Exploring possibilities towards PeRsonalIsed MEdicine in Rheumatoid Arthritis (PRIMERA): tailored modifications to...

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).

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.

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.

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.

ISRCTN16170070.