Treatment strategies for ANCA-associated vasculitides: from standard protocols to future horizons

ABSTRACT

Introduction

ANCA-associated vasculitides (AAV), classified into granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis represent a group of disorders characterized by necrotizing vasculitis of small vessels, endothelial injury and tissue damage. The outcomes and prognosis of AAV have undergone significant changes with the introduction of glucocorticoids (GCs) and other immunosuppressants (cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil). The enhanced understanding of pathogenesis has subsequently led to the incorporation into clinical practice of drugs targeting specific therapeutic targets.

Areas covered

After an extensive literature search of Pubmed, Medline, Embase of the most recent evidence, we provide an overview of available treatments, highlighting how newer drugs have integrated into standard protocols. Our review also explores potential new therapeutic targets, including B cell depletion and inhibition, T cell inhibition, complement inhibition, and IL-5 and IgE inhibition.

Expert opinion

There is hope that the new treatment targets currently under study in AAV may enable a faster and more lasting clinical response, ensuring the reduction of possible side effects from therapies. Moreover, numerous aspects necessitate further exploration in the future, such as tailoring of GCs, integration of GCs-sparing agents, efficacy of combination therapy, optimal maintenance therapy, to reduce organ-damage and improve quality of life.

KEYWORDS:

• ANCA-associated vasculitides
• granulomatosis with polyangiitis
• microscopic polyangiitis
• eosinophilic granulomatosis with polyangiitis
• glucocorticoids
• immunosuppressants
• monoclonal antibodies

Article highlights

• Untreated cases of AAV show an alarming one-year mortality rate of 80%, underscoring the critical importance of prompt and effective intervention.

• The history of treatment for AAV has evolved significantly, starting with glucocorticoids and cyclophosphamide, followed by safer immunosuppressants (azathioprine, mycophenolate mofetil, methotrexate), and later the introduction of rituximab after the 2000s, reflecting a refined understanding of pathogenesis.

• Achieving a prompt remission is crucial to prevent disease progression and minimize the risk of irreversible organ damage.

• The standard treatment for MPA and GPA involves immunosuppressive therapy tailored based on the severity of organ-threatening or life-threatening disease. Non-inferiority of rituximab compared to cyclophosphamide in induction therapy has been demonstrated, and the choice between the two depends on factors like age, renal function, and specific clinical conditions.

• Once remission is achieved, maintenance therapy is crucial, and rituximab is considered the preferred choice, although alternatives like azathioprine, mycophenolate mofetil and methotrexate are also viable options, depending on patient factors.

• The ongoing development of new drugs targeting CD20, complement factor C5, BAFF, T cell costimulation, JAK, IL5, IL4Rα, and IgE underscores the focus on achieving a more rapid and persistent remission while concurrently mitigating the adverse effects of treatments.

• Several aspects require additional exploration in the future, encompassing the refinement of glucocorticoid dosage and tailored adjustment based on diverse clinical presentations, the incorporation of glucocorticoids sparing agents, the assessment of combination therapy effectiveness, and determination of optimal maintenance therapy.

Declaration of interests

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 or other relationships to disclose.

Additional information

Funding

This paper was not funded.