trials to be effective for the treatment of low sexual desire with moderate to large effect sizes,” she said.

Dr. Abumusa, Dr. Leyens, and Dr. Thomas reported no relevant financial relationships.

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

AURORA, COLO. – Artificial Intelligence has arrived at medical offices, whether or not clinicians feel ready for it.

AI might result in more accurate, efficient, and cost-effective care. But it’s possible it could cause harm. That’s according to Benjamin Collins, MD, at Vanderbilt University Medical Center, Nashville, Tenn., who spoke on the subject at the annual meeting of the Society of General Internal Medicine.

Understanding the nuances of AI is even more important because of the quick development of the algorithms.

“When I submitted this workshop, there was no ChatGPT,” said Dr. Collins, referring to Chat Generative Pre-trained Transformer, a recently released natural language processing model. “A lot has already changed.”
 

Biased data

Biased data are perhaps the biggest pitfall of AI algorithms, Dr. Collins said. If garbage data go in, garbage predictions come out.

If the dataset that trains the algorithm underrepresents a particular gender or ethnic group, for example, the algorithm may not respond accurately to prompts. When an AI tool compounds existing inequalities related to socioeconomic status, ethnicity, or sexual orientation, the algorithm is biased, according to Harvard researchers.

“People often assume that artificial intelligence is free of bias due to the use of scientific processes and its development,” he said. “But whatever flaws exist in data collection and old data can lead to poor representation or underrepresentation in the data used to train the AI tool.”

Racial minorities are underrepresented in studies; therefore, data input into an AI tool might skew results for these patients.

The Framingham Heart Study, for example, which began in 1948, examined heart disease in mainly White participants. The findings from the study resulted in the creation of a sex-specific algorithm that was used to estimate the 10-year cardiovascular risk of a patient. While the cardiovascular risk score was accurate for White persons, it was less accurate for Black patients.

A study published in Science in 2019 revealed bias in an algorithm that used health care costs as a proxy for health needs. Because less money was spent on Black patients who had the same level of need as their White counterparts, the output inaccurately showed that Black patients were healthier and thus did not require extra care.

Developers can also be a source of bias, inasmuch as AI often reflects preexisting human biases, Dr. Collins said.

“Algorithmic bias presents a clear risk of harm that clinicians must play against the benefits of using AI,” Dr. Collins said. “That risk of harm is often disproportionately distributed to marginalized populations.”

As clinicians use AI algorithms to diagnose and detect disease, predict outcomes, and guide treatment, trouble comes when those algorithms perform well for some patients and poorly for others. This gap can exacerbate existing disparities in health care outcomes.

Dr. Collins advised clinicians to push to find out what data were used to train AI algorithms to determine how bias could have influenced the model and whether the developers risk-adjusted for bias. If the training data are not available, clinicians should ask their employers and AI developers to know more about the system.

Clinicians may face the so-called black box phenomenon, which occurs when developers cannot or will not explain what data went into an AI model, Dr. Collins said.

According to Stanford (Calif.) University, AI must be trained on large datasets of images that have been annotated by human experts. Those datasets can cost millions of dollars to create, meaning corporations often fund them and do not always share the data publicly.

Some groups, such as Stanford’s Center for Artificial Intelligence in Medicine and Imaging, are working to acquire annotated datasets so researchers who train AI models can know where the data came from.

Paul Haidet, MD, MPH, an internist at Penn State College of Medicine, Hershey, sees the technology as a tool that requires careful handling.

“It takes a while to learn how to use a stethoscope, and AI is like that,” Dr. Haidet said. “The thing about AI, though, is that it can be just dropped into a system and no one knows how it works.”

Dr. Haidet said he likes knowing how the sausage is made, something AI developers are often reticent to make known.

“If you’re just putting blind faith in a tool, that’s scary,” Dr. Haidet said.
 

Transparency and ‘explainability’

The ability to explain what goes into tools is essential to maintaining trust in the health care system, Dr. Collins said.

“Part of knowing how much trust to place in the system is the transparency of those systems and the ability to audit how well the algorithm is performing,” Dr. Collins said. “The system should also regularly report to users the level of certainty with which it is providing an output rather than providing a simple binary output.”

Dr. Collins recommends that providers develop an understanding of the limits of AI regulations as well, which might including learning how the system was approved and how it is monitored.

“The FDA has oversight over some applications of AI and health care for software as a medical device, but there’s currently no dedicated process to evaluate the systems for the presence of bias,” Dr. Collins said. “The gaps in regulation leave the door open for the use of AI in clinical care that contain significant biases.”

Dr. Haidet likened AI tools to the Global Positioning System: A good GPS system will let users see alternate routes, opt out of toll roads or highways, and will highlight why routes have changed. But users need to understand how to read the map so they can tell when something seems amiss.

Dr. Collins and Dr. Haidet report no relevant financial relationships

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

AURORA, COLO. – Artificial Intelligence has arrived at medical offices, whether or not clinicians feel ready for it.

AI might result in more accurate, efficient, and cost-effective care. But it’s possible it could cause harm. That’s according to Benjamin Collins, MD, at Vanderbilt University Medical Center, Nashville, Tenn., who spoke on the subject at the annual meeting of the Society of General Internal Medicine.

Understanding the nuances of AI is even more important because of the quick development of the algorithms.

“When I submitted this workshop, there was no ChatGPT,” said Dr. Collins, referring to Chat Generative Pre-trained Transformer, a recently released natural language processing model. “A lot has already changed.”
 

Biased data

Biased data are perhaps the biggest pitfall of AI algorithms, Dr. Collins said. If garbage data go in, garbage predictions come out.

If the dataset that trains the algorithm underrepresents a particular gender or ethnic group, for example, the algorithm may not respond accurately to prompts. When an AI tool compounds existing inequalities related to socioeconomic status, ethnicity, or sexual orientation, the algorithm is biased, according to Harvard researchers.

“People often assume that artificial intelligence is free of bias due to the use of scientific processes and its development,” he said. “But whatever flaws exist in data collection and old data can lead to poor representation or underrepresentation in the data used to train the AI tool.”

Racial minorities are underrepresented in studies; therefore, data input into an AI tool might skew results for these patients.

The Framingham Heart Study, for example, which began in 1948, examined heart disease in mainly White participants. The findings from the study resulted in the creation of a sex-specific algorithm that was used to estimate the 10-year cardiovascular risk of a patient. While the cardiovascular risk score was accurate for White persons, it was less accurate for Black patients.

A study published in Science in 2019 revealed bias in an algorithm that used health care costs as a proxy for health needs. Because less money was spent on Black patients who had the same level of need as their White counterparts, the output inaccurately showed that Black patients were healthier and thus did not require extra care.

Developers can also be a source of bias, inasmuch as AI often reflects preexisting human biases, Dr. Collins said.

“Algorithmic bias presents a clear risk of harm that clinicians must play against the benefits of using AI,” Dr. Collins said. “That risk of harm is often disproportionately distributed to marginalized populations.”

As clinicians use AI algorithms to diagnose and detect disease, predict outcomes, and guide treatment, trouble comes when those algorithms perform well for some patients and poorly for others. This gap can exacerbate existing disparities in health care outcomes.

Dr. Collins advised clinicians to push to find out what data were used to train AI algorithms to determine how bias could have influenced the model and whether the developers risk-adjusted for bias. If the training data are not available, clinicians should ask their employers and AI developers to know more about the system.

Clinicians may face the so-called black box phenomenon, which occurs when developers cannot or will not explain what data went into an AI model, Dr. Collins said.

According to Stanford (Calif.) University, AI must be trained on large datasets of images that have been annotated by human experts. Those datasets can cost millions of dollars to create, meaning corporations often fund them and do not always share the data publicly.

Some groups, such as Stanford’s Center for Artificial Intelligence in Medicine and Imaging, are working to acquire annotated datasets so researchers who train AI models can know where the data came from.

Paul Haidet, MD, MPH, an internist at Penn State College of Medicine, Hershey, sees the technology as a tool that requires careful handling.

“It takes a while to learn how to use a stethoscope, and AI is like that,” Dr. Haidet said. “The thing about AI, though, is that it can be just dropped into a system and no one knows how it works.”

Dr. Haidet said he likes knowing how the sausage is made, something AI developers are often reticent to make known.

“If you’re just putting blind faith in a tool, that’s scary,” Dr. Haidet said.
 

Transparency and ‘explainability’

The ability to explain what goes into tools is essential to maintaining trust in the health care system, Dr. Collins said.

“Part of knowing how much trust to place in the system is the transparency of those systems and the ability to audit how well the algorithm is performing,” Dr. Collins said. “The system should also regularly report to users the level of certainty with which it is providing an output rather than providing a simple binary output.”

Dr. Collins recommends that providers develop an understanding of the limits of AI regulations as well, which might including learning how the system was approved and how it is monitored.

“The FDA has oversight over some applications of AI and health care for software as a medical device, but there’s currently no dedicated process to evaluate the systems for the presence of bias,” Dr. Collins said. “The gaps in regulation leave the door open for the use of AI in clinical care that contain significant biases.”

Dr. Haidet likened AI tools to the Global Positioning System: A good GPS system will let users see alternate routes, opt out of toll roads or highways, and will highlight why routes have changed. But users need to understand how to read the map so they can tell when something seems amiss.

Dr. Collins and Dr. Haidet report no relevant financial relationships

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

AURORA, COLO. – Artificial Intelligence has arrived at medical offices, whether or not clinicians feel ready for it.

AI might result in more accurate, efficient, and cost-effective care. But it’s possible it could cause harm. That’s according to Benjamin Collins, MD, at Vanderbilt University Medical Center, Nashville, Tenn., who spoke on the subject at the annual meeting of the Society of General Internal Medicine.

Understanding the nuances of AI is even more important because of the quick development of the algorithms.

“When I submitted this workshop, there was no ChatGPT,” said Dr. Collins, referring to Chat Generative Pre-trained Transformer, a recently released natural language processing model. “A lot has already changed.”
 

Biased data

Biased data are perhaps the biggest pitfall of AI algorithms, Dr. Collins said. If garbage data go in, garbage predictions come out.

If the dataset that trains the algorithm underrepresents a particular gender or ethnic group, for example, the algorithm may not respond accurately to prompts. When an AI tool compounds existing inequalities related to socioeconomic status, ethnicity, or sexual orientation, the algorithm is biased, according to Harvard researchers.

“People often assume that artificial intelligence is free of bias due to the use of scientific processes and its development,” he said. “But whatever flaws exist in data collection and old data can lead to poor representation or underrepresentation in the data used to train the AI tool.”

Racial minorities are underrepresented in studies; therefore, data input into an AI tool might skew results for these patients.

The Framingham Heart Study, for example, which began in 1948, examined heart disease in mainly White participants. The findings from the study resulted in the creation of a sex-specific algorithm that was used to estimate the 10-year cardiovascular risk of a patient. While the cardiovascular risk score was accurate for White persons, it was less accurate for Black patients.

A study published in Science in 2019 revealed bias in an algorithm that used health care costs as a proxy for health needs. Because less money was spent on Black patients who had the same level of need as their White counterparts, the output inaccurately showed that Black patients were healthier and thus did not require extra care.

Developers can also be a source of bias, inasmuch as AI often reflects preexisting human biases, Dr. Collins said.

“Algorithmic bias presents a clear risk of harm that clinicians must play against the benefits of using AI,” Dr. Collins said. “That risk of harm is often disproportionately distributed to marginalized populations.”

As clinicians use AI algorithms to diagnose and detect disease, predict outcomes, and guide treatment, trouble comes when those algorithms perform well for some patients and poorly for others. This gap can exacerbate existing disparities in health care outcomes.

Dr. Collins advised clinicians to push to find out what data were used to train AI algorithms to determine how bias could have influenced the model and whether the developers risk-adjusted for bias. If the training data are not available, clinicians should ask their employers and AI developers to know more about the system.

Clinicians may face the so-called black box phenomenon, which occurs when developers cannot or will not explain what data went into an AI model, Dr. Collins said.

According to Stanford (Calif.) University, AI must be trained on large datasets of images that have been annotated by human experts. Those datasets can cost millions of dollars to create, meaning corporations often fund them and do not always share the data publicly.

Some groups, such as Stanford’s Center for Artificial Intelligence in Medicine and Imaging, are working to acquire annotated datasets so researchers who train AI models can know where the data came from.

Paul Haidet, MD, MPH, an internist at Penn State College of Medicine, Hershey, sees the technology as a tool that requires careful handling.

“It takes a while to learn how to use a stethoscope, and AI is like that,” Dr. Haidet said. “The thing about AI, though, is that it can be just dropped into a system and no one knows how it works.”

Dr. Haidet said he likes knowing how the sausage is made, something AI developers are often reticent to make known.

“If you’re just putting blind faith in a tool, that’s scary,” Dr. Haidet said.
 

Transparency and ‘explainability’

The ability to explain what goes into tools is essential to maintaining trust in the health care system, Dr. Collins said.

“Part of knowing how much trust to place in the system is the transparency of those systems and the ability to audit how well the algorithm is performing,” Dr. Collins said. “The system should also regularly report to users the level of certainty with which it is providing an output rather than providing a simple binary output.”

Dr. Collins recommends that providers develop an understanding of the limits of AI regulations as well, which might including learning how the system was approved and how it is monitored.

“The FDA has oversight over some applications of AI and health care for software as a medical device, but there’s currently no dedicated process to evaluate the systems for the presence of bias,” Dr. Collins said. “The gaps in regulation leave the door open for the use of AI in clinical care that contain significant biases.”

Dr. Haidet likened AI tools to the Global Positioning System: A good GPS system will let users see alternate routes, opt out of toll roads or highways, and will highlight why routes have changed. But users need to understand how to read the map so they can tell when something seems amiss.

Dr. Collins and Dr. Haidet report no relevant financial relationships

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

AURORA, COLO. – How often do you talk with patients about how to lower their out-of-pocket costs for medical care?

For most clinicians, the answer is: not often enough. But having those conversations can improve medication adherence and strengthen the patient-clinician relationship, according to panelists at the annual meeting of the Society of General Internal Medicine.

The inverse association between out-of-pocket expenditures and fidelity to prescriptions is clear. A 2020 study by the IQVIA Institute for Human Data Science, for example, found that rates of prescription abandonment are less than 5% when a given medication carries no out-of-pocket cost for patients. That figure rises to 45% when the cost is more than $125, and to 60% when it exceeds $500. One in five Americans said cost prevented them from adhering to medication regimens, according to a new study in JAMA Network Open.

The researchers surveyed more than 2,000 men and women, 40.4% of whom were aged 75 or older. They found that nearly 90% of respondents said they would not be uncomfortable being asked about drug costs before a visit with a physician. A similar share (89.5%) said they would welcome the use by their physician of a real-time tool to determine the cost of their medication.

But the survey results contained a note of warning for clinicians: A significant number of respondents said they would be “extremely” upset if the cost of their medication exceeded the estimate from the pricing tool. And many also said they would be “moderately” or “extremely” angry if their physician used a pricing tool but failed to share the results with them.

“Real-time benefit tools may support medication cost conversations and cost-conscious prescribing, and patients are enthusiastic about their use,” the authors write. “However, if disclosed prices are inaccurate, there is potential for harm through loss of confidence in the physician and nonadherence to prescribed medications.”

While having conversations about cost can be difficult for both clinicians and patients, studies have shown that patients who discuss cost concerns with their doctors feel as if they have stronger relationships as a result.

Clinicians often avoid conversations about out-of-pocket expenses because they don’t know specific price information, they lack solutions to address cost, or they are uncomfortable bringing up the issue.

One member of the audience at the SGIM meeting recalled a patient who worked in a warehouse for a large company. The man, who had type 2 diabetes, had medical insurance, but even with insurance, insulin was going to cost him $150 per month. He struggled to afford the necessary treatment.

“He looked at me and said, ‘What do they want me to do? Do they want me to actually not be able to work for them and not manage my diabetes?’ ”

The clinician said he offered empathy in the moment but felt he could do little else.

Panelists acknowledged that clinicians are crunched on time when seeing patients, but being willing to initiate conversations about cost with patients and to offer resources can help patients get necessary treatment.
 

Start the conversation

Panel member Caroline Sloan, MD, an assistant professor of medicine at Duke University, Durham, N.C., said making patients aware that you know cost can make a big difference.

The American College of Physicians advises clinicians to ask patients whether they are worried about the cost of care and to not assume which patients may have concerns.

The conversation could be started like this: “I’d like to discuss any concerns you might have about the cost of your health care.”

Normalize the concern by making it more general, and reassure your patient that your goal is to get them the best care. Say something like, “I’ve heard from many patients the cost of medications or tests is becoming hard to manage.”

Once a patient’s concerns are clear, you can direct them to resources for assistance in reducing their costs, Dr. Sloan said, such as ClearHealthCosts, FAIR Health, Healthcare Bluebook, New Choice Health, GoodRx, PharmacyChecker, HealthWell Foundation, Patient Advocate Foundation, Good Days, Good Health Will, Mercy Medical Angels, and the American Association of Family Physicians Neighborhood Navigator.

Dr. Sloan said she knows clinicians don’t have time to understand every insurance plan and other issues related to cost. “But at least know to ask about costs,” she said. “Practice, practice, practice. It feels awkward at first, but it gets easier every time.”

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

AURORA, COLO. – How often do you talk with patients about how to lower their out-of-pocket costs for medical care?

For most clinicians, the answer is: not often enough. But having those conversations can improve medication adherence and strengthen the patient-clinician relationship, according to panelists at the annual meeting of the Society of General Internal Medicine.

The inverse association between out-of-pocket expenditures and fidelity to prescriptions is clear. A 2020 study by the IQVIA Institute for Human Data Science, for example, found that rates of prescription abandonment are less than 5% when a given medication carries no out-of-pocket cost for patients. That figure rises to 45% when the cost is more than $125, and to 60% when it exceeds $500. One in five Americans said cost prevented them from adhering to medication regimens, according to a new study in JAMA Network Open.

The researchers surveyed more than 2,000 men and women, 40.4% of whom were aged 75 or older. They found that nearly 90% of respondents said they would not be uncomfortable being asked about drug costs before a visit with a physician. A similar share (89.5%) said they would welcome the use by their physician of a real-time tool to determine the cost of their medication.

But the survey results contained a note of warning for clinicians: A significant number of respondents said they would be “extremely” upset if the cost of their medication exceeded the estimate from the pricing tool. And many also said they would be “moderately” or “extremely” angry if their physician used a pricing tool but failed to share the results with them.

“Real-time benefit tools may support medication cost conversations and cost-conscious prescribing, and patients are enthusiastic about their use,” the authors write. “However, if disclosed prices are inaccurate, there is potential for harm through loss of confidence in the physician and nonadherence to prescribed medications.”

While having conversations about cost can be difficult for both clinicians and patients, studies have shown that patients who discuss cost concerns with their doctors feel as if they have stronger relationships as a result.

Clinicians often avoid conversations about out-of-pocket expenses because they don’t know specific price information, they lack solutions to address cost, or they are uncomfortable bringing up the issue.

One member of the audience at the SGIM meeting recalled a patient who worked in a warehouse for a large company. The man, who had type 2 diabetes, had medical insurance, but even with insurance, insulin was going to cost him $150 per month. He struggled to afford the necessary treatment.

“He looked at me and said, ‘What do they want me to do? Do they want me to actually not be able to work for them and not manage my diabetes?’ ”

The clinician said he offered empathy in the moment but felt he could do little else.

Panelists acknowledged that clinicians are crunched on time when seeing patients, but being willing to initiate conversations about cost with patients and to offer resources can help patients get necessary treatment.
 

Start the conversation

Panel member Caroline Sloan, MD, an assistant professor of medicine at Duke University, Durham, N.C., said making patients aware that you know cost can make a big difference.

The American College of Physicians advises clinicians to ask patients whether they are worried about the cost of care and to not assume which patients may have concerns.

The conversation could be started like this: “I’d like to discuss any concerns you might have about the cost of your health care.”

Normalize the concern by making it more general, and reassure your patient that your goal is to get them the best care. Say something like, “I’ve heard from many patients the cost of medications or tests is becoming hard to manage.”

Once a patient’s concerns are clear, you can direct them to resources for assistance in reducing their costs, Dr. Sloan said, such as ClearHealthCosts, FAIR Health, Healthcare Bluebook, New Choice Health, GoodRx, PharmacyChecker, HealthWell Foundation, Patient Advocate Foundation, Good Days, Good Health Will, Mercy Medical Angels, and the American Association of Family Physicians Neighborhood Navigator.

Dr. Sloan said she knows clinicians don’t have time to understand every insurance plan and other issues related to cost. “But at least know to ask about costs,” she said. “Practice, practice, practice. It feels awkward at first, but it gets easier every time.”

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

AURORA, COLO. – How often do you talk with patients about how to lower their out-of-pocket costs for medical care?

For most clinicians, the answer is: not often enough. But having those conversations can improve medication adherence and strengthen the patient-clinician relationship, according to panelists at the annual meeting of the Society of General Internal Medicine.

The inverse association between out-of-pocket expenditures and fidelity to prescriptions is clear. A 2020 study by the IQVIA Institute for Human Data Science, for example, found that rates of prescription abandonment are less than 5% when a given medication carries no out-of-pocket cost for patients. That figure rises to 45% when the cost is more than $125, and to 60% when it exceeds $500. One in five Americans said cost prevented them from adhering to medication regimens, according to a new study in JAMA Network Open.

The researchers surveyed more than 2,000 men and women, 40.4% of whom were aged 75 or older. They found that nearly 90% of respondents said they would not be uncomfortable being asked about drug costs before a visit with a physician. A similar share (89.5%) said they would welcome the use by their physician of a real-time tool to determine the cost of their medication.

But the survey results contained a note of warning for clinicians: A significant number of respondents said they would be “extremely” upset if the cost of their medication exceeded the estimate from the pricing tool. And many also said they would be “moderately” or “extremely” angry if their physician used a pricing tool but failed to share the results with them.

“Real-time benefit tools may support medication cost conversations and cost-conscious prescribing, and patients are enthusiastic about their use,” the authors write. “However, if disclosed prices are inaccurate, there is potential for harm through loss of confidence in the physician and nonadherence to prescribed medications.”

While having conversations about cost can be difficult for both clinicians and patients, studies have shown that patients who discuss cost concerns with their doctors feel as if they have stronger relationships as a result.

Clinicians often avoid conversations about out-of-pocket expenses because they don’t know specific price information, they lack solutions to address cost, or they are uncomfortable bringing up the issue.

One member of the audience at the SGIM meeting recalled a patient who worked in a warehouse for a large company. The man, who had type 2 diabetes, had medical insurance, but even with insurance, insulin was going to cost him $150 per month. He struggled to afford the necessary treatment.

“He looked at me and said, ‘What do they want me to do? Do they want me to actually not be able to work for them and not manage my diabetes?’ ”

The clinician said he offered empathy in the moment but felt he could do little else.

Panelists acknowledged that clinicians are crunched on time when seeing patients, but being willing to initiate conversations about cost with patients and to offer resources can help patients get necessary treatment.
 

Start the conversation

Panel member Caroline Sloan, MD, an assistant professor of medicine at Duke University, Durham, N.C., said making patients aware that you know cost can make a big difference.

The American College of Physicians advises clinicians to ask patients whether they are worried about the cost of care and to not assume which patients may have concerns.

The conversation could be started like this: “I’d like to discuss any concerns you might have about the cost of your health care.”

Normalize the concern by making it more general, and reassure your patient that your goal is to get them the best care. Say something like, “I’ve heard from many patients the cost of medications or tests is becoming hard to manage.”

Once a patient’s concerns are clear, you can direct them to resources for assistance in reducing their costs, Dr. Sloan said, such as ClearHealthCosts, FAIR Health, Healthcare Bluebook, New Choice Health, GoodRx, PharmacyChecker, HealthWell Foundation, Patient Advocate Foundation, Good Days, Good Health Will, Mercy Medical Angels, and the American Association of Family Physicians Neighborhood Navigator.

Dr. Sloan said she knows clinicians don’t have time to understand every insurance plan and other issues related to cost. “But at least know to ask about costs,” she said. “Practice, practice, practice. It feels awkward at first, but it gets easier every time.”

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