Mepolizumab for the treatment of eosinophilic granulomatosis with polyangiitis

ABSTRACT

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis characterized by asthma, hypereosinophilia, and progressive multiorgan involvement. Although not fully elucidated, advancement in our understanding of the pathophysiology of EGPA has led to the development of multiple new treatment targets.

Areas covered: Herein we review the epidemiology, clinical manifestations, pathophysiology, treatments, and ongoing research in the management of EGPA. The central role of Interleukin-5 (IL-5) in the development and maintenance of hypereosinophilia will be discussed. The value of mepolizumab, an anti-IL-5 monoclonal antibody, in the treatment of EGPA is reviewed in detail.

Expert Opinion: The available literature supports the use of mepolizumab for the induction and maintenance of remission of refractory, relapsing, or glucocorticoid-dependent EGPA with potentially greater benefit in those who are ANCA-positive or those with greater eosinophilia ($\ge$150 cells/$\mu$L). Despite these positive results, relapses remain frequent, and the need for both short- and long-term glucocorticoid use remains common. More research is needed to address these needs and determine the precise role of mepolizumab.

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KEYWORDS:

• Vasculitis
• eosinophilic granulomatosis with polyangiitis
• mepolizumab

Article Highlights

• The pathophysiology of EGPA is not fully elucidated, but evidence supports a complex interplay of genetics risk factors, T-cell hyperactivity (especially Th2), IL-5 driven hypereosinophilia, and B-cell activation.

• Standard treatment depends on the severity of disease: GC and CYC are used to treat severe disease while GC monotherapy can be sufficient for mild to moderate disease. Whereas remission is often achieved, relapses and persistent GC-dependent asthma are common and call for more effective and safe treatments.

• Mepolizumab, an anti-IL-5 monoclonal antibody, has shown benefit in a subset of patients with eosinophilia-driven disorders such as asthma, chronic obstructive pulmonary disease, eosinophilic colitis, eosinophilic esophagitis, nasal polyposis, and atopic dermatitis.

• Recent data, including from a randomized controlled trial, also support the use of mepolizumab (at the specific dose of 300mg per month, subcutaneously) for relapsing or refractory EGPA. The hazard ratio for relapse was 0.32 in favor of mepolizumab with an annualized relapse rate that was 50% lower compared to placebo.

• The most common adverse events with mepolizumab were headache (32%), nasopharyngitis (18%), arthralgias (22%), sinusitis (21%) and upper respiratory tract infections (21%).

This box summarizes key points contained in the article.

Declaration of interest

JK Lee reports receiving speakers fees from Novartis, AstraZeneca, ALK, Stallergens, Mylan, Meda, Sanofi, Aralez, Pediapharm, Regeneron, Merck, Takeda. Fees for advisory boards from Novartis, Astrazeneca, Mylan, Pediapharm, Aralez, CSL, Sanofi. Research funding from Astrazeneca, Novartis, Sanofi, Genentech, Regeneron, GSK. Medical consultancy fees from GSK, Astrazeneca, Novartis, and Sanofi. C Pagnoux reports receiving fees for serving on advisory boards from Chemocentryx, GlaxoSmithKline, Sanofi and Hoffman-LaRoche; for lecture fees from Hoffman-La Roche and Novartis Pharmaceuticals; and research grant support from Hoffman-La Roche. D Ennis was funded through a vasculitis fellowship granted by the Vasculitis program (University of Toronto) and an educational grant from the University of British Columbia. 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 relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded,