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THU0390 Management of Primary and Secondary Non-Response to B Cell Depletion Therapy in Systemic Lupus Erythematosus: 10-Year Experience at a Single Centre
  1. M.Y. Md Yusof1,2,
  2. D. Shaw1,
  3. Y. El-Sherbiny1,2,
  4. S. Dass1,2,
  5. A.C. Rawstron3,
  6. E.M. Vital1,2,
  7. P. Emery1,2
  1. 1Rheumatology, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds
  2. 2Rheumatology, NIHR Leeds Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust
  3. 3Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom

Abstract

Background Rituximab (RTX) is widely used for refractory SLE based on strong evidence for efficacy of remission induction in open label case series [1,2]. In first-cycle responders, data are required on the outcome of repeat cycles and management of patients who lose response. In first-cycle non-responders there are few data on whether repeat cycles would be effective (as previously shown in RA).

Objectives To evaluate the outcome of repeat cycles of rituximab in SLE responders and non-responders.

Methods We conducted a retrospective observational study of SLE patients treated with RTX in a single centre between September 2004 and September 2014 (total follow-up: 406 patient-years). Each cycle of RTX consisted of 2x1000mg infusions repeated on clinical relapse. Patients who demonstrated features of human anti-chimeric antibody (HACA, ie: infusion reaction >24 hours after the second infusion with <50% B cell depletion) were treated either with RTX desensitising regimen or 2x1000mg ocrelizumab. Response was defined as improvement to ≤1 persistent BILAG B and no A/B flare.

Results 82 patients were studied (75 female and 7 male; median age prior to RTX: 40 (range 20-79) and median (IQR) disease duration: 6 (2-10) years). Median time-to-retreatment for cycles 1-4 were 52, 60, 57 and 51 weeks respectively. In cycle 1 (C1), there were 8/82 (10%) primary non-responders. Of these, 3 were retreated at 6 months but none responded to retreatment. The remaining 5 patients were treated with different therapies. Of the 74/82 (90%) primary responders in C1, 60 were treated on relapse. Of these, 51 continued to respond (median time to C1 relapse: 49 IQR (34-89) weeks) while 9 were secondary non-responders (median time to C1 relapse: 58 (IQR 47-123) weeks). Of the secondary non-responders, 3/9 were treated with ocrelizumab, which resulted in complete peripheral B cell depletion and response in 3/3; while 1 patient was retreated using RTX desensitising regimen but still experienced HACA.

Conclusions Although initial responses were good, duration of response may not necessarily be predictive to response in a subsequent cycle. Retreatment of first cycle non-responders did not appear to be effective in SLE, in contrast to rheumatoid arthritis. Humanised anti CD-20 antibodies induce depletion in RTX-resistant patients and may be more effective than RTX in SLE.

References

  1. Vital et al. Arthritis and Rheumatism 2011 [2] Ramos-Casals et al. Lupus 2009

Acknowledgements Dr Sudipto Das, Dr Mike Martin, Dr Maya Buch, Dr Jacqueline Andrews, Dr Colin Pease, Dr Sinisa Savic, Dr Emma Dunn, Dr Mark Goodfield, Dr Paul Beirne and Dr John Bamford and Dr Miriam Wittmann.

Disclosure of Interest None declared

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