Md Yusof MY, et al. - The objectives of this study are to evaluate factors related to primary and secondary non-response to rituximab in systemic lupus erythematosus (SLE) and assess the management of secondary non-depletion non-response (2NDNR). The outcome of this study uncovered that the treatment with anti-CD20 agents can be guided by B-cell monitoring and should aim to achieve complete depletion. 2NDNR is related to anti-rituximab antibodies, and switching to humanised agents restores depletion and response. They also suggest that alternative anti-CD20 antibodies may be more consistently effective in SLE.

Methods

• For this research, total 125 patients with SLE treated with rituximab for more than 12 years were studied prospectively.
• A major clinical response was characterized as an improvement of all active British Isles Lupus Assessment Group (BILAG)-2004 domains to grade C/better and no A/B flare.
• Partial responders were characterized by one persistent BILAG B.
• B-cell subsets were measured utilizing highly sensitive flow cytometry.
• Patients with 2NDNR, characterized by infusion reaction and defective depletion, were treated with ocrelizumab or ofatumumab.

Results

• They found total 117 patients had evaluable data.
• 96/117 (82%) achieved BILAG response (major=50%, partial=32%) in cycle 1 (C1).
• In multivariable analysis, younger age (OR 0.97, 95% CI 0.94 to 1.00) and B-cell depletion at 6 weeks (OR 3.22, 95% CI 1.24 to 8.33) increased the odds of major response.
• Complete depletion was predicted by normal complement and lower pre-rituximab plasmablasts and was not related to increased serious infection post-rituximab.
• Seventy-seven (with data on 72) C1 responders were retreated on clinical relapse.
• Of these, 61/72 (85%) responded in cycle 2 (C2).
• Of the 11 C2 non-responders, nine met 2NDNR criteria (incidence=12%) and tested positive for anti-rituximab antibodies.
• Lack of concomitant immunosuppressant and higher pre-rituximab plasmablasts predicted 2NDNR.
• Five were switched to ocrelizumab/ofatumumab, and all depleted and responded.