Induction of Cure in Early Arthritis (I CEA): results of a randomised clinical trial to compare three treatment strategies in recent onset undifferentiated arthritis.

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-naïve 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.