Treatment of systemic necrotizing vasculitides: recent advances and important clinical considerations

ABSTRACT

Introduction: Primary systemic necrotizing vasculitides (SNVs) include polyarteritis nodosa, Kawasaki disease, ANCA-associated vasculitides, IgA vasculitis, and cryoglobulinemic vasculitis. All are rare but potentially severe, life-threatening conditions. Evidence-based treatments are well established, but continue to evolve and management requires some expertise.

Areas covered: The objectives of this review are to outline results of the main recent therapeutic studies for SNV, which have led to the establishment of current treatment strategies and significant improvement in patients’ outcomes, and to describe knowledge gaps that ongoing research hopes to bridge.

Expert opinion: Therapy is mainly dictated by diagnosis, disease extent, and severity. In ANCA-associated vasculitis, an initial induction phase consists of tapering glucocorticoids combined with specific immunosuppressants. Maintenance therapy begins after 3 to 6 months, once all evidence of active disease has resolved, and can require years of therapy to prevent relapse. Results from ongoing and future trials for vasculitis will likely impact these treatment approaches. Entirely avoiding GC may become possible, perhaps even the next gold standard, if medications such as avacopan are confirmed to be safe and effective. New combination strategies, more individualized for each patient, may also prove to be more effective, faster.

KEYWORDS:

• Vasculitis
• granulomatosis with polyangiitis
• microscopic polyangiitis
• eosinophilic granulomatosis with polyangiitis
• IgA vasculitis
• cryoglobulinemic vasculitis
• Kawasaki disease
• polyarteritis nodosa

Article highlights

• The optimal management of systemic necrotizing vasculitides depends on the individual diagnosis, but especially in the case of ANCA-associated vasculitis and polyarteritis nodosa, includes induction therapy followed by an agent to maintain remission.

• Distinct therapeutic strategies are used for idiopathic polyarteritis nodosa, hepatitis B virus-associated vasculitis, and the recently identified genetically acquired deficiency of adenosine deaminase 2.

• The past decade has witnessed significant advances in the treatment of granulomatosis with polyangiitis and microscopic polyangiitis, from the addition of rituximab to the armamentarium for induction and maintenance of remission to the significant investigative efforts made toward clarifying the utility of plasma exchange in life-threatening disease.

• Upcoming clinical trials in eosinophilic granulomatosis with polyangiitis hold promise to elucidate the role of novel biologic therapies in the management of distinct allergic and vasculitic disease manifestations.

• Treatment outcomes in hepatitis C virus-associated cryoglobulinemic vasculitis have improved following the introduction of less toxic antiviral therapies, and rituximab can be effective in severe cases.

• Therapy in systemic necrotizing vasculitides is likely to become more individualized toward evolving phenotypic subsets and further dictated by advances in risk stratification.

• A key goal for the future is to reduce glucocorticoids exposure and toxicity, by investigating reduced-dose tapering regimens and evaluation of novel and potentially glucocorticoid-sparing therapies.

Declaration of interest

C Pagnoux has received fees for serving on advisory boards from Chemocentryx, GlaxoSmithKline, Sanofi and Hoffman-LaRoche; for lecture fees from Hoffman-La Roche and Novartis Pharmaceuticals; and educational grant support from Hoffman-La Roche and GlaxoSmithKline. 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.

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Funding

This paper was not funded.