Exploring possibilities towards PeRsonalIsed MEdicine in Rheumatoid Arthritis (PRIMERA): tailored modifications to standard treat-to-target management-a multicentre, randomised, open-label trial.

Abstract

Objectives: Guidelines for early rheumatoid arthritis (RA) recommend starting methotrexate, with optional glucocorticoid (GC) bridging, followed by treat-to-target intensifications after at least 3 months (routine care). Given RA's heterogeneity, we evaluated a stratified treat-to-target approach (tailor-made approach) consisting of two modifications to routine care: first-line disease-modifying antirheumatic drug (DMARD) selection stratified by autoantibody status and rapid treatment intensifications guided by early treatment response (within 1 month).

Methods: This multicentre, open-label randomised controlled trial included adults with DMARD-naïve RA (2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) criteria) who were randomly assigned (1:1) to the tailor-made approach or routine care. Both arms followed a treat-to-target strategy, intensifying every 3-4 months until Disease Activity Score (DAS) ≤2.4. The tailor-made approach started MTX in autoantibody-positive patients and hydroxychloroquine in autoantibody-negative patients, both with intramuscular GC bridging. Additional intensifications at months 1 and 4 were allowed when DAS >2.4, 1 month after DMARD initiation or intensification, enabling treatment escalation before the standard 3-month reassessment. Routine care started MTX with GC bridging regardless of autoantibody status and without extra intensifications. The two primary outcomes were targeted synthetic/biologic (ts/b)DMARD use at 10 months and mean DAS over time; superiority required both to favour the tailor-made approach.

Results: In total, 308 included patients were randomised(152 tailor-made; 156 routine care). At 10 months, ts/bDMARD use was 21% in the tailor-made approach vs 17% in routine care (one-sided p=0.20). Mean DAS trajectories were similar (p=0.57). No differences were observed in mean patient-reported outcome measure trajectories or adverse events.

Conclusion: Modifying the standard treat-to-target strategy, by stratifying the initial DMARD according to autoantibody status combined with rapidly intensifying therapy based on early treatment response, did not result in superior clinical outcomes.

Trial registration number: ISRCTN16170070.