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

Florence E. Roufosse, Jean Emmanuel Kahn, Gerald J. Gleich, Lawrence B. Schwartz, Anish D. Singh, Lanny J. Rosenwasser, Judah A. Denburg, Johannes Ring, Marc E. Rothenberg, Javed Sheikh, Ann E. Haig, Stephen A. Mallett, Deborah N. Templeton, Hector G. Ortega, Amy D. Klion

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

Background: Hypereosinophilic syndromes (HESs) 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 humanized monoclonal anti-IL-5 antibody, showed corticosteroid-sparing effects in a double-blind, placebo-controlled study of FIP1L1/PDGFRA-negative, corticosteroid-responsive subjects with HESs. Objective: We evaluated long-term safety and efficacy of mepolizumab (750 mg) in HES. Methods: MHE100901 is an open-label extension study. The primary end point was the frequency of adverse events (AEs). Optimal dosing frequency, corticosteroid-sparing effect of mepolizumab, and development of antimepolizumab antibodies were also explored. Results: Seventy-eight subjects received 1 to 66 mepolizumab infusions each (including mepolizumab infusions received in the placebo-controlled trial). Mean exposure was 251 weeks (range, 4-302 weeks). The most common dosing interval was 9 to 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 1 death, were reported by the investigator as possibly due to mepolizumab in 3 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 before 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.

Original languageEnglish
Pages (from-to)461-467.e5
JournalJournal of Allergy and Clinical Immunology
Volume131
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Eosinophil
  • corticosteroid
  • interleukin-5
  • monoclonal antibody

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