127 Inefficacy of belimumab in SLE patients who lose response to rituximab

Background: Rituximab is commonly used for SLE but there is a significant rate of secondary non-depletion and non-response (2NDNR) due to development of anti-drug antibodies. We previously showed that switching to another anti-CD20 therapy restores response. Belimumab is another B cell-directed therapy, licensed in SLE. Our objective was to assess the efficacy of belimumab in patients with 2NDNR to rituximab from a large single centre cohort. Methods: We reviewed 8 patients who received belimumab following 2NDNR to rituximab. We studied their baseline characteristics, disease activity, organ system involvement, previous immunosuppression, BILAG, SLEDAI and SRI-4 response to belimumab, and outcome of therapy. Results: All of the patients were female with a median age of 45.5 years (age range 22-68). At baseline median (IQR) SLEDAI was 12 (9.5,16.25). Baseline disease activity (BILAG A or B): was active in the musculoskeletal (8/8); mucocutaneous (6/8); and renal (1/8) organ systems. 6/8 patients had positive anti-dsDNA and low complement in line with data predicting better response to rituximab AND current NICE guidance. The other two had been treated prior to the publication of this guidance. Response was assessed at 6 months. No patient achieved an SRI-4 (although two patients had a 4-point reduction in SLEDAI, SLEDAI scores at follow up remained high at 10 and 18, and both had new BILAG activity). Median(IQR) SLEDAI at 6 months was unchanged at 12(7.5,15.5). 5/8 patients discontinued therapy after 5, 6, 6, 11, and 36 months. All 5 of these were due to inefficacy. In 2/5 of these cases, there was a new episode of nephritis during the course of belimumab (1 relapse and 1 de novo nephritis in a patient who previously only had skin, joint and general involvement). These patients were switched to IV cyclophosphamide. Conclusion: We found unexpected differences in response between two B cell-targeted biologics in a group of patients known to have previously responded to B cell depletion. The most common reason for discontinuation of rituximab in our previous study of 125 patients over 12 years was 2NDNR associated with anti-drug antibodies, which occurred in > 14% of patients. While 5/5 of patients with 2NDNR to rituximab regained response on switching to another humanised CD20 antibody, efficacy of belimumab in the same scenario was poor, with no patient achieving SRI-4 or low disease activity and two developing nephritis while on therapy. Given the good response to B cell depletion but poor response to belimumab seen here, use of alternative anti-CD20 agents may be a more effective treatment strategy for this group of patients with severe and resistant disease. Disclosures: S. Hassan: None. M.Y.M. Yusof: None. K. Dutton: None. S. Dass: None. E. Vital: None.