Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes

Abstract

Background Hypereosinophilic syndromes (HES) are chronic disorders that require long-term therapy to suppress eosinophilia and clinical manifestations. Corticosteroids are usually effective, yet many patients become corticosteroid-refractory or develop corticosteroid toxicity. Mepolizumab, a humanised monoclonal anti-interleukin-5 antibody, demonstrated corticosteroid-sparing effects in a double-blind, placebo-controlled study of FIP1L1/PDGFRA-negative, corticosteroid-responsive subjects with HES. Objective To evaluate long-term safety and efficacy of mepolizumab (750 mg) in HES. Methods MHE100901 is an open-label extension study. The primary endpoint was the frequency of adverse events (AEs). Optimal dosing frequency, corticosteroid-sparing effect of mepolizumab, and development of anti-mepolizumab antibodies were also explored. Results Seventy-eight subjects received 1–66 mepolizumab infusions each (including mepolizumab infusions received in the placebo-controlled trial). Mean exposure was 251 weeks (range 4–302). The most common dosing interval was 9–12 weeks. The incidence of AEs was 932 events per 100 subject-years in the first year, declining to 461 events per 100 subject-years after 48 months. Serious AEs, including one death, were reported by the investigator as possibly due to mepolizumab in three subjects. The median daily prednisone dose decreased from 20.0 to 0 mg in the first 24 weeks. The median average daily dose for all subjects over the course of the study was 1.8 mg. Sixty-two percent of subjects were prednisone-free without other HES medications for ≥12 consecutive weeks. No neutralizing antibodies were detected. Twenty-four subjects withdrew prior to study completion for death (n=4), lack of efficacy (n=6), or other reasons. Conclusion Mepolizumab was well tolerated and effective as a long-term corticosteroid-sparing agent in PDGFRA-negative HES.

How I treat hypereosinophilic syndromes

“…After promising results in pilot studies, a double-blind, placebo-controlled trial in 85 PDGFRAnegative patients demonstrated that monthly mepolizumab was safe and effective as a steroid-sparing agent in HES, including L-HES. 92,93 Long-term safety and efficacy was confirmed in a second study. 92 Mepolizumab is currently available only on clinical protocols for patients with life-threatening HES refractory to standard therapies (as in the case presented) or with EGPA (http://www.…”

“…92,93 Long-term safety and efficacy was confirmed in a second study. 92 Mepolizumab is currently available only on clinical protocols for patients with life-threatening HES refractory to standard therapies (as in the case presented) or with EGPA (http://www. clinicaltrials.gov).…”

Eosinophils promote inducible NOS–mediated lung allograft acceptance

“…IL-5 is the critical factor for eosinophil generation, migration, maintenance, and survival (17). Neutralization of this cytokine is a commonly accepted method for global eosinophil ablation in experimental murine models (15,18) and therapeutic intervention for asthma (19) and hypereosinophilic patients (20 …”

Eosinophilic Vasculitis: Time for Recognition of a New Entity?

“…Patients with other forms of HES should receive treatment with corticosteroids as initial therapy and may require further immunosuppressive therapy with cyclosporine, tacrolimus or cyclophosphamide [15]. Anti Interleukin-5 directed therapy with the monoclonal antibody Mepolizumab has also been used [16].…”