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
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.