How best to manage relapse and remission in ANCA-associated vasculitis

ABSTRACT

Introduction

A two-stage therapeutic approach is now applied as standard-of-care to treat antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs): first, glucocorticoids (GCs) combined with cyclophosphamide (CYC) or rituximab (RTX) to induce remission, and then relapse prevention with remission-maintenance therapy. Nonetheless, a substantial risk of relapse persists.

Areas covered

The authors provide an overview of the current state of AAV remission-induction after relapse and maintenance therapies, and discuss new strategies recommended to prevent and treat relapses, focusing on granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

Expert opinion

For remission-induction after GPA or MPA relapse with organ-threatening manifestations, reintroduction or intensification of GCs in combination with CYC or RTX cycle is recommended; we prefer RTX in light of its superior responses obtained in patients with relapsing disease. Rapid tapering of GCs has been shown not to alter AAV evolution while decreasing the risk of serious infections. In contrast, for non-severe, active MPA, we recommend GCs alone as first-line therapy. For patients whose MPA remains uncontrolled by GCs alone, immunosuppressant adjunction can be a GC-sparing option or to counter GC intolerance. Once remission is achieved, we recommend prolonged maintenance therapy with preemptive low-dose (500 mg) RTX infusion biannually.

KEYWORDS:

• Cyclophosphamide
• granulomatosis with polyangiitis
• induction treatment
• maintenance therapy
• microscopic polyangiitis
• plasma exchange
• prognostic factors
• relapse
• rituximab

Article highlights

• When a relapse of ANCA-associated vasculitis (AAV) is suspected, the initial objectives are to identify its clinical manifestations, confirm the diagnosis, eliminate other potential diagnoses, specify its severity, and define the choice of treatments to be prescribed.

• The main principles of AAV-relapse management consist of rapid initiation of early induction-remission treatment, followed by remission-maintenance therapy with less toxic immunosuppressive regimens.

• For remission-induction of AAV relapse with organ-threatening manifestations, we recommend reintroduction or intensification of the glucocorticoid (GC) dose in combination with an additional cycle of cyclophosphamide (CYC) or rituximab (RTX); the latter is preferred because of its better responses obtained against relapsing AAVs.

• For non-severe, active MPA, we recommend first-line GCs alone. An immunosuppressant can be prescribed to control the disease activity when MPA remains uncontrolled by GCs alone, or to achieve GC-sparing or abrogate GC intolerance.

• Once remission is achieved, we recommend prolonged maintenance therapy with a preemptive low-dose (500 mg) RTX every 6 months.

Acknowledgments

The authors thank Janet Jacobson for editorial assistance.

Declaration of interest

X Puéchal and L Guillevin have been coinvestigators in academic studies for which rituximab was provided by Roche Pharma. X Puéchal declares consultancies, speaking fees, and congress inscription/travel/accommodations: Boehringer Ingelheim, Sanofi, GSK. 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.