Obinutuzumab and Ofatumumab are More Effective Than Rituximab in the Treatment of Membranous Nephropathy Patients With Anti-Rituximab Antibodies
Among 34 patients with membranous nephropathy who had developed antibodies against rituximab, switching to obinutuzumab or ofatumumab achieved clinical remission far more often than continuing rituximab (87% vs. 37% at six months), with no serious adverse events reported.
Background
Rituximab has transformed the management of membranous nephropathy, but a substantial minority of patients do not respond. One recognised mechanism of resistance is the development of antidrug antibodies against rituximab. Obinutuzumab (humanized) and ofatumumab (fully human) are alternative anti-CD20 agents, but had not been compared with rituximab specifically in patients carrying anti-rituximab antibodies.
Key findings
Thirty-four patients with membranous nephropathy and documented anti-rituximab antibodies were enrolled across five nephrology departments in France, India and Italy; 19 received rituximab, 12 obinutuzumab and 3 ofatumumab. Clinical remission was more frequent with obinutuzumab or ofatumumab than with rituximab at month 6 (87% vs. 37%, P = 0.005) and month 12 (87% vs. 42%, P = 0.01). Immunological remission (92% vs. 56%, P = 0.04) and B-cell depletion (93% vs. 35%, P = 0.002) at month 6 also favoured the alternative agents. No serious adverse events were reported in the obinutuzumab or ofatumumab group.
Clinical implications
The authors argue that anti-rituximab antibodies should be monitored systematically so that non-responders can be switched to obinutuzumab or ofatumumab rather than re-treated with rituximab. Numbers are small and the design retrospective, so the effect size should be treated as indicative; nonetheless the biological rationale and the consistency of clinical, immunological and B-cell endpoints make this a practical consideration in refractory disease.
Category
Research
Source
Kidney International Reports
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