Short-term efficacy and safety of rituximab therapy in refractory systemic lupus erythematosus: results from the British Isles Lupus Assessment Group Biologics Register

Abstract

ObjectivesTo describe the baseline characteristics of SLE patients requiring biologic therapy in the UK and to explore short term efficacy and infection rates associated with rituximab (RTX) use.MethodsPatients commencing biologic therapy for refractory SLE and who consented to join BILAG-BR were analysed. Baseline characteristics, disease activity (BILAG 2004/SLEDAI-2K) and rates of infection over follow-up were analysed. Response was defined as loss of all A and B BILAG scores to ⩽ 1 B score with no new A/B scores in other organ systems at 6 months.ResultsTwo hundred and seventy SLE patients commenced biologic therapy from September 2010 to September 2015, most commonly RTX (n = 261). Two hundred and fifty (93%) patients were taking glucocorticoids at baseline at a median [interquartile range (IQR)] oral dose of 10 mg (5–20 mg) daily. Response rates at 6 months were available for 68% of patients. The median (IQR) BILAG score was 15 (10–23) at baseline and 3 (2–12) at 6 months (P < 0.0001). The median (IQR) SLEDAI-2K reduced from 8 (5–12) to 4 (0–7) (P < 0.001). Response was achieved in 49% of patients. There was also a reduction in glucocorticoid use to a median (IQR) dose of 7.5 mg (5–12 mg) at 6 months (P < 0.001). Serious infections occurred in 26 (10%) patients, being more frequent in the first 3 months post-RTX therapy. A higher proportion of early infections were non-respiratory (odds ratio = 1.98, 95% CI: 0.99, 3.9; P = 0.049).ConclusionRTX is safe and is associated with improvement in disease activity in refractory SLE patients with concomitant reductions in glucocorticoid use. Early vigilance for infection post-infusion is important to further improve treatment risks and benefits.

Rituximab as Maintenance Treatment for Systemic Lupus Erythematosus: A Multicenter Observational Study of 147 Patients

“…Although there have been no prospective trials showing the superiority of RTX compared to placebo , RTX is widely used. Our cohort of 147 patients treated with RTX is one of the largest studied so far and the overall positive response further supports the role of this drug in SLE management. Patients with low C4 levels, those who had received fewer previous immunosuppressive drugs, and those with severe disease were more likely to respond favorably to RTX.…”

New therapies for systemic lupus erythematosus — past imperfect, future tense

“…Many of these therapies, including rituximab (an anti-CD20 monoclonal antibody (mAb)) 11 , epratuzumab (an anti-CD22 mAb), abatacept (which stops APCs from interacting with T cells via CD80 and CD86) and tabalumab (an anti-BAFF mAb), have not shown a statistically significant benefit in clinical trials for SLE, reviewed recently 12 Rituximab and belimumab (an anti-BAFF mAb), are the biologic drugs most commonly used to treat SLE in clinical practice. The results of a large number of open-label studies of rituximab 11 and the encouraging data from national registries 12,13 were sufficient for both the ACR 14 and EULAR 15 to recommend rituximab as a treatment for lupus nephritis, and for the National Health Service (NHS) England to sanction its use in difficult-to-treat patients 16 . For example, in the Lupus Clinic at University College Hospital, London, ~140 patients have been treated with rituximab since 2000 owing to inefficacy of treatment or adverse events following immunosuppression with steroids, azathioprine, mycophenolate mofetil (MMF) or cyclophosphamide (D.A.I.…”

Current challenges in the development of new treatments for lupus

“…This creates a disconnect between clinical trial data and information that is meaningful to a practitioner or patient and might delay the uptake of newly approved therapies into practice, since physicians are unclear about the expected clinical response and are often inexperienced at using the component instruments (SLEDAI, BILAG and PGA). Nevertheless, there is now a requirement to use BILAG and SLEDAI when assessing patients for treatment with rituximab or belimumab in the National Health Service in England 43–45. However, both of these instruments have significant limitations, including low interobserver correlation and high complexity in the case of the BILAG.…”