Effect of concomitant statins on rituximab efficacy in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) are at an increased risk for cardiovascular disease. In order to lower this risk, statins are used in clinical practice in addition to biologics. Rituximab, an anti-CD20 antibody approved for the treatment of RA, induces B-cell apoptosis by crosslinking and redistributing CD20 to cholesterol-rich lipid rafts. Statins have been shown in vitro to induce conformational changes on the CD20 epitope, potentially influencing the apoptotic effect of rituximab. There are conflicting reports about the effect of statins on the clinical efficacy of rituximab in RA. We investigated the impact of statin coadministration on rituximab efficacy in patients from a global clinical trial programme in RA. This was a retrospective, pooled, observed case analysis from four placebo-controlled phase II/III randomised clinical trials (DANCER, REFLEX, SERENE and IMAGE) in patients with moderate-to-severe active RA. All patients received concomitant methotrexate 10−25 mg/week at a stable dose and were permitted to receive stable background doses of oral corticosteroids (prednisolone ≤10 mg/day or equivalent) and non-steroidal antiinflammatory drugs throughout. Efficacy responses (change in Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) from baseline, American College of Rheumatology 20% or 50% (ACR20/50) response) and and peripheral blood CD19+ B-cell counts at 24 weeks following one course of rituximab were compared between patients who received concomitant statins for ≥8 weeks (‘statins’, STY) and those who received statins for <8 weeks or not at all (‘no statins’, STN). Differences in outcome measures between STN and STY groups were tested using either an analysis of covariance model for continuous