B Cell Activation Biomarkers as Predictive Factors for the Response to Rituximab in Rheumatoid Arthritis

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 kappa and lambda 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.