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

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• 作者：Florence E. Roufosse ; MD^a ; Jean-Emmanuel Kahn ; MD^b ; Gerald J. Gleich ; MD^c ; Lawrence B. Schwartz ; MD^d ; Anish D. Singh ; MD^e ; Lanny J. Rosenwasser ; MD^f ; Judah A. Denburg ; MD^g ; Johannes Ring ; MD^h ; Marc E. Rothenberg ; MD ; PhDⁱ ; Javed Sheikh ; MD^j ; Ann E. Haig ; BSN^k ; Stephen A. Mallett ; MSc^l ; Deborah N. Templeton ; MSN^m ; Hector G. Ortega ; MD ; ScD^m ; Amy D. Klion ; MDⁿ ; ^{aklion@niaid.nih.gov}
• 关键词：Eosinophil ; monoclonal antibody ; interleukin-5 ; corticosteroid
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：131
• 期：2
• 页码：461-467.e5
• 全文大小：434 K

文摘

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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 ¡Ý12 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.