Association between initial treatment strategy and progression to difficult-to-treat rheumatoid arthritis (D2T-RA): evidence from a 20-year-old real-world cohort
In brief
About 1 in 5 developed difficult-to-treat RA; first drug choice did not distinguish risk
In this real-world cohort of 675 people with rheumatoid arthritis followed for an average of about 18 years, 18.7% progressed to difficult-to-treat disease. Among patients treated after 2000, starting with a tumor necrosis factor inhibitor versus another drug type was not linked to a different risk; glucocorticoid exposure was associated with higher risk, but the observational findings need prospective confirmation.
- Journal
- RMD open (Q1)
- Published
- 23 September 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Cécile Van Mullem, Francesco Natalucci, Alexandra Avramovska, Tatiana Sokolova, Clément Triaille, Patrick Durez
- PMID
- 42778329
- DOI
- 10.1136/rmdopen-2026-007098
Why clinicians should know about it
- Picked for Rheumatology (paper of the day, 24 September 2026): Initial treatment strategy and progression to difficult-to-treat RA
Abstract
BACKGROUND/OBJECTIVES: Despite major advances in rheumatoid arthritis (RA) management, a substantial proportion of patients evolve to difficult-to-treat RA (D2T-RA). We estimated the probability of progression to D2T-RA and assessed whether the initial choice of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) is associated with this risk. METHODS: We retrospectively analysed 675 patients with established RA from the first consultation through all b/tsDMARD lines to the last follow-up or D2T-RA classification. Kaplan-Meier, log-rank and multivariable Cox regression analyses were performed to identify factors associated with D2T-RA progression. RESULTS: Of the 675 patients (mean follow-up of 217.1±131.16 months), 126 (18.7%) fulfilled the D2T-RA criteria. Tumour necrosis factor inhibitor (TNFi) accounted for most first-line and second-line treatments (81.0% and 53.2%). In the post-2000 subcohort (498 patients), no significant difference in D2T-RA risk was observed between TNFi and non-TNFi starters nor between TNFi-cycling or other mechanism of action (MoA)-switching strategies. Glucocorticoid exposure was independently associated with increased risk (HR 2.47, 95% CI 1.38 to 4.42) and delayed b/tsDMARD initiation with decreased hazard (HR 0.990, 95% CI 0.98 to 0.996). CONCLUSION: In this observational cohort, initial MoA choice was not associated with D2T-RA progression. Disease severity markers appeared more prominent than treatment strategies in driving refractory evolution. Validation in a prospective/randomised setting is required before potential transition into clinical practice.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.