Background Rituximab (RTX) is effective for refractory SLE based on strong evidence for efficacy from open label evidence. We have observed cases of SLE patients who previously responded well to RTX developing anti-rituximab antibodies (HACA). We have therefore treated these patients with alternative, humanised anti-CD20 antibodies.
Objectives To evaluate the incidence of secondary non-response to RTX and efficacy of switching to humanised anti-CD20 antibodies in SLE.
Methods We conducted a retrospective observational study of the first 100 consecutive SLE patients treated with RTX at a single centre (total follow-up: 445 patient-years). Each cycle of RTX consisted of 2x1000mg infusions repeated on clinical relapse. Patients who demonstrated features of HACA, ie: infusion reaction >24 hours after the second infusion with <50% B cell depletion as analysed using HSFC were treated either with 2x1000mg ocrelizumab (OCR) or 2x700mg ofatumumab (OFT). Response was defined as improvement to ≤1 persistent BILAG B and no A/B flare.
Results 94 patients with complete response data at 6 months were studied. In Cycle 1 (C1), 81/94 (86%) achieved a BILAG response. 1 patient with severe SLE whom B cell had not depleted and C1 non-responder was retreated with RTX but subsequently developed HACA. She was treated with OCR resulted in depletion and biological response ie: normalisation of anti-dsDNA but died 6 months later with multi-organ failure. Of the C1 responders, 63 patients received RTX on clinical relapse. Of this, 54/63 (86%) responded and 8/9 (13%) were non-responders due to HACA. Of the C2 non-responders, 3/9 patients were treated with OCR resulted in depletion in 2/3 and all responded. 1/9 was treated with OFT achieved depletion for the first time as well as stabilisation of renal function. In C3, 1 had HACA and was treated with OFT, resulted in depletion and response.
Conclusions Following initial response to RTX, the incidence of secondary non-response was 15%, mostly due to HACA. Switching to alternative humanised anti-CD20 antibodies improves depletion and clinical response in rituximab-resistant patients in this largest case series to date. Humanised anti-CD20 may be more appropriate than RTX in SLE.
Disclosure of Interest None declared
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