Rheumatology News

VANCOUVER – The use of tricyclic antidepressants (TCAs) conferred the highest risk for a new, first-time clinical fracture in people with type 2 diabetes with overweight or obesity, independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.

Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.

Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.

Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.

The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m² or higher and hemoglobin A1c levels of 11% or below.

Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.

Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).

During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.

Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.

Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.

The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.

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

VANCOUVER – The use of tricyclic antidepressants (TCAs) conferred the highest risk for a new, first-time clinical fracture in people with type 2 diabetes with overweight or obesity, independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.

Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.

Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.

Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.

The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m² or higher and hemoglobin A1c levels of 11% or below.

Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.

Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).

During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.

Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.

Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.

The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.

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

VANCOUVER – The use of tricyclic antidepressants (TCAs) conferred the highest risk for a new, first-time clinical fracture in people with type 2 diabetes with overweight or obesity, independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.

Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.

Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.

Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.

The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m² or higher and hemoglobin A1c levels of 11% or below.

Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.

Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).

During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.

Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.

Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.

The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.

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

WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.

“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.

A deep dive into the tissue

Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.

The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.

Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.

“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”

The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.

Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.

Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.

With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”

The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
 

Finding biomarkers, diagnostic signatures

The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”

A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.

Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.

Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.

At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)

Eyes on combination therapy

“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”

Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.

A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.

In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”

It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.

In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”

Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.

WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.

“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.

A deep dive into the tissue

Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.

The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.

Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.

“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”

The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.

Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.

Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.

With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”

The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
 

Finding biomarkers, diagnostic signatures

The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”

A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.

Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.

Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.

At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)

Eyes on combination therapy

“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”

Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.

A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.

In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”

It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.

In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”

Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.

WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.

“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.

A deep dive into the tissue

Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.

The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.

Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.

“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”

The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.

Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.

Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.

With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”

The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
 

Finding biomarkers, diagnostic signatures

The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”

A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.

Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.

Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.

At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)

Eyes on combination therapy

“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”

Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.

A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.

In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”

It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.

In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”

Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.

Alexandra Kharazi, MD, a California-based cardiothoracic surgeon, previously worked as an employed physician and is now in private practice. Though she appreciates that there are some trade-offs to working with her small group of three surgeons, Dr. Kharazi has no qualms about her choice.

“For me, it’s an issue of autonomy,” she said. “While I have to work a lot of hours, I don’t have to adhere to a strict schedule. I also don’t have to follow specific policies and rules.”

In contrast, Cassandra Boduch, MD, an employed psychiatrist with PsychPlus in Houston, is very satisfied with working as an employee. “I looked into private practice, but no one really prepares you for the complications that come with it,” she said. “There’s a lot more that goes into it than people realize.”

By hanging up her own shingle, Dr. Kharazi may be living a rapidly shrinking dream. According to the American Medical Association, between 2012 and 2022, the share of physicians working in private practice fell from 60% to 47%. The share of physicians working in hospitals as direct employees or contractors increased from about 6% to about 10% during the same time period.

Many factors contribute to these shifting trends, a major factor being economic stress stemming from payment cuts in Medicare. Add in rising practice costs and administrative burdens, and more doctors than ever are seeking employment, according to the AMA.

Though the traditional dream of owning your own practice may be slipping away, are employed physicians less happy than are their self-employed peers? By many measures, the answer is no.

In Medscape’s Employed Physicians Report 2023, doctors weighed in on the pros and cons of their jobs.

When asked what they like most about their jobs, employed physician respondents reported “not having to run a business” as their number-one benefit, followed closely by a stable income. The fact that employers pay for malpractice insurance ranked third, followed by work-life balance.

“We get no business classes in medical school or residency,” said one employed physician. “Having a good salary feels good,” said another. Yet another respondent chimed in: “Running a practice as a small business has become undoable over the past 10-12 years.”

And 50% of employed physicians said that they were “very satisfied/satisfied” with their degree of autonomy.

Still, employed physicians also had plenty to say about the downsides of their jobs.

Many pointed to “feeling like a cog in the machine,” and one doctor pointed to the hassle of dealing with bureaucracy. Others complained about the fact that nonphysicians ran the business and lacked an understanding of what physicians really need from their jobs. When asked whether administrative rules made sense, 63% of physician respondents said that yes, the rules make sense for the business; but, only 52% said that the rules make sense for the doctors themselves.

Other complaints included the requirement to reach high productivity targets and too low an income potential. In the 9 years since Medscape’s 2104 Employed Physicians Report, the share of employed doctors paid on a straight salary has declined from 46% to 31%. Those compensated on a base salary plus productivity targets and other performance metrics rose from 13% in 2014 to 32% now.

“Many doctors go into private practice because of the freedom it brings and the potential financial incentives,” added Dr. Boduch. “I know that many doctors have a dream of working for themselves, and in many cases, that works out great for them.”

Dr. Boduch noted that in her job as chief medical officer at PsychPlus, she still has flexibility plus the perks of working with a bigger practice. In this scenario, Dr. Boduch said, the company can negotiate with insurance companies, allowing her the financial rewards of private practice.
 

What’s right for you?

“I think it might be somewhat generational,” said Cody Futch, senior recruiting executive at AMN Healthcare. “It used to be that fewer hospitals offered employment, so private practice was the way to go. Now, there are fewer privates because hospitals and corporations are buying them up.”

This reality has potentially shaped the way younger generations approach their workplace. Also, Gen Z tends to have less intention to stay with a current employer for the long term than did their parents. “Older physicians were trained to expect they’d run their own business and build it over the years,” said Mr. Futch. “The younger generations look at it as a job, something they may want to switch in a few years. It’s a combination of candidates wanting more options, and also the fact that there are more options to be employed.”

Along those lines, younger generations in general tend to place work-life balance as a higher priority than do older generations, and employed physicians place this equation high on the list as well. In the Employed Physicians Report 2023, 54% said that they are satisfied or better with their work-life balance, up from 51% in the 2022 report.

With that in mind, Dr. Kharazi noted that flexibility is one of the chief reasons why she likes private practice. “If my kid has an event I want to attend, I don’t have to adhere to a strict schedule,” she said.

Satisfaction as an employee vs. employed doctor sometimes changes based on the type of medicine you practice too. With specialties that tend to be primarily outpatient, such as dermatology and allergy, private practice may be the best option regardless. “Hospitals don’t seek out those specialists as much and the specialists can operate successfully without a hospital,” said Mr. Futch.

Hospitals try to incentivize doctors with perks like hefty sign-on bonuses, student loan forgiveness, plenty of vacation time, and more. They also put money into marketing their doctors, a time-consuming and expensive aspect that is tough to shoulder in private practice, especially in the early years. Mr. Futch adds that many doctors view employment as a more stable option. “As the government changes reimbursement policies, the income from private practice fluctuates,” he said. “So many doctors worry that if they buy into a private practice, it is a risky endeavor.”

Hospitals aren’t always a sure bet in that regard, either: They go through tough financial times, lay off staff, or make salary cuts. Historically, however, employment tends to be the safer route, which can make it an attractive option.

Ultimately, the pros and cons of each scenario are individual. It’s up to physicians to do their own math and balance sheet before making a decision.

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

Alexandra Kharazi, MD, a California-based cardiothoracic surgeon, previously worked as an employed physician and is now in private practice. Though she appreciates that there are some trade-offs to working with her small group of three surgeons, Dr. Kharazi has no qualms about her choice.

“For me, it’s an issue of autonomy,” she said. “While I have to work a lot of hours, I don’t have to adhere to a strict schedule. I also don’t have to follow specific policies and rules.”

In contrast, Cassandra Boduch, MD, an employed psychiatrist with PsychPlus in Houston, is very satisfied with working as an employee. “I looked into private practice, but no one really prepares you for the complications that come with it,” she said. “There’s a lot more that goes into it than people realize.”

By hanging up her own shingle, Dr. Kharazi may be living a rapidly shrinking dream. According to the American Medical Association, between 2012 and 2022, the share of physicians working in private practice fell from 60% to 47%. The share of physicians working in hospitals as direct employees or contractors increased from about 6% to about 10% during the same time period.

Many factors contribute to these shifting trends, a major factor being economic stress stemming from payment cuts in Medicare. Add in rising practice costs and administrative burdens, and more doctors than ever are seeking employment, according to the AMA.

Though the traditional dream of owning your own practice may be slipping away, are employed physicians less happy than are their self-employed peers? By many measures, the answer is no.

In Medscape’s Employed Physicians Report 2023, doctors weighed in on the pros and cons of their jobs.

When asked what they like most about their jobs, employed physician respondents reported “not having to run a business” as their number-one benefit, followed closely by a stable income. The fact that employers pay for malpractice insurance ranked third, followed by work-life balance.

“We get no business classes in medical school or residency,” said one employed physician. “Having a good salary feels good,” said another. Yet another respondent chimed in: “Running a practice as a small business has become undoable over the past 10-12 years.”

And 50% of employed physicians said that they were “very satisfied/satisfied” with their degree of autonomy.

Still, employed physicians also had plenty to say about the downsides of their jobs.

Many pointed to “feeling like a cog in the machine,” and one doctor pointed to the hassle of dealing with bureaucracy. Others complained about the fact that nonphysicians ran the business and lacked an understanding of what physicians really need from their jobs. When asked whether administrative rules made sense, 63% of physician respondents said that yes, the rules make sense for the business; but, only 52% said that the rules make sense for the doctors themselves.

Other complaints included the requirement to reach high productivity targets and too low an income potential. In the 9 years since Medscape’s 2104 Employed Physicians Report, the share of employed doctors paid on a straight salary has declined from 46% to 31%. Those compensated on a base salary plus productivity targets and other performance metrics rose from 13% in 2014 to 32% now.

“Many doctors go into private practice because of the freedom it brings and the potential financial incentives,” added Dr. Boduch. “I know that many doctors have a dream of working for themselves, and in many cases, that works out great for them.”

Dr. Boduch noted that in her job as chief medical officer at PsychPlus, she still has flexibility plus the perks of working with a bigger practice. In this scenario, Dr. Boduch said, the company can negotiate with insurance companies, allowing her the financial rewards of private practice.
 

What’s right for you?

“I think it might be somewhat generational,” said Cody Futch, senior recruiting executive at AMN Healthcare. “It used to be that fewer hospitals offered employment, so private practice was the way to go. Now, there are fewer privates because hospitals and corporations are buying them up.”

This reality has potentially shaped the way younger generations approach their workplace. Also, Gen Z tends to have less intention to stay with a current employer for the long term than did their parents. “Older physicians were trained to expect they’d run their own business and build it over the years,” said Mr. Futch. “The younger generations look at it as a job, something they may want to switch in a few years. It’s a combination of candidates wanting more options, and also the fact that there are more options to be employed.”

Along those lines, younger generations in general tend to place work-life balance as a higher priority than do older generations, and employed physicians place this equation high on the list as well. In the Employed Physicians Report 2023, 54% said that they are satisfied or better with their work-life balance, up from 51% in the 2022 report.

With that in mind, Dr. Kharazi noted that flexibility is one of the chief reasons why she likes private practice. “If my kid has an event I want to attend, I don’t have to adhere to a strict schedule,” she said.

Satisfaction as an employee vs. employed doctor sometimes changes based on the type of medicine you practice too. With specialties that tend to be primarily outpatient, such as dermatology and allergy, private practice may be the best option regardless. “Hospitals don’t seek out those specialists as much and the specialists can operate successfully without a hospital,” said Mr. Futch.

Hospitals try to incentivize doctors with perks like hefty sign-on bonuses, student loan forgiveness, plenty of vacation time, and more. They also put money into marketing their doctors, a time-consuming and expensive aspect that is tough to shoulder in private practice, especially in the early years. Mr. Futch adds that many doctors view employment as a more stable option. “As the government changes reimbursement policies, the income from private practice fluctuates,” he said. “So many doctors worry that if they buy into a private practice, it is a risky endeavor.”

Hospitals aren’t always a sure bet in that regard, either: They go through tough financial times, lay off staff, or make salary cuts. Historically, however, employment tends to be the safer route, which can make it an attractive option.

Ultimately, the pros and cons of each scenario are individual. It’s up to physicians to do their own math and balance sheet before making a decision.

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

Alexandra Kharazi, MD, a California-based cardiothoracic surgeon, previously worked as an employed physician and is now in private practice. Though she appreciates that there are some trade-offs to working with her small group of three surgeons, Dr. Kharazi has no qualms about her choice.

“For me, it’s an issue of autonomy,” she said. “While I have to work a lot of hours, I don’t have to adhere to a strict schedule. I also don’t have to follow specific policies and rules.”

In contrast, Cassandra Boduch, MD, an employed psychiatrist with PsychPlus in Houston, is very satisfied with working as an employee. “I looked into private practice, but no one really prepares you for the complications that come with it,” she said. “There’s a lot more that goes into it than people realize.”

By hanging up her own shingle, Dr. Kharazi may be living a rapidly shrinking dream. According to the American Medical Association, between 2012 and 2022, the share of physicians working in private practice fell from 60% to 47%. The share of physicians working in hospitals as direct employees or contractors increased from about 6% to about 10% during the same time period.

Many factors contribute to these shifting trends, a major factor being economic stress stemming from payment cuts in Medicare. Add in rising practice costs and administrative burdens, and more doctors than ever are seeking employment, according to the AMA.

Though the traditional dream of owning your own practice may be slipping away, are employed physicians less happy than are their self-employed peers? By many measures, the answer is no.

In Medscape’s Employed Physicians Report 2023, doctors weighed in on the pros and cons of their jobs.

When asked what they like most about their jobs, employed physician respondents reported “not having to run a business” as their number-one benefit, followed closely by a stable income. The fact that employers pay for malpractice insurance ranked third, followed by work-life balance.

“We get no business classes in medical school or residency,” said one employed physician. “Having a good salary feels good,” said another. Yet another respondent chimed in: “Running a practice as a small business has become undoable over the past 10-12 years.”

And 50% of employed physicians said that they were “very satisfied/satisfied” with their degree of autonomy.

Still, employed physicians also had plenty to say about the downsides of their jobs.

Many pointed to “feeling like a cog in the machine,” and one doctor pointed to the hassle of dealing with bureaucracy. Others complained about the fact that nonphysicians ran the business and lacked an understanding of what physicians really need from their jobs. When asked whether administrative rules made sense, 63% of physician respondents said that yes, the rules make sense for the business; but, only 52% said that the rules make sense for the doctors themselves.

Other complaints included the requirement to reach high productivity targets and too low an income potential. In the 9 years since Medscape’s 2104 Employed Physicians Report, the share of employed doctors paid on a straight salary has declined from 46% to 31%. Those compensated on a base salary plus productivity targets and other performance metrics rose from 13% in 2014 to 32% now.

“Many doctors go into private practice because of the freedom it brings and the potential financial incentives,” added Dr. Boduch. “I know that many doctors have a dream of working for themselves, and in many cases, that works out great for them.”

Dr. Boduch noted that in her job as chief medical officer at PsychPlus, she still has flexibility plus the perks of working with a bigger practice. In this scenario, Dr. Boduch said, the company can negotiate with insurance companies, allowing her the financial rewards of private practice.
 

What’s right for you?

“I think it might be somewhat generational,” said Cody Futch, senior recruiting executive at AMN Healthcare. “It used to be that fewer hospitals offered employment, so private practice was the way to go. Now, there are fewer privates because hospitals and corporations are buying them up.”

This reality has potentially shaped the way younger generations approach their workplace. Also, Gen Z tends to have less intention to stay with a current employer for the long term than did their parents. “Older physicians were trained to expect they’d run their own business and build it over the years,” said Mr. Futch. “The younger generations look at it as a job, something they may want to switch in a few years. It’s a combination of candidates wanting more options, and also the fact that there are more options to be employed.”

Along those lines, younger generations in general tend to place work-life balance as a higher priority than do older generations, and employed physicians place this equation high on the list as well. In the Employed Physicians Report 2023, 54% said that they are satisfied or better with their work-life balance, up from 51% in the 2022 report.

With that in mind, Dr. Kharazi noted that flexibility is one of the chief reasons why she likes private practice. “If my kid has an event I want to attend, I don’t have to adhere to a strict schedule,” she said.

Satisfaction as an employee vs. employed doctor sometimes changes based on the type of medicine you practice too. With specialties that tend to be primarily outpatient, such as dermatology and allergy, private practice may be the best option regardless. “Hospitals don’t seek out those specialists as much and the specialists can operate successfully without a hospital,” said Mr. Futch.

Hospitals try to incentivize doctors with perks like hefty sign-on bonuses, student loan forgiveness, plenty of vacation time, and more. They also put money into marketing their doctors, a time-consuming and expensive aspect that is tough to shoulder in private practice, especially in the early years. Mr. Futch adds that many doctors view employment as a more stable option. “As the government changes reimbursement policies, the income from private practice fluctuates,” he said. “So many doctors worry that if they buy into a private practice, it is a risky endeavor.”

Hospitals aren’t always a sure bet in that regard, either: They go through tough financial times, lay off staff, or make salary cuts. Historically, however, employment tends to be the safer route, which can make it an attractive option.

Ultimately, the pros and cons of each scenario are individual. It’s up to physicians to do their own math and balance sheet before making a decision.

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

VANCOUVER – A new calculator that predicts short-term fracture risk at both 1 year and 3 years in patients on dialysis performed well in a study presented at the annual meeting of the American Society for Bone and Mineral Research.

The tool will soon be available on QxMD Calculate, which provides free decision-support tools for physicians, said presenter Andrea Cowan, MD, an assistant professor of medicine at the University of Western Ontario, London.

Dialysis patients have an approximately fivefold increased risk for fracture, Dr. Cowan noted, compared with the general population. However, treatments to prevent fracture risk are relatively limited and can have significant side effects. Therefore, “you really want to make sure that the person you’re targeting for treatment is actually going to be at a reasonable risk of fracture,” she said.

The Fracture Risk Assessment Tool (FRAX) is useful, but it estimates 10-year fracture risk, which is too long of a time frame to be useful for dialysis patients who experience a 50% 5-year mortality, according to Dr. Cowan. It does not take kidney failure or severe hyperparathyroidism into account, and it also requires information like bone mineral density, which poses an additional burden for a dialysis patient already undergoing multiple tests.

The new calculator could also be useful for research because it doesn’t rely on clinical data that might not be generally available, such as parental fracture, smoking status, or body mass index. “There’s a move towards things like pragmatic trials, which use more routinely collected data, have broader inclusion criteria, and are often more cost efficient to run. This calculator should be relatively easy to implement in trials using routinely collected data to perhaps define a subgroup of patients who may be at high risk of fracture without having to apply really cumbersome tools,” Dr. Cowan said.

The researchers included 11,599 patients between ages 40 and 89 years who were treated at a single center in Ontario between 2010 and 2017. The mean age was 66.18 years, 38.6% were women, 64.1% had diabetes, 11.9% had liver disease, and median time on dialysis was 0.81 years. The patients’ median parathyroid hormone level was 30 pmol/L.

At 3 years, the cumulative incidence of any fracture was 7.36% (95% confidence interval, 6.89-7.85), including 2.62% for hip fracture (95% CI, 2.34-2.93), 1.36% for spine fracture (95% CI, 1.16-1.59), 1.93% for wrist or forearm (95% CI, 1.69-2.20), and 2.15% for the pelvis (95% CI, 1.89-2.43). The incidence for all fractures at 1 year was 2.93 (95% CI, 2.62-3.26).

Variables associated with fracture risk included female sex (hazard ratio, 1.46; 95% CI, 1.27-1.67), a previous fracture more than 1 year in the past (HR, 1.65; 95% CI, 1.37-2.00), a fracture in the past year (HR, 3.63; 95% CI, 2.86-4.60), and proton pump inhibitor use (HR, 1.23; 95% CI, 1.04-1.45). After inclusion of vitamin D use, steroid use, time on dialysis, calcium levels, phosphate levels, presence of diabetes, rheumatoid arthritis, and chronic liver disease, the full model had an area under the curve of 77.7 at 1 year (95% CI, 73.3-84.4) and 69.9 at 3 years (95% CI, 68.0-72.2). For hip fracture, the model had an AUC of 80.1 at 1 year (95% CI, 77.0-83.5) and 71.9 at 3 years (95% CI, 70.1-74.2).

During the Q&A session, Dr. Cowan was asked how the tool could be implemented clinically. She said that it could have value in discussing fracture prediction and prevention with patients, but it could also increase fracture risk awareness among nephrologists. “I need to convince a lot of my colleagues because they’re focused on other things, so having this [calculator] I think is both good from a patient as well as a practitioner perspective. And the treatments that we have in people with end-stage renal disease are limited, so you want to know that you’re really targeting the high-risk person before you potentially put them on denosumab and increase the risk of severe hypercalcemia and things like that,” Dr. Cowan said.

The study points out the challenges of predicting fracture risk for specific populations, according to session comoderator Evelyn Hsieh, MD. She noted that the study needs follow-up. “I don’t think they had gotten to a validation [in a separate cohort] yet,” said Dr. Hsieh, an associate professor of medicine (rheumatology) and epidemiology (chronic diseases) at Yale University, New Haven, Conn.

Dr. Cowan and Dr. Hsieh have no relevant financial disclosures.

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

VANCOUVER – A new calculator that predicts short-term fracture risk at both 1 year and 3 years in patients on dialysis performed well in a study presented at the annual meeting of the American Society for Bone and Mineral Research.

The tool will soon be available on QxMD Calculate, which provides free decision-support tools for physicians, said presenter Andrea Cowan, MD, an assistant professor of medicine at the University of Western Ontario, London.

Dialysis patients have an approximately fivefold increased risk for fracture, Dr. Cowan noted, compared with the general population. However, treatments to prevent fracture risk are relatively limited and can have significant side effects. Therefore, “you really want to make sure that the person you’re targeting for treatment is actually going to be at a reasonable risk of fracture,” she said.

The Fracture Risk Assessment Tool (FRAX) is useful, but it estimates 10-year fracture risk, which is too long of a time frame to be useful for dialysis patients who experience a 50% 5-year mortality, according to Dr. Cowan. It does not take kidney failure or severe hyperparathyroidism into account, and it also requires information like bone mineral density, which poses an additional burden for a dialysis patient already undergoing multiple tests.

The new calculator could also be useful for research because it doesn’t rely on clinical data that might not be generally available, such as parental fracture, smoking status, or body mass index. “There’s a move towards things like pragmatic trials, which use more routinely collected data, have broader inclusion criteria, and are often more cost efficient to run. This calculator should be relatively easy to implement in trials using routinely collected data to perhaps define a subgroup of patients who may be at high risk of fracture without having to apply really cumbersome tools,” Dr. Cowan said.

The researchers included 11,599 patients between ages 40 and 89 years who were treated at a single center in Ontario between 2010 and 2017. The mean age was 66.18 years, 38.6% were women, 64.1% had diabetes, 11.9% had liver disease, and median time on dialysis was 0.81 years. The patients’ median parathyroid hormone level was 30 pmol/L.

At 3 years, the cumulative incidence of any fracture was 7.36% (95% confidence interval, 6.89-7.85), including 2.62% for hip fracture (95% CI, 2.34-2.93), 1.36% for spine fracture (95% CI, 1.16-1.59), 1.93% for wrist or forearm (95% CI, 1.69-2.20), and 2.15% for the pelvis (95% CI, 1.89-2.43). The incidence for all fractures at 1 year was 2.93 (95% CI, 2.62-3.26).

Variables associated with fracture risk included female sex (hazard ratio, 1.46; 95% CI, 1.27-1.67), a previous fracture more than 1 year in the past (HR, 1.65; 95% CI, 1.37-2.00), a fracture in the past year (HR, 3.63; 95% CI, 2.86-4.60), and proton pump inhibitor use (HR, 1.23; 95% CI, 1.04-1.45). After inclusion of vitamin D use, steroid use, time on dialysis, calcium levels, phosphate levels, presence of diabetes, rheumatoid arthritis, and chronic liver disease, the full model had an area under the curve of 77.7 at 1 year (95% CI, 73.3-84.4) and 69.9 at 3 years (95% CI, 68.0-72.2). For hip fracture, the model had an AUC of 80.1 at 1 year (95% CI, 77.0-83.5) and 71.9 at 3 years (95% CI, 70.1-74.2).

During the Q&A session, Dr. Cowan was asked how the tool could be implemented clinically. She said that it could have value in discussing fracture prediction and prevention with patients, but it could also increase fracture risk awareness among nephrologists. “I need to convince a lot of my colleagues because they’re focused on other things, so having this [calculator] I think is both good from a patient as well as a practitioner perspective. And the treatments that we have in people with end-stage renal disease are limited, so you want to know that you’re really targeting the high-risk person before you potentially put them on denosumab and increase the risk of severe hypercalcemia and things like that,” Dr. Cowan said.

The study points out the challenges of predicting fracture risk for specific populations, according to session comoderator Evelyn Hsieh, MD. She noted that the study needs follow-up. “I don’t think they had gotten to a validation [in a separate cohort] yet,” said Dr. Hsieh, an associate professor of medicine (rheumatology) and epidemiology (chronic diseases) at Yale University, New Haven, Conn.

Dr. Cowan and Dr. Hsieh have no relevant financial disclosures.

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

VANCOUVER – A new calculator that predicts short-term fracture risk at both 1 year and 3 years in patients on dialysis performed well in a study presented at the annual meeting of the American Society for Bone and Mineral Research.

The tool will soon be available on QxMD Calculate, which provides free decision-support tools for physicians, said presenter Andrea Cowan, MD, an assistant professor of medicine at the University of Western Ontario, London.

Dialysis patients have an approximately fivefold increased risk for fracture, Dr. Cowan noted, compared with the general population. However, treatments to prevent fracture risk are relatively limited and can have significant side effects. Therefore, “you really want to make sure that the person you’re targeting for treatment is actually going to be at a reasonable risk of fracture,” she said.

The Fracture Risk Assessment Tool (FRAX) is useful, but it estimates 10-year fracture risk, which is too long of a time frame to be useful for dialysis patients who experience a 50% 5-year mortality, according to Dr. Cowan. It does not take kidney failure or severe hyperparathyroidism into account, and it also requires information like bone mineral density, which poses an additional burden for a dialysis patient already undergoing multiple tests.

The new calculator could also be useful for research because it doesn’t rely on clinical data that might not be generally available, such as parental fracture, smoking status, or body mass index. “There’s a move towards things like pragmatic trials, which use more routinely collected data, have broader inclusion criteria, and are often more cost efficient to run. This calculator should be relatively easy to implement in trials using routinely collected data to perhaps define a subgroup of patients who may be at high risk of fracture without having to apply really cumbersome tools,” Dr. Cowan said.

The researchers included 11,599 patients between ages 40 and 89 years who were treated at a single center in Ontario between 2010 and 2017. The mean age was 66.18 years, 38.6% were women, 64.1% had diabetes, 11.9% had liver disease, and median time on dialysis was 0.81 years. The patients’ median parathyroid hormone level was 30 pmol/L.

At 3 years, the cumulative incidence of any fracture was 7.36% (95% confidence interval, 6.89-7.85), including 2.62% for hip fracture (95% CI, 2.34-2.93), 1.36% for spine fracture (95% CI, 1.16-1.59), 1.93% for wrist or forearm (95% CI, 1.69-2.20), and 2.15% for the pelvis (95% CI, 1.89-2.43). The incidence for all fractures at 1 year was 2.93 (95% CI, 2.62-3.26).

Variables associated with fracture risk included female sex (hazard ratio, 1.46; 95% CI, 1.27-1.67), a previous fracture more than 1 year in the past (HR, 1.65; 95% CI, 1.37-2.00), a fracture in the past year (HR, 3.63; 95% CI, 2.86-4.60), and proton pump inhibitor use (HR, 1.23; 95% CI, 1.04-1.45). After inclusion of vitamin D use, steroid use, time on dialysis, calcium levels, phosphate levels, presence of diabetes, rheumatoid arthritis, and chronic liver disease, the full model had an area under the curve of 77.7 at 1 year (95% CI, 73.3-84.4) and 69.9 at 3 years (95% CI, 68.0-72.2). For hip fracture, the model had an AUC of 80.1 at 1 year (95% CI, 77.0-83.5) and 71.9 at 3 years (95% CI, 70.1-74.2).

During the Q&A session, Dr. Cowan was asked how the tool could be implemented clinically. She said that it could have value in discussing fracture prediction and prevention with patients, but it could also increase fracture risk awareness among nephrologists. “I need to convince a lot of my colleagues because they’re focused on other things, so having this [calculator] I think is both good from a patient as well as a practitioner perspective. And the treatments that we have in people with end-stage renal disease are limited, so you want to know that you’re really targeting the high-risk person before you potentially put them on denosumab and increase the risk of severe hypercalcemia and things like that,” Dr. Cowan said.

The study points out the challenges of predicting fracture risk for specific populations, according to session comoderator Evelyn Hsieh, MD. She noted that the study needs follow-up. “I don’t think they had gotten to a validation [in a separate cohort] yet,” said Dr. Hsieh, an associate professor of medicine (rheumatology) and epidemiology (chronic diseases) at Yale University, New Haven, Conn.

Dr. Cowan and Dr. Hsieh have no relevant financial disclosures.

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

VANCOUVER – With treatment with a bisphosphonate following sequential use of teriparatide (Forteo) and denosumab (Prolia) for premenopausal women with idiopathic osteoporosis, bone mineral density (BMD) was maintained over the first year following denosumab cessation, according to results from a small, nonrandomized extension of a phase 2 study.

Bisphosphonates are recommended for patients after they have completed a course of denosumab because cessation of the bone resorption blocker is known to increase bone turnover markers, decrease BMD, and raise the risk of vertebral fractures. Although there is evidence to support this treatment sequence for postmenopausal women, there was no evidence regarding premenopausal women with idiopathic osteoporosis, said Adi Cohen, MD, who presented the results of the study at the annual meeting of the American Society for Bone and Mineral Research.

In the extension study, neither length of treatment with denosumab nor transition to menopause affected BMD results. Weekly doses of alendronate (ALN) better suppressed C-terminal telopeptide (CTX) than did zoledronic acid (ZOL) and led to better maintenance of BMD than did a single dose of ZOL. The researchers suggested that single-dose ZOL may not prevent bone loss for an entire year.

It is too early to call the results practice changing, said Dr. Cohen, professor of medicine and endocrinology at Columbia University Irving Medical Center, New York, but she noted, “It’s important just to provide information about how sequences of osteoporosis medications might be used in a rare but certainly understudied group of premenopausal women with osteoporosis who need treatment, and these data hopefully will help make some treatment decisions.”

In the early 2000s, researchers initially believed that premenopausal women with low BMD had experienced some kind of temporary event and that they would likely improve on their own over time. “I think we now recognize that whatever it is that causes this is an ongoing issue and that this is a problem they’re going to have to deal with for the rest of their lives. This is something that they have to stay on top of,” said coauthor Elizabeth Shane, MD, who is a professor of medicine at CUIMC.

However, there are no practice guidelines for the management of osteoporosis in premenopausal women, according to Dr. Shane. She noted that there is controversy as to whether to treat women with low bone density who do not have a history of fractures. “I think that there’s pretty much agreement that anybody who has a lot of fractures has an early-onset form of osteoporosis. The controversy is what to do about the person who just has a low bone density and hasn’t yet fractured and what is the utility of trying to treat them at that point and perhaps prevent a fracture. I don’t think we have enough data to address that,” Dr. Shane said.

Still, the research has provided some clarity in her own practice. “I think if somebody would come to my office who had very low bone density, I would probably treat them. If they have fractures, I would definitely treat them. I think that our work has provided a framework for people to approach that,” she said.

The study was an extension of a sequential treatment approach that began with 2 years of teriparatide (20 mcg daily) followed by an extension study of 2–3 years of treatment with denosumab (60 mg every 6 months). Seven months after the last dose of denosumab, patients underwent 1 year of treatment with ALN (70 mg weekly; n = 18) or a single dose of ZOL (5 mg IV; n = 6), according to patient choice.

The original phase 2 study started with 41 women. At 24 months, teriparatide treatment led to BMD increases of 13% in the lumbar spine (LS), 5% in the total hip (TH), and 5% in the femoral neck (FN). There was a 2% decline in BMD in the forearm (distal radius [DR]). A group of 32 of the women participated in an extension study and took denosumab for 12 months. Of those patients, 29 continued to take it for another 12 months. At 12 months, BMD increased 5% in the LS, 3% in the TH, 3% in the FN, and 1% in the DR (P < .05 for all). At 24 months, BMD rose by 22%, 10%, and 10% at the first three of those locations. BMD in the DR remained stable, compared with the baseline after taking teriparatide.

The bisphosphonate phase of the extension study included 24 women (mean age, 43 years). The mean body mass index of the patients was 23.0 kg/m². The patients had experienced a mean of 3.0 fractures in adulthood, and 38% of patients had a history of vertebral fracture.

Over 12 months of follow-up, the researchers found no statistically significant difference in BMD in the LS, TH, or FN, compared with bisphosphonate extension baseline. There was also no statistically significant change in serum CTX. There was evidence that, among patients with higher rates of bone turnover, there were higher rates of LS and FN bone loss during bisphosphonate treatment.

Among patients taking ZOL, at 12 months there was a statistically significant rise in CTX levels, but not among patients taking ALN. There were no new vertebral fractures among any participants during the bisphosphonate extension period.

The results represent critical data for an understudied population, according to Yumie Rhee, MD, PhD, who was comoderator of the session in which the study was presented. “They are showing that by using a bisphosphonate [patients] have this just slight decrease, but within error, so it’s maintaining the BMD, at least. I think it’s very important. It will be fascinating to see next year’s follow-up,” said Dr. Rhee, a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea. “The problem with premenopausal osteoporosis is that we don’t have good evidence. Even though this study is very small, we’re just following that data, all of us.”

Comoderator Maria Zanchetta, MD, a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires, agreed. “We know what to do when we stop denosumab in postmenopausal women. We didn’t have any work about what to do when we stopped in premenopausal women. You can think that probably it’s going to be the same, but this is the first time you have the evidence that if you give bisphosphonate, you will maintain BMD.”

Limitations to the study include its small size and the lack of a placebo-treated control group. In addition, the bisphosphonate extension was not randomized.

The studies were funded by the U.S. Food and Drug Administration and Amgen. Dr. Cohen and Dr. Shane received research funding from Amgen. Dr. Rhee and Dr. Zanchetta have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER – With treatment with a bisphosphonate following sequential use of teriparatide (Forteo) and denosumab (Prolia) for premenopausal women with idiopathic osteoporosis, bone mineral density (BMD) was maintained over the first year following denosumab cessation, according to results from a small, nonrandomized extension of a phase 2 study.

Bisphosphonates are recommended for patients after they have completed a course of denosumab because cessation of the bone resorption blocker is known to increase bone turnover markers, decrease BMD, and raise the risk of vertebral fractures. Although there is evidence to support this treatment sequence for postmenopausal women, there was no evidence regarding premenopausal women with idiopathic osteoporosis, said Adi Cohen, MD, who presented the results of the study at the annual meeting of the American Society for Bone and Mineral Research.

In the extension study, neither length of treatment with denosumab nor transition to menopause affected BMD results. Weekly doses of alendronate (ALN) better suppressed C-terminal telopeptide (CTX) than did zoledronic acid (ZOL) and led to better maintenance of BMD than did a single dose of ZOL. The researchers suggested that single-dose ZOL may not prevent bone loss for an entire year.

It is too early to call the results practice changing, said Dr. Cohen, professor of medicine and endocrinology at Columbia University Irving Medical Center, New York, but she noted, “It’s important just to provide information about how sequences of osteoporosis medications might be used in a rare but certainly understudied group of premenopausal women with osteoporosis who need treatment, and these data hopefully will help make some treatment decisions.”

In the early 2000s, researchers initially believed that premenopausal women with low BMD had experienced some kind of temporary event and that they would likely improve on their own over time. “I think we now recognize that whatever it is that causes this is an ongoing issue and that this is a problem they’re going to have to deal with for the rest of their lives. This is something that they have to stay on top of,” said coauthor Elizabeth Shane, MD, who is a professor of medicine at CUIMC.

However, there are no practice guidelines for the management of osteoporosis in premenopausal women, according to Dr. Shane. She noted that there is controversy as to whether to treat women with low bone density who do not have a history of fractures. “I think that there’s pretty much agreement that anybody who has a lot of fractures has an early-onset form of osteoporosis. The controversy is what to do about the person who just has a low bone density and hasn’t yet fractured and what is the utility of trying to treat them at that point and perhaps prevent a fracture. I don’t think we have enough data to address that,” Dr. Shane said.

Still, the research has provided some clarity in her own practice. “I think if somebody would come to my office who had very low bone density, I would probably treat them. If they have fractures, I would definitely treat them. I think that our work has provided a framework for people to approach that,” she said.

The study was an extension of a sequential treatment approach that began with 2 years of teriparatide (20 mcg daily) followed by an extension study of 2–3 years of treatment with denosumab (60 mg every 6 months). Seven months after the last dose of denosumab, patients underwent 1 year of treatment with ALN (70 mg weekly; n = 18) or a single dose of ZOL (5 mg IV; n = 6), according to patient choice.

The original phase 2 study started with 41 women. At 24 months, teriparatide treatment led to BMD increases of 13% in the lumbar spine (LS), 5% in the total hip (TH), and 5% in the femoral neck (FN). There was a 2% decline in BMD in the forearm (distal radius [DR]). A group of 32 of the women participated in an extension study and took denosumab for 12 months. Of those patients, 29 continued to take it for another 12 months. At 12 months, BMD increased 5% in the LS, 3% in the TH, 3% in the FN, and 1% in the DR (P < .05 for all). At 24 months, BMD rose by 22%, 10%, and 10% at the first three of those locations. BMD in the DR remained stable, compared with the baseline after taking teriparatide.

The bisphosphonate phase of the extension study included 24 women (mean age, 43 years). The mean body mass index of the patients was 23.0 kg/m². The patients had experienced a mean of 3.0 fractures in adulthood, and 38% of patients had a history of vertebral fracture.

Over 12 months of follow-up, the researchers found no statistically significant difference in BMD in the LS, TH, or FN, compared with bisphosphonate extension baseline. There was also no statistically significant change in serum CTX. There was evidence that, among patients with higher rates of bone turnover, there were higher rates of LS and FN bone loss during bisphosphonate treatment.

Among patients taking ZOL, at 12 months there was a statistically significant rise in CTX levels, but not among patients taking ALN. There were no new vertebral fractures among any participants during the bisphosphonate extension period.

The results represent critical data for an understudied population, according to Yumie Rhee, MD, PhD, who was comoderator of the session in which the study was presented. “They are showing that by using a bisphosphonate [patients] have this just slight decrease, but within error, so it’s maintaining the BMD, at least. I think it’s very important. It will be fascinating to see next year’s follow-up,” said Dr. Rhee, a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea. “The problem with premenopausal osteoporosis is that we don’t have good evidence. Even though this study is very small, we’re just following that data, all of us.”

Comoderator Maria Zanchetta, MD, a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires, agreed. “We know what to do when we stop denosumab in postmenopausal women. We didn’t have any work about what to do when we stopped in premenopausal women. You can think that probably it’s going to be the same, but this is the first time you have the evidence that if you give bisphosphonate, you will maintain BMD.”

Limitations to the study include its small size and the lack of a placebo-treated control group. In addition, the bisphosphonate extension was not randomized.

The studies were funded by the U.S. Food and Drug Administration and Amgen. Dr. Cohen and Dr. Shane received research funding from Amgen. Dr. Rhee and Dr. Zanchetta have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER – With treatment with a bisphosphonate following sequential use of teriparatide (Forteo) and denosumab (Prolia) for premenopausal women with idiopathic osteoporosis, bone mineral density (BMD) was maintained over the first year following denosumab cessation, according to results from a small, nonrandomized extension of a phase 2 study.

Bisphosphonates are recommended for patients after they have completed a course of denosumab because cessation of the bone resorption blocker is known to increase bone turnover markers, decrease BMD, and raise the risk of vertebral fractures. Although there is evidence to support this treatment sequence for postmenopausal women, there was no evidence regarding premenopausal women with idiopathic osteoporosis, said Adi Cohen, MD, who presented the results of the study at the annual meeting of the American Society for Bone and Mineral Research.

In the extension study, neither length of treatment with denosumab nor transition to menopause affected BMD results. Weekly doses of alendronate (ALN) better suppressed C-terminal telopeptide (CTX) than did zoledronic acid (ZOL) and led to better maintenance of BMD than did a single dose of ZOL. The researchers suggested that single-dose ZOL may not prevent bone loss for an entire year.

It is too early to call the results practice changing, said Dr. Cohen, professor of medicine and endocrinology at Columbia University Irving Medical Center, New York, but she noted, “It’s important just to provide information about how sequences of osteoporosis medications might be used in a rare but certainly understudied group of premenopausal women with osteoporosis who need treatment, and these data hopefully will help make some treatment decisions.”

In the early 2000s, researchers initially believed that premenopausal women with low BMD had experienced some kind of temporary event and that they would likely improve on their own over time. “I think we now recognize that whatever it is that causes this is an ongoing issue and that this is a problem they’re going to have to deal with for the rest of their lives. This is something that they have to stay on top of,” said coauthor Elizabeth Shane, MD, who is a professor of medicine at CUIMC.

However, there are no practice guidelines for the management of osteoporosis in premenopausal women, according to Dr. Shane. She noted that there is controversy as to whether to treat women with low bone density who do not have a history of fractures. “I think that there’s pretty much agreement that anybody who has a lot of fractures has an early-onset form of osteoporosis. The controversy is what to do about the person who just has a low bone density and hasn’t yet fractured and what is the utility of trying to treat them at that point and perhaps prevent a fracture. I don’t think we have enough data to address that,” Dr. Shane said.

Still, the research has provided some clarity in her own practice. “I think if somebody would come to my office who had very low bone density, I would probably treat them. If they have fractures, I would definitely treat them. I think that our work has provided a framework for people to approach that,” she said.

The study was an extension of a sequential treatment approach that began with 2 years of teriparatide (20 mcg daily) followed by an extension study of 2–3 years of treatment with denosumab (60 mg every 6 months). Seven months after the last dose of denosumab, patients underwent 1 year of treatment with ALN (70 mg weekly; n = 18) or a single dose of ZOL (5 mg IV; n = 6), according to patient choice.

The original phase 2 study started with 41 women. At 24 months, teriparatide treatment led to BMD increases of 13% in the lumbar spine (LS), 5% in the total hip (TH), and 5% in the femoral neck (FN). There was a 2% decline in BMD in the forearm (distal radius [DR]). A group of 32 of the women participated in an extension study and took denosumab for 12 months. Of those patients, 29 continued to take it for another 12 months. At 12 months, BMD increased 5% in the LS, 3% in the TH, 3% in the FN, and 1% in the DR (P < .05 for all). At 24 months, BMD rose by 22%, 10%, and 10% at the first three of those locations. BMD in the DR remained stable, compared with the baseline after taking teriparatide.

The bisphosphonate phase of the extension study included 24 women (mean age, 43 years). The mean body mass index of the patients was 23.0 kg/m². The patients had experienced a mean of 3.0 fractures in adulthood, and 38% of patients had a history of vertebral fracture.

Over 12 months of follow-up, the researchers found no statistically significant difference in BMD in the LS, TH, or FN, compared with bisphosphonate extension baseline. There was also no statistically significant change in serum CTX. There was evidence that, among patients with higher rates of bone turnover, there were higher rates of LS and FN bone loss during bisphosphonate treatment.

Among patients taking ZOL, at 12 months there was a statistically significant rise in CTX levels, but not among patients taking ALN. There were no new vertebral fractures among any participants during the bisphosphonate extension period.

The results represent critical data for an understudied population, according to Yumie Rhee, MD, PhD, who was comoderator of the session in which the study was presented. “They are showing that by using a bisphosphonate [patients] have this just slight decrease, but within error, so it’s maintaining the BMD, at least. I think it’s very important. It will be fascinating to see next year’s follow-up,” said Dr. Rhee, a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea. “The problem with premenopausal osteoporosis is that we don’t have good evidence. Even though this study is very small, we’re just following that data, all of us.”

Comoderator Maria Zanchetta, MD, a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires, agreed. “We know what to do when we stop denosumab in postmenopausal women. We didn’t have any work about what to do when we stopped in premenopausal women. You can think that probably it’s going to be the same, but this is the first time you have the evidence that if you give bisphosphonate, you will maintain BMD.”

Limitations to the study include its small size and the lack of a placebo-treated control group. In addition, the bisphosphonate extension was not randomized.

The studies were funded by the U.S. Food and Drug Administration and Amgen. Dr. Cohen and Dr. Shane received research funding from Amgen. Dr. Rhee and Dr. Zanchetta have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Researchers have identified two genes that may contribute to Raynaud’s phenomenon, a condition where blood vessels in the extremities constrict and limit blood flow.

Raynaud’s is a relatively common condition, affecting 2%-5% of the general population. Though Raynaud’s can be an annoyance for some, it can also cause severe pain and can require medication.

Barb Elkin/iStock/Getty Images Plus

These newly identified genes will hopefully lead to new therapeutic options, said Maik Pietzner, PhD, chair in health data modeling at Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and group leader in the Computational Medicine Group at the Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Germany.

Berlin Institute of Health at Charité - Universitätsmedizin Berlin

Dr. Pietzner led the research along with Claudia Langenberg, MD, PhD, director of PHURI.

The study was published in Nature Communications.


 

Largest genomic study of Raynaud’s to date

The researchers looked through electronic medical records from the UK Biobank, a large-scale database that contains genetic and health information on half a million participants. They identified more than 5,100 individuals with Raynaud’s, of which 68% had primary Raynaud’s. These participants were compared with more than 439,000 controls who did not have Raynaud’s.

In a secondary analysis, the team also used health records from the Queen Mary University of London Genes & Health Study, which contains health information on individuals of South Asian ancestry.

The researchers identified two genes that are likely involved with Raynaud’s. The first, ADRA2A, encodes for the alpha-2A adrenergic receptor that can cause vasoconstriction of small blood vessels in response to stress hormones. Researchers have long suspected that this type of receptor could be involved with Raynaud’s, but there was debate over which receptor subtype was responsible.

“Our finding of alpha-2A receptors is quite interesting because the focus has always been on alpha-2C receptors,” said Dr. Pietzner. “It’s only a letter, but it’s a massive difference in terms of biology and physiology,” he said, and could be why therapies targeting 2C receptors have been ineffective.

The second strongest association was for the transcription factor IRX1. Less is known about this gene, but the data we do have suggest that it is involved with regulating the dilation of blood vessels, Dr. Pietzner noted.

“There might be balance between the ADRA2A finding being responsible for constriction and the IRX1 finding indirectly linked to the dilation of those vessels following constrictions. Having both may explain why these prolonged episodes of vasoconstriction lead to a loss of oxygen to the tissues,” so they turn white and then blue, he said.

Because the Biobank cohort was European-centric, Dr. Pietzner and colleagues also identified 400 cases of Raynaud’s in British individuals of Bangladeshi and Pakistani ancestry and were able to replicate the association between IRX1 and Raynaud’s. Data on ADRA2A were unavailable.

The genes identified are associated with primary Raynaud’s. Secondary Raynaud’s is a rarer type of the condition that occurs along with autoimmune disorders, such as scleroderma, and is generally more severe.

It’s long been suspected that Raynaud’s had some genetic component, because half of patients with Raynaud’s have another family member with the same condition, said Laura Hummers, MD, who codirects the John Hopkins Scleroderma Center in Baltimore. She was not involved with the study.

Johns Hopkins University

This is “the largest study of this kind that’s been done,” she said, and the first to show a potential mechanism behind this genetic association.

The main gene finding, ADRA2A, “points to a receptor on the cells that regulate the tone of these blood vessels,” she continued. “It suggests maybe there’s too many of these receptors or they’re overly sensitive; something about them is different that makes patients more susceptible to these cold triggers. Knowing that is potentially really important, because it could give you a direct way to intervene, if true.”
 

New therapeutic avenues

The first-line treatment for primary Raynaud’s is behavioral interventions, such as maintaining body and extremity warmth and avoiding certain vasoconstricting drugs, said Kimberly Lakin, MD, a rheumatologist at the Hospital for Special Surgery in New York, who not involved in the research. These drugs could include over-the-counter decongestants and certain medications for attention-deficit/hyperactivity disorder.

Hospital for Special Surgery

If these behavioral interventions are not enough, clinicians most commonly prescribe calcium channel blockers. These medications are vasodilators but can be a concern for people with normal or already low blood pressure, Dr. Lakin said. They can also cause symptoms such as headache, leg swelling, constipation, and other gastrointestinal symptoms.

Other medications, such as fluoxetine, may also be considered as a later-line therapy, “but the effectiveness is fairly limited in Raynaud’s,” she said. “Certainly, other medication options that would be helpful and driven by the mechanisms of Raynaud’s would add to our ability to help patients.”

As it turns out, one of the genes identified in the study, ADRA2A, “is actually one of the most commonly targeted genes by drugs,” said Dr. Pietzner. Because the findings suggest that ADRA2A is overexpressed in Raynaud, a selective inhibitor like the antidepressant mirtazapine could be a promising candidate to repurpose for treating Raynaud’s, he said.
 

Limitations to electronic medical record analyses

Both Dr. Hummers and Dr. Lakin noted that research using diagnostic codes from medical records to identify cases has some limitations. The study may have included patients misdiagnosed with Raynaud’s when perhaps they had another condition. Patients with milder Raynaud’s who have not sought medical attention for the condition would not be represented in the study, Dr. Lakin said.

The UK Biobank includes individuals of mostly European descent, so an analysis confirming these findings in a more diverse population would be helpful, she said.

However, both Dr. Lakin and Dr. Hummers agreed that the study contributes to the understanding of the mechanisms behind Raynaud’s. Although the two identified genes were tied to primary Raynaud’s, the study’s findings could potentially apply to secondary Raynaud’s as well, Dr. Hummers said.

“Anything we learn about primary Raynaud’s may have implication for Raynaud’s more broadly,” she noted.

Dr. Hummers and Dr. Lakin disclosed no relevant financial relationships. Dr. Pietzner has received partnership funding for the MRC Clinical Pharmacology Training Scheme (cofunded by MRC and Roche, UCB, Eli Lilly, and Novartis) and a PhD studentship jointly funded by the UK Engineering and Physical Sciences Research Council and AstraZeneca. Dr. Pietzner also has unrestricted educational grant support for the UK Pharmacogenetics and Stratified Medicine Network from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

Researchers have identified two genes that may contribute to Raynaud’s phenomenon, a condition where blood vessels in the extremities constrict and limit blood flow.

Raynaud’s is a relatively common condition, affecting 2%-5% of the general population. Though Raynaud’s can be an annoyance for some, it can also cause severe pain and can require medication.

Barb Elkin/iStock/Getty Images Plus

These newly identified genes will hopefully lead to new therapeutic options, said Maik Pietzner, PhD, chair in health data modeling at Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and group leader in the Computational Medicine Group at the Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Germany.

Berlin Institute of Health at Charité - Universitätsmedizin Berlin

Dr. Pietzner led the research along with Claudia Langenberg, MD, PhD, director of PHURI.

The study was published in Nature Communications.


 

Largest genomic study of Raynaud’s to date

The researchers looked through electronic medical records from the UK Biobank, a large-scale database that contains genetic and health information on half a million participants. They identified more than 5,100 individuals with Raynaud’s, of which 68% had primary Raynaud’s. These participants were compared with more than 439,000 controls who did not have Raynaud’s.

In a secondary analysis, the team also used health records from the Queen Mary University of London Genes & Health Study, which contains health information on individuals of South Asian ancestry.

The researchers identified two genes that are likely involved with Raynaud’s. The first, ADRA2A, encodes for the alpha-2A adrenergic receptor that can cause vasoconstriction of small blood vessels in response to stress hormones. Researchers have long suspected that this type of receptor could be involved with Raynaud’s, but there was debate over which receptor subtype was responsible.

“Our finding of alpha-2A receptors is quite interesting because the focus has always been on alpha-2C receptors,” said Dr. Pietzner. “It’s only a letter, but it’s a massive difference in terms of biology and physiology,” he said, and could be why therapies targeting 2C receptors have been ineffective.

The second strongest association was for the transcription factor IRX1. Less is known about this gene, but the data we do have suggest that it is involved with regulating the dilation of blood vessels, Dr. Pietzner noted.

“There might be balance between the ADRA2A finding being responsible for constriction and the IRX1 finding indirectly linked to the dilation of those vessels following constrictions. Having both may explain why these prolonged episodes of vasoconstriction lead to a loss of oxygen to the tissues,” so they turn white and then blue, he said.

Because the Biobank cohort was European-centric, Dr. Pietzner and colleagues also identified 400 cases of Raynaud’s in British individuals of Bangladeshi and Pakistani ancestry and were able to replicate the association between IRX1 and Raynaud’s. Data on ADRA2A were unavailable.

The genes identified are associated with primary Raynaud’s. Secondary Raynaud’s is a rarer type of the condition that occurs along with autoimmune disorders, such as scleroderma, and is generally more severe.

It’s long been suspected that Raynaud’s had some genetic component, because half of patients with Raynaud’s have another family member with the same condition, said Laura Hummers, MD, who codirects the John Hopkins Scleroderma Center in Baltimore. She was not involved with the study.

Johns Hopkins University

This is “the largest study of this kind that’s been done,” she said, and the first to show a potential mechanism behind this genetic association.

The main gene finding, ADRA2A, “points to a receptor on the cells that regulate the tone of these blood vessels,” she continued. “It suggests maybe there’s too many of these receptors or they’re overly sensitive; something about them is different that makes patients more susceptible to these cold triggers. Knowing that is potentially really important, because it could give you a direct way to intervene, if true.”
 

New therapeutic avenues

The first-line treatment for primary Raynaud’s is behavioral interventions, such as maintaining body and extremity warmth and avoiding certain vasoconstricting drugs, said Kimberly Lakin, MD, a rheumatologist at the Hospital for Special Surgery in New York, who not involved in the research. These drugs could include over-the-counter decongestants and certain medications for attention-deficit/hyperactivity disorder.

Hospital for Special Surgery

If these behavioral interventions are not enough, clinicians most commonly prescribe calcium channel blockers. These medications are vasodilators but can be a concern for people with normal or already low blood pressure, Dr. Lakin said. They can also cause symptoms such as headache, leg swelling, constipation, and other gastrointestinal symptoms.

Other medications, such as fluoxetine, may also be considered as a later-line therapy, “but the effectiveness is fairly limited in Raynaud’s,” she said. “Certainly, other medication options that would be helpful and driven by the mechanisms of Raynaud’s would add to our ability to help patients.”

As it turns out, one of the genes identified in the study, ADRA2A, “is actually one of the most commonly targeted genes by drugs,” said Dr. Pietzner. Because the findings suggest that ADRA2A is overexpressed in Raynaud, a selective inhibitor like the antidepressant mirtazapine could be a promising candidate to repurpose for treating Raynaud’s, he said.
 

Limitations to electronic medical record analyses

Both Dr. Hummers and Dr. Lakin noted that research using diagnostic codes from medical records to identify cases has some limitations. The study may have included patients misdiagnosed with Raynaud’s when perhaps they had another condition. Patients with milder Raynaud’s who have not sought medical attention for the condition would not be represented in the study, Dr. Lakin said.

The UK Biobank includes individuals of mostly European descent, so an analysis confirming these findings in a more diverse population would be helpful, she said.

However, both Dr. Lakin and Dr. Hummers agreed that the study contributes to the understanding of the mechanisms behind Raynaud’s. Although the two identified genes were tied to primary Raynaud’s, the study’s findings could potentially apply to secondary Raynaud’s as well, Dr. Hummers said.

“Anything we learn about primary Raynaud’s may have implication for Raynaud’s more broadly,” she noted.

Dr. Hummers and Dr. Lakin disclosed no relevant financial relationships. Dr. Pietzner has received partnership funding for the MRC Clinical Pharmacology Training Scheme (cofunded by MRC and Roche, UCB, Eli Lilly, and Novartis) and a PhD studentship jointly funded by the UK Engineering and Physical Sciences Research Council and AstraZeneca. Dr. Pietzner also has unrestricted educational grant support for the UK Pharmacogenetics and Stratified Medicine Network from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

Researchers have identified two genes that may contribute to Raynaud’s phenomenon, a condition where blood vessels in the extremities constrict and limit blood flow.

Raynaud’s is a relatively common condition, affecting 2%-5% of the general population. Though Raynaud’s can be an annoyance for some, it can also cause severe pain and can require medication.

Barb Elkin/iStock/Getty Images Plus

These newly identified genes will hopefully lead to new therapeutic options, said Maik Pietzner, PhD, chair in health data modeling at Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and group leader in the Computational Medicine Group at the Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Germany.

Berlin Institute of Health at Charité - Universitätsmedizin Berlin

Dr. Pietzner led the research along with Claudia Langenberg, MD, PhD, director of PHURI.

The study was published in Nature Communications.


 

Largest genomic study of Raynaud’s to date

The researchers looked through electronic medical records from the UK Biobank, a large-scale database that contains genetic and health information on half a million participants. They identified more than 5,100 individuals with Raynaud’s, of which 68% had primary Raynaud’s. These participants were compared with more than 439,000 controls who did not have Raynaud’s.

In a secondary analysis, the team also used health records from the Queen Mary University of London Genes & Health Study, which contains health information on individuals of South Asian ancestry.

The researchers identified two genes that are likely involved with Raynaud’s. The first, ADRA2A, encodes for the alpha-2A adrenergic receptor that can cause vasoconstriction of small blood vessels in response to stress hormones. Researchers have long suspected that this type of receptor could be involved with Raynaud’s, but there was debate over which receptor subtype was responsible.

“Our finding of alpha-2A receptors is quite interesting because the focus has always been on alpha-2C receptors,” said Dr. Pietzner. “It’s only a letter, but it’s a massive difference in terms of biology and physiology,” he said, and could be why therapies targeting 2C receptors have been ineffective.

The second strongest association was for the transcription factor IRX1. Less is known about this gene, but the data we do have suggest that it is involved with regulating the dilation of blood vessels, Dr. Pietzner noted.

“There might be balance between the ADRA2A finding being responsible for constriction and the IRX1 finding indirectly linked to the dilation of those vessels following constrictions. Having both may explain why these prolonged episodes of vasoconstriction lead to a loss of oxygen to the tissues,” so they turn white and then blue, he said.

Because the Biobank cohort was European-centric, Dr. Pietzner and colleagues also identified 400 cases of Raynaud’s in British individuals of Bangladeshi and Pakistani ancestry and were able to replicate the association between IRX1 and Raynaud’s. Data on ADRA2A were unavailable.

The genes identified are associated with primary Raynaud’s. Secondary Raynaud’s is a rarer type of the condition that occurs along with autoimmune disorders, such as scleroderma, and is generally more severe.

It’s long been suspected that Raynaud’s had some genetic component, because half of patients with Raynaud’s have another family member with the same condition, said Laura Hummers, MD, who codirects the John Hopkins Scleroderma Center in Baltimore. She was not involved with the study.

Johns Hopkins University

This is “the largest study of this kind that’s been done,” she said, and the first to show a potential mechanism behind this genetic association.

The main gene finding, ADRA2A, “points to a receptor on the cells that regulate the tone of these blood vessels,” she continued. “It suggests maybe there’s too many of these receptors or they’re overly sensitive; something about them is different that makes patients more susceptible to these cold triggers. Knowing that is potentially really important, because it could give you a direct way to intervene, if true.”
 

New therapeutic avenues

The first-line treatment for primary Raynaud’s is behavioral interventions, such as maintaining body and extremity warmth and avoiding certain vasoconstricting drugs, said Kimberly Lakin, MD, a rheumatologist at the Hospital for Special Surgery in New York, who not involved in the research. These drugs could include over-the-counter decongestants and certain medications for attention-deficit/hyperactivity disorder.

Hospital for Special Surgery

If these behavioral interventions are not enough, clinicians most commonly prescribe calcium channel blockers. These medications are vasodilators but can be a concern for people with normal or already low blood pressure, Dr. Lakin said. They can also cause symptoms such as headache, leg swelling, constipation, and other gastrointestinal symptoms.

Other medications, such as fluoxetine, may also be considered as a later-line therapy, “but the effectiveness is fairly limited in Raynaud’s,” she said. “Certainly, other medication options that would be helpful and driven by the mechanisms of Raynaud’s would add to our ability to help patients.”

As it turns out, one of the genes identified in the study, ADRA2A, “is actually one of the most commonly targeted genes by drugs,” said Dr. Pietzner. Because the findings suggest that ADRA2A is overexpressed in Raynaud, a selective inhibitor like the antidepressant mirtazapine could be a promising candidate to repurpose for treating Raynaud’s, he said.
 

Limitations to electronic medical record analyses

Both Dr. Hummers and Dr. Lakin noted that research using diagnostic codes from medical records to identify cases has some limitations. The study may have included patients misdiagnosed with Raynaud’s when perhaps they had another condition. Patients with milder Raynaud’s who have not sought medical attention for the condition would not be represented in the study, Dr. Lakin said.

The UK Biobank includes individuals of mostly European descent, so an analysis confirming these findings in a more diverse population would be helpful, she said.

However, both Dr. Lakin and Dr. Hummers agreed that the study contributes to the understanding of the mechanisms behind Raynaud’s. Although the two identified genes were tied to primary Raynaud’s, the study’s findings could potentially apply to secondary Raynaud’s as well, Dr. Hummers said.

“Anything we learn about primary Raynaud’s may have implication for Raynaud’s more broadly,” she noted.

Dr. Hummers and Dr. Lakin disclosed no relevant financial relationships. Dr. Pietzner has received partnership funding for the MRC Clinical Pharmacology Training Scheme (cofunded by MRC and Roche, UCB, Eli Lilly, and Novartis) and a PhD studentship jointly funded by the UK Engineering and Physical Sciences Research Council and AstraZeneca. Dr. Pietzner also has unrestricted educational grant support for the UK Pharmacogenetics and Stratified Medicine Network from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

VANCOUVER – In patients with type 2 diabetes, sodium-glucose cotransporter 2 (SGLT2) inhibitors as an adjunct to metformin were not associated with an increase in fracture risk, according to a new real-world study.

There have been some reports of an increase in fracture risk associated with SGLT2 inhibitors, and it was observed in the phase 3 CANVAS trial of canagliflozin (Invokana), which led to a Food and Drug Administration warning of fracture risks associated with canagliflozin use. Some ensuing studies did not show an increased risk, but these studies were generally less than a year in duration and may have missed longer-term risk, according to Veerle van Hulten, MSc.

“Fracture risk is something that takes a long time to develop, so we wanted to have a longer follow-up. We looked into the CPRD [Clinical Practice Research Datalink], which is a beautiful database containing real-world data from primary care practices,” said Ms. van Hulten, a PhD student at Maastricht (the Netherlands) University, who presented the study at the annual meeting of the American Society for Bone and Mineral Research.

Ms. van Hulten and colleagues compared SGLT2 inhibitors with dipeptidyl peptidase–4 (DPP-4) inhibitors because the latter are used in similar populations and have been shown to have no effect on fracture risk.

“What we found is that SGLT2 inhibitors are not associated with an increased fracture risk. Even with a duration of use of over 811 days, we did not observe an increased hazard ratio for fractures when compared DPP-4 inhibitor users,” Ms. van Hulten said.

SGLT2 inhibitors reduce blood sugar by increasing elimination of sugar in the urine. They also increase phosphate, reduce calcium, and increase parathyroid hormone, which could in turn negatively affect bone turnover, according to Ms. van Hulten.

In the new study, conducted between January 2013 and June 2020, the researchers used propensity score matching to compare adult patients, including 13,807 who were prescribed SGLT2 inhibitors and 28,524 who were prescribed DPP-4 inhibitors for the first time. They matched patients based on demographics, comorbidities, comedication, and lifestyle factors.

There was no association between SGLT2 inhibitor use and overall fracture risk or major osteoporotic, hip, vertebral, humerus, radius, or ulna fractures. There was no difference in risk for any duration of use, even with the longest duration of use of 811 days (adjusted hazard ratio, 1.0). There were no differences among specific SGLT2 inhibitors, including canagliflozin (aHR, 1.12; 95% confidence interval, 0.73-1.72). Analyses by sex and age also revealed no statistically significant differences between the two drug classes.

During the Q&A session after the presentation, Sarah Berry, MD, MPH, an associate professor of medicine at Harvard Medical School and a clinical researcher at the Marcus Institute for Aging Research, both in Boston, noted the trend toward an increase in fracture risk in the first 90 days. “It looked like there was something going on in the first 90 days, and then after that the results were much closer to the null. I would put out maybe another potential mechanism whereby the SGLT2 inhibitors might cause fracture, and that’s falls. They cause polyuria, and any drug you give that causes women to rush to the bathroom may well cause fractures, particularly in the short term,” Dr. Berry said.

Ms. van Hulten agreed, and also brought up that the drugs can cause osmotic diuresis. That can lead to hypovolemia, the symptoms of which include weakness, fatigue, and dizziness. “And increased falls, of course, increases fracture risk. We do not expect anything to happen to bone metabolism in the first 90 days. I think we can agree that there would be more time needed to alter the bone enough to increase fracture risk, so we expect that this trend toward an increased risk might be attributable to that increased fall risk that might occur with SGLT2 inhibitor use,” she said.

It’s possible that such a mechanism explains increased fracture risk seen in some earlier short-term studies, she added.

Overall, Ms. van Hulten said that the results should provide some confidence in SGLT2 inhibitors, though more work needs to be done. “I think we provide reassurance that SGLT2 inhibitors are safe to use. However, we still only have a median follow-up of 1.6 years. It’s not as long as we maybe would like, but it’s the best we can do with the data available, since the SGLT2 inhibitors have only been used since 2013. So maybe it’s best to prescribe it and keep [fall risk] in mind and look into the effects later on again, but it seems to be safe to use.”

The study received funding from the Novo Nordisk Foundation. Ms. van Hulten and Dr. Berry reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER – In patients with type 2 diabetes, sodium-glucose cotransporter 2 (SGLT2) inhibitors as an adjunct to metformin were not associated with an increase in fracture risk, according to a new real-world study.

There have been some reports of an increase in fracture risk associated with SGLT2 inhibitors, and it was observed in the phase 3 CANVAS trial of canagliflozin (Invokana), which led to a Food and Drug Administration warning of fracture risks associated with canagliflozin use. Some ensuing studies did not show an increased risk, but these studies were generally less than a year in duration and may have missed longer-term risk, according to Veerle van Hulten, MSc.

“Fracture risk is something that takes a long time to develop, so we wanted to have a longer follow-up. We looked into the CPRD [Clinical Practice Research Datalink], which is a beautiful database containing real-world data from primary care practices,” said Ms. van Hulten, a PhD student at Maastricht (the Netherlands) University, who presented the study at the annual meeting of the American Society for Bone and Mineral Research.

Ms. van Hulten and colleagues compared SGLT2 inhibitors with dipeptidyl peptidase–4 (DPP-4) inhibitors because the latter are used in similar populations and have been shown to have no effect on fracture risk.

“What we found is that SGLT2 inhibitors are not associated with an increased fracture risk. Even with a duration of use of over 811 days, we did not observe an increased hazard ratio for fractures when compared DPP-4 inhibitor users,” Ms. van Hulten said.

SGLT2 inhibitors reduce blood sugar by increasing elimination of sugar in the urine. They also increase phosphate, reduce calcium, and increase parathyroid hormone, which could in turn negatively affect bone turnover, according to Ms. van Hulten.

In the new study, conducted between January 2013 and June 2020, the researchers used propensity score matching to compare adult patients, including 13,807 who were prescribed SGLT2 inhibitors and 28,524 who were prescribed DPP-4 inhibitors for the first time. They matched patients based on demographics, comorbidities, comedication, and lifestyle factors.

There was no association between SGLT2 inhibitor use and overall fracture risk or major osteoporotic, hip, vertebral, humerus, radius, or ulna fractures. There was no difference in risk for any duration of use, even with the longest duration of use of 811 days (adjusted hazard ratio, 1.0). There were no differences among specific SGLT2 inhibitors, including canagliflozin (aHR, 1.12; 95% confidence interval, 0.73-1.72). Analyses by sex and age also revealed no statistically significant differences between the two drug classes.

During the Q&A session after the presentation, Sarah Berry, MD, MPH, an associate professor of medicine at Harvard Medical School and a clinical researcher at the Marcus Institute for Aging Research, both in Boston, noted the trend toward an increase in fracture risk in the first 90 days. “It looked like there was something going on in the first 90 days, and then after that the results were much closer to the null. I would put out maybe another potential mechanism whereby the SGLT2 inhibitors might cause fracture, and that’s falls. They cause polyuria, and any drug you give that causes women to rush to the bathroom may well cause fractures, particularly in the short term,” Dr. Berry said.

Ms. van Hulten agreed, and also brought up that the drugs can cause osmotic diuresis. That can lead to hypovolemia, the symptoms of which include weakness, fatigue, and dizziness. “And increased falls, of course, increases fracture risk. We do not expect anything to happen to bone metabolism in the first 90 days. I think we can agree that there would be more time needed to alter the bone enough to increase fracture risk, so we expect that this trend toward an increased risk might be attributable to that increased fall risk that might occur with SGLT2 inhibitor use,” she said.

It’s possible that such a mechanism explains increased fracture risk seen in some earlier short-term studies, she added.

Overall, Ms. van Hulten said that the results should provide some confidence in SGLT2 inhibitors, though more work needs to be done. “I think we provide reassurance that SGLT2 inhibitors are safe to use. However, we still only have a median follow-up of 1.6 years. It’s not as long as we maybe would like, but it’s the best we can do with the data available, since the SGLT2 inhibitors have only been used since 2013. So maybe it’s best to prescribe it and keep [fall risk] in mind and look into the effects later on again, but it seems to be safe to use.”

The study received funding from the Novo Nordisk Foundation. Ms. van Hulten and Dr. Berry reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER – In patients with type 2 diabetes, sodium-glucose cotransporter 2 (SGLT2) inhibitors as an adjunct to metformin were not associated with an increase in fracture risk, according to a new real-world study.

There have been some reports of an increase in fracture risk associated with SGLT2 inhibitors, and it was observed in the phase 3 CANVAS trial of canagliflozin (Invokana), which led to a Food and Drug Administration warning of fracture risks associated with canagliflozin use. Some ensuing studies did not show an increased risk, but these studies were generally less than a year in duration and may have missed longer-term risk, according to Veerle van Hulten, MSc.

“Fracture risk is something that takes a long time to develop, so we wanted to have a longer follow-up. We looked into the CPRD [Clinical Practice Research Datalink], which is a beautiful database containing real-world data from primary care practices,” said Ms. van Hulten, a PhD student at Maastricht (the Netherlands) University, who presented the study at the annual meeting of the American Society for Bone and Mineral Research.

Ms. van Hulten and colleagues compared SGLT2 inhibitors with dipeptidyl peptidase–4 (DPP-4) inhibitors because the latter are used in similar populations and have been shown to have no effect on fracture risk.

“What we found is that SGLT2 inhibitors are not associated with an increased fracture risk. Even with a duration of use of over 811 days, we did not observe an increased hazard ratio for fractures when compared DPP-4 inhibitor users,” Ms. van Hulten said.

SGLT2 inhibitors reduce blood sugar by increasing elimination of sugar in the urine. They also increase phosphate, reduce calcium, and increase parathyroid hormone, which could in turn negatively affect bone turnover, according to Ms. van Hulten.

In the new study, conducted between January 2013 and June 2020, the researchers used propensity score matching to compare adult patients, including 13,807 who were prescribed SGLT2 inhibitors and 28,524 who were prescribed DPP-4 inhibitors for the first time. They matched patients based on demographics, comorbidities, comedication, and lifestyle factors.

There was no association between SGLT2 inhibitor use and overall fracture risk or major osteoporotic, hip, vertebral, humerus, radius, or ulna fractures. There was no difference in risk for any duration of use, even with the longest duration of use of 811 days (adjusted hazard ratio, 1.0). There were no differences among specific SGLT2 inhibitors, including canagliflozin (aHR, 1.12; 95% confidence interval, 0.73-1.72). Analyses by sex and age also revealed no statistically significant differences between the two drug classes.

During the Q&A session after the presentation, Sarah Berry, MD, MPH, an associate professor of medicine at Harvard Medical School and a clinical researcher at the Marcus Institute for Aging Research, both in Boston, noted the trend toward an increase in fracture risk in the first 90 days. “It looked like there was something going on in the first 90 days, and then after that the results were much closer to the null. I would put out maybe another potential mechanism whereby the SGLT2 inhibitors might cause fracture, and that’s falls. They cause polyuria, and any drug you give that causes women to rush to the bathroom may well cause fractures, particularly in the short term,” Dr. Berry said.

Ms. van Hulten agreed, and also brought up that the drugs can cause osmotic diuresis. That can lead to hypovolemia, the symptoms of which include weakness, fatigue, and dizziness. “And increased falls, of course, increases fracture risk. We do not expect anything to happen to bone metabolism in the first 90 days. I think we can agree that there would be more time needed to alter the bone enough to increase fracture risk, so we expect that this trend toward an increased risk might be attributable to that increased fall risk that might occur with SGLT2 inhibitor use,” she said.

It’s possible that such a mechanism explains increased fracture risk seen in some earlier short-term studies, she added.

Overall, Ms. van Hulten said that the results should provide some confidence in SGLT2 inhibitors, though more work needs to be done. “I think we provide reassurance that SGLT2 inhibitors are safe to use. However, we still only have a median follow-up of 1.6 years. It’s not as long as we maybe would like, but it’s the best we can do with the data available, since the SGLT2 inhibitors have only been used since 2013. So maybe it’s best to prescribe it and keep [fall risk] in mind and look into the effects later on again, but it seems to be safe to use.”

The study received funding from the Novo Nordisk Foundation. Ms. van Hulten and Dr. Berry reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

The strike by health care workers at Kaiser Permanente may not involve physicians (yet). But as more doctors in the United States are finding themselves working as salaried employees, physicians can – and probably will – become a powerful force for change in a health care system that has shown itself to be increasingly hostile to employee concerns over issues involving patient care, wages and benefits, safety, and well-being.

Salaried employment has its challenges. Physician-employees may have less autonomy and voice in decision-making that affects patients. They may splinter into fragmented work groups; feel isolated; and have different imperatives based on who they are, what they want, and where they work. They may feel more removed from their patients and struggle to build strong relationships, with their employers in the way.

Yet important opportunities exist for doctors when embracing their employee side. These opportunities can help them and other health care workers fight effectively for their interests and those of patients in a corporatized health care system. Examples of these interests include adequate compensation, wellness, job security, patient and worker safety, health care quality, reasonable workloads and schedules, and fair treatment by employers, including the need to exhibit a strong collective voice in organizational decision-making.

Some believe that physician-employees must be unionized to maximize their rights and power as employees. Many expect physician unionization to take hold more fully over time. Medical residents, the doctors of tomorrow, are already considering unionization in greater numbers. Some are also doing it in the same employment setting alongside other health professionals, such as nurses.

Having studied doctors and their employment situations for years, I am convinced that whether through unionization or another approach, physicians must also change how they think about control; train and learn alongside other health care workers who share similar interests; and elevate at an early career stage their knowledge of the business side of health care.
 

Adopt a more pragmatic definition of autonomy

Doctors must embrace an updated definition of autonomy – one that matches their status as highly paid labor.

When I have spoken to physicians in my research about what autonomy means to them, many seem unable to reconceptualize it from a vague and absolute form of their profession’s strategic control over their economic fates and technical skills toward an individualized control that is situation-specific, one centered on winning the daily fights about workplace bread-and-butter issues such as those mentioned above.

But a more pragmatic definition of autonomy could get doctors focused on influencing important issues of the patient-care day and enhance their negotiating power with employers. It would allow physicians to break out of what often seems a paralysis of inaction – waiting for employers, insurers, or the government to reinstate the profession’s idealized version of control by handing it back the keys to the health care system through major regulatory, structural, and reimbursement-related changes. This fantasy is unlikely to become reality.

Physician-employees I’ve talked to over the years understand their everyday challenges. But when it comes to engaging in localized and sustained action to overcome them, they often perform less well, leading to feelings of helplessness and burnout. Valuing tactical control over their jobs and work setting will yield smaller but more impactful wins as employees intent on making their everyday work lives better.
 

Train alongside other health care professionals

Physicians must accept that how they are trained no longer prepares them for the employee world into which most are dropped. For instance, unless doctors are trained collaboratively alongside other health care professionals – such as nurses – they are less likely to identify closely with these colleagues once in practice. There is strength in numbers, so this mutual identification empowers both groups of employees. Yet, medical education remains largely the same: training young medical students in isolation for the first couple of years, then placing them into clerkships and residencies where true interprofessional care opportunities remain stunted and secondary to the “physician as captain of the team” mantra.

Unfortunately, the “hidden curriculum” of medicine helps convince medical students and residents early in their careers that they are the unquestioned leaders in patient care settings. This hierarchy encourages some doctors to keep their psychological distance from other members of the health care team and to resist sharing power, concerns, or insights with less skilled health care workers. This socialization harms the ability of physicians to act in a unified fashion alongside these other workers. Having physicians learn and train alongside other health professionals yields positive benefits for collective advocacy, including a shared sense of purpose, positive views on collaboration with others in the health setting, and greater development of bonds with nonphysician coworkers.
 

Integrate business with medical training in real time

Medical students and residents generally lack exposure to the everyday business realities of the U.S. health care system. This gap hinders their ability to understand the employee world and push for the types of changes and work conditions that benefit all health care workers. Formal business and management training should be a required part of every U.S. medical school and residency curriculum from day one. If you see it at all in medical schools now, it is mostly by accident, or given separate treatment in the form of standalone MBA or MPH degrees that rarely integrate organically and in real time with actual medical training. Not every doctor needs an MBA or MPH degree. However, all of them require a stronger contextual understanding of how the medicine they wish to practice is shaped by the economic and fiscal circumstances surrounding it – circumstances they do not control.

This is another reason why young doctors are unhappy and burned out. They cannot push for specific changes or properly critique the pros and cons of how their work is structured because they have not been made aware, in real time as they learn clinical practice, how their jobs are shaped by realities such as insurance coverage and reimbursement, the fragmentation of the care delivery system, their employer’s financial health , and the socioeconomic circumstances of their patients. They aren’t given the methods and tools related to process and quality improvement, budgeting, negotiation, risk management, leadership, and talent management that might help them navigate these undermining forces. They also get little advance exposure in their training to important workplace “soft” skills in such areas as how to work in teams, networking, communication and listening, empathy, and problem-solving – all necessary foci for bringing them closer to other health care workers and advocating alongside them effectively with health care employers.

Now is the time for physicians to embrace their identity as employees. Doing so is in their own best interest as professionals. It will help others in the health care workforce as well as patients. Moreover, it provides a needed counterbalance to the powerful corporate ethos now ascendant in U.S. health care.

Timothy Hoff, PhD, is a professor of management and healthcare systems at Northeastern University, Boston, and an associate fellow at the University of Oxford, England. He disclosed no relevant conflicts of interest.

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

The strike by health care workers at Kaiser Permanente may not involve physicians (yet). But as more doctors in the United States are finding themselves working as salaried employees, physicians can – and probably will – become a powerful force for change in a health care system that has shown itself to be increasingly hostile to employee concerns over issues involving patient care, wages and benefits, safety, and well-being.

Salaried employment has its challenges. Physician-employees may have less autonomy and voice in decision-making that affects patients. They may splinter into fragmented work groups; feel isolated; and have different imperatives based on who they are, what they want, and where they work. They may feel more removed from their patients and struggle to build strong relationships, with their employers in the way.

Yet important opportunities exist for doctors when embracing their employee side. These opportunities can help them and other health care workers fight effectively for their interests and those of patients in a corporatized health care system. Examples of these interests include adequate compensation, wellness, job security, patient and worker safety, health care quality, reasonable workloads and schedules, and fair treatment by employers, including the need to exhibit a strong collective voice in organizational decision-making.

Some believe that physician-employees must be unionized to maximize their rights and power as employees. Many expect physician unionization to take hold more fully over time. Medical residents, the doctors of tomorrow, are already considering unionization in greater numbers. Some are also doing it in the same employment setting alongside other health professionals, such as nurses.

Having studied doctors and their employment situations for years, I am convinced that whether through unionization or another approach, physicians must also change how they think about control; train and learn alongside other health care workers who share similar interests; and elevate at an early career stage their knowledge of the business side of health care.
 

Adopt a more pragmatic definition of autonomy

Doctors must embrace an updated definition of autonomy – one that matches their status as highly paid labor.

When I have spoken to physicians in my research about what autonomy means to them, many seem unable to reconceptualize it from a vague and absolute form of their profession’s strategic control over their economic fates and technical skills toward an individualized control that is situation-specific, one centered on winning the daily fights about workplace bread-and-butter issues such as those mentioned above.

But a more pragmatic definition of autonomy could get doctors focused on influencing important issues of the patient-care day and enhance their negotiating power with employers. It would allow physicians to break out of what often seems a paralysis of inaction – waiting for employers, insurers, or the government to reinstate the profession’s idealized version of control by handing it back the keys to the health care system through major regulatory, structural, and reimbursement-related changes. This fantasy is unlikely to become reality.

Physician-employees I’ve talked to over the years understand their everyday challenges. But when it comes to engaging in localized and sustained action to overcome them, they often perform less well, leading to feelings of helplessness and burnout. Valuing tactical control over their jobs and work setting will yield smaller but more impactful wins as employees intent on making their everyday work lives better.
 

Train alongside other health care professionals

Physicians must accept that how they are trained no longer prepares them for the employee world into which most are dropped. For instance, unless doctors are trained collaboratively alongside other health care professionals – such as nurses – they are less likely to identify closely with these colleagues once in practice. There is strength in numbers, so this mutual identification empowers both groups of employees. Yet, medical education remains largely the same: training young medical students in isolation for the first couple of years, then placing them into clerkships and residencies where true interprofessional care opportunities remain stunted and secondary to the “physician as captain of the team” mantra.

Unfortunately, the “hidden curriculum” of medicine helps convince medical students and residents early in their careers that they are the unquestioned leaders in patient care settings. This hierarchy encourages some doctors to keep their psychological distance from other members of the health care team and to resist sharing power, concerns, or insights with less skilled health care workers. This socialization harms the ability of physicians to act in a unified fashion alongside these other workers. Having physicians learn and train alongside other health professionals yields positive benefits for collective advocacy, including a shared sense of purpose, positive views on collaboration with others in the health setting, and greater development of bonds with nonphysician coworkers.
 

Integrate business with medical training in real time

Medical students and residents generally lack exposure to the everyday business realities of the U.S. health care system. This gap hinders their ability to understand the employee world and push for the types of changes and work conditions that benefit all health care workers. Formal business and management training should be a required part of every U.S. medical school and residency curriculum from day one. If you see it at all in medical schools now, it is mostly by accident, or given separate treatment in the form of standalone MBA or MPH degrees that rarely integrate organically and in real time with actual medical training. Not every doctor needs an MBA or MPH degree. However, all of them require a stronger contextual understanding of how the medicine they wish to practice is shaped by the economic and fiscal circumstances surrounding it – circumstances they do not control.

This is another reason why young doctors are unhappy and burned out. They cannot push for specific changes or properly critique the pros and cons of how their work is structured because they have not been made aware, in real time as they learn clinical practice, how their jobs are shaped by realities such as insurance coverage and reimbursement, the fragmentation of the care delivery system, their employer’s financial health , and the socioeconomic circumstances of their patients. They aren’t given the methods and tools related to process and quality improvement, budgeting, negotiation, risk management, leadership, and talent management that might help them navigate these undermining forces. They also get little advance exposure in their training to important workplace “soft” skills in such areas as how to work in teams, networking, communication and listening, empathy, and problem-solving – all necessary foci for bringing them closer to other health care workers and advocating alongside them effectively with health care employers.

Now is the time for physicians to embrace their identity as employees. Doing so is in their own best interest as professionals. It will help others in the health care workforce as well as patients. Moreover, it provides a needed counterbalance to the powerful corporate ethos now ascendant in U.S. health care.

Timothy Hoff, PhD, is a professor of management and healthcare systems at Northeastern University, Boston, and an associate fellow at the University of Oxford, England. He disclosed no relevant conflicts of interest.

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

The strike by health care workers at Kaiser Permanente may not involve physicians (yet). But as more doctors in the United States are finding themselves working as salaried employees, physicians can – and probably will – become a powerful force for change in a health care system that has shown itself to be increasingly hostile to employee concerns over issues involving patient care, wages and benefits, safety, and well-being.

Salaried employment has its challenges. Physician-employees may have less autonomy and voice in decision-making that affects patients. They may splinter into fragmented work groups; feel isolated; and have different imperatives based on who they are, what they want, and where they work. They may feel more removed from their patients and struggle to build strong relationships, with their employers in the way.

Yet important opportunities exist for doctors when embracing their employee side. These opportunities can help them and other health care workers fight effectively for their interests and those of patients in a corporatized health care system. Examples of these interests include adequate compensation, wellness, job security, patient and worker safety, health care quality, reasonable workloads and schedules, and fair treatment by employers, including the need to exhibit a strong collective voice in organizational decision-making.

Some believe that physician-employees must be unionized to maximize their rights and power as employees. Many expect physician unionization to take hold more fully over time. Medical residents, the doctors of tomorrow, are already considering unionization in greater numbers. Some are also doing it in the same employment setting alongside other health professionals, such as nurses.

Having studied doctors and their employment situations for years, I am convinced that whether through unionization or another approach, physicians must also change how they think about control; train and learn alongside other health care workers who share similar interests; and elevate at an early career stage their knowledge of the business side of health care.
 

Adopt a more pragmatic definition of autonomy

Doctors must embrace an updated definition of autonomy – one that matches their status as highly paid labor.

When I have spoken to physicians in my research about what autonomy means to them, many seem unable to reconceptualize it from a vague and absolute form of their profession’s strategic control over their economic fates and technical skills toward an individualized control that is situation-specific, one centered on winning the daily fights about workplace bread-and-butter issues such as those mentioned above.

But a more pragmatic definition of autonomy could get doctors focused on influencing important issues of the patient-care day and enhance their negotiating power with employers. It would allow physicians to break out of what often seems a paralysis of inaction – waiting for employers, insurers, or the government to reinstate the profession’s idealized version of control by handing it back the keys to the health care system through major regulatory, structural, and reimbursement-related changes. This fantasy is unlikely to become reality.

Physician-employees I’ve talked to over the years understand their everyday challenges. But when it comes to engaging in localized and sustained action to overcome them, they often perform less well, leading to feelings of helplessness and burnout. Valuing tactical control over their jobs and work setting will yield smaller but more impactful wins as employees intent on making their everyday work lives better.
 

Train alongside other health care professionals

Physicians must accept that how they are trained no longer prepares them for the employee world into which most are dropped. For instance, unless doctors are trained collaboratively alongside other health care professionals – such as nurses – they are less likely to identify closely with these colleagues once in practice. There is strength in numbers, so this mutual identification empowers both groups of employees. Yet, medical education remains largely the same: training young medical students in isolation for the first couple of years, then placing them into clerkships and residencies where true interprofessional care opportunities remain stunted and secondary to the “physician as captain of the team” mantra.

Unfortunately, the “hidden curriculum” of medicine helps convince medical students and residents early in their careers that they are the unquestioned leaders in patient care settings. This hierarchy encourages some doctors to keep their psychological distance from other members of the health care team and to resist sharing power, concerns, or insights with less skilled health care workers. This socialization harms the ability of physicians to act in a unified fashion alongside these other workers. Having physicians learn and train alongside other health professionals yields positive benefits for collective advocacy, including a shared sense of purpose, positive views on collaboration with others in the health setting, and greater development of bonds with nonphysician coworkers.
 

Integrate business with medical training in real time

Medical students and residents generally lack exposure to the everyday business realities of the U.S. health care system. This gap hinders their ability to understand the employee world and push for the types of changes and work conditions that benefit all health care workers. Formal business and management training should be a required part of every U.S. medical school and residency curriculum from day one. If you see it at all in medical schools now, it is mostly by accident, or given separate treatment in the form of standalone MBA or MPH degrees that rarely integrate organically and in real time with actual medical training. Not every doctor needs an MBA or MPH degree. However, all of them require a stronger contextual understanding of how the medicine they wish to practice is shaped by the economic and fiscal circumstances surrounding it – circumstances they do not control.

This is another reason why young doctors are unhappy and burned out. They cannot push for specific changes or properly critique the pros and cons of how their work is structured because they have not been made aware, in real time as they learn clinical practice, how their jobs are shaped by realities such as insurance coverage and reimbursement, the fragmentation of the care delivery system, their employer’s financial health , and the socioeconomic circumstances of their patients. They aren’t given the methods and tools related to process and quality improvement, budgeting, negotiation, risk management, leadership, and talent management that might help them navigate these undermining forces. They also get little advance exposure in their training to important workplace “soft” skills in such areas as how to work in teams, networking, communication and listening, empathy, and problem-solving – all necessary foci for bringing them closer to other health care workers and advocating alongside them effectively with health care employers.

Now is the time for physicians to embrace their identity as employees. Doing so is in their own best interest as professionals. It will help others in the health care workforce as well as patients. Moreover, it provides a needed counterbalance to the powerful corporate ethos now ascendant in U.S. health care.

Timothy Hoff, PhD, is a professor of management and healthcare systems at Northeastern University, Boston, and an associate fellow at the University of Oxford, England. He disclosed no relevant conflicts of interest.

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

The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx) for the treatment of moderate to severe plaque psoriasis in adults, the manufacturer announced in a press release.

The indication is for adults who are candidates for systemic therapy or phototherapy.

With this approval, bimekizumab becomes the only interleukin (IL)-17A and IL-17F inhibitor approved for the treatment of these patients. Psoriasis affects more than 7.5 million U.S. adults, according to the National Psoriasis Foundation.

“We have been eagerly awaiting bimekizumab,” Mark Lebwohl, MD, bimekizumab investigator and dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai, New York City, said in the press release.

Dr. Lebwohl states that bimekizumab “achieved superior levels of skin clearance at week 16 compared to placebo and three existing biologics for psoriasis, with responses being rapid and lasting up to a year. Long-term data have also shown that the majority of patients maintained high levels of clinical response through three years.”

The most common adverse reactions (occurring in at least 1% of patients) are upper respiratory infections, oral candidiasis, headache, tinea infections, gastroenteritis, herpes simplex infections, acne, folliculitis, other Candida infections, fatigue, and injection site reactions, according to the company, UCB.