Ofatumumab for B cell depletion in patients with systemic lupus erythematosus who are allergic to rituximab

• Published in: Rheumatology (Oxford, England) Vol. 57; no. 7; pp. 1156 - 1161
• Main Authors: Masoud, Sherry, McAdoo, Stephen P, Bedi, Rachna, Cairns, Thomas D, Lightstone, Liz
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.07.2018; Oxford Publishing Limited (England)
• Subjects: Anti-DNA antibodies; CD20 antigen; Immunosuppression; Immunotherapy; Lupus; Monoclonal antibodies; Remission; Rituximab; Systemic lupus erythematosus; Targeted cancer therapy; systemic lupus erythematosus; anti-CD20; biologic therapy; ofatumumab; human-anti-chimeric antibodies; lupus nephritis; B cell depletion; monoclonal antibody; rituximab
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/key042

Abstract Objective B cell depletion, most commonly with rituximab, is an evolving therapeutic approach in SLE. Infusion reactions after rituximab are common, and may prevent re-treatment in patients who previously demonstrated beneficial response. We have used ofatumumab, a fully humanized anti-CD20 mAb, as an alternative B cell-depleting agent in patients with SLE who are rituximab-intolerant due to severe infusion reactions. Methods A single-centre retrospective case series of 16 patients were treated with ofatumumab for SLE between 2012 and 2015. Results Ofatumumab infusion was well tolerated in 14/16 patients, in whom the median age was 34 (range 19-55) and the median duration of SLE 9.2 years (0.6-28.5). The cohort was heavily pre-treated, with 50% having prior CYC exposure, and a median cumulative dose of prior rituximab 4 g (1-6). Twelve patients were treated for LN, one for extra-renal flare and one for remission maintenance. B cell-depletion was achieved in 12/14 patients, with comparable reconstitution kinetics to a previous cohort treated with rituximab at our centre, and was associated with improvements in serological markers of disease activity, including ANA, anti-dsDNA antibody and complement levels. Half of the patients with LN achieved renal remission by 6 months. Progressive disease that was unresponsive to augmented immunosuppression with CYC was seen in five patients. During long-term follow-up (median 28 months), five grade III infections were reported, and there were no malignancies or deaths. Conclusion In this pre-treated cohort with long-standing SLE, ofatumumab was a well-tolerated, safe and effective alternative to rituximab for B cell-depletion therapy.