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For the last several years, conversations about JAK inhibitors have often started and ended with safety. The shadow cast by ORAL Surveillance has made clinicians more cautious and regulators more restrictive.
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Methotrexate (MTX) remains the cornerstone of rheumatoid arthritis (RA) treatment, yet it remains unclear as to how to predict who will respond to it. Two studies presented at ACR (Abstracts 2639 and 2643) suggest the answer may be hiding in the gut.
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At ACR 2025, the session “27M02: Nutrition for Rheumatic Disease: Where Aging Biology, Sarcopenia, and Diet Intersect” invited the audience to view rheumatic disease through the lens of biological aging and to consider how nutrition and exercise can serve as integrative lifestyle interventions.
Aurelie Najm
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Effectiveness of b/tsDMARDs RA pts kidney dysfunction
CorEvitas RA registry 9,569 pts
Pts low eGFR = older more comorbidities less NSAIDs
Reduced eGFR = 30% less likely to achieve remission
Persists indeed of GC intake
Is it a PK/PD related issue or somehow the reflection of https://t.co/KZuvPVa6eg
Nouf Al hemmadi
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Cellular Biomarkers of Rheumatoid Arthritis https://t.co/mLYZRX9ypm
Biomarkers of RA by @jeffsparks
Lots of promising biomarkers, we need validation and hopefully translation to clinical practice.
@RheumNow
#ACR25
Aurelie Najm
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Microbiome signature for prediction of response to MTX in RA: Yay or Nay?
Microbiome analysis 60pts, 23 MTX NR
BL enrichment in specific species in MTX NR
Looking at the graphs though, seems to be driven by a few pts
Prediction model doesn't seem to perform greatly
Sens 88% https://t.co/1yrSXdE6DG
Antoni Chan MD (Prof)
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Regulate-RA study, first-in-human Phase 1 study data show citrullinated protein (CitP)-targeted CAR-Tregs (SBT777101) are safe and show early efficacy in refractory RA. 67% had ≥50% joint count reduction by Week 4. A novel, non-cytotoxic approach to immune modulation for https://t.co/g153w3XVEK
Aurelie Najm
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Ph2B RCT of Rosnilimab Tcell depleter (PD-1high Tph/Tfh, Teff)
Wk 12 Primary Endpoint met
Mean change DAS28-CRP at Wk 12
SC rosnilimab 100mg Q4W -2.06
400mg Q4W -2.12
600mg Q2W -2.06
PBO -1.69
>90% peripheral and synovial depletion pathogenic T cells 28 Wk
Safety profile: https://t.co/XyVhJamFdp
Jiha Lee
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Not all RA meds are equal for the heart.
In >10K older adults w/ RA, advanced therapies lowered MACE risk (HR 0.63) vs csDMARDs, while GCs ↑ risk (HR 1.54) and undertreatment ↑ it 13-fold.
Control inflammation, protect the heart.
@RheumNow #ACR25 Abstract #2642
David Liew
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PD-1 agonist as an induction therapy in refractory RA??
Rosnilimab ph2b:
- still responding 3mo after Rx stopped
- no difference between type of prior b/tsDMARD failure
- safety here looks good *so far*
A lot of cautious excitement in the room for this
#ACR25 LB19 @RheumNow https://t.co/CmfPlP4g0N
Jiha Lee
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A new approach in RA:
Rosnilimab targets & depletes PD-1–high pathogenic T cells, acting upstream of cytokine pathways. In Ph2b, all doses improved DAS28-CRP & ACR responses vs placebo, with durable efficacy & good safety.
@RheumNow #ACR25 Abstract#LB19 https://t.co/cIxi7NEu6C
Md Yuzaiful Md Yusof
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#ACR25 Abstr#LB19 New T-cell therapy on the block! In Phase 2b RCT of #RA (~50% b/tsDMARD-IR), Rosnilimab, PD-1 agonist met its endpoint (DAS28-CRP) at WK12. Effective despite type of previous therapy. No safety concern/malignancy/death. To proceed to Phase 3 @RheumNow #ACRBest https://t.co/MecTYMpH0o
Richard Conway
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Emery et al. Rosnilimab, selective T cell (PD-1high Tph/Tfh, Teff) monoclonal antibody in RA. Phase 2 RCT. 424 patients. 41% prior bDMARD. 69% CDAI LDA week 14. Week 12 ACR20 70%, ACR50 40%, ACR70 21%. @RheumNow #ACR25 Abstr#LB19 https://t.co/479q6COWvk
Jiha Lee
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b/tsDMARD in RA + CKD (eGFR <60)
From >12K pts in CorEvitas:
- overall effective but 30% ↓ CDAI-emission (HR 0.71)
- Findings consistent across TNFi, IL-6i, ABA BCDT, JAKi
@RheumNow #ACR25 A#2640 https://t.co/UOP9ejZKoA
Nouf Al hemmadi
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Secrets and Pearls in Rheumatology https://t.co/SwnlB8UbHO
@Janetbirdope pearls in rheumatology.
Sero negative inflammatory arthritis ? Or is it? Look at the toes for early signs of PsA.
In my clinic ITS inflammatory arthritis to determine etiology .
@RheumNow
#ACR25
Md Yuzaiful Md Yusof
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#ACR25 Abstr#LB15 Tell #RA patients on methotrexate that eating high fibre diet is good for them! An RCT showed improved EULAR response vs PBO. Likely due to restoration of Th17/Treg balance @RheumNow https://t.co/NbwQFqJNho
Jiha Lee
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CDAI appropriately guided therapy escalation in RA, but not for everyone. Treatment adjustments were less likely in pts with public or no insurance. Even data-driven care can fall short when access barriers persist.
@RheumNow #ACR25 Abstract#2616
Bella Mehta
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Large Canada ICES dataset- DMARD use is not associated with adverse pregnancy outcomes. In pts with RA, SlE and other rheumatic diseases.
Abst#2627 #ACR25 @RheumNow https://t.co/T9Ll1FNjT7
Mrinalini Dey
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#1748 Higher air pollution, esp PM2.5, linked to ⬆️RA disease activity and more flares in >1000 Korean patients. Each rise in PM2.5 significantly boosted DAS28, CDAI & joint counts.
Does cleaner air mean calmer joints?
@RheumNow #ACR25
Aurelie Najm
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US Electronic Health Record cohort 2000+pts
Incidence Heart Failure over 10 yrs 6.8%
HF asso w/
Older
Male
Lower eGFR
Hypertensive medication
Diabetes
TTMTS MTX, TNFi
Higher CRP
Probably surrogates for High Disease Activity...
How do we detect it?
Maybe not by using the https://t.co/s9SjEyk3WF
