Certolizumab Pegol Remains an Equally Efficacious Treatment of Rheumatoid Arthritis Over a Range of Background Methotrexate Regimens.

Objective. Anti-tumor necrosis factor agents (anti-TNFs) are frequently used in combination with methotrexate to treat rheumatoid arthritis (RA). We investigated the effect of background methotrexate dose, in combination with anti-TNF certolizumab pegol (CZP), on treatment efficacy and safety in RA patients. Methods. A pre-specified subgroup analysis comparing two methotrexate dose categories (<15 mg/week and ≥15 mg/week) was carried out using data pooled from phase III clinical trials RAPID1 (NCT00152386) and RAPID2 (NCT00160602) according to treatment group: CZP 200 mg, CZP 400 mg or placebo, every two weeks. Inclusion criteria required methotrexate dose ≥10 mg/week. Efficacy endpoints included Week 24 ACR20/50/70 responses analyzed by logistic regression, and changes from baseline in DAS28(ESR) and van der Heijde modified Total Sharp Score (mTSS) analyzed by ANCOVA. Incidence rates of treatment-emergent adverse events (TEAEs) were categorized by baseline MTX dose. Post-hoc sensitivity analysis investigated three methotrexate dose categories: ≤10 mg/week; >10 and ≤15 mg/week; and >15 mg/week. Results. 638, 635 and 325 patients received CZP 200 mg, CZP 400 mg and placebo, respectively. At Week 24, treatment responses in both CZP groups were uninfluenced by baseline methotrexate dose category, and were superior to placebo group, for all investigated endpoints: ACR20/50/70, DAS28(ESR) and mTSS. TEAE incidence rates were higher in patients receiving methotrexate ≥15 mg/week for most TEAE types, across treatment groups. Conclusion. CZP efficacy was not affected by background methotrexate dose category. It can be hypothesized that to minimize TEAEs, background methotrexate doses could