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

Sherry Masoud; Stephen P McAdoo; Rachna Bedi; Thomas D Cairns; Liz Lightstone

doi:10.1093/rheumatology/key042

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

Rheumatology (Oxford). 2018 Jul 1;57(7):1156-1161. doi: 10.1093/rheumatology/key042.

Authors

Sherry Masoud¹, Stephen P McAdoo^{1

2}, Rachna Bedi¹, Thomas D Cairns¹, Liz Lightstone^{1

2}

Affiliations

¹ Imperial College Lupus Centre, Imperial College Healthcare NHS Trust, Imperial College London, London, UK.
² Renal and Vascular Inflammation Section, Department of Medicine, Imperial College London, London, UK.

PMID: 29562252
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.

Keywords: B cell depletion; anti-CD20; biologic therapy; human-anti-chimeric antibodies; lupus nephritis; monoclonal antibody; ofatumumab; rituximab; systemic lupus erythematosus.