Induction of cure in early arthritis (I CEA): results of a randomised clinical trial to compare three treatment strategies in recent onset undifferentiated arthritis

Abstract

Objectives: To investigate whether in undifferentiated arthritis (UA) it is beneficial to start early treatment with disease-modifying antirheumatic drugs (DMARDs) compared with symptomatic therapy. Methods: The Induction of Cure in Early Arthritis study is a 3-month multicentre single-blinded randomised controlled trial followed by a 9-month observational period. Patients with early DMARD-na & iuml;ve UA (arthritis >= 2 joints, not fulfilling American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2010 Rheumatoid Arthritis criteria) received a glucocorticoid injection (40 mg intra-articular or intramuscular) and were randomised (1:1:1) to a 3-month intervention with (1) non-steroidal anti-inflammatory drugs (NSAIDs) in standard daily dose or (2) methotrexate (MTX) 15 mg/week increased to 25 mg/week or (3) baricitinib 4 mg/day. Primary endpoint was Disease Activity Score (DAS) (44/53 joints) improvement at 3 months. Differences between treatment arms were assessed with analysis of covariance, adjusted for baseline DAS. Results: Patients were randomised to NSAID (n=29), MTX (n=28) or baricitinib (n=28). After 3 months, baricitinib gave a significant improvement in DAS compared with NSAIDs: adjusted mean change in DAS: -0.52 (95% CI -0.93 to -0.11; p=0.01). MTX gave a numerically similar improvement: -0.39 (95% CI -0.84 to 0.06, p=0.09). Although non-significant, at 12 months DAS was lowest in the MTX treatment arm 1.3 (SD 0.7), NSAID 1.6 (SD 0.9), baricitinib 1.7 (SD 0.9), p=0.38. Incidence rates of severe adverse events remained low during the study across all treatment arms. Conclusions: In patients with UA, early DMARD treatment led to greater improvement in disease activity over 3 months compared with NSAIDs, with the improvement for baricitinib reaching statistical significance. Over 12 months, disease activity was not significantly different across treatment arms, with overall favourable outcomes.