Rituximab treatment of ANCA-associated vasculitis

ABSTRACT

Introduction

Rituximab, an anti–B-cell biological therapy, has been investigated in several clinical trials on antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs).

Areas covered

In this paper, the clinical trials and open-label studies on rituximab efficacy and safety in treating AAVs are reviewed.

Expert opinion

Rituximab achieved high remission-induction and sustained-maintenance rates for patients with these severe diseases, thereby challenging the cornerstone treatment of corticosteroids and cyclophosphamide followed by azathioprine. Rituximab should be used as first-line therapy with corticosteroids to induce remission of severe AAVs, especially in situations in which cyclophosphamide may be problematic (relapse after cyclophosphamide, women of childbearing age, risk of malignancy). Cyclophosphamide indications are likely to be restricted in the future. Whenever possible, rituximab should be preferred to azathioprine to maintain remission. The current maintenance regimen has been extended to at least 18 months but its optimal duration remains unknown and recent data suggest the possibility to extend treatment to 4 years. Future challenges include defining the best dose regimen: at present, different schedules are used as alternatives to those recognized as standards by health authorities. In addition, it remains to identify which patients will benefit the most from long-term retreatment: potentially those with relapsing disease or anti-proteinase-3 ANCA-positivity.

KEYWORDS:

• ANCA
• B lymphocytes
• rituximab
• therapeutic monoclonal antibodies
• vasculitis
• granulomatosis with polyangiitis
• microscopic polyangiitis
• eosinophilic granulomatosis with polyangiitis

Article highlights

• B cells participate in the pathophysiology of ANCA-associated vasculitides (AAVs).

• The anti–B-cell biological therapy rituximab has been evaluated in several published randomized–controlled trials on AAVs, and is currently being assessed to treat eosinophilic granulomatosis with polyangiitis.

• To induce remission of severe flares, rituximab is not inferior to the historical reference treatment of sequential corticosteroids and cyclophosphamide then azathioprine.

• For remission-maintenance therapy, rituximab is superior to azathioprine, the historical reference.

• Further studies are needed to optimize rituximab regimens for remission induction and maintenance of severe and perhaps non-severe AAV flares.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.