Biologics for eosinophilic granulomatosis with polyangiitis

Abstract

Purpose of reviewThe link between severe asthma and eosinophilic granulomatosis with polyangiitis (EGPA) in terms of pathophysiological background, clinical manifestations and disease evolution has leaded to investigate the relevance of anti T2 monoclonal antibodies licensed for severe asthma patients as a treatment option for EGPA. The present review aimed to provide un update on EGPA pathophysiology and to critically summarize the most robust evidence coming from trials and real-life setting on the use of anti T2 biologics in EGPA patients.Recent findingsMepolizumab, an anti-interleukin-5 monoclonal antibody, is the only biologic drug targeting eosinophilic inflammation currently approved for EGPA treatment at the dose of 300 mg/4 weeks. Its use is restricted by the American College of Rheumatology guidelines to specific diseases phases and severity grades. However the most appropriate mepolizumab positioning and dose is still under investigation in the real life practice, which is providing an increasing amount of evidence confirming its efficacy, alone or in combination with other options in different disease stages. The relevance of other monoclonal antibodies interfering with T2 inflammation, including omalizumab and benralizumab, is under investigation but the evidence is still scarceSummaryTaking into account the suboptimal medium-long term safety profile of conventional EGPA treatments, the opportunity of selectively targeting eosinophilic inflammation certainly represents a revolutionary approach. However, further real-word evidence is required to effectively position the new treatments in the light of the disease complexity, including different immunological drivers, and individual variability.

Eosinophilic granulomatosis with polyangiitis onset in severe asthma patients on monoclonal antibodies targeting type 2 inflammation: Report from the European EGPA study group

“…To the Editor, Anti-T2 monoclonal antibodies (mAbs) for severe-eosinophilc asthma have been recently investigated for EGPA. 1 Few cases of severe asthma patients developing EGPA while on omalizumab, 2 benralizumab 3 or dupilumab 4 have been published.…”

“…Besides the approval of mepolizumab 300 mg for EGPA, real-life data also support benralizumab efficacy and mepolizumab 100 mg relevance, the last in the remission maintenance. 1 Omalizumab and dupilumab molecular targets are less involved in EGPA pathobiology, but still their mechanism of action is unlikely to induce the disease.…”

“…It further suggests that timing of anti-T2-targeted therapy initiation in respect of the disease stage is crucial, even more when taking into consideration that biologics only partially address EGPA pathobiology. 1 occurrence or inducing its remission, but once it has been achieved, it seems to be the most appropriate time for anti-T2 biological drug initiation.…”

Long-term mepolizumab treatment reduces relapse rates in super-responders with eosinophilic granulomatosis with polyangiitis

“…The mainstay of treatment for EGPA is systemic corticosteroid therapy; some patients receive additional treatment with other immunosuppressive agents, such as cyclophosphamide, azathioprine, methotrexate, interferon-α [ 10 , 11 ], rituximab [ 12 – 14 ], intravenous immunoglobulins (IVIGs) [ 15 – 17 ], and other biologics [ 18 , 19 ]. Biologics include omalizumab [ 20 , 21 ], mepolizumab [ 21 – 28 ], benralizumab [ 29 ] dupilumab [ 30 ], reslizumab, and lebrikizumab; the latter three are being tested in ongoing clinical trials [ 31 ].…”

Long-term treatment by mepolizumab reduces the relapse rate in patients with eosinophilic granulomatosis with polyangiitis

“…The mainstay of treatment for EGPA is systemic corticosteroid therapy; some patients receive additional treatment with other immunosuppressive agents, such as cyclophosphamide, azathioprine, methotrexate, interferon-α [10,11], rituximab [12][13][14], intravenous immunoglobulins (IVIGs) [15][16][17], and other biologics [18,19]. Biologics include omalizumab [20,21], mepolizumab [21][22][23][24][25][26][27][28], benralizumab [29] dupilumab [30], reslizumab, and lebrikizumab; the latter three are being tested in ongoing clinical trials [31].…”