Joint Ventures: Aiming for Targeted First-Line Therapy in Early RA at EULAR 2026

In this episode of Joint Ventures, hosts Jack Arnold, MBBS, PhD, academic clinical lecturer in rheumatology, University of Leeds, was joined at the European Alliance of Associations for Rheumatology (EULAR) 2026 annual congress in London by Laurence Duquenne, MD, a rheumatology researcher, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, an investigator on one of the meeting's standout studies to examine whether baseline naïve CD4+ T cell frequency can identify which newly diagnosed patients with rheumatoid arthritis (RA) are unlikely to respond to methotrexate monotherapy, and whether adding a biologic at the outset can close that gap.

Duquenne opened by describing the challenge the TEEMS trial was designed to address. Remission rates in early RA remain stubbornly low — approximately 35% at 3 months in population-level data from England and Wales¹— despite treat-to-target strategies and guidelines recommending methotrexate (MTX) as universal first-line therapy.² The question TEEMS posed was whether stratifying patients by a measurable immunological feature at presentation could allow clinicians to identify poor MTX responders before treatment even begins, and direct them toward more intensive therapy from the start.

"If we manage to target those who are at higher risk of having poor outcomes, it seems very logical to start and treat them as early as possible,” Duquenne said.

The trial enrolled 103 DMARD-naive, anticitrullinated protein antibody (ACPA)-positive patients with early RA and stratified them by naïve CD4+ T cell frequency against age- and sex-matched controls. Those with normal T cell frequency (Arm A) received MTX with treat-to-target care. Those with subnormal frequency were randomised 1:1 to MTX alone (Arm B) or MTX plus biosimilar etanercept (Arm C). Remission rates by arm at weeks 12 and 24 were 28.6%, 11.5%, and 48%, and 41.5%, 25.9%, and 41.7%, respectively — meaning patients in Arm C, despite carrying the poor-prognosis immunological phenotype, reached remission rates comparable to those of the good-prognosis group, and did so earlier. Odds of clinical remission in Arm C versus Arm B were significantly higher at week 12 (odds ratio [OR], 11; 95% confidence interval [CI], 2–57; P <0.010), with a numerically lower but non-significantly different cumulative steroid dose in Arm C (mean [standard deviation (SD)], 123 mg [91]) compared to Arm A (184 mg [217]) and Arm B (178 mg [118]).

The conversation broadens from trial results to the strategic and economic logic underpinning them. With biosimilar TNF inhibitors now dramatically cheaper than the originator products, the historic cost argument against early biologic use is substantially weakened. Duquenne makes the case that combining a cost-effective biomarker screen with targeted biologic prescribing represents a form of treatment stewardship — one that could be particularly valuable in resource-limited settings. Arnold connects this to the wider shift in RA care toward earlier intervention and prognostication, and both speakers discuss the under-quantified social value of keeping patients in employment. A question raised at the conference session by an attendee about workplace participation is noted as a compelling framing for health-economic arguments to policymakers.

Duquenne closes by sketching where the field might travel next: beyond newly diagnosed disease toward the preclinical phase of RA, where identifying individuals at highest risk before clinical inflammation is fully established — potentially using naïve CD4+ T cell frequency alongside other emerging biomarkers — could push the window of opportunity even earlier. She also highlights a session on nutrition and the gut microbiome as among the conference's most thought-provoking scientific programming so far.

Arnold’s disclosures include Alumis, Roche, and Novartis. Duquenne had no disclosures to report.

References

1. Alveyn E, Coalwood C, Farrell G, et al. Trends in remission rates for rheumatoid arthritis in England and Wales: a population-level cohort study. Rheumatology (Oxford). 2025;64(9):4957-4967. doi:10.1093/rheumatology/keaf233

2. Combe B, Landewe R, Lukas C, et al. EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2007;66(1):34-45. doi:10.1136/ard.2005.044354

3. Mankia K, Duquenne L, Garcia-Montoya L, et al. Improving remission rates in early rheumatoid arthritis: targeting predicted poor methotrexate responders, based on naïve CD4+ T-cell frequency, with additional etanercept: the TEEMS trial, a pilot proof of concept study [abstract OP045]. Presented at: European Alliance of Associations for Rheumatology (EULAR) Annual Congress 2026; June 3–6, 2026; London, United Kingdom. doi:10.1136/annrheumdis-2026-eular.B.4255