Ofatumumab for B cell depletion therapy in ANCA-associated vasculitis: a single-centre case series

• Published in: Rheumatology (Oxford, England) Vol. 55; no. 8; pp. 1437 - 1442
• Main Authors: McAdoo, Stephen P, Bedi, Rachna, Tarzi, Ruth, Griffith, Megan, Pusey, Charles D, Cairns, Thomas D
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.08.2016
• Subjects: Adult; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - therapy; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; B-Lymphocytes; Clinical Science; Female; Humans; Immunologic Factors - therapeutic use; Lymphocyte Depletion - methods; Male; Middle Aged; Remission Induction - methods; Renal Insufficiency, Chronic - physiopathology; Renal Insufficiency, Chronic - therapy; Young Adult; granulomatosis with polyangiitis; B cells; ANCA; biologic therapies; microscopic polyangiitis; vasculitis
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kew199

B cell depletion is an effective treatment strategy in ANCA-associated vasculitis (AAV). Ofatumumab is a fully humanized anti-CD20 mAb that has shown efficacy in the treatment of haematological malignancy and RA. The use of ofatumumab in the treatment of AAV has not previously been reported. This study was based on a case series of eight patients who received ofatumumab, in conjunction with low-dose CYC and oral steroids, in the treatment of AAV. Eight patients received ofatumumab: seven for remission induction in active disease (three relapsing; four with new disease) and one for remission maintenance. B cell depletion was achieved in all patients by 1 month, and was sustained for at least 6 months. All patients with active disease achieved clinical remission (BVAS of zero, or BVAS ⩽5 if all scores due to persistent urinary abnormalities in the presence of stable or improving renal function) by 3 months. This was associated with a rapid fall in ANCA titres, reduced inflammatory responses and improvements in renal function. At 12 months, three patients had repopulated B cells associated with the recurrence of circulating ANCAs, although no patients experienced major clinical relapse in the first 24 months. No unexpected side effects were observed. Treatment with ofatumumab resulted in similar serological and clinical responses to those seen in previous cohorts treated at our centre with a comparable CS, CYC and rituximab-based regimen. Ofatumumab should be considered an alternative B cell depleting agent in patients who are intolerant of, or unresponsive to, rituximab.