First-line maintenance was with AZA; MMF was used in those who were intolerant

First-line maintenance was with AZA; MMF was used in those who were intolerant. 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 experienced 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. Conclusion. Treatment with ofatumumab resulted in comparable 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. [4]. It is licensed for use in haematological malignancies, where it has shown biologic activity in rituximab-resistant disease [5, 6]. Notably, ofatumumab has also shown efficacy in rituximab-resistant cases of paediatric nephrotic syndrome [7], and has exhibited biological activity in RA [8C10]. Here, we statement our preliminary experience using ofatumumab for the treatment of AAV. This was based on experience of ofatumumab use in patients with LN who experienced exhibited anaphylactic reactions to rituximab, and was initially used in a patient with AAV who experienced similarly exhibited an anaphylactic reaction to rituximab. This approach was subsequently extended to include rituximab-na?ve patients, based on our positive initial experience. Our treatment regimen using ofatumumab was based on our previously published protocol for using rituximab (in conjunction with low-dose pulsed i.v. CYC and a reduced steroid dose) [11]. This regimen, which has been standard of care for AAV with renal involvement at our centre since 2006, is Ac-LEHD-AFC usually associated with low cumulative exposure to CYC and steroids, and prolonged disease-free remission. In the present study, ofatumumab was substituted in for rituximab at the initiation of remission-induction therapy, and we statement 2-year outcomes. Methods This study is based on a case series of eight patients treated between November 2012 and July 2013 at our centre, who received ofatumumab as a component of their CD244 treatment regimen for AAV. Ofatumumab was initially used at our centre on compassionate grounds for patients who were intolerant to rituximab due to anaphylaxis, but for whom anti-CD20 treatment was deemed appropriate (both in LN and AAV; the lupus cohort will be reported separately). Following our positive initial experience in these patients, rituximab-naive patients with AAV were also treated. Ofatumumab use was off-label, based on evidence supporting the use of anti-CD20 therapy in AAV at that time, and predated the licensing of rituximab for this indication in 2013 (when use of the latter agent was similarly off-label). Use of ofatumumab was guided by Ac-LEHD-AFC expert opinion at our centre and approved by the Glomerulonephritis Protocol and Research Group at Imperial College Healthcare National Health Service Trust. The treatment protocol was based on our previously reported regimen using low-dose pulsed i.v. CYC and steroids, in conjunction with anti-CD20 treatment [11], and this has been standard of care at our centre since 2006. Herein, ofatumumab 2 700 mg was substituted in for rituximab 2 1 g administered at days 0 and 14. The additional components of the protocol included i.v. CYC 10 mg/kg administered at days 0 and 14 (maximum 750 mg each) and then every 14 days for a further four doses (maximum 500 mg each). Oral prednisolone 1 mg/kg was started at day 0 (maximum Ac-LEHD-AFC 60 mg) and reduced sequentially to achieve a dose of 10 mg by week 13. Further steroid weaning Ac-LEHD-AFC was at the discretion of the treating physician. Where patients were treated for relapsing disease or for remission maintenance, or experienced received pulsed i.v. methylprednisolone before referral to our centre, altered doses of either steroids or CYC may have been used. Therapeutic plasma exchange was offered for patients who presented with dialysis-dependent renal failure..