B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: A six‐month, national, multicenter, open‐label study

Abstract

Objective To examine whether serum B cell markers can predict response to rituximab, a B cell–depleting monoclonal antibody, in patients with refractory rheumatoid arthritis (RA). Methods This rituximab re‐treatment dose study (SMART [eSsai MAbthera sur la dose de Re‐Traitement]) involved 208 patients with refractory RA. Serum markers of B cell activation (anti–cyclic citrullinated peptide [anti‐CCP] antibodies, rheumatoid factor [RF], serum IgG, IgA, and IgM levels, serum κ and λ free light chains, and serum BAFF) were assessed before the first rituximab cycle (1,000 mg on days 1 and 15). Univariate and multivariate analyses were performed to identify factors associated with a European League Against Rheumatism (EULAR) response at 24 weeks. Results There were 149 responders (72%). Two baseline factors were associated with a EULAR response at 24 weeks in multivariate analysis: the presence of anti‐CCP antibodies or RF (odds ratio 3.5 [95% confidence interval 1.6–7.6]) and a serum IgG concentration above normal (odds ratio 2.11 [95% confidence interval 1.02–4.33]), with synergy between them (odds ratio 6.0 [95% confidence interval 2.2–16.2]). Conclusion The presence of RF or anti‐CCP antibodies and elevated IgG are 2 simple biomarkers that can be used routinely before therapy to predict response to rituximab in patients with refractory RA.