Background/Purpose: Response to the anti-CD20 agent rituximab (RTX) in SLE is variable but it is still widely used for refractory SLE. Our aim was to describe the rate of response and adverse events to RTX in a large multicentre cohort.

Methods: We established a national multicentre prospective registry of patients with SLE. Patients are recruited who receive either standard therapy or a biologic, including RTX. BILAG 2004 and SLEDAI-2K are collected at baseline, 3, 6 and 12 months, then annually. We included patients who received RTX before November 2015. For efficacy analysis, we analysed those who had active SLE at baseline according to the national RTX prescribing guidelines (≥1 BILAG A or ≥2 BILAG B scores or a SLEDAI-2K ≥6 or oral steroids ≥20mg daily) and who had BILAG 2004 and SLEDAI-2K at baseline and 6 months. The primary endpoint was a modified BILAG-Based Composite Lupus Assessment (BICLA) endpoint defined as: improvement of active systems on BILAG 2004 with no worsening in other systems (all BILAG As at entry to B/C/D, all Bs to C/D, no new As, <2 new Bs); no worsening of SLEDAI-2K; no increase in oral steroid dose at 6 months. Secondary endpoints included change in global BILAG 2004 score; change in SLEDAI-2K score; change in steroid dose from baseline. We also explored a Major Clinical Response (MCR) defined as BILAG 2004 C/D/E only; SLEDAI-2K ≤4; daily oral steroid dose ≤7.5mg.

Results: 167 prospective patients commenced RTX before November 2015. 158 fulfilled ≥4 of 11 ACR criteria for classification of SLE, 3 of the remaining 9 had lupus nephritis. Baseline demographics and disease activity are shown in Table 1. The commonest RTX regime was 2x1000mg dose 14 days apart, given to 134/136 patients (98.5%) for whom dosing schedules were available. 118 patients have complete baseline and 6 month disease activity data. A BICLA response at 6 months was achieved in 57(48.3%). Over 6 months, mean global BILAG 2004 fell from 20.4 to 9.6 (mean difference 10.8, 95%CI 9.0 – 12.6, p <0.01). Mean SLEDAI-2K fell from 9.6 to 4.5 (mean difference 5.1, 95%CI 4.2 – 6.1 p<0.01) and mean daily oral steroid dose reduced from 17.0 to 11.6mg (mean difference 5.4 95%CI 3.2-7.6 p<0.01). Twelve (10.2%) patients discontinued oral steroids by 6 months and 2 commenced oral steroids. MCR was achieved in 18(15.2%) patients. In the first 6 months, 189 adverse events were reported in 90/167(54%) patients. There were 10 infusion reactions and 90 infections in 53(32%) patients including 14 serious infections. Four deaths occurred: one due to infection, two of organ failure, one of cause unknown.

Conclusion: In a large national cohort of SLE patients receiving RTX, disease activity and steroid use reduced significantly by 6 months and 48.3% achieved a BICLA response. Steroid withdrawal and MCR was evident by 6 months in some, suggesting excellent early responses in a subset warranting further characterisation.

Table 1: Baseline demographics and disease activity

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-and-efficacy-of-rituximab-in-the-treatment-of-refractory-systemic-lupus-erythematosus-results-from-a-national-register/