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Introducing Polyrefractory RA: A New Frontier in Difficult-to-Treat RA

Jiha Lee, MD

At a EULAR 2025 session titled “What makes ‘Difficult-to-treat RA’ so difficult to treat? And what can we do?”, Drs. Paula David and Dennis McGonagle introduced the emerging concept of polyrefractory rheumatoid arthritis (RA), a term now being used to describe a subset of patients who have failed to respond to five or more biologic or targeted synthetic DMARDs. This new classification, derived from recent multinational registry data, represents a significant step in refining our understanding and management of the most treatment-resistant forms of RA.

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IL17

Expanding the IL-17 Therapeutic Landscape

Adela Castro, MD

IL-17 inhibitors are an effective therapeutic for a broad spectrum of inflammatory and autoimmune diseases and its blockade has revolutionized management of diseases such as psoriasis, psoriatic arthritis and SpA. Is there a need for more medications within the same therapeutic class?

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Cancer.risk_.jpg

Cancer risk in rheumatoid arthritis: anything new?

Aurelie Najm, MD, PhD

Is there a higher risk of cancer that comes with the disease? Or with the treatments? So many confounding parameters, such as disease duration, disease state, and disease activity come into play. A promising session explored comorbidities in Rheumatoid Arthritis, in particular cancer and cardiovascular events. Here are my takeaways.

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EULAR,poster

EULAR 2025 – Day 2 Report

Jack Cush, MD

Day 2 was a full agenda for those attending EULAR 2025 in Barcelona with sessions on the management of RA, Behcets, Lupus and Hand Osteoarthritis. Clinical overviews on MAS, Ehlers-Danlos, Difficult to treat RA and PsA offered a wide variety of options to rheumatologists. Here are a few interesting presentations from today.

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Puzzle pieces

Clinical and Therapeutic Challenges in Connective Tissue Disease and ILD

Mrinalini Dey, MD

Connective tissue diseases (CTDs) and interstitial lung disease (ILD) represent a challenging intersection of systemic autoimmunity and progressive respiratory impairment. Research presented at EULAR 2025 continues to highlight the importance of CTD-ILD and the evolving landscape of therapeutic options for patients with autoimmune ILDs.

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Is #PDE5i protective in development of #SSc #ILD? Maybe 444 w ILD of >4000 #EUSTAR Pts over 1 to 2 yrs f/u #immunesuppressive use maybe or not 🤷‍♀️channeling bias Reduction in new #ILD in #scleroderma PDE5i ✅ Immunesuppression ? @RheumNow #EULAR2025 @eular_org #OP0334 https://t.co/6dtLfybkRV

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Janet Pope Janetbirdope ( View Tweet)
In CareRA pooled analysis, 1 in 3 early RA pts had persistent impact (pain, fatigue, HAQ) despite improved inflammation. Female sex, longer symptom duration & low CRP were predictive. Pts more often escalated to b/tsDMARDs → risk of overtreatment? @RheumNow #EULAR2025 #OP0330

Mrinalini Dey DrMiniDey ( View Tweet)

We can control inflammation in RA, but some pts still struggle with disease impact, despite improving with bDMARDs: - lower inflamm - higher comorbidities Doesn’t necessarily map to fibromyalgia dx Beyond Rx, this is the critical question CareRA/2000 #EULAR2025 OP0330 @RheumNow https://t.co/Th3smMgtVb

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David Liew drdavidliew ( View Tweet)
@RheumNow So rheumatoid nodule treatment might target some of that pathophysiology. Rituximab, abatacept, or JAKi? And while surgery often isn’t great (plus they often grow back), definitely an option for some. Christopher Edwards #EULAR2025 @RheumNow https://t.co/sFWnQN8uC4

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David Liew drdavidliew ( View Tweet)
SLE Preview: advances to achieve deep B-cell depletion The race is on for the first chimeric antigen receptor (CAR)-based therapy to be approved for the treatment of systemic lupus erythematosus (SLE). Its main principle is to induce deep B-cell depletion, with the hope to reset https://t.co/OzQ05YFZfb
Dr. John Cush RheumNow ( View Tweet)
#EULAR2025 Abstr#POS0325 Immunosuppressant-free is not only confined to CAR-T. Our cohort study in #SLE: 20% patients were “Super-Responder” (>3yrs response) inc. 7% IS-free after one Rituximab cycle. Non-European, APS & shorter disease duration predicted super-response @RheumNow https://t.co/nPIYpGoynR

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Md Yuzaiful Md Yusof Yuz6Yusof ( View Tweet)
#EULAR2025 Abstr#OP0198 Long-term extension study of Phase 2 #SLE showed efficacy of Upadacitinib and UPA + Elsubrutinib were maintained through to Week 104. Those who switched from PBO at WK48 to UPA + ELSU also improved. No VTE or MACE. Is add-on ELSU really needed? @RheumNow https://t.co/x8NbAtsHh0

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Md Yuzaiful Md Yusof Yuz6Yusof ( View Tweet)
#Vagal #nerve #stimulation Hand held device #BDMARD failure Plausible - improved pro inflammatory cytokines wears off benefit if stopped Attenuates in ~half over yrs Open label uncontrolled @RheumNow @eular_org #EULAR2025 Session D2T-RA https://t.co/98K5gwasHv

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Janet Pope Janetbirdope ( View Tweet)
Management of HLH/MAS and modes of action of advanced therapies Jessica Manson @RheumNow #EULAR2025 https://t.co/Op3u53ZXeK

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Antoni Chan MD (Prof) synovialjoints ( View Tweet)
Fascinating to see JAKi uptake in European JAK-pot centres - tofa was already on the decline pre-ORAL Surveillance - JAKi use (driven by upadacitinib) continues to grow, although maybe it’s slowed Hopefully rational JAKi has its place #EULAR2025 POS0150 @RheumNow https://t.co/XRyHJVw821

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David Liew drdavidliew ( View Tweet)
New dual-action RA drug? OP0193: CPL’116 targets both JAK & ROCK. In 12-wk RCT, highest dose improved DAS28-CRP, joint counts & pain, with clean labs. Is this a future option for RA-ILD or patients with comorbid CVD risk? #EULAR2025 @RheumNow

Jiha Lee JihaRheum ( View Tweet)

PHOENYCS GO🏃: Dapirolizumab pegol (DZP) led to higher rates of LLDAS (41% vs 20%) & DORIS remission (19% vs 8%) at wk48 vs PBO+SOC. DZP showed earlier & more sustained disease control, advancing T2T in SLE. @RheumNow #EULAR2025 #OP0201 https://t.co/zuxBELxTDd

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Mrinalini Dey DrMiniDey ( View Tweet)
Ph 2 RCT CPL'116 dual inhibition JAK/ROCK 106 MTX IR pts wk12 primary endpoint met (DAS28-CRP decrease) in 240mg arm vs. PBO 75% >= AEs, SAE 2: 1 MI, 1 bladder cancer Authors suggest absence of lipids/LFTs disruption compared to other JAKs Ph3 is awaited!! #OP0193 #EULAR2025 https://t.co/TnnM410LfM

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Aurelie Najm AurelieRheumo ( View Tweet)
#MITIGATE subgroup analysis: Inebilizumab reduced flares & boosted remission across all #IgG4-RD subgroups. HR for flare vs PBO: 0.12-0.16 across sex/race. Similar results for all subgroups in achieving flare-free, treatment-free complete remission. @RheumNow #EULAR2025 #OP0189

Mrinalini Dey DrMiniDey ( View Tweet)

There is still hope for vagal nerve stimulation in RA! RCT RESET-RA 240+pts multibioIR Implantable cervical device Meets Primary endpoint ACR 20 wk12 Subgroup 1 prior bioDMARD ACR 20 wk12 46% vs 19% sham EULAR Good response 61% vs 42% sham Wk 12 SAE rate 1.7% #OP0190 #EULAR2025 https://t.co/DCON01XXgd

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Aurelie Najm AurelieRheumo ( View Tweet)
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