Ofatumumab for B cell depletion therapy in ANCA-associated vasculitis: a single-centre case series
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Published version
Accepted version
Author(s)
Type
Journal Article
Abstract
Objectives: B cell depletion is an effective treatment strategy in ANCA-associated vasculitis (AAV). Ofatumumab is a fully humanised anti-CD20 monoclonal antibody that has shown efficacy in the treatment of haematological malignancy and rheumatoid arthritis. The use of ofatumumab in the treatment of AAV has not previously been reported.
Methods: A case series of eight patients who received ofatumumab, in conjunction with low-dose cyclophosphamide and oral steroids, in the treatment of AAV.
Results: 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 one month, and sustained until six months at least. 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 three months. This was associated with rapid fall in ANCA titres, reduced inflammatory responses, and improvements in renal function. At 12 months, three patients had repopulated B cells associated with recurrence of circulating ANCA, although no patients experienced major clinical relapse in the first 24 months. No unexpected safety signals were observed.
Conclusion: Treatment with ofatumumab resulted in similar serological and clinical responses to previous cohorts treated at our centre with a comparable corticosteroid, cyclophosphamide and rituximab-based regimen. Ofatumumab should be considered an alternative B cell depleting agent in patients who are intolerant of, or unresponsive to, rituximab.
Methods: A case series of eight patients who received ofatumumab, in conjunction with low-dose cyclophosphamide and oral steroids, in the treatment of AAV.
Results: 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 one month, and sustained until six months at least. 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 three months. This was associated with rapid fall in ANCA titres, reduced inflammatory responses, and improvements in renal function. At 12 months, three patients had repopulated B cells associated with recurrence of circulating ANCA, although no patients experienced major clinical relapse in the first 24 months. No unexpected safety signals were observed.
Conclusion: Treatment with ofatumumab resulted in similar serological and clinical responses to previous cohorts treated at our centre with a comparable corticosteroid, cyclophosphamide and rituximab-based regimen. Ofatumumab should be considered an alternative B cell depleting agent in patients who are intolerant of, or unresponsive to, rituximab.
Date Issued
2016-04-19
Date Acceptance
2016-03-15
Citation
Rheumatology, 2016, 55 (8), pp.1437-1442
ISSN
1462-0332
Publisher
Oxford University Press
Start Page
1437
End Page
1442
Journal / Book Title
Rheumatology
Volume
55
Issue
8
Copyright Statement
© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
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Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Grant Number
RDA04 79560
Subjects
ANCA
B cells
biologic therapies
granulomatosis with polyangiitis
microscopic polyangiitis
vasculitis
Arthritis & Rheumatology
Clinical Sciences
Immunology
Public Health And Health Services
Publication Status
Published