Mepolizumab as the first targeted treatment for eosinophilic granulomatosis with polyangiitis: a review of current evidence and potential place in therapy

Abstract

Mepolizumab is an anti-interleukin-5 (IL-5) humanized monoclonal antibody that binds to free IL-5. It induces bone marrow eosinophil maturation arrest and decreases eosinophil progenitors and subsequent maturation in the blood and bronchial mucosa. Its use has been extensively studied in severe eosinophilic asthma at a dose of 100 mg subcutaneously (SC) every 4 weeks and, more recently, in other hypereosinophilic syndromes. Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophilic vasculitis that may involve multiple organs. Characteristic clinical manifestations are asthma, sinusitis, transient pulmonary infiltrates and neuropathy. Among the numerous pathways involved in the pathogenesis of EGPA, the Th-2 phenotype has a main role, as suggested by the prominence of the asthmatic component, in triggering the release of key cytokines for the activation, maturation and survival of eosinophils. In particular, IL-5 is highly increased in active EGPA and its inhibition can represent a potential therapeutic target. In this scenario, mepolizumab may play a therapeutic role. After some positive preliminary observations on the use of mepolizumab in small case series of EGPA patients with refractory or relapsing disease despite standard of care treatment, a randomized controlled trial was published in 2017. Mepolizumab at a dose of 300 mg administered by SC injection every 4 weeks proved effective in prolonging the period of remission of the disease, allowing for reduced steroid use. The positive results of this study, which met both of the primary endpoints, led to the approval in the USA of mepolizumab in adult patients with EGPA by the Food and Drug Administration in 2017. Therefore, mepolizumab can be officially considered as an add-on therapy with steroid-sparing effect in cases of relapsing or refractory EGPA. However, the most appropriate dose and duration of therapy still need to be determined. Future studies on larger multinational populations with prolonged follow-up are warranted.

A Pediatric Case of Relapsing Eosinophilic Granulomatosis with Polyangiitis Successfully Treated with Mepolizumab

“…In a randomized controlled trial published in 2017 (22), mepolizumab at a dose of 300 mg administered subcutaneously every 4 weeks proved effective in prolonging the period of disease remission, allowing for reduced steroid use. The positive results of this study led to the approval of mepolizumab in adult patients with EGPA by the United States Food and Drug Administration in 2017 (21). Nucala (mepolizumab) is currently licensed in the United States, Japan, and more than 30 countries worldwide (23).…”

“…Mepolizumab has recently been used as an anti-IL-5 agent to treat severe eosinophilic asthma (20). Furthermore, its use has also been explored in other diseases that share some pathogenic mechanisms with eosinophilic asthma, including GPA (21). In a randomized controlled trial published in 2017 (22), mepolizumab at a dose of 300 mg administered subcutaneously every 4 weeks proved effective in prolonging the period of disease remission, allowing for reduced steroid use.…”

Biological therapy improves myocarditis and disease activity in eosinophilic granulomatosis with polyangiitis patients

“…Nevertheless, owing to no speci c dose evaluation in that study, it remains to be determined whether 300 mg is superior to 100 mg dosage for EGPA therapy [8]. Subsequent trials with a regimen of 100 mg quadri-weekly have been carried out in EGPA with relapsing disease [25,26]. In particular, a clinic cohort with disease relapse under the long-term CS use received low-dose MEP therapy for 16…”

“…weeks, resulting in clinical improvement with weaning off CS in all enrolled patients [25]. In this study, a similar 100 mg dosage was prescribed in a EGPA victim for 52 weeks at induction for relapsing disease (case no.…”

The significance of cutaneous manifestations in EGPA (eosinophilic granulomatosis with polyangiitis)

“…Az ANCA pozitivitást a betegek 30-70%-ban lehet kimutatni (ANCA-MPO), de az ANCA negativitás önmagában még nem zárja ki a betegség fennállását. Fontos megemlíteni, hogy az össz-IgE szint minden betegben magas, nem tisztázott, hogy változása aktivitási markernek tekinthető-e. A betegség kezelése függ a súlyosságától, az enyhébb esetekben elég a steroid monoterápia alkalmazása, míg súlyosabb esetekben masszív immunszuppresszió -steroid-cyclophosphamid kombinált kezelés, esetleg rituximab adása szükséges (2), újabban már célzott biológiai terápia, az IL-5 ellenes antitest, a mepolizumab is elérhető (3).…”