Conference Coverage

WASHINGTON — After more than a decade, the American College of Rheumatology has developed new draft guidance for the use of musculoskeletal ultrasound (MSUS) to help with diagnosis, monitoring, and prognosis of rheumatoid arthritis (RA). Though not yet finalized, the statements that came out of a first round of committee voting were unveiled at the annual meeting of the American College of Rheumatology (ACR).

The committee was charged with updating the 2012 recommendations on using MSUS in rheumatology clinical practice, explained Veena K. Ranganath, MD, professor of clinical medicine at the University of California, Los Angeles, and director of their Rheumatology Fellowship Musculoskeletal Ultrasound Training Program. 

More than 30,000 articles on MSUS and any arthritis have been published since 2012, and there have been significant advances and improvements in technology as well as more widespread education and use in rheumatologic clinical practice, Ranganath said. 

“There’s also been advancements in therapeutic agents and therapeutic strategies in use of these medications in rheumatoid arthritis,” Ranganath said. “We all know that the patient of today is very different than the patient of 10 years ago or 20 years ago, so this really impacts the clinical questions we ask of how we need to incorporate musculoskeletal ultrasound into our rheumatology clinical practice.” 

The process of developing the guidance involved determining key domains and then relevant clinical questions for ultrasonography using the PICO model (patient/population, intervention, comparison, and outcomes). Evidence came from a review of relevant literature published since 1993 in PubMed, Embase, and the Cochrane Database. A panel of 11 experts voted on the quality of the evidence as being moderate or strong for 33 statements, rejecting three that had no consensus. The committee will hold another round of voting before the guidance is published.

Erin Arnold, MD, a rheumatologist at Arnold Arthritis & Rheumatology in Skokie, Illinois, said in an interview she believes the new guidance will be “tremendously helpful,” particularly in getting “everybody on the same page” with similar practices and helping enhance diagnosis and response to therapy. 

Having used MSUS for over 20 years, Arnold said watching it evolve and seeing “this type of manuscript being put together as a resource for physicians who are taking care of inflammatory arthritis is exciting.”

“There’s not a single way we really can assess disease activity in our patients, and so having a composite of things that you’re looking at really enhances our ability to understand people’s pain,” Arnold said. 

“When you have a patient in front of you that is in so much pain but doesn’t have any active inflammation, it’s hard to want to further put them at risk with more medication,” she said. “It’s so meaningful to be able to have a conversation about ... what are other complementary interventions? How are they sleeping? How are they eating? What are they taking as far as supplements? What are they doing to decrease that kind of fear and fight-or-flight response that often can drive some of our pain?” 

 

Use of MSUS for Diagnosis Confirmation and Treatment Decisions

Gurjit S. Kaeley, MBBS, professor of medicine, division chief of rheumatology and clinical immunology, and medical director of the Musculoskeletal Ultrasound Program at the University of Florida College of Medicine, Jacksonville, reviewed the final statements for MSUS use with RA.

He said there was strong consensus that adding MSUS to clinical examination can aid diagnosis of early RA in patients with suspected RA, particularly with detection of synovitis, tenosynovitis, and erosions. There was moderate consensus that MSUS detection of tenosynovitis could predict later development of RA. 

“Furthermore, erosions do have a predictive prognostic value in telling us that these patients need more attention and more urgent attention to getting urgent care with disease-modifying medications,” Kaeley said. “Ultrasound scanning for bone erosions on a few target joints was found to be feasible in literature and provides information not available with clinical examination. Furthermore, ultrasound is more sensitive than plain radiography for the detection of erosions.” 

Moderate consensus supported a cutoff of at least 2 mm for erosions when using MSUS for diagnostic purposes. 

Strong consensus supported using MSUS of the wrist, second and third metacarpophalangeal (MCP) joints, and second and third interphalangeal (PIP) joints to aid early RA diagnosis, with moderate consensus that cutoffs of least 2 grayscale (GS) or at least 1 GS with at least 1 power Doppler (PD) at the joint level supports both an RA diagnosis and, in patients already diagnosed with RA, a positive joint.

“Grayscale-only definitions were included since equipment may not have sensitive Doppler,” Kaeley said.

Strong consensus supported scanning only a reduced set of representative or symptomatic joints to monitor disease activity with MSUS. 

 

Inflammatory Signs, Disease Progression, and Flares

There was also strong consensus for using MSUS in patients with established RA and comorbidities to help distinguish between RA-related inflammation versus inflammation from other conditions, such as gout or calcium pyrophosphate deposition disease, or versus non–RA-related pain, such as that from fibromyalgia. 

Patients with fibromyalgia, for example, “tend to have more steroid exposure and a high prevalence of biologic use because the composite disease scores tend to overestimate disease activity, especially when compared to ultrasound assessment,” Kaeley said.

Moderate consensus supported using MSUS in patients with established RA to objectively evaluate inflammation so as to eliminate age-related bias.

While MSUS signs of synovitis had only moderate consensus to be associated with radiographic progression and decline in patient-reported outcomes for patients with early RA, consensus was strong for this association in patients with established RA.

In terms of predicting disease progression with MSUS monitoring of RA disease activity, moderate consensus supported scanning the wrists and MCPs and PIPs of the hands and using the dorsal view. Kaeley emphasized that ultrasound is a clinical tool that should be used to answer a clinical question, so the sonographer or clinician needs to provide guidance on the areas to be scanned. 

Multiple standardized scoring systems exist for predicting RA disease progression, but there is no consensus on which is the most effective, and there is only moderate consensus about the validity of using dichotomous scoring with an established cutoff for a positive joint.

The combination of MSUS with clinical examination appears to be more effective at confirming RA flares than using only clinical examination, and in certain patients with established RA, MSUS may provide insights into subclinical disease activity to help maintain remission and/or potentially guide treatment decisions, “especially when coming across de-escalation therapy decisions,” Kaeley said.

Despite the negative results of treat-to-target trials that tested MSUS as a routine tool in all patients, the committee achieved strong consensus on the potential value of using MSUS in early RA to clarify clinical status and/or help achieve low disease activity or remission in certain patient populations, “such as those with patient/provider discordance or difficult physical examinations,” Kaeley said. 

 

Therapy Response, Remission, and Shared Decision-Making

Moderate consensus supported acknowledgment that using MSUS to assess response to therapy could be affected by obesity and that MSUS can distinguish active synovitis symptoms from other pain sources in difficult-to-treat RA.

In patients with established RA, the feasibility of scanning the wrists, MCPs, PIPs, and relevant symptomatic joints for remission evaluation received moderate consensus. Meanwhile, strong consensus supported the idea that increasing the number of joints scanned with MSUS could increase the certainty of the patient having achieved remission, though the guidance acknowledges that “this must be balanced against the feasibility within the context of clinical care.” 

For confirming RA remission via MSUS, strong consensus supported using GS and PD synovitis and tenosynovitis findings. But consensus was moderate for using the combination of no PD signal and minimal synovial hypertrophy to define ultrasonographic remission and for the use of MSUS detection of subclinical inflammation to predict higher flare rates for those in clinical remission.

The committee moderately agreed that MSUS can enhance patient engagement and understanding of their disease to support personalized treatment decisions, such as adjusting disease-modifying antirheumatic drug regimens.

Finally, the committee broadly agreed that “the integration of musculoskeletal ultrasound presents significant advantages in shared decision-making between healthcare providers and patients,” Kaeley said. “Ultrasound, especially with Doppler technique, provides critical insights into disease activity and structural changes not always apparent during standard examination.” 

Arnold said she particularly appreciated that the committee, rather than prescribing a specific exam, opted to be more generalizable so that people use the guidance in the context that makes the most sense for them clinically. She said it’s an incredible tool, without excluding the importance of a patient’s labs and physical examination. 

“It’s helped us make diagnoses in patients who were difficult to diagnose. It’s helped us to understand response to therapy or no response to therapy,” she said. “It makes me question all the studies that I see done on medications where they’re not looking at some type of advanced imaging.” 

No external funding was noted for the development of the guidance. Ranganath has reported receiving research support from Bristol-Myers Squibb and Mallinckrodt. Kaeley has reported receiving research funding from AbbVie, Bristol-Myers Squibb, Gilead/Galapagos, Janssen, and Novartis. Arnold had no disclosures.

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

WASHINGTON — After more than a decade, the American College of Rheumatology has developed new draft guidance for the use of musculoskeletal ultrasound (MSUS) to help with diagnosis, monitoring, and prognosis of rheumatoid arthritis (RA). Though not yet finalized, the statements that came out of a first round of committee voting were unveiled at the annual meeting of the American College of Rheumatology (ACR).

The committee was charged with updating the 2012 recommendations on using MSUS in rheumatology clinical practice, explained Veena K. Ranganath, MD, professor of clinical medicine at the University of California, Los Angeles, and director of their Rheumatology Fellowship Musculoskeletal Ultrasound Training Program. 

More than 30,000 articles on MSUS and any arthritis have been published since 2012, and there have been significant advances and improvements in technology as well as more widespread education and use in rheumatologic clinical practice, Ranganath said. 

“There’s also been advancements in therapeutic agents and therapeutic strategies in use of these medications in rheumatoid arthritis,” Ranganath said. “We all know that the patient of today is very different than the patient of 10 years ago or 20 years ago, so this really impacts the clinical questions we ask of how we need to incorporate musculoskeletal ultrasound into our rheumatology clinical practice.” 

The process of developing the guidance involved determining key domains and then relevant clinical questions for ultrasonography using the PICO model (patient/population, intervention, comparison, and outcomes). Evidence came from a review of relevant literature published since 1993 in PubMed, Embase, and the Cochrane Database. A panel of 11 experts voted on the quality of the evidence as being moderate or strong for 33 statements, rejecting three that had no consensus. The committee will hold another round of voting before the guidance is published.

Erin Arnold, MD, a rheumatologist at Arnold Arthritis & Rheumatology in Skokie, Illinois, said in an interview she believes the new guidance will be “tremendously helpful,” particularly in getting “everybody on the same page” with similar practices and helping enhance diagnosis and response to therapy. 

Having used MSUS for over 20 years, Arnold said watching it evolve and seeing “this type of manuscript being put together as a resource for physicians who are taking care of inflammatory arthritis is exciting.”

“There’s not a single way we really can assess disease activity in our patients, and so having a composite of things that you’re looking at really enhances our ability to understand people’s pain,” Arnold said. 

“When you have a patient in front of you that is in so much pain but doesn’t have any active inflammation, it’s hard to want to further put them at risk with more medication,” she said. “It’s so meaningful to be able to have a conversation about ... what are other complementary interventions? How are they sleeping? How are they eating? What are they taking as far as supplements? What are they doing to decrease that kind of fear and fight-or-flight response that often can drive some of our pain?” 

 

Use of MSUS for Diagnosis Confirmation and Treatment Decisions

Gurjit S. Kaeley, MBBS, professor of medicine, division chief of rheumatology and clinical immunology, and medical director of the Musculoskeletal Ultrasound Program at the University of Florida College of Medicine, Jacksonville, reviewed the final statements for MSUS use with RA.

He said there was strong consensus that adding MSUS to clinical examination can aid diagnosis of early RA in patients with suspected RA, particularly with detection of synovitis, tenosynovitis, and erosions. There was moderate consensus that MSUS detection of tenosynovitis could predict later development of RA. 

“Furthermore, erosions do have a predictive prognostic value in telling us that these patients need more attention and more urgent attention to getting urgent care with disease-modifying medications,” Kaeley said. “Ultrasound scanning for bone erosions on a few target joints was found to be feasible in literature and provides information not available with clinical examination. Furthermore, ultrasound is more sensitive than plain radiography for the detection of erosions.” 

Moderate consensus supported a cutoff of at least 2 mm for erosions when using MSUS for diagnostic purposes. 

Strong consensus supported using MSUS of the wrist, second and third metacarpophalangeal (MCP) joints, and second and third interphalangeal (PIP) joints to aid early RA diagnosis, with moderate consensus that cutoffs of least 2 grayscale (GS) or at least 1 GS with at least 1 power Doppler (PD) at the joint level supports both an RA diagnosis and, in patients already diagnosed with RA, a positive joint.

“Grayscale-only definitions were included since equipment may not have sensitive Doppler,” Kaeley said.

Strong consensus supported scanning only a reduced set of representative or symptomatic joints to monitor disease activity with MSUS. 

 

Inflammatory Signs, Disease Progression, and Flares

There was also strong consensus for using MSUS in patients with established RA and comorbidities to help distinguish between RA-related inflammation versus inflammation from other conditions, such as gout or calcium pyrophosphate deposition disease, or versus non–RA-related pain, such as that from fibromyalgia. 

Patients with fibromyalgia, for example, “tend to have more steroid exposure and a high prevalence of biologic use because the composite disease scores tend to overestimate disease activity, especially when compared to ultrasound assessment,” Kaeley said.

Moderate consensus supported using MSUS in patients with established RA to objectively evaluate inflammation so as to eliminate age-related bias.

While MSUS signs of synovitis had only moderate consensus to be associated with radiographic progression and decline in patient-reported outcomes for patients with early RA, consensus was strong for this association in patients with established RA.

In terms of predicting disease progression with MSUS monitoring of RA disease activity, moderate consensus supported scanning the wrists and MCPs and PIPs of the hands and using the dorsal view. Kaeley emphasized that ultrasound is a clinical tool that should be used to answer a clinical question, so the sonographer or clinician needs to provide guidance on the areas to be scanned. 

Multiple standardized scoring systems exist for predicting RA disease progression, but there is no consensus on which is the most effective, and there is only moderate consensus about the validity of using dichotomous scoring with an established cutoff for a positive joint.

The combination of MSUS with clinical examination appears to be more effective at confirming RA flares than using only clinical examination, and in certain patients with established RA, MSUS may provide insights into subclinical disease activity to help maintain remission and/or potentially guide treatment decisions, “especially when coming across de-escalation therapy decisions,” Kaeley said.

Despite the negative results of treat-to-target trials that tested MSUS as a routine tool in all patients, the committee achieved strong consensus on the potential value of using MSUS in early RA to clarify clinical status and/or help achieve low disease activity or remission in certain patient populations, “such as those with patient/provider discordance or difficult physical examinations,” Kaeley said. 

 

Therapy Response, Remission, and Shared Decision-Making

Moderate consensus supported acknowledgment that using MSUS to assess response to therapy could be affected by obesity and that MSUS can distinguish active synovitis symptoms from other pain sources in difficult-to-treat RA.

In patients with established RA, the feasibility of scanning the wrists, MCPs, PIPs, and relevant symptomatic joints for remission evaluation received moderate consensus. Meanwhile, strong consensus supported the idea that increasing the number of joints scanned with MSUS could increase the certainty of the patient having achieved remission, though the guidance acknowledges that “this must be balanced against the feasibility within the context of clinical care.” 

For confirming RA remission via MSUS, strong consensus supported using GS and PD synovitis and tenosynovitis findings. But consensus was moderate for using the combination of no PD signal and minimal synovial hypertrophy to define ultrasonographic remission and for the use of MSUS detection of subclinical inflammation to predict higher flare rates for those in clinical remission.

The committee moderately agreed that MSUS can enhance patient engagement and understanding of their disease to support personalized treatment decisions, such as adjusting disease-modifying antirheumatic drug regimens.

Finally, the committee broadly agreed that “the integration of musculoskeletal ultrasound presents significant advantages in shared decision-making between healthcare providers and patients,” Kaeley said. “Ultrasound, especially with Doppler technique, provides critical insights into disease activity and structural changes not always apparent during standard examination.” 

Arnold said she particularly appreciated that the committee, rather than prescribing a specific exam, opted to be more generalizable so that people use the guidance in the context that makes the most sense for them clinically. She said it’s an incredible tool, without excluding the importance of a patient’s labs and physical examination. 

“It’s helped us make diagnoses in patients who were difficult to diagnose. It’s helped us to understand response to therapy or no response to therapy,” she said. “It makes me question all the studies that I see done on medications where they’re not looking at some type of advanced imaging.” 

No external funding was noted for the development of the guidance. Ranganath has reported receiving research support from Bristol-Myers Squibb and Mallinckrodt. Kaeley has reported receiving research funding from AbbVie, Bristol-Myers Squibb, Gilead/Galapagos, Janssen, and Novartis. Arnold had no disclosures.

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

WASHINGTON — After more than a decade, the American College of Rheumatology has developed new draft guidance for the use of musculoskeletal ultrasound (MSUS) to help with diagnosis, monitoring, and prognosis of rheumatoid arthritis (RA). Though not yet finalized, the statements that came out of a first round of committee voting were unveiled at the annual meeting of the American College of Rheumatology (ACR).

The committee was charged with updating the 2012 recommendations on using MSUS in rheumatology clinical practice, explained Veena K. Ranganath, MD, professor of clinical medicine at the University of California, Los Angeles, and director of their Rheumatology Fellowship Musculoskeletal Ultrasound Training Program. 

More than 30,000 articles on MSUS and any arthritis have been published since 2012, and there have been significant advances and improvements in technology as well as more widespread education and use in rheumatologic clinical practice, Ranganath said. 

“There’s also been advancements in therapeutic agents and therapeutic strategies in use of these medications in rheumatoid arthritis,” Ranganath said. “We all know that the patient of today is very different than the patient of 10 years ago or 20 years ago, so this really impacts the clinical questions we ask of how we need to incorporate musculoskeletal ultrasound into our rheumatology clinical practice.” 

The process of developing the guidance involved determining key domains and then relevant clinical questions for ultrasonography using the PICO model (patient/population, intervention, comparison, and outcomes). Evidence came from a review of relevant literature published since 1993 in PubMed, Embase, and the Cochrane Database. A panel of 11 experts voted on the quality of the evidence as being moderate or strong for 33 statements, rejecting three that had no consensus. The committee will hold another round of voting before the guidance is published.

Erin Arnold, MD, a rheumatologist at Arnold Arthritis & Rheumatology in Skokie, Illinois, said in an interview she believes the new guidance will be “tremendously helpful,” particularly in getting “everybody on the same page” with similar practices and helping enhance diagnosis and response to therapy. 

Having used MSUS for over 20 years, Arnold said watching it evolve and seeing “this type of manuscript being put together as a resource for physicians who are taking care of inflammatory arthritis is exciting.”

“There’s not a single way we really can assess disease activity in our patients, and so having a composite of things that you’re looking at really enhances our ability to understand people’s pain,” Arnold said. 

“When you have a patient in front of you that is in so much pain but doesn’t have any active inflammation, it’s hard to want to further put them at risk with more medication,” she said. “It’s so meaningful to be able to have a conversation about ... what are other complementary interventions? How are they sleeping? How are they eating? What are they taking as far as supplements? What are they doing to decrease that kind of fear and fight-or-flight response that often can drive some of our pain?” 

 

Use of MSUS for Diagnosis Confirmation and Treatment Decisions

Gurjit S. Kaeley, MBBS, professor of medicine, division chief of rheumatology and clinical immunology, and medical director of the Musculoskeletal Ultrasound Program at the University of Florida College of Medicine, Jacksonville, reviewed the final statements for MSUS use with RA.

He said there was strong consensus that adding MSUS to clinical examination can aid diagnosis of early RA in patients with suspected RA, particularly with detection of synovitis, tenosynovitis, and erosions. There was moderate consensus that MSUS detection of tenosynovitis could predict later development of RA. 

“Furthermore, erosions do have a predictive prognostic value in telling us that these patients need more attention and more urgent attention to getting urgent care with disease-modifying medications,” Kaeley said. “Ultrasound scanning for bone erosions on a few target joints was found to be feasible in literature and provides information not available with clinical examination. Furthermore, ultrasound is more sensitive than plain radiography for the detection of erosions.” 

Moderate consensus supported a cutoff of at least 2 mm for erosions when using MSUS for diagnostic purposes. 

Strong consensus supported using MSUS of the wrist, second and third metacarpophalangeal (MCP) joints, and second and third interphalangeal (PIP) joints to aid early RA diagnosis, with moderate consensus that cutoffs of least 2 grayscale (GS) or at least 1 GS with at least 1 power Doppler (PD) at the joint level supports both an RA diagnosis and, in patients already diagnosed with RA, a positive joint.

“Grayscale-only definitions were included since equipment may not have sensitive Doppler,” Kaeley said.

Strong consensus supported scanning only a reduced set of representative or symptomatic joints to monitor disease activity with MSUS. 

 

Inflammatory Signs, Disease Progression, and Flares

There was also strong consensus for using MSUS in patients with established RA and comorbidities to help distinguish between RA-related inflammation versus inflammation from other conditions, such as gout or calcium pyrophosphate deposition disease, or versus non–RA-related pain, such as that from fibromyalgia. 

Patients with fibromyalgia, for example, “tend to have more steroid exposure and a high prevalence of biologic use because the composite disease scores tend to overestimate disease activity, especially when compared to ultrasound assessment,” Kaeley said.

Moderate consensus supported using MSUS in patients with established RA to objectively evaluate inflammation so as to eliminate age-related bias.

While MSUS signs of synovitis had only moderate consensus to be associated with radiographic progression and decline in patient-reported outcomes for patients with early RA, consensus was strong for this association in patients with established RA.

In terms of predicting disease progression with MSUS monitoring of RA disease activity, moderate consensus supported scanning the wrists and MCPs and PIPs of the hands and using the dorsal view. Kaeley emphasized that ultrasound is a clinical tool that should be used to answer a clinical question, so the sonographer or clinician needs to provide guidance on the areas to be scanned. 

Multiple standardized scoring systems exist for predicting RA disease progression, but there is no consensus on which is the most effective, and there is only moderate consensus about the validity of using dichotomous scoring with an established cutoff for a positive joint.

The combination of MSUS with clinical examination appears to be more effective at confirming RA flares than using only clinical examination, and in certain patients with established RA, MSUS may provide insights into subclinical disease activity to help maintain remission and/or potentially guide treatment decisions, “especially when coming across de-escalation therapy decisions,” Kaeley said.

Despite the negative results of treat-to-target trials that tested MSUS as a routine tool in all patients, the committee achieved strong consensus on the potential value of using MSUS in early RA to clarify clinical status and/or help achieve low disease activity or remission in certain patient populations, “such as those with patient/provider discordance or difficult physical examinations,” Kaeley said. 

 

Therapy Response, Remission, and Shared Decision-Making

Moderate consensus supported acknowledgment that using MSUS to assess response to therapy could be affected by obesity and that MSUS can distinguish active synovitis symptoms from other pain sources in difficult-to-treat RA.

In patients with established RA, the feasibility of scanning the wrists, MCPs, PIPs, and relevant symptomatic joints for remission evaluation received moderate consensus. Meanwhile, strong consensus supported the idea that increasing the number of joints scanned with MSUS could increase the certainty of the patient having achieved remission, though the guidance acknowledges that “this must be balanced against the feasibility within the context of clinical care.” 

For confirming RA remission via MSUS, strong consensus supported using GS and PD synovitis and tenosynovitis findings. But consensus was moderate for using the combination of no PD signal and minimal synovial hypertrophy to define ultrasonographic remission and for the use of MSUS detection of subclinical inflammation to predict higher flare rates for those in clinical remission.

The committee moderately agreed that MSUS can enhance patient engagement and understanding of their disease to support personalized treatment decisions, such as adjusting disease-modifying antirheumatic drug regimens.

Finally, the committee broadly agreed that “the integration of musculoskeletal ultrasound presents significant advantages in shared decision-making between healthcare providers and patients,” Kaeley said. “Ultrasound, especially with Doppler technique, provides critical insights into disease activity and structural changes not always apparent during standard examination.” 

Arnold said she particularly appreciated that the committee, rather than prescribing a specific exam, opted to be more generalizable so that people use the guidance in the context that makes the most sense for them clinically. She said it’s an incredible tool, without excluding the importance of a patient’s labs and physical examination. 

“It’s helped us make diagnoses in patients who were difficult to diagnose. It’s helped us to understand response to therapy or no response to therapy,” she said. “It makes me question all the studies that I see done on medications where they’re not looking at some type of advanced imaging.” 

No external funding was noted for the development of the guidance. Ranganath has reported receiving research support from Bristol-Myers Squibb and Mallinckrodt. Kaeley has reported receiving research funding from AbbVie, Bristol-Myers Squibb, Gilead/Galapagos, Janssen, and Novartis. Arnold had no disclosures.

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

WASHINGTON — Patients with granulomatosis with polyangiitis (GPA) completely tapered off prednisone have a more than fourfold risk of relapse by 6 months, compared with those tapered to 5 mg/day of prednisone; however, this benefit was only seen in patients not on rituximab, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“For patients treated with rituximab, fully tapering off glucocorticoids is reasonable to consider as the first approach,” said Peter Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, during his presentation of the findings.

Although a low dose of glucocorticoids can prevent some minor relapses in patients on other treatment regimens such as methotrexate or azathioprine, “fully tapering off prednisone presents relatively little risk of major relapse, and that major relapse can be treated rather quickly,” Merkel added.

The Assessment of Prednisone in Remission (TAPIR) trial enrolled 143 patients with GPA who were in remission (defined as a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis [BVAS/WG] of 0) within 1 year of treatment to induce remission for active disease and who were taking 5-10 mg of prednisone per day. After all patients tapered to 5 mg/day of prednisone, 71 patients completely tapered off prednisone over 4 weeks and remained off glucocorticoids until month 6. The remaining patients maintained a 5-mg/day dose over the study period. Placement in either treatment group was randomized, and patients continued other immunosuppressive therapy during the study.

Researchers evaluated the rate of relapse by 6 months, defined as a physician’s decision to increase the dose of glucocorticoids to treat GPA, in both groups.

Across all participants, the median age was 58 years, and 52% of patients were male. Most patients were White, and 47% of all patients were prescribed rituximab. 

At 6 months, 15.5% of participants who completely tapered off prednisone experienced a relapse of GPA, compared with 4.2% of those taking low-dose prednisone. Time to relapse was also shorter in the 0-mg prednisone group (P = .026), and relapses occurred continually over 6 months, Merkel said.

When stratified by rituximab use, relapse rates at 6 months between the 5-mg and 0-mg prednisone groups in patients taking rituximab showed no difference. Among patients not taking rituximab, those who completely stopped prednisone were nine and a half times as likely to experience relapse as those in the low-dose group. 

Despite these differences in relapse rates, “surprisingly, there were no differences in patient-reported outcomes [such as pain interference, physical function, and fatigue],” Merkel said. 

Across all patients, all but one relapse was characterized as minor. There were five serious adverse events and 10 infections in the 0-mg group versus one adverse event and 4 infections in the 5-mg group, but these differences were not statistically significant. 

In patients who relapsed, musculoskeletal and ear, nose, and throat manifestations of GPA were most common, and these are “the kind of stuff we see that is helped by low-dose glucocorticoids,” Merkel said.

It’s a good sign that for patients who were completely weaned off glucocorticoids, nearly all relapses were minor, Galina Marder, MD, a rheumatologist and associate professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said in an interview. She was not involved with the research. 

The study “can reinforce the message [of] trying to get them off steroids completely [when possible],” she said.

The findings also provide insight for future clinical trials, Merkel noted. For patients taking non–rituximab-based regimens, completely tapering off glucocorticoids or maintaining a low dose can affect study outcomes.

“[These data are] even more important for clinical trials because they are [reinforcing] the fact that you can have a diminishing signal if you allow some patients to stay on 5 mg prednisone” when GPA flares are the primary outcome, Marder added.

The Vasculitis Clinical Research Consortium received funding for this research through grants from the National Institutes of Health. Merkel has disclosed financial relationships with AbbVie/Abbott, Amgen, argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, ChemoCentryx, CSL Behring, Dynacure, Eicos, Electra, EMD Serono, Forbius, Genentech/Roche, Genzyme/Sanofi, GSK, HI-Bio, Inmagene, InflaRx, Janssen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, NS Pharma, Pfizer, Regeneron, Sanofi, Sparrow, Takeda, Talaris, UpToDate, and Visterra. Marder consults for Amgen and Boehringer Ingelheim.

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

WASHINGTON — Patients with granulomatosis with polyangiitis (GPA) completely tapered off prednisone have a more than fourfold risk of relapse by 6 months, compared with those tapered to 5 mg/day of prednisone; however, this benefit was only seen in patients not on rituximab, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“For patients treated with rituximab, fully tapering off glucocorticoids is reasonable to consider as the first approach,” said Peter Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, during his presentation of the findings.

Although a low dose of glucocorticoids can prevent some minor relapses in patients on other treatment regimens such as methotrexate or azathioprine, “fully tapering off prednisone presents relatively little risk of major relapse, and that major relapse can be treated rather quickly,” Merkel added.

The Assessment of Prednisone in Remission (TAPIR) trial enrolled 143 patients with GPA who were in remission (defined as a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis [BVAS/WG] of 0) within 1 year of treatment to induce remission for active disease and who were taking 5-10 mg of prednisone per day. After all patients tapered to 5 mg/day of prednisone, 71 patients completely tapered off prednisone over 4 weeks and remained off glucocorticoids until month 6. The remaining patients maintained a 5-mg/day dose over the study period. Placement in either treatment group was randomized, and patients continued other immunosuppressive therapy during the study.

Researchers evaluated the rate of relapse by 6 months, defined as a physician’s decision to increase the dose of glucocorticoids to treat GPA, in both groups.

Across all participants, the median age was 58 years, and 52% of patients were male. Most patients were White, and 47% of all patients were prescribed rituximab. 

At 6 months, 15.5% of participants who completely tapered off prednisone experienced a relapse of GPA, compared with 4.2% of those taking low-dose prednisone. Time to relapse was also shorter in the 0-mg prednisone group (P = .026), and relapses occurred continually over 6 months, Merkel said.

When stratified by rituximab use, relapse rates at 6 months between the 5-mg and 0-mg prednisone groups in patients taking rituximab showed no difference. Among patients not taking rituximab, those who completely stopped prednisone were nine and a half times as likely to experience relapse as those in the low-dose group. 

Despite these differences in relapse rates, “surprisingly, there were no differences in patient-reported outcomes [such as pain interference, physical function, and fatigue],” Merkel said. 

Across all patients, all but one relapse was characterized as minor. There were five serious adverse events and 10 infections in the 0-mg group versus one adverse event and 4 infections in the 5-mg group, but these differences were not statistically significant. 

In patients who relapsed, musculoskeletal and ear, nose, and throat manifestations of GPA were most common, and these are “the kind of stuff we see that is helped by low-dose glucocorticoids,” Merkel said.

It’s a good sign that for patients who were completely weaned off glucocorticoids, nearly all relapses were minor, Galina Marder, MD, a rheumatologist and associate professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said in an interview. She was not involved with the research. 

The study “can reinforce the message [of] trying to get them off steroids completely [when possible],” she said.

The findings also provide insight for future clinical trials, Merkel noted. For patients taking non–rituximab-based regimens, completely tapering off glucocorticoids or maintaining a low dose can affect study outcomes.

“[These data are] even more important for clinical trials because they are [reinforcing] the fact that you can have a diminishing signal if you allow some patients to stay on 5 mg prednisone” when GPA flares are the primary outcome, Marder added.

The Vasculitis Clinical Research Consortium received funding for this research through grants from the National Institutes of Health. Merkel has disclosed financial relationships with AbbVie/Abbott, Amgen, argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, ChemoCentryx, CSL Behring, Dynacure, Eicos, Electra, EMD Serono, Forbius, Genentech/Roche, Genzyme/Sanofi, GSK, HI-Bio, Inmagene, InflaRx, Janssen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, NS Pharma, Pfizer, Regeneron, Sanofi, Sparrow, Takeda, Talaris, UpToDate, and Visterra. Marder consults for Amgen and Boehringer Ingelheim.

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

WASHINGTON — Patients with granulomatosis with polyangiitis (GPA) completely tapered off prednisone have a more than fourfold risk of relapse by 6 months, compared with those tapered to 5 mg/day of prednisone; however, this benefit was only seen in patients not on rituximab, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“For patients treated with rituximab, fully tapering off glucocorticoids is reasonable to consider as the first approach,” said Peter Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, during his presentation of the findings.

Although a low dose of glucocorticoids can prevent some minor relapses in patients on other treatment regimens such as methotrexate or azathioprine, “fully tapering off prednisone presents relatively little risk of major relapse, and that major relapse can be treated rather quickly,” Merkel added.

The Assessment of Prednisone in Remission (TAPIR) trial enrolled 143 patients with GPA who were in remission (defined as a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis [BVAS/WG] of 0) within 1 year of treatment to induce remission for active disease and who were taking 5-10 mg of prednisone per day. After all patients tapered to 5 mg/day of prednisone, 71 patients completely tapered off prednisone over 4 weeks and remained off glucocorticoids until month 6. The remaining patients maintained a 5-mg/day dose over the study period. Placement in either treatment group was randomized, and patients continued other immunosuppressive therapy during the study.

Researchers evaluated the rate of relapse by 6 months, defined as a physician’s decision to increase the dose of glucocorticoids to treat GPA, in both groups.

Across all participants, the median age was 58 years, and 52% of patients were male. Most patients were White, and 47% of all patients were prescribed rituximab. 

At 6 months, 15.5% of participants who completely tapered off prednisone experienced a relapse of GPA, compared with 4.2% of those taking low-dose prednisone. Time to relapse was also shorter in the 0-mg prednisone group (P = .026), and relapses occurred continually over 6 months, Merkel said.

When stratified by rituximab use, relapse rates at 6 months between the 5-mg and 0-mg prednisone groups in patients taking rituximab showed no difference. Among patients not taking rituximab, those who completely stopped prednisone were nine and a half times as likely to experience relapse as those in the low-dose group. 

Despite these differences in relapse rates, “surprisingly, there were no differences in patient-reported outcomes [such as pain interference, physical function, and fatigue],” Merkel said. 

Across all patients, all but one relapse was characterized as minor. There were five serious adverse events and 10 infections in the 0-mg group versus one adverse event and 4 infections in the 5-mg group, but these differences were not statistically significant. 

In patients who relapsed, musculoskeletal and ear, nose, and throat manifestations of GPA were most common, and these are “the kind of stuff we see that is helped by low-dose glucocorticoids,” Merkel said.

It’s a good sign that for patients who were completely weaned off glucocorticoids, nearly all relapses were minor, Galina Marder, MD, a rheumatologist and associate professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said in an interview. She was not involved with the research. 

The study “can reinforce the message [of] trying to get them off steroids completely [when possible],” she said.

The findings also provide insight for future clinical trials, Merkel noted. For patients taking non–rituximab-based regimens, completely tapering off glucocorticoids or maintaining a low dose can affect study outcomes.

“[These data are] even more important for clinical trials because they are [reinforcing] the fact that you can have a diminishing signal if you allow some patients to stay on 5 mg prednisone” when GPA flares are the primary outcome, Marder added.

The Vasculitis Clinical Research Consortium received funding for this research through grants from the National Institutes of Health. Merkel has disclosed financial relationships with AbbVie/Abbott, Amgen, argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, ChemoCentryx, CSL Behring, Dynacure, Eicos, Electra, EMD Serono, Forbius, Genentech/Roche, Genzyme/Sanofi, GSK, HI-Bio, Inmagene, InflaRx, Janssen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, NS Pharma, Pfizer, Regeneron, Sanofi, Sparrow, Takeda, Talaris, UpToDate, and Visterra. Marder consults for Amgen and Boehringer Ingelheim.

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

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

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

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

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

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

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

LAS VEGAS — Early in his career as a physician associate in dermatology, Joe Cari, MPAS, PA-C, received a negative online review from a patient that really got under his skin.

“It said something like, ‘Do not see Joe the fake doctor. Joe should have his medical license pulled. He didn’t listen to me. He threw drugs at me and he only talked to me for 5 minutes,’ ” Cari, who practices at the University of Colorado Anschutz Medical Campus, Aurora, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “Being early in my practice, that hurt; it was a jab to the heart. I had about 20-30 five-star reviews, but I laser-focused on the bad one.”

When a review questions competence, it can feel personal, he continued, even though it often reflects the reviewer’s emotions or experience. Cari, a former Marine, said that clinicians can mitigate emotional responses to negative reviews by building emotional resilience. He draws inspiration from Stoicism (the school of philosophy that originated during the Hellenistic period), which emphasizes developing inner resilience, managing emotions, “and cultivating virtues such as wisdom, courage, and self-discipline,” he said. 

Cari often cites a quote from Marcus Aurelius, the former Roman Emperor and Stoic philosopher: “You have power over your mind — not outside events. Realize this, and you will find strength.” Another quote that changed his perspective comes from the Stoic Epictetus: “We cannot control the external events around us, but we can control our reactions to them.”

On a practical level, Cari shared several ways that clinicians can cultivate emotional resilience when faced with a negative review.

Practice mindfulness. Reading reviews in a nonjudgmental way “allows us to pause, reflect, and respond thoughtfully rather than react emotionally,” he explained. He also recommended setting clear boundaries between work and personal life to prevent burnout and maintain a healthy work–life balance. Realizing he needed time to decompress after a previous job that involved a 1-hour drive, he began listening to audiobooks on his way home. “I set that time aside for myself to listen, relax, and let all my troubles from work melt away,” Cari said. 

Develop a support network. This includes both professionals, such as therapists, and personal connections, such as colleagues, mentors, and friends.

Practice self-care. Whether it’s yoga, running, jogging, spending time with loved ones, or playing with your dog, find activities that help you recharge. “Most importantly, get some rest and take a vacation,” Cari advised. “Your body is like a machine. If you do not rest it and take care of it, it will slowly breakdown and burnout.”

Practice equanimity. Cari defined this as mental calmness, composure, and evenness of temper, especially in a difficult situation. “Maintaining a calm and balanced state of mind, regardless of external circumstances, is a core Stoic and military practice,” he said.

According to data he attributed to reviewtrackers, an estimated 60% of reviews are influenced by the reviewer’s personal stress or mood, “so don’t take [bad reviews] personally,” he said. Instead, view criticism as an opportunity for self-improvement and to gain insight into others’ perspectives. Cari recommended practicing indifference to both praise and blame. “Do not seek validation or be disheartened by negative reviews,” he said. “Remain focused on your own standards of excellence.”

Cari has reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

LAS VEGAS — Early in his career as a physician associate in dermatology, Joe Cari, MPAS, PA-C, received a negative online review from a patient that really got under his skin.

“It said something like, ‘Do not see Joe the fake doctor. Joe should have his medical license pulled. He didn’t listen to me. He threw drugs at me and he only talked to me for 5 minutes,’ ” Cari, who practices at the University of Colorado Anschutz Medical Campus, Aurora, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “Being early in my practice, that hurt; it was a jab to the heart. I had about 20-30 five-star reviews, but I laser-focused on the bad one.”

When a review questions competence, it can feel personal, he continued, even though it often reflects the reviewer’s emotions or experience. Cari, a former Marine, said that clinicians can mitigate emotional responses to negative reviews by building emotional resilience. He draws inspiration from Stoicism (the school of philosophy that originated during the Hellenistic period), which emphasizes developing inner resilience, managing emotions, “and cultivating virtues such as wisdom, courage, and self-discipline,” he said. 

Cari often cites a quote from Marcus Aurelius, the former Roman Emperor and Stoic philosopher: “You have power over your mind — not outside events. Realize this, and you will find strength.” Another quote that changed his perspective comes from the Stoic Epictetus: “We cannot control the external events around us, but we can control our reactions to them.”

On a practical level, Cari shared several ways that clinicians can cultivate emotional resilience when faced with a negative review.

Practice mindfulness. Reading reviews in a nonjudgmental way “allows us to pause, reflect, and respond thoughtfully rather than react emotionally,” he explained. He also recommended setting clear boundaries between work and personal life to prevent burnout and maintain a healthy work–life balance. Realizing he needed time to decompress after a previous job that involved a 1-hour drive, he began listening to audiobooks on his way home. “I set that time aside for myself to listen, relax, and let all my troubles from work melt away,” Cari said. 

Develop a support network. This includes both professionals, such as therapists, and personal connections, such as colleagues, mentors, and friends.

Practice self-care. Whether it’s yoga, running, jogging, spending time with loved ones, or playing with your dog, find activities that help you recharge. “Most importantly, get some rest and take a vacation,” Cari advised. “Your body is like a machine. If you do not rest it and take care of it, it will slowly breakdown and burnout.”

Practice equanimity. Cari defined this as mental calmness, composure, and evenness of temper, especially in a difficult situation. “Maintaining a calm and balanced state of mind, regardless of external circumstances, is a core Stoic and military practice,” he said.

According to data he attributed to reviewtrackers, an estimated 60% of reviews are influenced by the reviewer’s personal stress or mood, “so don’t take [bad reviews] personally,” he said. Instead, view criticism as an opportunity for self-improvement and to gain insight into others’ perspectives. Cari recommended practicing indifference to both praise and blame. “Do not seek validation or be disheartened by negative reviews,” he said. “Remain focused on your own standards of excellence.”

Cari has reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

LAS VEGAS — Early in his career as a physician associate in dermatology, Joe Cari, MPAS, PA-C, received a negative online review from a patient that really got under his skin.

“It said something like, ‘Do not see Joe the fake doctor. Joe should have his medical license pulled. He didn’t listen to me. He threw drugs at me and he only talked to me for 5 minutes,’ ” Cari, who practices at the University of Colorado Anschutz Medical Campus, Aurora, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “Being early in my practice, that hurt; it was a jab to the heart. I had about 20-30 five-star reviews, but I laser-focused on the bad one.”

When a review questions competence, it can feel personal, he continued, even though it often reflects the reviewer’s emotions or experience. Cari, a former Marine, said that clinicians can mitigate emotional responses to negative reviews by building emotional resilience. He draws inspiration from Stoicism (the school of philosophy that originated during the Hellenistic period), which emphasizes developing inner resilience, managing emotions, “and cultivating virtues such as wisdom, courage, and self-discipline,” he said. 

Cari often cites a quote from Marcus Aurelius, the former Roman Emperor and Stoic philosopher: “You have power over your mind — not outside events. Realize this, and you will find strength.” Another quote that changed his perspective comes from the Stoic Epictetus: “We cannot control the external events around us, but we can control our reactions to them.”

On a practical level, Cari shared several ways that clinicians can cultivate emotional resilience when faced with a negative review.

Practice mindfulness. Reading reviews in a nonjudgmental way “allows us to pause, reflect, and respond thoughtfully rather than react emotionally,” he explained. He also recommended setting clear boundaries between work and personal life to prevent burnout and maintain a healthy work–life balance. Realizing he needed time to decompress after a previous job that involved a 1-hour drive, he began listening to audiobooks on his way home. “I set that time aside for myself to listen, relax, and let all my troubles from work melt away,” Cari said. 

Develop a support network. This includes both professionals, such as therapists, and personal connections, such as colleagues, mentors, and friends.

Practice self-care. Whether it’s yoga, running, jogging, spending time with loved ones, or playing with your dog, find activities that help you recharge. “Most importantly, get some rest and take a vacation,” Cari advised. “Your body is like a machine. If you do not rest it and take care of it, it will slowly breakdown and burnout.”

Practice equanimity. Cari defined this as mental calmness, composure, and evenness of temper, especially in a difficult situation. “Maintaining a calm and balanced state of mind, regardless of external circumstances, is a core Stoic and military practice,” he said.

According to data he attributed to reviewtrackers, an estimated 60% of reviews are influenced by the reviewer’s personal stress or mood, “so don’t take [bad reviews] personally,” he said. Instead, view criticism as an opportunity for self-improvement and to gain insight into others’ perspectives. Cari recommended practicing indifference to both praise and blame. “Do not seek validation or be disheartened by negative reviews,” he said. “Remain focused on your own standards of excellence.”

Cari has reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

LAS VEGAS — After antifungal therapy for fungal nail disease, some dystrophy may persist, which can be addressed by several available treatments. 

“With the fingernails, we don’t often see onychomycosis, but with toenails, we certainly do,” Tracey C. Vlahovic, DPM, a professor at the Samuel Merritt University College of Podiatric Medicine, Oakland, California, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “But toenails are subject to a lot of forces beyond just fungal [infections]. We have the wear and tear of wearing shoes, gait, and other physical activity.”

 

For example, she continued, some runners develop second-toenail dystrophy “because there’s constant repetitive trauma to the toenail, and [poorly fitting] shoes can contribute to that. Biomechanical issues are a unique consideration when you’re dealing with toenail issues.”

Vlahovic highlighted several options that can help improve the appearance of dystrophic nails as they recover or grow back:

Urea nail preparations: To temporarily soften the nail.

Genadur (hydroxypropyl chitosan): This product “is used mainly for psoriatic nails, but I use it for all different kinds of nail dystrophy,” she said.

DermaNail (acetyl mandelic acid solution): This can be used for brittle nails and fingernails. Vlahovic said she recommends it be used on toenails “in addition to the onychomycosis and other nail dystrophy treatments that I’m doing because it really helps to hydrate the nail unit.”

Kerasal Fungal Nail Renewal (ingredients include propylene glycol, urea, glycerin, and lactic acid): This product is used “for smoothing out the appearance of the nail,” she said.

KeryFlex: Applied in an office setting, this resin-based product restores the appearance of an individual’s natural nails. “It comes in two colors [and] absorbs the shock of what is going on mechanically with the feet,” Vlahovic said. “So, if I’m treating a ballet dancer performing en pointe, or a soccer player, it’s something I can use to protect the nail, but also to make it cosmetically more acceptable.”

NECPro: A nail reconstruction method that involves the use of a composite used mainly by podiatrists, it “helps you not only create a barrier, but to create a natural-looking color that matches your own nail color,” she said.

In Vlahovic’s experience, KeryFlex and NECPro last 6-8 weeks. “You can use nail polish on top of them if you’d like, but they’re basically cosmetic barriers to protect the nail unit,” she said.

Vlahovic has disclosed being a consultant and investigator for Ortho Dermatologics and Sagis Diagnostics.

 

A version of this article appeared on Medscape.com.

LAS VEGAS — After antifungal therapy for fungal nail disease, some dystrophy may persist, which can be addressed by several available treatments. 

“With the fingernails, we don’t often see onychomycosis, but with toenails, we certainly do,” Tracey C. Vlahovic, DPM, a professor at the Samuel Merritt University College of Podiatric Medicine, Oakland, California, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “But toenails are subject to a lot of forces beyond just fungal [infections]. We have the wear and tear of wearing shoes, gait, and other physical activity.”

 

For example, she continued, some runners develop second-toenail dystrophy “because there’s constant repetitive trauma to the toenail, and [poorly fitting] shoes can contribute to that. Biomechanical issues are a unique consideration when you’re dealing with toenail issues.”

Vlahovic highlighted several options that can help improve the appearance of dystrophic nails as they recover or grow back:

Urea nail preparations: To temporarily soften the nail.

Genadur (hydroxypropyl chitosan): This product “is used mainly for psoriatic nails, but I use it for all different kinds of nail dystrophy,” she said.

DermaNail (acetyl mandelic acid solution): This can be used for brittle nails and fingernails. Vlahovic said she recommends it be used on toenails “in addition to the onychomycosis and other nail dystrophy treatments that I’m doing because it really helps to hydrate the nail unit.”

Kerasal Fungal Nail Renewal (ingredients include propylene glycol, urea, glycerin, and lactic acid): This product is used “for smoothing out the appearance of the nail,” she said.

KeryFlex: Applied in an office setting, this resin-based product restores the appearance of an individual’s natural nails. “It comes in two colors [and] absorbs the shock of what is going on mechanically with the feet,” Vlahovic said. “So, if I’m treating a ballet dancer performing en pointe, or a soccer player, it’s something I can use to protect the nail, but also to make it cosmetically more acceptable.”

NECPro: A nail reconstruction method that involves the use of a composite used mainly by podiatrists, it “helps you not only create a barrier, but to create a natural-looking color that matches your own nail color,” she said.

In Vlahovic’s experience, KeryFlex and NECPro last 6-8 weeks. “You can use nail polish on top of them if you’d like, but they’re basically cosmetic barriers to protect the nail unit,” she said.

Vlahovic has disclosed being a consultant and investigator for Ortho Dermatologics and Sagis Diagnostics.

 

A version of this article appeared on Medscape.com.

LAS VEGAS — After antifungal therapy for fungal nail disease, some dystrophy may persist, which can be addressed by several available treatments. 

“With the fingernails, we don’t often see onychomycosis, but with toenails, we certainly do,” Tracey C. Vlahovic, DPM, a professor at the Samuel Merritt University College of Podiatric Medicine, Oakland, California, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “But toenails are subject to a lot of forces beyond just fungal [infections]. We have the wear and tear of wearing shoes, gait, and other physical activity.”

 

For example, she continued, some runners develop second-toenail dystrophy “because there’s constant repetitive trauma to the toenail, and [poorly fitting] shoes can contribute to that. Biomechanical issues are a unique consideration when you’re dealing with toenail issues.”

Vlahovic highlighted several options that can help improve the appearance of dystrophic nails as they recover or grow back:

Urea nail preparations: To temporarily soften the nail.

Genadur (hydroxypropyl chitosan): This product “is used mainly for psoriatic nails, but I use it for all different kinds of nail dystrophy,” she said.

DermaNail (acetyl mandelic acid solution): This can be used for brittle nails and fingernails. Vlahovic said she recommends it be used on toenails “in addition to the onychomycosis and other nail dystrophy treatments that I’m doing because it really helps to hydrate the nail unit.”

Kerasal Fungal Nail Renewal (ingredients include propylene glycol, urea, glycerin, and lactic acid): This product is used “for smoothing out the appearance of the nail,” she said.

KeryFlex: Applied in an office setting, this resin-based product restores the appearance of an individual’s natural nails. “It comes in two colors [and] absorbs the shock of what is going on mechanically with the feet,” Vlahovic said. “So, if I’m treating a ballet dancer performing en pointe, or a soccer player, it’s something I can use to protect the nail, but also to make it cosmetically more acceptable.”

NECPro: A nail reconstruction method that involves the use of a composite used mainly by podiatrists, it “helps you not only create a barrier, but to create a natural-looking color that matches your own nail color,” she said.

In Vlahovic’s experience, KeryFlex and NECPro last 6-8 weeks. “You can use nail polish on top of them if you’d like, but they’re basically cosmetic barriers to protect the nail unit,” she said.

Vlahovic has disclosed being a consultant and investigator for Ortho Dermatologics and Sagis Diagnostics.

 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Weight loss treatments aren’t reaching many of the people who need them most because of coverage barriers, new data suggested.

Findings from three studies presented at The Obesity Society’s Obesity Week 2024 meeting illustrate different aspects of the problem.

One, presented by Alissa S. Chen, MD, MPH, a postdoctoral fellow at Yale University, New Haven, Connecticut, found that people with obesity, particularly those with cardiovascular disease (CVD) and those who are Black and Hispanic, have high rates of cost-related prescription drug rationing. Those findings were simultaneously published as a research letter in JAMA Network Open.

“The implications are that structural barriers impede access to medications for Black and Hispanic adults with obesity, which might worsen if there’s not expanding coverage for GLP-1 RAs [glucagon-like peptide 1 receptor agonists], and it’s possible that broader insurance coverage could ameliorate some of these issues,” Chen said.

She noted that patients don’t always volunteer that information. “In my clinical practice, I always start by saying something like, ‘I have a lot of patients who can’t afford their medications. In the last week, was there a time [you didn’t take your medications due to cost]?’ ”

State Medicaid programs vary widely in the degree to which they cover weight loss treatments. But not a single one covers all modalities — nutrition counseling (NC), intensive behavioral therapy (IBT), obesity medications (OMs), and metabolic and bariatric surgery (MBS) — without restrictions or limitations, and only seven states cover them all with restrictions, according to a dual presentation by Christine Gallagher, MPAff, associate director for research and policy with the STOP Obesity Alliance at George Washington University, Washington, DC, and Tracy Zvenyach, PhD, MS, RN, director of policy strategy and alliances at the Obesity Action Coalition, also in Washington, DC.

Detailed Medicaid coverage data for each state are posted on the STOP Obesity Alliance website. (As of now, Medicare doesn’t cover medications specifically for obesity at all.)

A third presentation, by Treah Haggerty, MD, of the Department of Family Medicine and director of the Pediatric Medical Weight Management program at West Virginia University, Morgantown, was of a qualitative descriptive study exploring the impact on 22 individuals enrolled in a medical weight loss management program whose state employee insurance carrier made a policy decision to stop covering all anti-OMs in March 2024. All had been prescribed GLP-1 agonists for weight loss, and the decision forced most to stop using them.

Those findings were published in the September 2024 issue of Obesity Pillars.

“Patients perceive the discontinuation of anti-obesity medication coverage as stigmatizing and unjust, leading to feelings of hopelessness and fear. With more insurance companies denying coverage for these costly medications, more information is needed to identify best ways to address the loss of coverage with patients. Clinical management of these patients should incorporate evidence-based obesity treatments while navigating insurance constraints,” Haggerty said.

 

Create a Safe Space to Discuss the Barriers

Asked to comment, Session Moderator John D. Clark, MD, PhD, chief population health officer at Sharp Rees-Stealy Medical Group, San Diego, California, told Medscape Medical News, “Health systems and payers are determining what can and can’t be covered, and at the end of the day, it frequently comes down to finances…I think the big challenge is really identifying patients who may have the greatest need. ... If we have limited resources, how and where should we be directing those resources? I would say the current system hasn’t really answered that question or identified patients for whom we would say that the cost truly is less than either the financial or long-term health benefits.”

But Clark said, “When some of these newer anti-obesity medications are able to go generic and be less expensive, which will happen eventually, I think things will change ... and in the future, there will be more options on the market as well.”

In the meantime, he advised that clinicians “try to have conversations with patients about these barriers, acknowledge that these barriers exist, and create a safe space to discuss those barriers. ... Let’s see where we are right now, and let’s come up with a plan.”

 

People With Obesity More Susceptible to Drug Rationing

Chen reported on a sample of 51,720 adults who participated in the 2020-2022 National Health Interview Survey who did not have diabetes and who used at least one prescription medication of any type. Of those, 80% were White, 9.7% were Hispanic, and 9.7% were Black, and 33.9% overall had obesity.

Cost-related prescription rationing, defined as any self-reported skipping, taking less, or delaying filling a prescription to save money, was reported by 8.3% of those with obesity vs 5.9% without. After adjustment, rationing among those with obesity was significantly associated with younger age (aged 18-44 years), female sex, lower incomes, lack of health insurance coverage, and CVD.

The adjusted estimated probability of cost-related prescription drug rationing was 7.4% for those with CVD vs 4.4% for those without. By race/ethnicity, the proportions reporting rationing were 7.7%, 9.8%, and 10.7% for White, Black, and Hispanics, respectively.

“Given that few insurance providers cover GLP-1 RAs for obesity, cost-related prescription drug rationing could be exacerbated if patients were prescribed GLP-1 RAs at their current price of more than $1000 a month,” Chen noted, adding that the high prices could worsen health disparities among Black and Hispanic individuals with obesity.

 

Medicaid Coverage Lacking for All Obesity Treatments

For their project, Gallagher and Zvenyach delved into a database that aggregates Medicaid manuals, fee schedules, statutes, regulations, and preferred drug lists for each US state, both for Medicaid fee for service and top Medicaid managed care plans, in order to determine 2024 levels of coverage for NC, IBT, OMs, and MBS for adults with obesity.

No state provides coverage for all those treatments without either limitations — such as body mass index (BMI) cutoffs, age, or “comorbidity regardless of body mass index (BMI)” for OM and MBS — or outright restrictions, such as “proof of failed attempts.” And only seven states provide coverage for the four modalities “with limitations”: California, Arizona, New Mexico, South Carolina, Delaware, Rhode Island, and Massachusetts.

Twenty-two states don’t cover NC, although just one state doesn’t cover IBT. Overall, 37 states don’t cover OMs, and other states ranged considerably in various restrictions and limitations for OMs and MBS. Only four states fully covered the surgery without limitations or restrictions.

“The vast majority of states have significant barriers and conditions of coverage for obesity care,” Gallagher said.

Zvenyach added, “Most of the applied exclusions, limitations, or restrictions do not align with evidence-based practice standards or guidelines.”

 

When Coverage Stops, Hopelessness and Anger Emerge

Haggerty and colleagues’ research involved semi-structured interviews of the 22 participants — all of them women — who had lost their obesity medication coverage due to their insurers’ decision. Four themes emerged:

• 1. Feelings of hope replaced by hopelessness upon loss of medication coverage: One person said, “I’m afraid for my mental health. It’s tough to be in a situation where you’re never right. And it doesn’t matter what you do; it’s not going to work, and then to have just a glimmer of hope, a little spark of hey, look, this might help. And for someone else to take that away from you for no reason. I don’t know what am I supposed to do.”
• 2. Anger regarding the perceived injustice of anti-obesity medication coverage termination: For example, “They can pay for heart attacks, they could pay for me to have a stroke, they could pay for me to have diabetes, but they won’t let me have this one medicine that could take all of that away. Makes no sense.”
• 3. Perceptions of past and present stigma within the healthcare system and insurance company: “I’m not trying for vanity. I’m way too old to be a Victoria’s Secret model. I’m not trying to do it to be cute and skinny and hot. I just want to make it through a day of work and not be exhausted.”
• 4. Generational influences on obesity treatment: “I’m married, and my husband, since I’ve started this medicine, he’s been eating better. He’s been eating what I eat, and he’s been losing weight as well.”
• Some participants said they planned to cope in different ways, including trying to obtain compounded versions of the drugs from “spas” or online pharmacies, as well as skipping doses, reducing doses, or sharing medications — in other words, rationing.

Asked by this news organization what clinicians should keep in mind, Haggerty said, “that there are big barriers and that we need to take care of the patients within this system that has their arm tied behind their back.

Chen was funded by a grant from the National Institute on Aging outside the submitted work, and she was funded as a Yale National Clinician Scholar. A coauthor received grants from the Food and Drug Administration, Johnson & Johnson, the National Institutes of Health, the Agency for Healthcare Research and Quality, and Arnold Ventures. Another coauthor reported receiving personal fees from UpToDate and the Centers for Medicare & Medicaid Services. Gallagher has received research funding from Altimmune, Amgen, Boehringer Ingelheim, Currax, Eli Lilly and Company, Found, Novo Nordisk, Pfizer, Structure Therapeutics, and WeightWatchers. Haggerty reported article publishing charge was provided by West Virginia Alliance for Creative Health Solutions. Zvenyach and Clark had no disclosures.

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

SAN ANTONIO — Weight loss treatments aren’t reaching many of the people who need them most because of coverage barriers, new data suggested.

Findings from three studies presented at The Obesity Society’s Obesity Week 2024 meeting illustrate different aspects of the problem.

One, presented by Alissa S. Chen, MD, MPH, a postdoctoral fellow at Yale University, New Haven, Connecticut, found that people with obesity, particularly those with cardiovascular disease (CVD) and those who are Black and Hispanic, have high rates of cost-related prescription drug rationing. Those findings were simultaneously published as a research letter in JAMA Network Open.

“The implications are that structural barriers impede access to medications for Black and Hispanic adults with obesity, which might worsen if there’s not expanding coverage for GLP-1 RAs [glucagon-like peptide 1 receptor agonists], and it’s possible that broader insurance coverage could ameliorate some of these issues,” Chen said.

She noted that patients don’t always volunteer that information. “In my clinical practice, I always start by saying something like, ‘I have a lot of patients who can’t afford their medications. In the last week, was there a time [you didn’t take your medications due to cost]?’ ”

State Medicaid programs vary widely in the degree to which they cover weight loss treatments. But not a single one covers all modalities — nutrition counseling (NC), intensive behavioral therapy (IBT), obesity medications (OMs), and metabolic and bariatric surgery (MBS) — without restrictions or limitations, and only seven states cover them all with restrictions, according to a dual presentation by Christine Gallagher, MPAff, associate director for research and policy with the STOP Obesity Alliance at George Washington University, Washington, DC, and Tracy Zvenyach, PhD, MS, RN, director of policy strategy and alliances at the Obesity Action Coalition, also in Washington, DC.

Detailed Medicaid coverage data for each state are posted on the STOP Obesity Alliance website. (As of now, Medicare doesn’t cover medications specifically for obesity at all.)

A third presentation, by Treah Haggerty, MD, of the Department of Family Medicine and director of the Pediatric Medical Weight Management program at West Virginia University, Morgantown, was of a qualitative descriptive study exploring the impact on 22 individuals enrolled in a medical weight loss management program whose state employee insurance carrier made a policy decision to stop covering all anti-OMs in March 2024. All had been prescribed GLP-1 agonists for weight loss, and the decision forced most to stop using them.

Those findings were published in the September 2024 issue of Obesity Pillars.

“Patients perceive the discontinuation of anti-obesity medication coverage as stigmatizing and unjust, leading to feelings of hopelessness and fear. With more insurance companies denying coverage for these costly medications, more information is needed to identify best ways to address the loss of coverage with patients. Clinical management of these patients should incorporate evidence-based obesity treatments while navigating insurance constraints,” Haggerty said.

 

Create a Safe Space to Discuss the Barriers

Asked to comment, Session Moderator John D. Clark, MD, PhD, chief population health officer at Sharp Rees-Stealy Medical Group, San Diego, California, told Medscape Medical News, “Health systems and payers are determining what can and can’t be covered, and at the end of the day, it frequently comes down to finances…I think the big challenge is really identifying patients who may have the greatest need. ... If we have limited resources, how and where should we be directing those resources? I would say the current system hasn’t really answered that question or identified patients for whom we would say that the cost truly is less than either the financial or long-term health benefits.”

But Clark said, “When some of these newer anti-obesity medications are able to go generic and be less expensive, which will happen eventually, I think things will change ... and in the future, there will be more options on the market as well.”

In the meantime, he advised that clinicians “try to have conversations with patients about these barriers, acknowledge that these barriers exist, and create a safe space to discuss those barriers. ... Let’s see where we are right now, and let’s come up with a plan.”

 

People With Obesity More Susceptible to Drug Rationing

Chen reported on a sample of 51,720 adults who participated in the 2020-2022 National Health Interview Survey who did not have diabetes and who used at least one prescription medication of any type. Of those, 80% were White, 9.7% were Hispanic, and 9.7% were Black, and 33.9% overall had obesity.

Cost-related prescription rationing, defined as any self-reported skipping, taking less, or delaying filling a prescription to save money, was reported by 8.3% of those with obesity vs 5.9% without. After adjustment, rationing among those with obesity was significantly associated with younger age (aged 18-44 years), female sex, lower incomes, lack of health insurance coverage, and CVD.

The adjusted estimated probability of cost-related prescription drug rationing was 7.4% for those with CVD vs 4.4% for those without. By race/ethnicity, the proportions reporting rationing were 7.7%, 9.8%, and 10.7% for White, Black, and Hispanics, respectively.

“Given that few insurance providers cover GLP-1 RAs for obesity, cost-related prescription drug rationing could be exacerbated if patients were prescribed GLP-1 RAs at their current price of more than $1000 a month,” Chen noted, adding that the high prices could worsen health disparities among Black and Hispanic individuals with obesity.

 

Medicaid Coverage Lacking for All Obesity Treatments

For their project, Gallagher and Zvenyach delved into a database that aggregates Medicaid manuals, fee schedules, statutes, regulations, and preferred drug lists for each US state, both for Medicaid fee for service and top Medicaid managed care plans, in order to determine 2024 levels of coverage for NC, IBT, OMs, and MBS for adults with obesity.

No state provides coverage for all those treatments without either limitations — such as body mass index (BMI) cutoffs, age, or “comorbidity regardless of body mass index (BMI)” for OM and MBS — or outright restrictions, such as “proof of failed attempts.” And only seven states provide coverage for the four modalities “with limitations”: California, Arizona, New Mexico, South Carolina, Delaware, Rhode Island, and Massachusetts.

Twenty-two states don’t cover NC, although just one state doesn’t cover IBT. Overall, 37 states don’t cover OMs, and other states ranged considerably in various restrictions and limitations for OMs and MBS. Only four states fully covered the surgery without limitations or restrictions.

“The vast majority of states have significant barriers and conditions of coverage for obesity care,” Gallagher said.

Zvenyach added, “Most of the applied exclusions, limitations, or restrictions do not align with evidence-based practice standards or guidelines.”

 

When Coverage Stops, Hopelessness and Anger Emerge

Haggerty and colleagues’ research involved semi-structured interviews of the 22 participants — all of them women — who had lost their obesity medication coverage due to their insurers’ decision. Four themes emerged:

• 1. Feelings of hope replaced by hopelessness upon loss of medication coverage: One person said, “I’m afraid for my mental health. It’s tough to be in a situation where you’re never right. And it doesn’t matter what you do; it’s not going to work, and then to have just a glimmer of hope, a little spark of hey, look, this might help. And for someone else to take that away from you for no reason. I don’t know what am I supposed to do.”
• 2. Anger regarding the perceived injustice of anti-obesity medication coverage termination: For example, “They can pay for heart attacks, they could pay for me to have a stroke, they could pay for me to have diabetes, but they won’t let me have this one medicine that could take all of that away. Makes no sense.”
• 3. Perceptions of past and present stigma within the healthcare system and insurance company: “I’m not trying for vanity. I’m way too old to be a Victoria’s Secret model. I’m not trying to do it to be cute and skinny and hot. I just want to make it through a day of work and not be exhausted.”
• 4. Generational influences on obesity treatment: “I’m married, and my husband, since I’ve started this medicine, he’s been eating better. He’s been eating what I eat, and he’s been losing weight as well.”
• Some participants said they planned to cope in different ways, including trying to obtain compounded versions of the drugs from “spas” or online pharmacies, as well as skipping doses, reducing doses, or sharing medications — in other words, rationing.

Asked by this news organization what clinicians should keep in mind, Haggerty said, “that there are big barriers and that we need to take care of the patients within this system that has their arm tied behind their back.

Chen was funded by a grant from the National Institute on Aging outside the submitted work, and she was funded as a Yale National Clinician Scholar. A coauthor received grants from the Food and Drug Administration, Johnson & Johnson, the National Institutes of Health, the Agency for Healthcare Research and Quality, and Arnold Ventures. Another coauthor reported receiving personal fees from UpToDate and the Centers for Medicare & Medicaid Services. Gallagher has received research funding from Altimmune, Amgen, Boehringer Ingelheim, Currax, Eli Lilly and Company, Found, Novo Nordisk, Pfizer, Structure Therapeutics, and WeightWatchers. Haggerty reported article publishing charge was provided by West Virginia Alliance for Creative Health Solutions. Zvenyach and Clark had no disclosures.

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

SAN ANTONIO — Weight loss treatments aren’t reaching many of the people who need them most because of coverage barriers, new data suggested.

Findings from three studies presented at The Obesity Society’s Obesity Week 2024 meeting illustrate different aspects of the problem.

One, presented by Alissa S. Chen, MD, MPH, a postdoctoral fellow at Yale University, New Haven, Connecticut, found that people with obesity, particularly those with cardiovascular disease (CVD) and those who are Black and Hispanic, have high rates of cost-related prescription drug rationing. Those findings were simultaneously published as a research letter in JAMA Network Open.

“The implications are that structural barriers impede access to medications for Black and Hispanic adults with obesity, which might worsen if there’s not expanding coverage for GLP-1 RAs [glucagon-like peptide 1 receptor agonists], and it’s possible that broader insurance coverage could ameliorate some of these issues,” Chen said.

She noted that patients don’t always volunteer that information. “In my clinical practice, I always start by saying something like, ‘I have a lot of patients who can’t afford their medications. In the last week, was there a time [you didn’t take your medications due to cost]?’ ”

State Medicaid programs vary widely in the degree to which they cover weight loss treatments. But not a single one covers all modalities — nutrition counseling (NC), intensive behavioral therapy (IBT), obesity medications (OMs), and metabolic and bariatric surgery (MBS) — without restrictions or limitations, and only seven states cover them all with restrictions, according to a dual presentation by Christine Gallagher, MPAff, associate director for research and policy with the STOP Obesity Alliance at George Washington University, Washington, DC, and Tracy Zvenyach, PhD, MS, RN, director of policy strategy and alliances at the Obesity Action Coalition, also in Washington, DC.

Detailed Medicaid coverage data for each state are posted on the STOP Obesity Alliance website. (As of now, Medicare doesn’t cover medications specifically for obesity at all.)

A third presentation, by Treah Haggerty, MD, of the Department of Family Medicine and director of the Pediatric Medical Weight Management program at West Virginia University, Morgantown, was of a qualitative descriptive study exploring the impact on 22 individuals enrolled in a medical weight loss management program whose state employee insurance carrier made a policy decision to stop covering all anti-OMs in March 2024. All had been prescribed GLP-1 agonists for weight loss, and the decision forced most to stop using them.

Those findings were published in the September 2024 issue of Obesity Pillars.

“Patients perceive the discontinuation of anti-obesity medication coverage as stigmatizing and unjust, leading to feelings of hopelessness and fear. With more insurance companies denying coverage for these costly medications, more information is needed to identify best ways to address the loss of coverage with patients. Clinical management of these patients should incorporate evidence-based obesity treatments while navigating insurance constraints,” Haggerty said.

 

Create a Safe Space to Discuss the Barriers

Asked to comment, Session Moderator John D. Clark, MD, PhD, chief population health officer at Sharp Rees-Stealy Medical Group, San Diego, California, told Medscape Medical News, “Health systems and payers are determining what can and can’t be covered, and at the end of the day, it frequently comes down to finances…I think the big challenge is really identifying patients who may have the greatest need. ... If we have limited resources, how and where should we be directing those resources? I would say the current system hasn’t really answered that question or identified patients for whom we would say that the cost truly is less than either the financial or long-term health benefits.”

But Clark said, “When some of these newer anti-obesity medications are able to go generic and be less expensive, which will happen eventually, I think things will change ... and in the future, there will be more options on the market as well.”

In the meantime, he advised that clinicians “try to have conversations with patients about these barriers, acknowledge that these barriers exist, and create a safe space to discuss those barriers. ... Let’s see where we are right now, and let’s come up with a plan.”

 

People With Obesity More Susceptible to Drug Rationing

Chen reported on a sample of 51,720 adults who participated in the 2020-2022 National Health Interview Survey who did not have diabetes and who used at least one prescription medication of any type. Of those, 80% were White, 9.7% were Hispanic, and 9.7% were Black, and 33.9% overall had obesity.

Cost-related prescription rationing, defined as any self-reported skipping, taking less, or delaying filling a prescription to save money, was reported by 8.3% of those with obesity vs 5.9% without. After adjustment, rationing among those with obesity was significantly associated with younger age (aged 18-44 years), female sex, lower incomes, lack of health insurance coverage, and CVD.

The adjusted estimated probability of cost-related prescription drug rationing was 7.4% for those with CVD vs 4.4% for those without. By race/ethnicity, the proportions reporting rationing were 7.7%, 9.8%, and 10.7% for White, Black, and Hispanics, respectively.

“Given that few insurance providers cover GLP-1 RAs for obesity, cost-related prescription drug rationing could be exacerbated if patients were prescribed GLP-1 RAs at their current price of more than $1000 a month,” Chen noted, adding that the high prices could worsen health disparities among Black and Hispanic individuals with obesity.

 

Medicaid Coverage Lacking for All Obesity Treatments

For their project, Gallagher and Zvenyach delved into a database that aggregates Medicaid manuals, fee schedules, statutes, regulations, and preferred drug lists for each US state, both for Medicaid fee for service and top Medicaid managed care plans, in order to determine 2024 levels of coverage for NC, IBT, OMs, and MBS for adults with obesity.

No state provides coverage for all those treatments without either limitations — such as body mass index (BMI) cutoffs, age, or “comorbidity regardless of body mass index (BMI)” for OM and MBS — or outright restrictions, such as “proof of failed attempts.” And only seven states provide coverage for the four modalities “with limitations”: California, Arizona, New Mexico, South Carolina, Delaware, Rhode Island, and Massachusetts.

Twenty-two states don’t cover NC, although just one state doesn’t cover IBT. Overall, 37 states don’t cover OMs, and other states ranged considerably in various restrictions and limitations for OMs and MBS. Only four states fully covered the surgery without limitations or restrictions.

“The vast majority of states have significant barriers and conditions of coverage for obesity care,” Gallagher said.

Zvenyach added, “Most of the applied exclusions, limitations, or restrictions do not align with evidence-based practice standards or guidelines.”

 

When Coverage Stops, Hopelessness and Anger Emerge

Haggerty and colleagues’ research involved semi-structured interviews of the 22 participants — all of them women — who had lost their obesity medication coverage due to their insurers’ decision. Four themes emerged:

• 1. Feelings of hope replaced by hopelessness upon loss of medication coverage: One person said, “I’m afraid for my mental health. It’s tough to be in a situation where you’re never right. And it doesn’t matter what you do; it’s not going to work, and then to have just a glimmer of hope, a little spark of hey, look, this might help. And for someone else to take that away from you for no reason. I don’t know what am I supposed to do.”
• 2. Anger regarding the perceived injustice of anti-obesity medication coverage termination: For example, “They can pay for heart attacks, they could pay for me to have a stroke, they could pay for me to have diabetes, but they won’t let me have this one medicine that could take all of that away. Makes no sense.”
• 3. Perceptions of past and present stigma within the healthcare system and insurance company: “I’m not trying for vanity. I’m way too old to be a Victoria’s Secret model. I’m not trying to do it to be cute and skinny and hot. I just want to make it through a day of work and not be exhausted.”
• 4. Generational influences on obesity treatment: “I’m married, and my husband, since I’ve started this medicine, he’s been eating better. He’s been eating what I eat, and he’s been losing weight as well.”
• Some participants said they planned to cope in different ways, including trying to obtain compounded versions of the drugs from “spas” or online pharmacies, as well as skipping doses, reducing doses, or sharing medications — in other words, rationing.

Asked by this news organization what clinicians should keep in mind, Haggerty said, “that there are big barriers and that we need to take care of the patients within this system that has their arm tied behind their back.

Chen was funded by a grant from the National Institute on Aging outside the submitted work, and she was funded as a Yale National Clinician Scholar. A coauthor received grants from the Food and Drug Administration, Johnson & Johnson, the National Institutes of Health, the Agency for Healthcare Research and Quality, and Arnold Ventures. Another coauthor reported receiving personal fees from UpToDate and the Centers for Medicare & Medicaid Services. Gallagher has received research funding from Altimmune, Amgen, Boehringer Ingelheim, Currax, Eli Lilly and Company, Found, Novo Nordisk, Pfizer, Structure Therapeutics, and WeightWatchers. Haggerty reported article publishing charge was provided by West Virginia Alliance for Creative Health Solutions. Zvenyach and Clark had no disclosures.

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

PHILADELPHIA — Gastrointestinal (GI) bleeding after percutaneous coronary intervention (PCI) among patients on dual antiplatelet therapy (DAPT) remains risky in terms of morbidity and mortality, but the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score could help predict that risk, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In a predominantly Hispanic population in Texas, 2.5% of post-PCI patients on DAPT had GI bleeding in the first year. The PRECISE-DAPT score helped to predict GI bleeding among high-risk and moderate-risk patients.

“Our study established that the PRECISE-DAPT score possesses a moderate predictive accuracy not only for overall bleeding risk but also specifically for gastrointestinal bleeding,” said lead author Jesus Guzman, MD, a gastroenterology fellow at the Texas Tech University Health Sciences Center El Paso.

Current guidelines from the American College of Cardiology and American Heart Association recommend DAPT for 6-12 months post-PCI, with consideration for shorter durations in patients with lower ischemic risks but higher bleeding risks.

“Interestingly, some of these patients were on DAPT for more than 2 years, which goes beyond the guidelines,” he said. “In this patient population, this has to do with them being lost to follow-up and getting reestablished, and they kept refilling their prescriptions.”

Guzman and colleagues conducted a retrospective cohort study of patients receiving DAPT after PCI from 2014 to 2021. They looked for GI bleeding rates at 1 year and across the duration of the study period, as well as endoscopic indications, findings, concurrent antiplatelet therapy, and the primary cause of bleeding.

In addition, the research team evaluated the predictive value of the PRECISE-DAPT score, which categorizes patients based on low risk (≤ 17), moderate risk (18-24), and high risk (≥ 25) for bleeding. The score aims to optimize the balance between bleeding and ischemic risks, Guzman said, by incorporating five factors: Age, creatinine clearance, hemoglobin, white blood cell count, and history of spontaneous bleeding.

Among 1067 patients, 563 (57.9%) received clopidogrel and 409 (42%) received ticagrelor. The overall cohort was 66.6% men, 77.1% Hispanic, and had a mean age of 62 years.

The GI bleeding rate was 2.5% at 1-year post-PCI among 27 patients and 3.7% for the study duration among 39 patients, with a median follow-up of 2.2 years.

Among the 39 GI bleeds, 41% were lower GI bleeds, 28% were upper GI bleeds, 15% were small bowel bleeds, and 15% were undetermined. The most frequent etiology was colon cancer, accounting for 18% of bleeds, followed by 15% for gastric ulcers, 10% for diverticular bleeds, and 10% for hemorrhoidal bleeds.

In general, analyses indicated no significant differences in GI bleeding between patients on clopidogrel (21.2%) and those on ticagrelor (19.2%).

However, the odds of GI bleeding were significantly higher in patients with high-risk PRECISE-DAPT scores (odds ratio [OR], 2.5) and moderate-risk scores (OR, 2.8) than in those with low-risk scores. The majority of patients without GI bleeding had scores < 17, whereas the majority of patients with GI bleeding had scores > 24. An optimal threshold for the PRECISE-DAPT score was identified as ≥ 19.

“When patients on DAPT present with GI bleeding, it can be a clinical conundrum for gastroenterologists and cardiologists, especially when it can be a life-or-death event, and stopping DAPT can increase risk of thrombosis,” said Jeff Taclob, MD, a hepatology fellow at The University of Tennessee Health Science Center in Memphis. Taclob, who wasn’t involved with the study, attended the conference session.

“In this population in El Paso, in particular, many patients don’t have adequate healthcare, may be lost to follow-up, and get their prescriptions filled elsewhere, such as Juárez, Mexico,” he said. “Then they come in with this life-threatening bleed, so we need to focus more on their risks.”

Paying attention to specific patient populations, cultures, and values remains important for patient communication and clinical decision-making, Taclob noted.

“In this population of older men, there’s often a macho persona where they don’t want to seek help,” he said. “DAPT criteria could differ in other populations, but here, the PRECISE-DAPT score appeared to help.”

The study was awarded the ACG Outstanding Research Award in the GI Bleeding Category (Trainee). Guzman and Taclob reported no relevant disclosures.

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

PHILADELPHIA — Gastrointestinal (GI) bleeding after percutaneous coronary intervention (PCI) among patients on dual antiplatelet therapy (DAPT) remains risky in terms of morbidity and mortality, but the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score could help predict that risk, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In a predominantly Hispanic population in Texas, 2.5% of post-PCI patients on DAPT had GI bleeding in the first year. The PRECISE-DAPT score helped to predict GI bleeding among high-risk and moderate-risk patients.

“Our study established that the PRECISE-DAPT score possesses a moderate predictive accuracy not only for overall bleeding risk but also specifically for gastrointestinal bleeding,” said lead author Jesus Guzman, MD, a gastroenterology fellow at the Texas Tech University Health Sciences Center El Paso.

Current guidelines from the American College of Cardiology and American Heart Association recommend DAPT for 6-12 months post-PCI, with consideration for shorter durations in patients with lower ischemic risks but higher bleeding risks.

“Interestingly, some of these patients were on DAPT for more than 2 years, which goes beyond the guidelines,” he said. “In this patient population, this has to do with them being lost to follow-up and getting reestablished, and they kept refilling their prescriptions.”

Guzman and colleagues conducted a retrospective cohort study of patients receiving DAPT after PCI from 2014 to 2021. They looked for GI bleeding rates at 1 year and across the duration of the study period, as well as endoscopic indications, findings, concurrent antiplatelet therapy, and the primary cause of bleeding.

In addition, the research team evaluated the predictive value of the PRECISE-DAPT score, which categorizes patients based on low risk (≤ 17), moderate risk (18-24), and high risk (≥ 25) for bleeding. The score aims to optimize the balance between bleeding and ischemic risks, Guzman said, by incorporating five factors: Age, creatinine clearance, hemoglobin, white blood cell count, and history of spontaneous bleeding.

Among 1067 patients, 563 (57.9%) received clopidogrel and 409 (42%) received ticagrelor. The overall cohort was 66.6% men, 77.1% Hispanic, and had a mean age of 62 years.

The GI bleeding rate was 2.5% at 1-year post-PCI among 27 patients and 3.7% for the study duration among 39 patients, with a median follow-up of 2.2 years.

Among the 39 GI bleeds, 41% were lower GI bleeds, 28% were upper GI bleeds, 15% were small bowel bleeds, and 15% were undetermined. The most frequent etiology was colon cancer, accounting for 18% of bleeds, followed by 15% for gastric ulcers, 10% for diverticular bleeds, and 10% for hemorrhoidal bleeds.

In general, analyses indicated no significant differences in GI bleeding between patients on clopidogrel (21.2%) and those on ticagrelor (19.2%).

However, the odds of GI bleeding were significantly higher in patients with high-risk PRECISE-DAPT scores (odds ratio [OR], 2.5) and moderate-risk scores (OR, 2.8) than in those with low-risk scores. The majority of patients without GI bleeding had scores < 17, whereas the majority of patients with GI bleeding had scores > 24. An optimal threshold for the PRECISE-DAPT score was identified as ≥ 19.

“When patients on DAPT present with GI bleeding, it can be a clinical conundrum for gastroenterologists and cardiologists, especially when it can be a life-or-death event, and stopping DAPT can increase risk of thrombosis,” said Jeff Taclob, MD, a hepatology fellow at The University of Tennessee Health Science Center in Memphis. Taclob, who wasn’t involved with the study, attended the conference session.

“In this population in El Paso, in particular, many patients don’t have adequate healthcare, may be lost to follow-up, and get their prescriptions filled elsewhere, such as Juárez, Mexico,” he said. “Then they come in with this life-threatening bleed, so we need to focus more on their risks.”

Paying attention to specific patient populations, cultures, and values remains important for patient communication and clinical decision-making, Taclob noted.

“In this population of older men, there’s often a macho persona where they don’t want to seek help,” he said. “DAPT criteria could differ in other populations, but here, the PRECISE-DAPT score appeared to help.”

The study was awarded the ACG Outstanding Research Award in the GI Bleeding Category (Trainee). Guzman and Taclob reported no relevant disclosures.

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

PHILADELPHIA — Gastrointestinal (GI) bleeding after percutaneous coronary intervention (PCI) among patients on dual antiplatelet therapy (DAPT) remains risky in terms of morbidity and mortality, but the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score could help predict that risk, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In a predominantly Hispanic population in Texas, 2.5% of post-PCI patients on DAPT had GI bleeding in the first year. The PRECISE-DAPT score helped to predict GI bleeding among high-risk and moderate-risk patients.

“Our study established that the PRECISE-DAPT score possesses a moderate predictive accuracy not only for overall bleeding risk but also specifically for gastrointestinal bleeding,” said lead author Jesus Guzman, MD, a gastroenterology fellow at the Texas Tech University Health Sciences Center El Paso.

Current guidelines from the American College of Cardiology and American Heart Association recommend DAPT for 6-12 months post-PCI, with consideration for shorter durations in patients with lower ischemic risks but higher bleeding risks.

“Interestingly, some of these patients were on DAPT for more than 2 years, which goes beyond the guidelines,” he said. “In this patient population, this has to do with them being lost to follow-up and getting reestablished, and they kept refilling their prescriptions.”

Guzman and colleagues conducted a retrospective cohort study of patients receiving DAPT after PCI from 2014 to 2021. They looked for GI bleeding rates at 1 year and across the duration of the study period, as well as endoscopic indications, findings, concurrent antiplatelet therapy, and the primary cause of bleeding.

In addition, the research team evaluated the predictive value of the PRECISE-DAPT score, which categorizes patients based on low risk (≤ 17), moderate risk (18-24), and high risk (≥ 25) for bleeding. The score aims to optimize the balance between bleeding and ischemic risks, Guzman said, by incorporating five factors: Age, creatinine clearance, hemoglobin, white blood cell count, and history of spontaneous bleeding.

Among 1067 patients, 563 (57.9%) received clopidogrel and 409 (42%) received ticagrelor. The overall cohort was 66.6% men, 77.1% Hispanic, and had a mean age of 62 years.

The GI bleeding rate was 2.5% at 1-year post-PCI among 27 patients and 3.7% for the study duration among 39 patients, with a median follow-up of 2.2 years.

Among the 39 GI bleeds, 41% were lower GI bleeds, 28% were upper GI bleeds, 15% were small bowel bleeds, and 15% were undetermined. The most frequent etiology was colon cancer, accounting for 18% of bleeds, followed by 15% for gastric ulcers, 10% for diverticular bleeds, and 10% for hemorrhoidal bleeds.

In general, analyses indicated no significant differences in GI bleeding between patients on clopidogrel (21.2%) and those on ticagrelor (19.2%).

However, the odds of GI bleeding were significantly higher in patients with high-risk PRECISE-DAPT scores (odds ratio [OR], 2.5) and moderate-risk scores (OR, 2.8) than in those with low-risk scores. The majority of patients without GI bleeding had scores < 17, whereas the majority of patients with GI bleeding had scores > 24. An optimal threshold for the PRECISE-DAPT score was identified as ≥ 19.

“When patients on DAPT present with GI bleeding, it can be a clinical conundrum for gastroenterologists and cardiologists, especially when it can be a life-or-death event, and stopping DAPT can increase risk of thrombosis,” said Jeff Taclob, MD, a hepatology fellow at The University of Tennessee Health Science Center in Memphis. Taclob, who wasn’t involved with the study, attended the conference session.

“In this population in El Paso, in particular, many patients don’t have adequate healthcare, may be lost to follow-up, and get their prescriptions filled elsewhere, such as Juárez, Mexico,” he said. “Then they come in with this life-threatening bleed, so we need to focus more on their risks.”

Paying attention to specific patient populations, cultures, and values remains important for patient communication and clinical decision-making, Taclob noted.

“In this population of older men, there’s often a macho persona where they don’t want to seek help,” he said. “DAPT criteria could differ in other populations, but here, the PRECISE-DAPT score appeared to help.”

The study was awarded the ACG Outstanding Research Award in the GI Bleeding Category (Trainee). Guzman and Taclob reported no relevant disclosures.

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

PHILADELPHIA — New research provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) do not increase the risk for pancreatic cancer.

Instead, the large electronic health record (EHR) analysis of patients with type 2 diabetes (T2D) found those taking GLP-1 RAs had a significantly lower risk for pancreatic cancer than peers on other antidiabetic medications. 

“Although there were previous reports suggesting possible association between pancreatic cancer and GLP-1 receptor agonist medications, this study provides reassurance that there is no observed increased incidence of pancreatic cancer in patients prescribed these medications,” said Khaled Alsabbagh Alchirazi, MD, a gastroenterology fellow with Aurora Healthcare in Brookfield, Wisconsin. 

He presented the study findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. 

 

Important Topic

Patients with T2D are at increased risk for several malignancies, including pancreatic cancer. Given the unique mechanism of action of GLP-1 RAs in the pancreas, it was important to investigate the relationship between use of these drugs and incidence of pancreatic cancer, he explained.

Using the TriNetX database, the study team identified 4.95 million antidiabetic drug naive T2D patients who were prescribed antidiabetic medications for the first time between 2005 and 2020. None had a history of pancreatic cancer. 

A total of 245,532 were prescribed a GLP-1 RA. The researchers compared GLP-1 RAs users to users of other antidiabetic medications — namely, insulin, metformin, alpha-glucosidase inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), sulfonylureas, and thiazolidinediones. 

Patients were propensity score-matched based on demographics, health determinants, lifestyle factors, medical history, family history of cancers, and acute/chronic pancreatitis. 

The risk for pancreatic cancer was significantly lower among patients on GLP-1 RAs vs insulin (hazard ratio [HR], 0.47; 95% CI, 0.40-0.55), DPP-4i (HR, 0.80; 95% CI, 0.73-0.89), SGLT2i (HR, 0.78; 95% CI, 0.69-0.89), and sulfonylureas (HR, 0.84; 95% CI, 0.74-0.95), Alchirazi reported.

The results were consistent across different groups, including patients with obesity/ overweight on GLP-1 RAs vs insulin (HR, 0.53; 95% CI, 0.43-0.65) and SGLT2i (HR, 0.81; 95% CI, 0.69-0.96).

Strengths of the analysis included the large and diverse cohort of propensity score-matched patients. Limitations included the retrospective design and use of claims data that did not provide granular data on pathology reports.

The study by Alchirazi and colleagues aligns with a large population-based cohort study from Israel that found no evidence that GLP-1 RAs increase risk for pancreatic cancer over 7 years following initiation.

Separately, a study of more than 1.6 million patients with T2D found that treatment with a GLP-1 RA (vs insulin or metformin) was associated with lower risks for specific types of obesity-related cancers, including pancreatic cancer.

The study had no specific funding. Alchirazi had no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — New research provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) do not increase the risk for pancreatic cancer.

Instead, the large electronic health record (EHR) analysis of patients with type 2 diabetes (T2D) found those taking GLP-1 RAs had a significantly lower risk for pancreatic cancer than peers on other antidiabetic medications. 

“Although there were previous reports suggesting possible association between pancreatic cancer and GLP-1 receptor agonist medications, this study provides reassurance that there is no observed increased incidence of pancreatic cancer in patients prescribed these medications,” said Khaled Alsabbagh Alchirazi, MD, a gastroenterology fellow with Aurora Healthcare in Brookfield, Wisconsin. 

He presented the study findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. 

 

Important Topic

Patients with T2D are at increased risk for several malignancies, including pancreatic cancer. Given the unique mechanism of action of GLP-1 RAs in the pancreas, it was important to investigate the relationship between use of these drugs and incidence of pancreatic cancer, he explained.

Using the TriNetX database, the study team identified 4.95 million antidiabetic drug naive T2D patients who were prescribed antidiabetic medications for the first time between 2005 and 2020. None had a history of pancreatic cancer. 

A total of 245,532 were prescribed a GLP-1 RA. The researchers compared GLP-1 RAs users to users of other antidiabetic medications — namely, insulin, metformin, alpha-glucosidase inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), sulfonylureas, and thiazolidinediones. 

Patients were propensity score-matched based on demographics, health determinants, lifestyle factors, medical history, family history of cancers, and acute/chronic pancreatitis. 

The risk for pancreatic cancer was significantly lower among patients on GLP-1 RAs vs insulin (hazard ratio [HR], 0.47; 95% CI, 0.40-0.55), DPP-4i (HR, 0.80; 95% CI, 0.73-0.89), SGLT2i (HR, 0.78; 95% CI, 0.69-0.89), and sulfonylureas (HR, 0.84; 95% CI, 0.74-0.95), Alchirazi reported.

The results were consistent across different groups, including patients with obesity/ overweight on GLP-1 RAs vs insulin (HR, 0.53; 95% CI, 0.43-0.65) and SGLT2i (HR, 0.81; 95% CI, 0.69-0.96).

Strengths of the analysis included the large and diverse cohort of propensity score-matched patients. Limitations included the retrospective design and use of claims data that did not provide granular data on pathology reports.

The study by Alchirazi and colleagues aligns with a large population-based cohort study from Israel that found no evidence that GLP-1 RAs increase risk for pancreatic cancer over 7 years following initiation.

Separately, a study of more than 1.6 million patients with T2D found that treatment with a GLP-1 RA (vs insulin or metformin) was associated with lower risks for specific types of obesity-related cancers, including pancreatic cancer.

The study had no specific funding. Alchirazi had no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — New research provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) do not increase the risk for pancreatic cancer.

Instead, the large electronic health record (EHR) analysis of patients with type 2 diabetes (T2D) found those taking GLP-1 RAs had a significantly lower risk for pancreatic cancer than peers on other antidiabetic medications. 

“Although there were previous reports suggesting possible association between pancreatic cancer and GLP-1 receptor agonist medications, this study provides reassurance that there is no observed increased incidence of pancreatic cancer in patients prescribed these medications,” said Khaled Alsabbagh Alchirazi, MD, a gastroenterology fellow with Aurora Healthcare in Brookfield, Wisconsin. 

He presented the study findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. 

 

Important Topic

Patients with T2D are at increased risk for several malignancies, including pancreatic cancer. Given the unique mechanism of action of GLP-1 RAs in the pancreas, it was important to investigate the relationship between use of these drugs and incidence of pancreatic cancer, he explained.

Using the TriNetX database, the study team identified 4.95 million antidiabetic drug naive T2D patients who were prescribed antidiabetic medications for the first time between 2005 and 2020. None had a history of pancreatic cancer. 

A total of 245,532 were prescribed a GLP-1 RA. The researchers compared GLP-1 RAs users to users of other antidiabetic medications — namely, insulin, metformin, alpha-glucosidase inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), sulfonylureas, and thiazolidinediones. 

Patients were propensity score-matched based on demographics, health determinants, lifestyle factors, medical history, family history of cancers, and acute/chronic pancreatitis. 

The risk for pancreatic cancer was significantly lower among patients on GLP-1 RAs vs insulin (hazard ratio [HR], 0.47; 95% CI, 0.40-0.55), DPP-4i (HR, 0.80; 95% CI, 0.73-0.89), SGLT2i (HR, 0.78; 95% CI, 0.69-0.89), and sulfonylureas (HR, 0.84; 95% CI, 0.74-0.95), Alchirazi reported.

The results were consistent across different groups, including patients with obesity/ overweight on GLP-1 RAs vs insulin (HR, 0.53; 95% CI, 0.43-0.65) and SGLT2i (HR, 0.81; 95% CI, 0.69-0.96).

Strengths of the analysis included the large and diverse cohort of propensity score-matched patients. Limitations included the retrospective design and use of claims data that did not provide granular data on pathology reports.

The study by Alchirazi and colleagues aligns with a large population-based cohort study from Israel that found no evidence that GLP-1 RAs increase risk for pancreatic cancer over 7 years following initiation.

Separately, a study of more than 1.6 million patients with T2D found that treatment with a GLP-1 RA (vs insulin or metformin) was associated with lower risks for specific types of obesity-related cancers, including pancreatic cancer.

The study had no specific funding. Alchirazi had no relevant disclosures.

A version of this article appeared on Medscape.com.