SAT0200 Effects of B cell depletion therapy on cutaneous lupus

Abstract

Background Systemic lupus erythematosus (SLE), subacute-cutaneous lupus (SCLE), and cutaneous lupus (CLE) are autoimmune disorders with a myriad of cutaneous manifestations which may present a therapeutic challenge. B cell depletion therapy (BCDT) with rituximab has demonstrated efficacy in SLE with visceral involvement. However, its usefulness for patients with major skin involvement has not been fully established. Objectives The aim of this study was to investigate the response of lupus-associated skin lesions in patients treated with BCDT at University College London Hospital since 2007. Methods 15 SLE patients with severe skin involvement (discoid lupus in 7, maculopapular rashes in 3, SCLE-like lesions in 1, and vasculitis or panniculitis in 4 patients), 2 SCLE patients, and 1 CLE patient were assessed in the study (1 man, 17 women; age 22-74 yrs.; 7 whites, 9 Afro-Caribbeans, 2 Asians). The median disease duration was 10 months (range 1-30 yrs.) and previous treatments included oral steroids, hydroxychloroquine, and immunosuppressants. All patients received 2 x rituximab 1000 mg and methylprednisolone 100 mg 2 weeks apart, and 1 x cyclophosphamide 750 mg. Clinical outcome was monitored using the mucocutaneous component of the BILAG activity index, anti-dsDNA antibodies, C3, and CD19 counts. Complete response (CR) was defined as absence of skin lesions (mucocutaneous BILAG D) for at least 2 months and treatment with ≤5mg prednisolone ± hydroxychloroquine. Partial remission (PR) was defined as improvement of cutaneous manifestations (BILAG C) of at least 50% or complete clearance of skin lesions (BILAG D) with continuation of immunosuppressants after BCDT. Stable disease was defined as no or only minor improvement of cutaneous lesions (mucocutaneous BILAG A or B). Median follow-up was 27 months. Results PR was achieved in 7 (39%) and CR in 7 patients (39%) after 1 cycle of BCDT, while 4 patients had stable disease (22%). In 9 patients with elevated dsDNA antibodies and/or low C3 levels pre-treatment, a median decrease of anti-dsDNA from 359 to 95 IU/ml (normal <50) was observed and an increase of C3 levels from 0,81 to 1,03 g/L (normal 0,9-1,8). Adverse events were experienced by 4 patients (urticaria post-infusion, recurrent infections). Median time to B cell repopulation was 7 months (3-18) and median time to relapse 8 months (3-24). 9 patients received a 2nd or 3rd cycle of BCDT resulting in CR in 3 (33%) and PR in 4 patients (44%). 2 SLE patients with stable disease after the 1st BCDT cycle again failed to achieve remission after the 2nd cycle. In total, 5 patients (2 with discoid lupus, 2 with maculopapular rashes, 1 with vasculitis) maintained CR for more than 12 months (28%). Retreatment led to a more sustained response (median time to relapse in patients with CR or PR increased from 6 months after 1st cycle of BCDT to 23 months after 2nd or 3rd cycle). Conclusions BCDT based on rituximab was relatively well tolerated, and induced PR or CR of cutaneous lesions in 78% of patients with 28% achieving a...