Remission maintenance in ANCA-associated vasculitis: does one size fit all?

ABSTRACT

Introduction: The majority of the patients with anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitis (AAV) achieve remission with effective induction therapy. Therefore, prevention of relapses and avoiding long-term damage and treatment-related toxicity are major challenges.

Areas covered: This review provides an update on maintenance therapy in AAV, emphasizing the available treatment options for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Among the spectrum of all patients with AAV, those at higher risk of relapse have recently been identified. Clinical trials have yielded robust results about various options for maintenance of remission including common disease-modifying anti-rheumatic drugs (DMARDs, i.e. azathioprine, methotrexate, and mycophenolate mofetil) and rituximab (RTX). However, outcomes of these studies are not easy to compare.

Expert opinion: Regardless of the treatment used, patients presenting with an anti-proteinase-3 ANCA, relapsing GPA have a substantially higher risk of relapse compared to patients with newly diagnosed MPA or positive anti-myeloperoxidase ANCA. While the efficacy of common DMARDs for remission maintenance is heterogeneous, the role of RTX seems particularly promising for the high-risk patients, although the most appropriate dose and timing of retreatment with RTX remain under controversial. Low-dose glucocorticoid use for remission maintenance versus complete discontinuation also remains under investigation.

KEYWORDS:

• ANCA-associated vasculitis
• ANCA
• RAVE
• Rituximab
• Azathioprine
• Maintenance therapy
• vasculitis

Article Highlights

• Patients with relapsing GPA with PR3-ANCA are at higher risk for relapse compared to newly-diagnosed, MPO-positive patients with MPA.

• For remission maintenance, the conventional DMARDs (i.e AZA, MTX and MMF) may be insufficient for patients with high relapse risk, whereas RTX seems to be more effective.

• A tailored administration of RTX has been shown to be superior to RTX at fixed scheduled, closely monitoring ANCA titers and B cells.

• In newly diagnosed MPO-ANCA positive patients with MPA, a shorter maintenance therapy or perhaps observation alone could suffice after induction therapy.

• Early GC withdrawal during follow-up in AAV is still debated, but lower dosing of GC during remission induction of AAV seems advantageous.

Declaration of interest

U Specks was the co-principal investigator of the RAVE trial targeting CD20 B cells in ANCA-associated vasculitis which was completed in 2010, sponsored by NIAID and supported in part by Genentech/Biogen IDEC. U Specks is currently a co-investigator of the RITAZAREM trial, sponsored by the Vasculitis Clinical Research Consortium (VCRC) and EUVAS and supported by Roche/Genentech and the ABROGATE trial which is sponsored by Bristol Myer Squibb. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.