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Bimekizumab Gains FDA Approval for Psoriatic Arthritis, Axial Spondyloarthritis
The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx; UCB) for adult patients with active psoriatic arthritis (PsA), active nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, and active ankylosing spondylitis (AS).
The drug, an interleukin (IL)–17A and IL-17F inhibitor, was first approved in October 2023 for treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
“In psoriatic arthritis and across the spectrum of axSpA, clinical study results and real-world experience outside the US have highlighted that Bimzelx can help patients achieve high thresholds of clinical response that are rapid in onset and sustained up to 2 years,” said Emmanuel Caeymaex, executive vice president, head of patient impact, and chief commercial officer of UCB in a press release.
The recommended dosage of bimekizumab for adult patients with active PsA, nr-axSpA, or AS is 160 mg by subcutaneous injection every 4 weeks. For patients with PsA and coexistent moderate to severe plaque psoriasis, the dosage is the same as for patients with plaque psoriasis. The dosing for plaque psoriasis is to administer 320 mg (two 160-mg injections) by subcutaneous injection at weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing ≥ 120 kg, consider a dose of 320 mg every 4 weeks after week 16.
PsA Clinical Trials
The approval for PsA was based on data from two phase 3 clinical trials, including 852 participants naive to biologics (BE OPTIMAL) and 400 participants with inadequate response to treatment with one or two tumor necrosis factor (TNF) inhibitors (BE COMPLETE). Both studies met their primary endpoint, 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, as well as ranked secondary endpoints. Secondary endpoints included minimal disease activity (MDA) and Psoriasis Area and Severity Index 100 (complete skin clearance) at week 16.
At 16 weeks:
- About 44% of both the biologic-naive (189 of 431) and TNF inhibitor–resistant (116 of 267) groups receiving bimekizumab achieved ACR50 response, compared with 10% (28 of 281) and 7% (9 of 133) receiving placebo, respectively.
- About 45% of all patients treated with bimekizumab achieved MDA.
- Nearly 60% of TNF inhibitor–resistant patients had complete skin clearance.
These responses generally were sustained for 1 year. The most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, and urinary tract infection.
NR-axSpA and AS Clinical Trials
The approval for active nr-axSpA and active AS was based on data from two clinical studies, BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS). Both studies met their primary endpoint, 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks.
Key findings included:
- In nr-axSpA patients, 47.7% (61 of 128) receiving bimekizumab achieved ASAS40 at week 16, compared with 21.4% (27 of 126) receiving placebo.
- In AS patients, 44.8% (99 of 221) in the bimekizumab group achieved ASAS40 response at week 16 vs 22.5% (25 of 111) receiving placebo.
- At 1 year in both groups, 60% treated with bimekizumab achieved an Ankylosing Spondylitis Disease Activity Score < 2.1.
In nr-axSpA, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, cough, fatigue, musculoskeletal pain, myalgia, tonsillitis, increase in transaminase, and urinary tract infection. In AS, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, injection-site pain, rash, and vulvovaginal mycotic infection.
Bimekizumab was approved by the European Commission for the same rheumatologic indications in June 2023.
Bimekizumab is currently available to eligible patients in the United States, according to the press release.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx; UCB) for adult patients with active psoriatic arthritis (PsA), active nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, and active ankylosing spondylitis (AS).
The drug, an interleukin (IL)–17A and IL-17F inhibitor, was first approved in October 2023 for treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
“In psoriatic arthritis and across the spectrum of axSpA, clinical study results and real-world experience outside the US have highlighted that Bimzelx can help patients achieve high thresholds of clinical response that are rapid in onset and sustained up to 2 years,” said Emmanuel Caeymaex, executive vice president, head of patient impact, and chief commercial officer of UCB in a press release.
The recommended dosage of bimekizumab for adult patients with active PsA, nr-axSpA, or AS is 160 mg by subcutaneous injection every 4 weeks. For patients with PsA and coexistent moderate to severe plaque psoriasis, the dosage is the same as for patients with plaque psoriasis. The dosing for plaque psoriasis is to administer 320 mg (two 160-mg injections) by subcutaneous injection at weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing ≥ 120 kg, consider a dose of 320 mg every 4 weeks after week 16.
PsA Clinical Trials
The approval for PsA was based on data from two phase 3 clinical trials, including 852 participants naive to biologics (BE OPTIMAL) and 400 participants with inadequate response to treatment with one or two tumor necrosis factor (TNF) inhibitors (BE COMPLETE). Both studies met their primary endpoint, 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, as well as ranked secondary endpoints. Secondary endpoints included minimal disease activity (MDA) and Psoriasis Area and Severity Index 100 (complete skin clearance) at week 16.
At 16 weeks:
- About 44% of both the biologic-naive (189 of 431) and TNF inhibitor–resistant (116 of 267) groups receiving bimekizumab achieved ACR50 response, compared with 10% (28 of 281) and 7% (9 of 133) receiving placebo, respectively.
- About 45% of all patients treated with bimekizumab achieved MDA.
- Nearly 60% of TNF inhibitor–resistant patients had complete skin clearance.
These responses generally were sustained for 1 year. The most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, and urinary tract infection.
NR-axSpA and AS Clinical Trials
The approval for active nr-axSpA and active AS was based on data from two clinical studies, BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS). Both studies met their primary endpoint, 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks.
Key findings included:
- In nr-axSpA patients, 47.7% (61 of 128) receiving bimekizumab achieved ASAS40 at week 16, compared with 21.4% (27 of 126) receiving placebo.
- In AS patients, 44.8% (99 of 221) in the bimekizumab group achieved ASAS40 response at week 16 vs 22.5% (25 of 111) receiving placebo.
- At 1 year in both groups, 60% treated with bimekizumab achieved an Ankylosing Spondylitis Disease Activity Score < 2.1.
In nr-axSpA, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, cough, fatigue, musculoskeletal pain, myalgia, tonsillitis, increase in transaminase, and urinary tract infection. In AS, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, injection-site pain, rash, and vulvovaginal mycotic infection.
Bimekizumab was approved by the European Commission for the same rheumatologic indications in June 2023.
Bimekizumab is currently available to eligible patients in the United States, according to the press release.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx; UCB) for adult patients with active psoriatic arthritis (PsA), active nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, and active ankylosing spondylitis (AS).
The drug, an interleukin (IL)–17A and IL-17F inhibitor, was first approved in October 2023 for treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
“In psoriatic arthritis and across the spectrum of axSpA, clinical study results and real-world experience outside the US have highlighted that Bimzelx can help patients achieve high thresholds of clinical response that are rapid in onset and sustained up to 2 years,” said Emmanuel Caeymaex, executive vice president, head of patient impact, and chief commercial officer of UCB in a press release.
The recommended dosage of bimekizumab for adult patients with active PsA, nr-axSpA, or AS is 160 mg by subcutaneous injection every 4 weeks. For patients with PsA and coexistent moderate to severe plaque psoriasis, the dosage is the same as for patients with plaque psoriasis. The dosing for plaque psoriasis is to administer 320 mg (two 160-mg injections) by subcutaneous injection at weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing ≥ 120 kg, consider a dose of 320 mg every 4 weeks after week 16.
PsA Clinical Trials
The approval for PsA was based on data from two phase 3 clinical trials, including 852 participants naive to biologics (BE OPTIMAL) and 400 participants with inadequate response to treatment with one or two tumor necrosis factor (TNF) inhibitors (BE COMPLETE). Both studies met their primary endpoint, 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, as well as ranked secondary endpoints. Secondary endpoints included minimal disease activity (MDA) and Psoriasis Area and Severity Index 100 (complete skin clearance) at week 16.
At 16 weeks:
- About 44% of both the biologic-naive (189 of 431) and TNF inhibitor–resistant (116 of 267) groups receiving bimekizumab achieved ACR50 response, compared with 10% (28 of 281) and 7% (9 of 133) receiving placebo, respectively.
- About 45% of all patients treated with bimekizumab achieved MDA.
- Nearly 60% of TNF inhibitor–resistant patients had complete skin clearance.
These responses generally were sustained for 1 year. The most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, and urinary tract infection.
NR-axSpA and AS Clinical Trials
The approval for active nr-axSpA and active AS was based on data from two clinical studies, BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS). Both studies met their primary endpoint, 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks.
Key findings included:
- In nr-axSpA patients, 47.7% (61 of 128) receiving bimekizumab achieved ASAS40 at week 16, compared with 21.4% (27 of 126) receiving placebo.
- In AS patients, 44.8% (99 of 221) in the bimekizumab group achieved ASAS40 response at week 16 vs 22.5% (25 of 111) receiving placebo.
- At 1 year in both groups, 60% treated with bimekizumab achieved an Ankylosing Spondylitis Disease Activity Score < 2.1.
In nr-axSpA, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, cough, fatigue, musculoskeletal pain, myalgia, tonsillitis, increase in transaminase, and urinary tract infection. In AS, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, injection-site pain, rash, and vulvovaginal mycotic infection.
Bimekizumab was approved by the European Commission for the same rheumatologic indications in June 2023.
Bimekizumab is currently available to eligible patients in the United States, according to the press release.
A version of this article first appeared on Medscape.com.
Benralizumab Now FDA Approved to Treat EGPA Vasculitis
The Food and Drug Administration (FDA) has approved benralizumab (Fasenra) for the treatment of adults with eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome.
The drug is the second approved biologic for the treatment of EGPA. The first, mepolizumab (Nucala), was approved in 2017.
“This disease has a devastating impact on patients and the quality of their life, and they need more treatment options. The approval of another treatment in EGPA is welcome news to the approximately 15,000 patients living in the US with this difficult-to-treat rare disease,” said Joyce Kullman, executive director of the Vasculitis Foundation, in a press release on September 18. 
Benralizumab, developed by AstraZeneca, is a monoclonal antibody against the interleukin-5 alpha receptor expressed on eosinophils. The drug was first approved in 2017 as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and is now approved for use in children aged 6 years and older.
The new indication was based on positive results from a noninferiority trial comparing benralizumab and mepolizumab. For the trial, published in the New England Journal of Medicine earlier in 2024, 140 adults with relapsing or refractory EGPA were randomized to a 30-mg subcutaneous injection of benralizumab or three separate 100-mg mepolizumab injections every 4 weeks for 1 year. At weeks 36 and 48, 59% of patients in the benralizumab group and 56% of patients in the mepolizumab group achieved remission (95% CI, –13 to 18; P = .73 for superiority). From week 42 to 52, 41% of patients who received benralizumab completely stopped taking oral glucocorticoids, compared with 26% of those who received mepolizumab.
“Patients often rely on long-term oral corticosteroids, which can cause serious and lasting side effects. Benralizumab is a much-needed treatment option, with data showing that not only is remission an achievable goal for EGPA patients, but benralizumab can also help patients taper off steroid therapy,” Michael Wechsler, MD, director of The Asthma Institute at National Jewish Health in Denver, Colorado, and the international coordinating investigator for the clinical trial, said in the press release.
Benralizumab is administered via subcutaneous injection. In adults with EGPA, the recommended dosage is 30 mg every 4 weeks for the first three doses, then once every 8 weeks.
The most common adverse reactions include headache and pharyngitis, according to the prescribing information.
Benralizumab is also in development for the treatment of chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, and hypereosinophilic syndrome.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration (FDA) has approved benralizumab (Fasenra) for the treatment of adults with eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome.
The drug is the second approved biologic for the treatment of EGPA. The first, mepolizumab (Nucala), was approved in 2017.
“This disease has a devastating impact on patients and the quality of their life, and they need more treatment options. The approval of another treatment in EGPA is welcome news to the approximately 15,000 patients living in the US with this difficult-to-treat rare disease,” said Joyce Kullman, executive director of the Vasculitis Foundation, in a press release on September 18.
Benralizumab, developed by AstraZeneca, is a monoclonal antibody against the interleukin-5 alpha receptor expressed on eosinophils. The drug was first approved in 2017 as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and is now approved for use in children aged 6 years and older.
The new indication was based on positive results from a noninferiority trial comparing benralizumab and mepolizumab. For the trial, published in the New England Journal of Medicine earlier in 2024, 140 adults with relapsing or refractory EGPA were randomized to a 30-mg subcutaneous injection of benralizumab or three separate 100-mg mepolizumab injections every 4 weeks for 1 year. At weeks 36 and 48, 59% of patients in the benralizumab group and 56% of patients in the mepolizumab group achieved remission (95% CI, –13 to 18; P = .73 for superiority). From week 42 to 52, 41% of patients who received benralizumab completely stopped taking oral glucocorticoids, compared with 26% of those who received mepolizumab.
“Patients often rely on long-term oral corticosteroids, which can cause serious and lasting side effects. Benralizumab is a much-needed treatment option, with data showing that not only is remission an achievable goal for EGPA patients, but benralizumab can also help patients taper off steroid therapy,” Michael Wechsler, MD, director of The Asthma Institute at National Jewish Health in Denver, Colorado, and the international coordinating investigator for the clinical trial, said in the press release.
Benralizumab is administered via subcutaneous injection. In adults with EGPA, the recommended dosage is 30 mg every 4 weeks for the first three doses, then once every 8 weeks.
The most common adverse reactions include headache and pharyngitis, according to the prescribing information.
Benralizumab is also in development for the treatment of chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, and hypereosinophilic syndrome.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration (FDA) has approved benralizumab (Fasenra) for the treatment of adults with eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome.
The drug is the second approved biologic for the treatment of EGPA. The first, mepolizumab (Nucala), was approved in 2017.
“This disease has a devastating impact on patients and the quality of their life, and they need more treatment options. The approval of another treatment in EGPA is welcome news to the approximately 15,000 patients living in the US with this difficult-to-treat rare disease,” said Joyce Kullman, executive director of the Vasculitis Foundation, in a press release on September 18.
Benralizumab, developed by AstraZeneca, is a monoclonal antibody against the interleukin-5 alpha receptor expressed on eosinophils. The drug was first approved in 2017 as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and is now approved for use in children aged 6 years and older.
The new indication was based on positive results from a noninferiority trial comparing benralizumab and mepolizumab. For the trial, published in the New England Journal of Medicine earlier in 2024, 140 adults with relapsing or refractory EGPA were randomized to a 30-mg subcutaneous injection of benralizumab or three separate 100-mg mepolizumab injections every 4 weeks for 1 year. At weeks 36 and 48, 59% of patients in the benralizumab group and 56% of patients in the mepolizumab group achieved remission (95% CI, –13 to 18; P = .73 for superiority). From week 42 to 52, 41% of patients who received benralizumab completely stopped taking oral glucocorticoids, compared with 26% of those who received mepolizumab.
“Patients often rely on long-term oral corticosteroids, which can cause serious and lasting side effects. Benralizumab is a much-needed treatment option, with data showing that not only is remission an achievable goal for EGPA patients, but benralizumab can also help patients taper off steroid therapy,” Michael Wechsler, MD, director of The Asthma Institute at National Jewish Health in Denver, Colorado, and the international coordinating investigator for the clinical trial, said in the press release.
Benralizumab is administered via subcutaneous injection. In adults with EGPA, the recommended dosage is 30 mg every 4 weeks for the first three doses, then once every 8 weeks.
The most common adverse reactions include headache and pharyngitis, according to the prescribing information.
Benralizumab is also in development for the treatment of chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, and hypereosinophilic syndrome.
A version of this article first appeared on Medscape.com.
Rheumatology Clinic Interventions for Smoking, Blood Pressure ‘Make a Big Difference’
Two relatively simple interventions — addressing high blood pressure (BP) and smoking cessation — could make a huge difference for patients with rheumatic disease. Patients with autoimmune disease are up to three times more likely to develop cardiovascular disease (CVD) than the general population. In addition to compounding CVD, smoking is tied to the development of certain autoimmune conditions, as well as worse outcomes. Christie Bartels, MD, chief of the Division of Rheumatology at the University of Wisconsin School of Medicine and Public Health, Madison, has focused her research on improving cardiac health in inflammatory diseases. This news organization spoke with Bartels about two short interventions she developed that tackle hypertension and smoking cessation during regular visits, each taking less than 3 minutes.
How Do These Programs Address Cardiac Disease Prevention?
The BP and Quit Connect programs help clinics systematically address the two most modifiable risk factors for CVD: high BP and smoking. There’s also evidence that addressing these two risk factors improves outcomes in rheumatic diseases. Hypertension predicts an increase in lupus damage. Particularly in lupus nephritis, hypertension will increase the risk for CVD and kidney failure. People who use tobacco have worse outcomes in diseases like rheumatoid arthritis, psoriatic arthritis, and lupus, as well as more CVD, and antirheumatic drugs may not work as well.
In 90 seconds to 3 minutes, staff can do protocol-based care, which we’ve done across 20,000-plus visits. We showed we can improve population level rates of high BP and BP control, as well as increase smoking quitting rates across different patient settings.
What Is the Quit Connect Program?
The Quit Connect program is a 10- to 90-second point of care intervention. During rooming, staff (medical assistants and nurses) ask patients: “A) Do you smoke? and B) Have you thought about cutting back or quitting in the next 30 days?”
It turns out, when you ask the question that way, between a third and a half of people say that they’ve thought about cutting back or quitting. Then, we can get patients connected directly to Quitline, a free public service across all 50 states that smokers can use to get cessation support.
If patients are ready, we ask if we can arrange for them to receive a call from a Quitline coach about setting a quit date or receiving free nicotine replacement therapy. The beautiful thing is when that all happens, A) it’s free to the patient, and B) the results from the Quitline can be recorded right back to the electronic health record.
In our most recent publication in Arthritis Care & Research, we documented bringing Quit Connect to Grady Hospital in downtown Atlanta. It’s a safety net hospital, where 80% patients are Black and 70%-80% patients are on public insurance or uninsured. Using this protocol, we improved Quitline referrals 20-fold.
What Is the BP Connect Program?
At least half of the encounters in United States happen in specialty clinics. Unfortunately, when patients get their BP measured in a specialty clinic that’s not a cardiology or a vascular clinic, often, even if the pressure is high, the clinic doesn’t give patients feedback on that. The problem is because we haven’t said anything, that gives people the false reassurance that their BP is okay.
We’ve developed a 3-minute protocol to ask, advise, and connect. The idea is that if we measure a high BP, then we remeasure and confirm that it’s high. Then, we advise why it matters in rheumatic disease: Patients with rheumatic diseases are already at an increased risk for heart disease, and controlling BP can make a big difference. Then, we connect patients with high BP back to primary care.
Specifically, a SmartSet — an electronic medical record feature — prompts different actions based on confirmed high BP readings:
- If systolic BP ≥ 140-159, the SmartSet directs scheduling a visit to a nurse or primary care provider.
- If systolic BP ≥ 160-179, the next primary care visit anticipates the need to see a prescriber.
- If systolic BP ≥ 180, then the medical assistant or nurse at the visit is instructed to notify the provider who can arrange a provider-to-provider handoff for safety to exclude a hypertensive emergency.
That order goes to the scheduler to call primary care to coordinate follow-up. BP Connect doubled the likelihood of a guideline-recommended follow-up in primary care within 30 days. All patients benefited, and disparities decreased. BP Connect has had 1100 downloads, and both BP and Quit Connect programs are endorsed by the Centers for Disease Control and Prevention and Million Hearts.
How Do These Programs Affect Clinical Practice?
We developed these interventions with a health system engineer, and we time stamped everything. Part of the sustainability of this model is that it fits within a regular workflow. As a practicing rheumatologist, I understand that time is a precious commodity.
The interventions are in partnership with frontline staff. We’ve received feedback that they feel pride participating in these initiatives. They can say, because of me, 30 patients followed up last month for high BP, or 10 patients took a referral to the Quitline last year. We celebrate these accomplishments with the staff.
What Are the Next Steps for These Programs?
Public-facing toolkits for both BP and Quit Connect programs are available online. We have implemented [these programs] in a rural setting, in an urban setting, in Milwaukee and in Atlanta, and we are looking in the future to do a larger, multistate implementation study. If folks are interested, we’d love to partner with them to look at disseminating this further.
A version of this article appeared on Medscape.com.
Two relatively simple interventions — addressing high blood pressure (BP) and smoking cessation — could make a huge difference for patients with rheumatic disease. Patients with autoimmune disease are up to three times more likely to develop cardiovascular disease (CVD) than the general population. In addition to compounding CVD, smoking is tied to the development of certain autoimmune conditions, as well as worse outcomes. Christie Bartels, MD, chief of the Division of Rheumatology at the University of Wisconsin School of Medicine and Public Health, Madison, has focused her research on improving cardiac health in inflammatory diseases. This news organization spoke with Bartels about two short interventions she developed that tackle hypertension and smoking cessation during regular visits, each taking less than 3 minutes.
How Do These Programs Address Cardiac Disease Prevention?
The BP and Quit Connect programs help clinics systematically address the two most modifiable risk factors for CVD: high BP and smoking. There’s also evidence that addressing these two risk factors improves outcomes in rheumatic diseases. Hypertension predicts an increase in lupus damage. Particularly in lupus nephritis, hypertension will increase the risk for CVD and kidney failure. People who use tobacco have worse outcomes in diseases like rheumatoid arthritis, psoriatic arthritis, and lupus, as well as more CVD, and antirheumatic drugs may not work as well.
In 90 seconds to 3 minutes, staff can do protocol-based care, which we’ve done across 20,000-plus visits. We showed we can improve population level rates of high BP and BP control, as well as increase smoking quitting rates across different patient settings.
What Is the Quit Connect Program?
The Quit Connect program is a 10- to 90-second point of care intervention. During rooming, staff (medical assistants and nurses) ask patients: “A) Do you smoke? and B) Have you thought about cutting back or quitting in the next 30 days?”
It turns out, when you ask the question that way, between a third and a half of people say that they’ve thought about cutting back or quitting. Then, we can get patients connected directly to Quitline, a free public service across all 50 states that smokers can use to get cessation support.
If patients are ready, we ask if we can arrange for them to receive a call from a Quitline coach about setting a quit date or receiving free nicotine replacement therapy. The beautiful thing is when that all happens, A) it’s free to the patient, and B) the results from the Quitline can be recorded right back to the electronic health record.
In our most recent publication in Arthritis Care & Research, we documented bringing Quit Connect to Grady Hospital in downtown Atlanta. It’s a safety net hospital, where 80% patients are Black and 70%-80% patients are on public insurance or uninsured. Using this protocol, we improved Quitline referrals 20-fold.
What Is the BP Connect Program?
At least half of the encounters in United States happen in specialty clinics. Unfortunately, when patients get their BP measured in a specialty clinic that’s not a cardiology or a vascular clinic, often, even if the pressure is high, the clinic doesn’t give patients feedback on that. The problem is because we haven’t said anything, that gives people the false reassurance that their BP is okay.
We’ve developed a 3-minute protocol to ask, advise, and connect. The idea is that if we measure a high BP, then we remeasure and confirm that it’s high. Then, we advise why it matters in rheumatic disease: Patients with rheumatic diseases are already at an increased risk for heart disease, and controlling BP can make a big difference. Then, we connect patients with high BP back to primary care.
Specifically, a SmartSet — an electronic medical record feature — prompts different actions based on confirmed high BP readings:
- If systolic BP ≥ 140-159, the SmartSet directs scheduling a visit to a nurse or primary care provider.
- If systolic BP ≥ 160-179, the next primary care visit anticipates the need to see a prescriber.
- If systolic BP ≥ 180, then the medical assistant or nurse at the visit is instructed to notify the provider who can arrange a provider-to-provider handoff for safety to exclude a hypertensive emergency.
That order goes to the scheduler to call primary care to coordinate follow-up. BP Connect doubled the likelihood of a guideline-recommended follow-up in primary care within 30 days. All patients benefited, and disparities decreased. BP Connect has had 1100 downloads, and both BP and Quit Connect programs are endorsed by the Centers for Disease Control and Prevention and Million Hearts.
How Do These Programs Affect Clinical Practice?
We developed these interventions with a health system engineer, and we time stamped everything. Part of the sustainability of this model is that it fits within a regular workflow. As a practicing rheumatologist, I understand that time is a precious commodity.
The interventions are in partnership with frontline staff. We’ve received feedback that they feel pride participating in these initiatives. They can say, because of me, 30 patients followed up last month for high BP, or 10 patients took a referral to the Quitline last year. We celebrate these accomplishments with the staff.
What Are the Next Steps for These Programs?
Public-facing toolkits for both BP and Quit Connect programs are available online. We have implemented [these programs] in a rural setting, in an urban setting, in Milwaukee and in Atlanta, and we are looking in the future to do a larger, multistate implementation study. If folks are interested, we’d love to partner with them to look at disseminating this further.
A version of this article appeared on Medscape.com.
Two relatively simple interventions — addressing high blood pressure (BP) and smoking cessation — could make a huge difference for patients with rheumatic disease. Patients with autoimmune disease are up to three times more likely to develop cardiovascular disease (CVD) than the general population. In addition to compounding CVD, smoking is tied to the development of certain autoimmune conditions, as well as worse outcomes. Christie Bartels, MD, chief of the Division of Rheumatology at the University of Wisconsin School of Medicine and Public Health, Madison, has focused her research on improving cardiac health in inflammatory diseases. This news organization spoke with Bartels about two short interventions she developed that tackle hypertension and smoking cessation during regular visits, each taking less than 3 minutes.
How Do These Programs Address Cardiac Disease Prevention?
The BP and Quit Connect programs help clinics systematically address the two most modifiable risk factors for CVD: high BP and smoking. There’s also evidence that addressing these two risk factors improves outcomes in rheumatic diseases. Hypertension predicts an increase in lupus damage. Particularly in lupus nephritis, hypertension will increase the risk for CVD and kidney failure. People who use tobacco have worse outcomes in diseases like rheumatoid arthritis, psoriatic arthritis, and lupus, as well as more CVD, and antirheumatic drugs may not work as well.
In 90 seconds to 3 minutes, staff can do protocol-based care, which we’ve done across 20,000-plus visits. We showed we can improve population level rates of high BP and BP control, as well as increase smoking quitting rates across different patient settings.
What Is the Quit Connect Program?
The Quit Connect program is a 10- to 90-second point of care intervention. During rooming, staff (medical assistants and nurses) ask patients: “A) Do you smoke? and B) Have you thought about cutting back or quitting in the next 30 days?”
It turns out, when you ask the question that way, between a third and a half of people say that they’ve thought about cutting back or quitting. Then, we can get patients connected directly to Quitline, a free public service across all 50 states that smokers can use to get cessation support.
If patients are ready, we ask if we can arrange for them to receive a call from a Quitline coach about setting a quit date or receiving free nicotine replacement therapy. The beautiful thing is when that all happens, A) it’s free to the patient, and B) the results from the Quitline can be recorded right back to the electronic health record.
In our most recent publication in Arthritis Care & Research, we documented bringing Quit Connect to Grady Hospital in downtown Atlanta. It’s a safety net hospital, where 80% patients are Black and 70%-80% patients are on public insurance or uninsured. Using this protocol, we improved Quitline referrals 20-fold.
What Is the BP Connect Program?
At least half of the encounters in United States happen in specialty clinics. Unfortunately, when patients get their BP measured in a specialty clinic that’s not a cardiology or a vascular clinic, often, even if the pressure is high, the clinic doesn’t give patients feedback on that. The problem is because we haven’t said anything, that gives people the false reassurance that their BP is okay.
We’ve developed a 3-minute protocol to ask, advise, and connect. The idea is that if we measure a high BP, then we remeasure and confirm that it’s high. Then, we advise why it matters in rheumatic disease: Patients with rheumatic diseases are already at an increased risk for heart disease, and controlling BP can make a big difference. Then, we connect patients with high BP back to primary care.
Specifically, a SmartSet — an electronic medical record feature — prompts different actions based on confirmed high BP readings:
- If systolic BP ≥ 140-159, the SmartSet directs scheduling a visit to a nurse or primary care provider.
- If systolic BP ≥ 160-179, the next primary care visit anticipates the need to see a prescriber.
- If systolic BP ≥ 180, then the medical assistant or nurse at the visit is instructed to notify the provider who can arrange a provider-to-provider handoff for safety to exclude a hypertensive emergency.
That order goes to the scheduler to call primary care to coordinate follow-up. BP Connect doubled the likelihood of a guideline-recommended follow-up in primary care within 30 days. All patients benefited, and disparities decreased. BP Connect has had 1100 downloads, and both BP and Quit Connect programs are endorsed by the Centers for Disease Control and Prevention and Million Hearts.
How Do These Programs Affect Clinical Practice?
We developed these interventions with a health system engineer, and we time stamped everything. Part of the sustainability of this model is that it fits within a regular workflow. As a practicing rheumatologist, I understand that time is a precious commodity.
The interventions are in partnership with frontline staff. We’ve received feedback that they feel pride participating in these initiatives. They can say, because of me, 30 patients followed up last month for high BP, or 10 patients took a referral to the Quitline last year. We celebrate these accomplishments with the staff.
What Are the Next Steps for These Programs?
Public-facing toolkits for both BP and Quit Connect programs are available online. We have implemented [these programs] in a rural setting, in an urban setting, in Milwaukee and in Atlanta, and we are looking in the future to do a larger, multistate implementation study. If folks are interested, we’d love to partner with them to look at disseminating this further.
A version of this article appeared on Medscape.com.
What’s Causing Raynaud Phenomenon Severity to Rise With High Temperatures?
TOPLINE:
In systemic sclerosis, Raynaud phenomenon is more severe at both high and low temperature extremes, according to new research.
BACKGROUND:
- Raynaud phenomenon, a condition that causes decreased blood flow to extremities, occurs in about 95% of individuals with systemic sclerosis.
- Episodes of Raynaud phenomenon can be triggered by cold exposure and ambient temperature changes.
- In severe cases, it can cause permanent damage to tissues of the fingers and toes.
METHODOLOGY:
- Researchers analyzed data from 2243 participants with Raynaud phenomenon secondary to systemic sclerosis from the Scleroderma Patient-centered Intervention Network (SPIN) Cohort.
- Participants completed past-week Raynaud phenomenon severity assessments using a 0-10 numerical rating scale at enrollment and every 3 months.
- The study included data from 20,233 Raynaud phenomenon severity assessments between April 15, 2014, and August 1, 2023.
- Researchers used average daily temperature from a weather site close to the participant’s recruiting center and mapped these ambient temperature changes to Raynaud’s phenomenon outcomes.
TAKEAWAY:
- Raynaud’s phenomenon severity was highest at –25 °C (–13 °F), with assessment scores at 6.8 points out of 10.0, and lowest at 25 °C (77 °F), with scores at 2.6.
- Severity scores increased again at temperatures above 35 °C (95 °F), reaching a high of 5.6 out of 10 at 40 °C (104 °F).
- This spike at higher temperatures is presumably due to air conditioning, the authors said.
- In an accompanying commentary, Cutolo et al. posited that increased sweating and hypotension could also lead to a relative hypovolemic state in patients, causing Raynaud-like symptoms.
IN PRACTICE:
“Temperature-related variations in Raynaud’s phenomenon severity scores should be considered in clinical trials to account for normal within-season temperature fluctuations, enhancing the accuracy of treatment outcomes,” wrote Cutolo and colleagues in their commentary.
SOURCE:
The study was led by Gabrielle Virgili-Gervais, MSc, McGill University Health Centre in Montreal, Quebec, Canada. It was published online on August 28 in The Lancet Rheumatology. The accompanying commentary, also published on August 28, was authored by Maurizio Cutolo, MD, and Elvis Hysa, MD, both of University of Genova, Italy, as well as Vanessa Smith, MD, PhD, of Ghent University in Ghent, Belgium.
LIMITATIONS:
The lower number of assessments at extreme temperatures (–25 °C and 40 °C) may affect the robustness of the findings at these ranges. The study did not account for vasodilator use, which could influence participants’ response to temperature. The study also did not account for other potential confounding factors such as sex, smoking status, psychosocial factors, and comorbid conditions like cardiovascular disease.
DISCLOSURES:
A variety of scleroderma-related patient advocacy groups helped to fund research on the SPIN cohort, in addition to the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University. Two authors reported having financial ties with pharmaceutical companies. Dr. Cutolo, Dr. Smith, and Dr. Hysa had no disclosures.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
In systemic sclerosis, Raynaud phenomenon is more severe at both high and low temperature extremes, according to new research.
BACKGROUND:
- Raynaud phenomenon, a condition that causes decreased blood flow to extremities, occurs in about 95% of individuals with systemic sclerosis.
- Episodes of Raynaud phenomenon can be triggered by cold exposure and ambient temperature changes.
- In severe cases, it can cause permanent damage to tissues of the fingers and toes.
METHODOLOGY:
- Researchers analyzed data from 2243 participants with Raynaud phenomenon secondary to systemic sclerosis from the Scleroderma Patient-centered Intervention Network (SPIN) Cohort.
- Participants completed past-week Raynaud phenomenon severity assessments using a 0-10 numerical rating scale at enrollment and every 3 months.
- The study included data from 20,233 Raynaud phenomenon severity assessments between April 15, 2014, and August 1, 2023.
- Researchers used average daily temperature from a weather site close to the participant’s recruiting center and mapped these ambient temperature changes to Raynaud’s phenomenon outcomes.
TAKEAWAY:
- Raynaud’s phenomenon severity was highest at –25 °C (–13 °F), with assessment scores at 6.8 points out of 10.0, and lowest at 25 °C (77 °F), with scores at 2.6.
- Severity scores increased again at temperatures above 35 °C (95 °F), reaching a high of 5.6 out of 10 at 40 °C (104 °F).
- This spike at higher temperatures is presumably due to air conditioning, the authors said.
- In an accompanying commentary, Cutolo et al. posited that increased sweating and hypotension could also lead to a relative hypovolemic state in patients, causing Raynaud-like symptoms.
IN PRACTICE:
“Temperature-related variations in Raynaud’s phenomenon severity scores should be considered in clinical trials to account for normal within-season temperature fluctuations, enhancing the accuracy of treatment outcomes,” wrote Cutolo and colleagues in their commentary.
SOURCE:
The study was led by Gabrielle Virgili-Gervais, MSc, McGill University Health Centre in Montreal, Quebec, Canada. It was published online on August 28 in The Lancet Rheumatology. The accompanying commentary, also published on August 28, was authored by Maurizio Cutolo, MD, and Elvis Hysa, MD, both of University of Genova, Italy, as well as Vanessa Smith, MD, PhD, of Ghent University in Ghent, Belgium.
LIMITATIONS:
The lower number of assessments at extreme temperatures (–25 °C and 40 °C) may affect the robustness of the findings at these ranges. The study did not account for vasodilator use, which could influence participants’ response to temperature. The study also did not account for other potential confounding factors such as sex, smoking status, psychosocial factors, and comorbid conditions like cardiovascular disease.
DISCLOSURES:
A variety of scleroderma-related patient advocacy groups helped to fund research on the SPIN cohort, in addition to the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University. Two authors reported having financial ties with pharmaceutical companies. Dr. Cutolo, Dr. Smith, and Dr. Hysa had no disclosures.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
In systemic sclerosis, Raynaud phenomenon is more severe at both high and low temperature extremes, according to new research.
BACKGROUND:
- Raynaud phenomenon, a condition that causes decreased blood flow to extremities, occurs in about 95% of individuals with systemic sclerosis.
- Episodes of Raynaud phenomenon can be triggered by cold exposure and ambient temperature changes.
- In severe cases, it can cause permanent damage to tissues of the fingers and toes.
METHODOLOGY:
- Researchers analyzed data from 2243 participants with Raynaud phenomenon secondary to systemic sclerosis from the Scleroderma Patient-centered Intervention Network (SPIN) Cohort.
- Participants completed past-week Raynaud phenomenon severity assessments using a 0-10 numerical rating scale at enrollment and every 3 months.
- The study included data from 20,233 Raynaud phenomenon severity assessments between April 15, 2014, and August 1, 2023.
- Researchers used average daily temperature from a weather site close to the participant’s recruiting center and mapped these ambient temperature changes to Raynaud’s phenomenon outcomes.
TAKEAWAY:
- Raynaud’s phenomenon severity was highest at –25 °C (–13 °F), with assessment scores at 6.8 points out of 10.0, and lowest at 25 °C (77 °F), with scores at 2.6.
- Severity scores increased again at temperatures above 35 °C (95 °F), reaching a high of 5.6 out of 10 at 40 °C (104 °F).
- This spike at higher temperatures is presumably due to air conditioning, the authors said.
- In an accompanying commentary, Cutolo et al. posited that increased sweating and hypotension could also lead to a relative hypovolemic state in patients, causing Raynaud-like symptoms.
IN PRACTICE:
“Temperature-related variations in Raynaud’s phenomenon severity scores should be considered in clinical trials to account for normal within-season temperature fluctuations, enhancing the accuracy of treatment outcomes,” wrote Cutolo and colleagues in their commentary.
SOURCE:
The study was led by Gabrielle Virgili-Gervais, MSc, McGill University Health Centre in Montreal, Quebec, Canada. It was published online on August 28 in The Lancet Rheumatology. The accompanying commentary, also published on August 28, was authored by Maurizio Cutolo, MD, and Elvis Hysa, MD, both of University of Genova, Italy, as well as Vanessa Smith, MD, PhD, of Ghent University in Ghent, Belgium.
LIMITATIONS:
The lower number of assessments at extreme temperatures (–25 °C and 40 °C) may affect the robustness of the findings at these ranges. The study did not account for vasodilator use, which could influence participants’ response to temperature. The study also did not account for other potential confounding factors such as sex, smoking status, psychosocial factors, and comorbid conditions like cardiovascular disease.
DISCLOSURES:
A variety of scleroderma-related patient advocacy groups helped to fund research on the SPIN cohort, in addition to the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University. Two authors reported having financial ties with pharmaceutical companies. Dr. Cutolo, Dr. Smith, and Dr. Hysa had no disclosures.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Do You Have Patients With JAKne — JAK Inhibitor–Associated Acne? Here’s What to Know
Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.
“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
What Is JAKne?
JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”
Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.
“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”
In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.
Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”
Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”
This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
How Do You Treat It?
“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.
“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”
Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)
In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.
If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.
“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”
Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.
“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
What Is JAKne?
JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”
Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.
“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”
In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.
Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”
Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”
This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
How Do You Treat It?
“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.
“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”
Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)
In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.
If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.
“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”
Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.
“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
What Is JAKne?
JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”
Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.
“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”
In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.
Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”
Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”
This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
How Do You Treat It?
“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.
“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”
Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)
In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.
If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.
“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”
Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Trends in Rheumatic Disease Pain Management Show Decline in Opioid Use
TOPLINE:
Since 2014, opioid use for autoimmune rheumatic diseases decreased by 15% annually while other management modalities increased or stabilized.
METHODOLOGY:
- Researchers analyzed de-identified US claims data from the MarketScan Database from 2007-2021.
- The study included nearly 142,000 patients with autoimmune rheumatic diseases: 10,927 with ankylosing spondylitis (AS); 21,438 with psoriatic arthritis (PsA); 71,393 with rheumatoid arthritis (RA); 16,718 with Sjögren disease; 18,018 with systemic lupus erythematosus; and 3468 with systemic sclerosis.
- Primary outcome was opioid use annual trends, with secondary outcomes including trends in the use of anticonvulsants, antidepressants, skeletal muscle relaxants, nonsteroidal anti-inflammatory drugs (NSAIDs), topical pain medications, and physical or occupational therapy.
TAKEAWAY:
- The incidence of opioid use increased annually by 4% until 2014 and decreased annually by 15% after 2014.
- NSAID use increased 2% annually until 2014, then declined by 5% afterward.
- The proportion of patients utilizing physical therapy or anticonvulsants doubled from 2008 to 2020.
- NSAID prescriptions were highest in AS, PsA, and RA, while they were lowest in Sjögren disease and systemic sclerosis.
IN PRACTICE:
“Our work, along with the published literature, highlights the need for future studies to evaluate the effectiveness of pain management modality changes over time and to understand the possible effects that changes have had on outcomes such as quality of life, disability, health status, and function,” wrote the authors of the study.
SOURCE:
The study was led by Titilola Falasinnu, PhD, Stanford University School of Medicine, Stanford, California. It was published online in The Lancet Rheumatology.
LIMITATIONS:
The study relied on administrative claims data, which did not contain information on use of over-the-counter medications like NSAIDs and topical analgesics. The study did not include the duration of pain treatment modalities, making it difficult to differentiate between acute and chronic use. The analysis did not include race or ethnicity, which is important for understanding pain outcomes across different sociodemographic groups.
DISCLOSURES:
The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Since 2014, opioid use for autoimmune rheumatic diseases decreased by 15% annually while other management modalities increased or stabilized.
METHODOLOGY:
- Researchers analyzed de-identified US claims data from the MarketScan Database from 2007-2021.
- The study included nearly 142,000 patients with autoimmune rheumatic diseases: 10,927 with ankylosing spondylitis (AS); 21,438 with psoriatic arthritis (PsA); 71,393 with rheumatoid arthritis (RA); 16,718 with Sjögren disease; 18,018 with systemic lupus erythematosus; and 3468 with systemic sclerosis.
- Primary outcome was opioid use annual trends, with secondary outcomes including trends in the use of anticonvulsants, antidepressants, skeletal muscle relaxants, nonsteroidal anti-inflammatory drugs (NSAIDs), topical pain medications, and physical or occupational therapy.
TAKEAWAY:
- The incidence of opioid use increased annually by 4% until 2014 and decreased annually by 15% after 2014.
- NSAID use increased 2% annually until 2014, then declined by 5% afterward.
- The proportion of patients utilizing physical therapy or anticonvulsants doubled from 2008 to 2020.
- NSAID prescriptions were highest in AS, PsA, and RA, while they were lowest in Sjögren disease and systemic sclerosis.
IN PRACTICE:
“Our work, along with the published literature, highlights the need for future studies to evaluate the effectiveness of pain management modality changes over time and to understand the possible effects that changes have had on outcomes such as quality of life, disability, health status, and function,” wrote the authors of the study.
SOURCE:
The study was led by Titilola Falasinnu, PhD, Stanford University School of Medicine, Stanford, California. It was published online in The Lancet Rheumatology.
LIMITATIONS:
The study relied on administrative claims data, which did not contain information on use of over-the-counter medications like NSAIDs and topical analgesics. The study did not include the duration of pain treatment modalities, making it difficult to differentiate between acute and chronic use. The analysis did not include race or ethnicity, which is important for understanding pain outcomes across different sociodemographic groups.
DISCLOSURES:
The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Since 2014, opioid use for autoimmune rheumatic diseases decreased by 15% annually while other management modalities increased or stabilized.
METHODOLOGY:
- Researchers analyzed de-identified US claims data from the MarketScan Database from 2007-2021.
- The study included nearly 142,000 patients with autoimmune rheumatic diseases: 10,927 with ankylosing spondylitis (AS); 21,438 with psoriatic arthritis (PsA); 71,393 with rheumatoid arthritis (RA); 16,718 with Sjögren disease; 18,018 with systemic lupus erythematosus; and 3468 with systemic sclerosis.
- Primary outcome was opioid use annual trends, with secondary outcomes including trends in the use of anticonvulsants, antidepressants, skeletal muscle relaxants, nonsteroidal anti-inflammatory drugs (NSAIDs), topical pain medications, and physical or occupational therapy.
TAKEAWAY:
- The incidence of opioid use increased annually by 4% until 2014 and decreased annually by 15% after 2014.
- NSAID use increased 2% annually until 2014, then declined by 5% afterward.
- The proportion of patients utilizing physical therapy or anticonvulsants doubled from 2008 to 2020.
- NSAID prescriptions were highest in AS, PsA, and RA, while they were lowest in Sjögren disease and systemic sclerosis.
IN PRACTICE:
“Our work, along with the published literature, highlights the need for future studies to evaluate the effectiveness of pain management modality changes over time and to understand the possible effects that changes have had on outcomes such as quality of life, disability, health status, and function,” wrote the authors of the study.
SOURCE:
The study was led by Titilola Falasinnu, PhD, Stanford University School of Medicine, Stanford, California. It was published online in The Lancet Rheumatology.
LIMITATIONS:
The study relied on administrative claims data, which did not contain information on use of over-the-counter medications like NSAIDs and topical analgesics. The study did not include the duration of pain treatment modalities, making it difficult to differentiate between acute and chronic use. The analysis did not include race or ethnicity, which is important for understanding pain outcomes across different sociodemographic groups.
DISCLOSURES:
The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Early RA Diagnosis and Treatment Lowers Treatment Costs
TOPLINE:
Early detection and treatment of rheumatoid arthritis (RA; within 12 weeks of symptom onset) results in lower treatment-related costs over 5 years compared with later diagnosis.
METHODOLOGY:
- The study enrolled 431 patients in the Leiden Early Arthritis Clinic at Leiden University Medical Center, Leiden, the Netherlands.
- Symptom duration was defined as time between symptom onset and first clinic visit.
- Early treatment was defined as a symptom duration of under 12 weeks, and later treatment defined as symptom duration over 12 weeks.
- Prescription data from patient records and 2022 disease-modifying antirheumatic drug prices (including biologics) was used to determine overall costs over 5 years.
- Autoantibody-negative and autoantibody-positive RA were studied separately because of possible differences in disease severity.
TAKEAWAY:
- For the 165 patients with autoantibody-negative RA, late treatment was associated with 316% higher costs over 5 years than early treatment (€4856/$5292 vs €1159/$1263)
- For antibody-positive RA, costs were 19% higher in the late-treatment group.
- In the 43 patients with antibody-positive RA only prescribed biologics, costs were 46% higher for those with delayed treatment.
IN PRACTICE:
“This is the first study showing the effect of early diagnosis and treatment on treatment-related costs,” wrote the authors. “When RA is detected within 12 weeks after symptom onset, treatment-related costs seem to be lower.”
SOURCE:
The study was led by Elise van Mulligen, PhD, Department of Rheumatology, Leiden University Medical Center. It was published online in Annals of the Rheumatic Diseases.
LIMITATIONS:
The division of symptom duration by 12 weeks was “arbitrary.” Baseline characteristics, though similar, showed differences for inflammatory markers in autoantibody-positive and autoantibody-negative RA. Thirty seven patients were lost to follow-up, which could induce attrition bias, though the percentage of these patients in the early- and late-treatment groups was similar.
DISCLOSURES:
This study was funded by ZonMw, a Dutch organization for healthcare research. The authors declared no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Early detection and treatment of rheumatoid arthritis (RA; within 12 weeks of symptom onset) results in lower treatment-related costs over 5 years compared with later diagnosis.
METHODOLOGY:
- The study enrolled 431 patients in the Leiden Early Arthritis Clinic at Leiden University Medical Center, Leiden, the Netherlands.
- Symptom duration was defined as time between symptom onset and first clinic visit.
- Early treatment was defined as a symptom duration of under 12 weeks, and later treatment defined as symptom duration over 12 weeks.
- Prescription data from patient records and 2022 disease-modifying antirheumatic drug prices (including biologics) was used to determine overall costs over 5 years.
- Autoantibody-negative and autoantibody-positive RA were studied separately because of possible differences in disease severity.
TAKEAWAY:
- For the 165 patients with autoantibody-negative RA, late treatment was associated with 316% higher costs over 5 years than early treatment (€4856/$5292 vs €1159/$1263)
- For antibody-positive RA, costs were 19% higher in the late-treatment group.
- In the 43 patients with antibody-positive RA only prescribed biologics, costs were 46% higher for those with delayed treatment.
IN PRACTICE:
“This is the first study showing the effect of early diagnosis and treatment on treatment-related costs,” wrote the authors. “When RA is detected within 12 weeks after symptom onset, treatment-related costs seem to be lower.”
SOURCE:
The study was led by Elise van Mulligen, PhD, Department of Rheumatology, Leiden University Medical Center. It was published online in Annals of the Rheumatic Diseases.
LIMITATIONS:
The division of symptom duration by 12 weeks was “arbitrary.” Baseline characteristics, though similar, showed differences for inflammatory markers in autoantibody-positive and autoantibody-negative RA. Thirty seven patients were lost to follow-up, which could induce attrition bias, though the percentage of these patients in the early- and late-treatment groups was similar.
DISCLOSURES:
This study was funded by ZonMw, a Dutch organization for healthcare research. The authors declared no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Early detection and treatment of rheumatoid arthritis (RA; within 12 weeks of symptom onset) results in lower treatment-related costs over 5 years compared with later diagnosis.
METHODOLOGY:
- The study enrolled 431 patients in the Leiden Early Arthritis Clinic at Leiden University Medical Center, Leiden, the Netherlands.
- Symptom duration was defined as time between symptom onset and first clinic visit.
- Early treatment was defined as a symptom duration of under 12 weeks, and later treatment defined as symptom duration over 12 weeks.
- Prescription data from patient records and 2022 disease-modifying antirheumatic drug prices (including biologics) was used to determine overall costs over 5 years.
- Autoantibody-negative and autoantibody-positive RA were studied separately because of possible differences in disease severity.
TAKEAWAY:
- For the 165 patients with autoantibody-negative RA, late treatment was associated with 316% higher costs over 5 years than early treatment (€4856/$5292 vs €1159/$1263)
- For antibody-positive RA, costs were 19% higher in the late-treatment group.
- In the 43 patients with antibody-positive RA only prescribed biologics, costs were 46% higher for those with delayed treatment.
IN PRACTICE:
“This is the first study showing the effect of early diagnosis and treatment on treatment-related costs,” wrote the authors. “When RA is detected within 12 weeks after symptom onset, treatment-related costs seem to be lower.”
SOURCE:
The study was led by Elise van Mulligen, PhD, Department of Rheumatology, Leiden University Medical Center. It was published online in Annals of the Rheumatic Diseases.
LIMITATIONS:
The division of symptom duration by 12 weeks was “arbitrary.” Baseline characteristics, though similar, showed differences for inflammatory markers in autoantibody-positive and autoantibody-negative RA. Thirty seven patients were lost to follow-up, which could induce attrition bias, though the percentage of these patients in the early- and late-treatment groups was similar.
DISCLOSURES:
This study was funded by ZonMw, a Dutch organization for healthcare research. The authors declared no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Pyzchiva Receives FDA Approval as Third Ustekinumab Biosimilar
The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.
In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.
Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:
- Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy
- Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis
It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial.
Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).
Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.
A version of this article appeared on Medscape.com.
The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.
In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.
Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:
- Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy
- Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis
It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial.
Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).
Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.
A version of this article appeared on Medscape.com.
The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.
In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.
Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:
- Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy
- Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis
It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial.
Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).
Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.
A version of this article appeared on Medscape.com.
Form of B12 Deficiency Affecting the Central Nervous System May Be New Autoimmune Disease
Discovered while studying a puzzling case of one patient with inexplicable neurological systems, the same autoantibody was detected in a small percentage of healthy individuals and was nearly four times as prevalent in patients with neuropsychiatric systemic lupus erythematosus (SLE).
“I didn’t think this single investigation was going to yield a broader phenomenon with other patients,” lead author John V. Pluvinage, MD, PhD, a neurology resident at the University of California San Francisco, said in an interview. “It started as an N-of-one study just based on scientific curiosity.”
“It’s a beautifully done study,” added Betty Diamond, MD, director of the Institute of Molecular Medicine at the Feinstein Institutes for Medical Research in Manhasset, New York, commenting on the research. It uncovers “yet another example of a disease where antibodies getting into the brain are the problem.”
The research was published in Science Translational Medicine.
The Patient
The investigation began in 2014 with a 67-year-old woman presenting with difficulty speaking, ataxia, and tremor. Her blood tests showed no signs of B12 deficiency, and testing for known autoantibodies came back negative.
Solving this mystery required a more exhaustive approach. The patient enrolled in a research study focused on identifying novel autoantibodies in suspected neuroinflammatory disease, using a screening technology called phage immunoprecipitation sequencing.
“We adapted this technology to screen for autoantibodies in an unbiased manner by displaying every peptide across the human proteome and then mixing those peptides with patient antibodies in order to figure out what the antibodies are binding to,” explained Dr. Pluvinage.
Using this method, he and colleagues discovered that this woman had autoantibodies that target CD320 — a receptor important in the cellular uptake of B12. While her blood tests were normal, B12 in the patient’s cerebral spinal fluid (CSF) was “nearly undetectable,” Dr. Pluvinage said. Using an in vitro model of the blood-brain barrier (BBB), the researchers determined that anti-CD320 impaired the transport of B12 across the BBB by targeting receptors on the cell surface.
Treating the patient with a combination of immunosuppressant medication and high-dose B12 supplementation increased B12 levels in the patient’s CSF and improved clinical symptoms.
Identifying More Cases
Dr. Pluvinage and colleagues tested the 254 other individuals enrolled in the neuroinflammatory disease study and identified seven participants with CSF anti-CD320 autoantibodies — four of whom had low B12 in the CSF.
In a group of healthy controls, anti-CD320 seropositivity was 6%, similar to the positivity rate in 132 paired serum and CSF samples from a cohort of patients with multiple sclerosis (5.7%). In this group of patients with multiple sclerosis, anti-CD320 presence in the blood was highly predictive of high levels of CSF methylmalonic acid, a metabolic marker of B12 deficiency.
Researchers also screened for anti-CD320 seropositivity in 408 patients with non-neurologic SLE and 28 patients with neuropsychiatric SLE and found that the autoantibody was nearly four times as prevalent in patients with neurologic symptoms (21.4%) compared with in those with non-neurologic SLE (5.6%).
“The clinical relevance of anti-CD320 in healthy controls remains uncertain,” the authors wrote. However, it is not uncommon to have healthy patients with known autoantibodies.
“There are always people who have autoantibodies who don’t get disease, and why that is we don’t know,” said Dr. Diamond. Some individuals may develop clinical symptoms later, or there may be other reasons why they are protected against disease.
Pluvinage is eager to follow some seropositive healthy individuals to track their neurologic health overtime, to see if the presence of anti-CD320 “alters their neurologic trajectories.”
Alternative Pathways
Lastly, Dr. Pluvinage and colleagues set out to explain why patients with anti-CD320 in their blood did not show any signs of B12 deficiency. They hypothesized that another receptor may be compensating and still allowing blood cells to take up B12. Using CRISPR screening, the team identified the low-density lipoprotein receptor as an alternative pathway to B12 uptake.
“These findings suggest a model in which anti-CD320 impairs transport of B12 across the BBB, leading to autoimmune B12 central deficiency (ABCD) with varied neurologic manifestations but sparing peripheral manifestations of B12 deficiency,” the authors wrote.
The work was supported by the National Institute of Mental Health, National Center for Chronic Disease Prevention and Health Promotion, Department of Defense, UCSF Helen Diller Family Comprehensive Cancer Center Laboratory for Cell Analysis Shared Resource Facility, National Multiple Sclerosis Society, Valhalla Foundation, and the Westridge Foundation. Dr. Pluvinage is a co-inventor on a patent application related to this work. Dr. Diamond had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Discovered while studying a puzzling case of one patient with inexplicable neurological systems, the same autoantibody was detected in a small percentage of healthy individuals and was nearly four times as prevalent in patients with neuropsychiatric systemic lupus erythematosus (SLE).
“I didn’t think this single investigation was going to yield a broader phenomenon with other patients,” lead author John V. Pluvinage, MD, PhD, a neurology resident at the University of California San Francisco, said in an interview. “It started as an N-of-one study just based on scientific curiosity.”
“It’s a beautifully done study,” added Betty Diamond, MD, director of the Institute of Molecular Medicine at the Feinstein Institutes for Medical Research in Manhasset, New York, commenting on the research. It uncovers “yet another example of a disease where antibodies getting into the brain are the problem.”
The research was published in Science Translational Medicine.
The Patient
The investigation began in 2014 with a 67-year-old woman presenting with difficulty speaking, ataxia, and tremor. Her blood tests showed no signs of B12 deficiency, and testing for known autoantibodies came back negative.
Solving this mystery required a more exhaustive approach. The patient enrolled in a research study focused on identifying novel autoantibodies in suspected neuroinflammatory disease, using a screening technology called phage immunoprecipitation sequencing.
“We adapted this technology to screen for autoantibodies in an unbiased manner by displaying every peptide across the human proteome and then mixing those peptides with patient antibodies in order to figure out what the antibodies are binding to,” explained Dr. Pluvinage.
Using this method, he and colleagues discovered that this woman had autoantibodies that target CD320 — a receptor important in the cellular uptake of B12. While her blood tests were normal, B12 in the patient’s cerebral spinal fluid (CSF) was “nearly undetectable,” Dr. Pluvinage said. Using an in vitro model of the blood-brain barrier (BBB), the researchers determined that anti-CD320 impaired the transport of B12 across the BBB by targeting receptors on the cell surface.
Treating the patient with a combination of immunosuppressant medication and high-dose B12 supplementation increased B12 levels in the patient’s CSF and improved clinical symptoms.
Identifying More Cases
Dr. Pluvinage and colleagues tested the 254 other individuals enrolled in the neuroinflammatory disease study and identified seven participants with CSF anti-CD320 autoantibodies — four of whom had low B12 in the CSF.
In a group of healthy controls, anti-CD320 seropositivity was 6%, similar to the positivity rate in 132 paired serum and CSF samples from a cohort of patients with multiple sclerosis (5.7%). In this group of patients with multiple sclerosis, anti-CD320 presence in the blood was highly predictive of high levels of CSF methylmalonic acid, a metabolic marker of B12 deficiency.
Researchers also screened for anti-CD320 seropositivity in 408 patients with non-neurologic SLE and 28 patients with neuropsychiatric SLE and found that the autoantibody was nearly four times as prevalent in patients with neurologic symptoms (21.4%) compared with in those with non-neurologic SLE (5.6%).
“The clinical relevance of anti-CD320 in healthy controls remains uncertain,” the authors wrote. However, it is not uncommon to have healthy patients with known autoantibodies.
“There are always people who have autoantibodies who don’t get disease, and why that is we don’t know,” said Dr. Diamond. Some individuals may develop clinical symptoms later, or there may be other reasons why they are protected against disease.
Pluvinage is eager to follow some seropositive healthy individuals to track their neurologic health overtime, to see if the presence of anti-CD320 “alters their neurologic trajectories.”
Alternative Pathways
Lastly, Dr. Pluvinage and colleagues set out to explain why patients with anti-CD320 in their blood did not show any signs of B12 deficiency. They hypothesized that another receptor may be compensating and still allowing blood cells to take up B12. Using CRISPR screening, the team identified the low-density lipoprotein receptor as an alternative pathway to B12 uptake.
“These findings suggest a model in which anti-CD320 impairs transport of B12 across the BBB, leading to autoimmune B12 central deficiency (ABCD) with varied neurologic manifestations but sparing peripheral manifestations of B12 deficiency,” the authors wrote.
The work was supported by the National Institute of Mental Health, National Center for Chronic Disease Prevention and Health Promotion, Department of Defense, UCSF Helen Diller Family Comprehensive Cancer Center Laboratory for Cell Analysis Shared Resource Facility, National Multiple Sclerosis Society, Valhalla Foundation, and the Westridge Foundation. Dr. Pluvinage is a co-inventor on a patent application related to this work. Dr. Diamond had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Discovered while studying a puzzling case of one patient with inexplicable neurological systems, the same autoantibody was detected in a small percentage of healthy individuals and was nearly four times as prevalent in patients with neuropsychiatric systemic lupus erythematosus (SLE).
“I didn’t think this single investigation was going to yield a broader phenomenon with other patients,” lead author John V. Pluvinage, MD, PhD, a neurology resident at the University of California San Francisco, said in an interview. “It started as an N-of-one study just based on scientific curiosity.”
“It’s a beautifully done study,” added Betty Diamond, MD, director of the Institute of Molecular Medicine at the Feinstein Institutes for Medical Research in Manhasset, New York, commenting on the research. It uncovers “yet another example of a disease where antibodies getting into the brain are the problem.”
The research was published in Science Translational Medicine.
The Patient
The investigation began in 2014 with a 67-year-old woman presenting with difficulty speaking, ataxia, and tremor. Her blood tests showed no signs of B12 deficiency, and testing for known autoantibodies came back negative.
Solving this mystery required a more exhaustive approach. The patient enrolled in a research study focused on identifying novel autoantibodies in suspected neuroinflammatory disease, using a screening technology called phage immunoprecipitation sequencing.
“We adapted this technology to screen for autoantibodies in an unbiased manner by displaying every peptide across the human proteome and then mixing those peptides with patient antibodies in order to figure out what the antibodies are binding to,” explained Dr. Pluvinage.
Using this method, he and colleagues discovered that this woman had autoantibodies that target CD320 — a receptor important in the cellular uptake of B12. While her blood tests were normal, B12 in the patient’s cerebral spinal fluid (CSF) was “nearly undetectable,” Dr. Pluvinage said. Using an in vitro model of the blood-brain barrier (BBB), the researchers determined that anti-CD320 impaired the transport of B12 across the BBB by targeting receptors on the cell surface.
Treating the patient with a combination of immunosuppressant medication and high-dose B12 supplementation increased B12 levels in the patient’s CSF and improved clinical symptoms.
Identifying More Cases
Dr. Pluvinage and colleagues tested the 254 other individuals enrolled in the neuroinflammatory disease study and identified seven participants with CSF anti-CD320 autoantibodies — four of whom had low B12 in the CSF.
In a group of healthy controls, anti-CD320 seropositivity was 6%, similar to the positivity rate in 132 paired serum and CSF samples from a cohort of patients with multiple sclerosis (5.7%). In this group of patients with multiple sclerosis, anti-CD320 presence in the blood was highly predictive of high levels of CSF methylmalonic acid, a metabolic marker of B12 deficiency.
Researchers also screened for anti-CD320 seropositivity in 408 patients with non-neurologic SLE and 28 patients with neuropsychiatric SLE and found that the autoantibody was nearly four times as prevalent in patients with neurologic symptoms (21.4%) compared with in those with non-neurologic SLE (5.6%).
“The clinical relevance of anti-CD320 in healthy controls remains uncertain,” the authors wrote. However, it is not uncommon to have healthy patients with known autoantibodies.
“There are always people who have autoantibodies who don’t get disease, and why that is we don’t know,” said Dr. Diamond. Some individuals may develop clinical symptoms later, or there may be other reasons why they are protected against disease.
Pluvinage is eager to follow some seropositive healthy individuals to track their neurologic health overtime, to see if the presence of anti-CD320 “alters their neurologic trajectories.”
Alternative Pathways
Lastly, Dr. Pluvinage and colleagues set out to explain why patients with anti-CD320 in their blood did not show any signs of B12 deficiency. They hypothesized that another receptor may be compensating and still allowing blood cells to take up B12. Using CRISPR screening, the team identified the low-density lipoprotein receptor as an alternative pathway to B12 uptake.
“These findings suggest a model in which anti-CD320 impairs transport of B12 across the BBB, leading to autoimmune B12 central deficiency (ABCD) with varied neurologic manifestations but sparing peripheral manifestations of B12 deficiency,” the authors wrote.
The work was supported by the National Institute of Mental Health, National Center for Chronic Disease Prevention and Health Promotion, Department of Defense, UCSF Helen Diller Family Comprehensive Cancer Center Laboratory for Cell Analysis Shared Resource Facility, National Multiple Sclerosis Society, Valhalla Foundation, and the Westridge Foundation. Dr. Pluvinage is a co-inventor on a patent application related to this work. Dr. Diamond had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM SCIENCE TRANSLATIONAL MEDICINE
Psoriatic Arthritis Symptoms Relieved with TYK2 Inhibitor in Phase 2 Trial
TOPLINE:
The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.
METHODOLOGY:
- Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
- A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
- The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.
TAKEAWAY:
- More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
- Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
- Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
- The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.
IN PRACTICE:
“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
SOURCE:
Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.
LIMITATIONS:
The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
DISCLOSURES:
The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.
METHODOLOGY:
- Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
- A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
- The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.
TAKEAWAY:
- More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
- Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
- Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
- The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.
IN PRACTICE:
“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
SOURCE:
Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.
LIMITATIONS:
The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
DISCLOSURES:
The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.
METHODOLOGY:
- Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
- A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
- The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.
TAKEAWAY:
- More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
- Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
- Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
- The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.
IN PRACTICE:
“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
SOURCE:
Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.
LIMITATIONS:
The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
DISCLOSURES:
The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.