Background Rituximab has been licensed for the treatment of Rheumatoid Arthritis (RA) for over a decade. We previously showed that the initial depth of B cell depletion was associated with clinical response; 96% complete versus 74% incomplete depletion at 6 months (p=0.02) and that retreatment of initial non-responders with incomplete depletion led to 72% response rate in cycle 2 (C2).
Objectives To validate B cell depletion after the first infusion as a predictor of response to rituximab (Project 1) and assess outcome of retreatment of first cycle non-responders (Project 2) as a basis for B cell monitoring during rituximab treatment.
Methods The published discovery cohorts included 60 patients in Project 1 and 25 patients in Project 2. For this validation study, we analysed the subsequent consecutive 180 patients with RA treated with rituximab at a single centre. Each cycle of rituximab consisted of 2×1000mg infusions, repeated on clinical relapse. B cell subsets (naïve, memory and plasmablast) were measured at baseline, after first infusion of rituximab (2 weeks) and at early B cell repopulation (6 months) using a flow cytometry protocol optimized to detect low numbers of B cell subsets and plasmablasts. Complete depletion was defined as total B cell count <0.0001×109/L. First cycle non-responders who had incomplete depletion at C1 were retreated at 6 months.
Results 180 patients (female=147 (81%), median age at rituximab initiation 62 (IQR 51–71) years and median disease duration 10 (IQR 5–18) years were studied. 72 (40%) patients were biologic-naïve. In C1, 126 (70%) achieved moderate-good EULAR response. The complete depletion rate for C1 was 54%. Complete depletion was associated with response; p=0.027 (Table 1). 30 patients who were C1 non-responders and had incomplete depletion were retreated at 6 months. Of these, 20 (67%) had complete depletion and 20 (67%) responded in C2. Non-responders in C2 had trend to higher plasmablast numbers at retreatment than responders (p=0.14).
Conclusions We have validated that the depth of B cell depletion after the first infusion is a predictor of response to rituximab in RA. A high degree of response in C2 was also confirmed when C1 non-responders who had incomplete depletion were retreated. B cell subsets therefore should be monitored in the routine care of RA patients receiving rituximab and repeat infusions considered if early depletion is incomplete and clinical response poor.
Dass S et al. A&R 2008
Vital EM et al. A&R 2010
Disclosure of Interest None declared