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SLE Preview: advances to achieve deep B-cell depletion

Md Yuzaiful Md Yusof, MRCP(UK), PhD

The race is on for the first chimeric antigen receptor (CAR)-based therapy to be approved for the treatment of systemic lupus erythematosus. Its main principle is to induce deep B-cell depletion, with the hope to reset the B-cell aberrant immunity for a sustained clinical remission. At EULAR 2025 in Barcelona, several advances of CAR-based therapies will be presented.

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Methotrexate Fails in Knee Osteoarthritis

MedPage Today

We'll be blunt: methotrexate flopped in a randomized placebo-controlled trial among patients with osteoarthritis (OA) of the knee.

Contrary to results from a previous trial in hand OA, the old-line disease-modifying anti-rheumatic drug (DMARD) failed to bring any improvement relative to placebo in either pain or an objective measure of joint inflammation after a year of treatment, according to Changhai Ding, PhD, MD, of Southern Medical University in Guangzhou, China, and colleagues.

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Choices

SLE Treatment Landscape: Abundance or Overload?

Janet Pope, MD, MPH, FRCPC

Imagine a world where the multiple drugs in Phase 2 and 3 trials actually get approved, and we get access to them? I know you may be thinking that I am overly optimistic, but there are so many drugs in development in lupus that we may have true difficulty choosing what to use.

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Do SGLT2 and GLP-1 therapies have a role in Lupus?

Maya Shumyatcher, MD,  , Arpitha Haranahalli Shivarudrappa, PhD , , Jennifer H. Anolik, MD, PhD

Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) and Glucagon-like peptide-1 receptor agonists (GLP1-RA) were initially developed as glucose-lowering agents for the treatment of Type 2 Diabetes. Since their introduction, they have been noted to have a myriad of other benefits, including cardiovascular and renal protective effects in patients both with and without diabetes. Here, we will review the evidence for SGLT2i and GLP1-RA in lupus.

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Belimumab in SLE with Mucocutaneous or Vasculitis Findings

Jack Cush, MD

A post hoc analysis of a belimumab (BEL) inn systemic lupus erythematosus (SLE) study showed lupus mucocutaneous and vasculitic manifestations improve with BEL and standard care.

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Dafna Gladman

50 Year Perspective on Lupus

Dafna Gladman, MD

An observational cohort study was started in Toronto by Dr. Murray Urowitz in 1970. The program was set up as a specialized clinic to provide care for patients with lupus, to study clinical laboratory correlations in the disease, and to better understand long-term outcomes of the disease. What have we learned from more than 50 years of follow-up of patients with lupus? Some of the important observations include the following.

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Otilimab, GM-CSF mAb, may have potential in #RA. Metanalysis of 4 RCTs, w/ 3933 RA pts had Moderate evidence for ACR20 response (vs PBO) at 90 mg (RR 1.50) & 150 mg (RR 1.39). but neither dose had signif different adverse events vs PBO. OTIL was less effective than tofacitinib. https://t.co/2WajWNnxE9
Dr. John Cush RheumNow ( View Tweet)
While there are trials in progress, there is no RCT data on the use of JAK inhibitors in Noninfectious Uveitis (NIU). But there is this metanalysis of many small case reports suggesting their potential efficacy in NIU. https://t.co/pBNsSmVjOz https://t.co/JrIGQGZjHt

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Dr. John Cush RheumNow ( View Tweet)
Positive results from Phase 2b RENOIR RCT of Rosnilimab, an agonist targeting PD-1+ T cells. 432 RA pts on MTX or csDMARDs, Rx w/ 6 mos of PBO vs ROS (100 or 200 mg q4wk or 600 mg q2wk). All 3 doses of rosnilimab achieved significant reductions DAS-28 CRP at Wk 12 https://t.co/g7lqQYXeJd
Dr. John Cush RheumNow ( View Tweet)
52 wk Phase 3 DBRPCT of daily anakinra (100 mg sc) vs PBO in 30 giant cell arteritis pts. At wk 16 (17 ANK vs 13 PBO) there was no significant difference in relapse rates (12% vs 23%; p = 0.63). Same at wk 52 (53% vs 49% relapse). ANK didnt reduce relapses or GC exposure https://t.co/RFkkaUchsW
Dr. John Cush RheumNow ( View Tweet)
Review of Emerging Treatments for Vitiligo an immune mediated dz that affects QOL & has psychosocial impact. JAKi only ruxolitinib is FDA-approved, but Tofa & Bari show promise. Emerging therapies include simvastatin, afamelanotide, and metformin https://t.co/Rp2yYx6SyZ https://t.co/3RbDFVtJR5

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Dr. John Cush RheumNow ( View Tweet)
SLE Treatment Landscape: Abundance or Overload? Imagine a world where the multiple drugs in Phase 2 and 3 trials actually get approved, and we get access to them? I know you may be thinking that I am overly optimistic, but there are so many drugs in development in lupus that we https://t.co/xLgSU4ZLgP
Dr. John Cush RheumNow ( View Tweet)
Positive results from Phase 2b RENOIR RCT of Rosnilimab, an agonist targeting PD-1+ T cells. 432 RA pts on MTX or csDMARDs, Rx w/ 6 mos of PBO vs ROS (100 or 200 mg q4wk or 600 mg q2wk). All 3 doses of rosnilimab achieved significant reductions DAS-28 CRP at Wk 12 https://t.co/6nF8KPRK2f
Dr. John Cush RheumNow ( View Tweet)
Review of Emerging Treatments for Vitiligo an immune mediated dz that affects QOL & has psychosocial impact. JAKi only ruxolitinib is FDA-approved, but Tofa & Bari show promise. Emerging therapies include simvastatin, afamelanotide, and metformin https://t.co/Rp2yYx6SyZ https://t.co/pBo1IDe8pQ

Links:

Dr. John Cush RheumNow ( View Tweet)
Systematic review of JAK inhibitor use in systemic sclerosis - 18 articles/87 SSc pts (80%F; ages 13–78 yrs). JAKi (83% tofa) mostly used for ILD & Skin Dz (45%) or GI+Skin Dz (39%). 87.5% improved, w/ 6% relapsed. Adverse events in 50% (20% infx). We need RCTs! This could be a https://t.co/VXFuHGpDjB
Dr. John Cush RheumNow ( View Tweet)
SLE Treatment Landscape: Abundance or Overload? Imagine a world where the multiple drugs in Phase 2 and 3 trials actually get approved, and we get access to them? I know you may be thinking that I am overly optimistic, but there are so many drugs in development in lupus that we https://t.co/1SsSMqfZWz
Dr. John Cush RheumNow ( View Tweet)
Do SGLT2 and GLP-1 therapies have a role in Lupus? Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) and Glucagon-like peptide-1 receptor agonists (GLP1-RA), initially developed to lower glucose in Type 2 Diabetes, also provide cardiovascular and renal protection for patients https://t.co/8JEfcv2BUz
Dr. John Cush RheumNow ( View Tweet)
A retrospective VEXAS cohort study of 59 pts receiving 71 targeted Rx - 98%male, mean 71 yrs & 46% had myelodysplastic syndr. Treatments included tocilizumab(19), anakinra (13), azacitidine(13), baricitinib (11), & pred only (10). Best responses w/ azacitidine & tocilizumab https://t.co/jqDmKinPDt
Dr. John Cush RheumNow ( View Tweet)
Using publicly available FAERS safety data, drug-induced photosensitivity (DIP) - among 17+ million safety reports, there 20,236 linked to DIP. The most common wereimmunosuppressants, monoclonal Abs, neoplastic agents, including adalimumab, adapalene, secukinumab, fingolimod https://t.co/QWg8FVvrZb
Dr. John Cush RheumNow ( View Tweet)
A retrospective VEXAS cohort study of 59 pts receiving 71 targeted Rx - 98%male, mean 71 yrs & 46% had myelodysplastic syndr. Treatments included tocilizumab(19), anakinra (13), azacitidine(13), baricitinib (11), & pred only (10). Best responses w/ azacitidine & tocilizumab https://t.co/fBdfrrZt1M
Dr. John Cush RheumNow ( View Tweet)
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