PT  - JOURNAL ARTICLE
AU  - Gurjit S.  Kaeley
AU  - Amy M.  Evangelisto
AU  - Midori J.  Nishio
AU  - Sandra L.  Goss
AU  - Shufang Liu
AU  - Jasmina Kalabic
AU  - Hartmut Kupper
TI  - Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial
AID  - 10.3899/jrheum.151009
DP  - 2016 Jun 15
TA  - The Journal of Rheumatology
PG  - jrheum.151009
4099  - http://www.jrheum.org/content/early/2016/06/09/jrheum.151009.short
4100  - http://www.jrheum.org/content/early/2016/06/09/jrheum.151009.full
AB  - Objective To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA). Methods MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions. Results Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07–0.66) comparing low-dosage (4.12, 95% CI 3.88–4.34) versus high-dosage MTX (3.75, 95% CI 3.52–3.97) was statistically significant and noninferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar. Conclusion In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet noninferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.