Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes - 30/01/13
Corresponding author: Amy D. Klion, MD, Bldg 4, Rm B1-28, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.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.
Le texte complet de cet article est disponible en PDF.Key words : Eosinophil, monoclonal antibody, interleukin-5, corticosteroid
Abbreviations used : AEC, AE, AITL, HES, L-HES, SAE, SEER
Plan
| Supported by GlaxoSmithKline, the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (A.D.K.), and the Belgian National Fund for Scientific Research (FNRS; grant no. 3.4545.11 to F.E.R.). |
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| Disclosure of potential conflict of interest: F. E. Roufosse has received consultancy fees from GlaxoSmithKline for advisory board meetings and for revision of clinical study report. J.-E. Kahn has received grants and travel expenses from GlaxoSmithKline. G. J. Gleich has received research support from GlaxoSmithKline, TRIA Bioscience Corp, and ImmViz; is on the APFED Board; has received consultancy fees from GlaxoSmithKline; has patents from ImmViz; received royalties from Teva for the sales of reslizumab; and has stock/stock options in Immune Design Corp. L. B. Schwartz has received research support from GlaxoSmithKline, Genentech, Carolus, and NeilMed; is president of the Clinical Immunology Society; is a board member of the Asthma & Allergy Foundation of America; has received consultancy fees from Genentech, Marshall Edwards Inc, and Sanofi-Aventis; and has received royalties from Thermo-Fisher, Hycult & BioLegend, and Millipore Santa Cruz. L. J. Rosenwasser has consultant arrangements with Regeneron and Sanofi-Aventis and has received payment for lectures from Genentech. J. A. Denburg has received grants from GlaxoSmithKline. J. Ring has participated in clinical trials sponsored by ALK-Abelló, Allergopharma, Almirall-Herman, Astellas, Bavarian Nordic, Bencard, Galderma, GlaxoSmithKline, Leo, Novartis, PLS Design, and Stallergenes; and has received research support from Biogen-Idec, MSD, Phadia, Proctor & Gamble, and Sanofi Aventis. M. E. Rothenberg is on the boards of the International Eosinophil Society and the American Partnership for Eosinophilic Disorders; has received consultancy fees from ImmunePharm; has received research support from the National Institutes of Health and the Department of Defense; has many patents all of which are owned by CCHMC; has received royalties from Teva Pharmaceuticals; has stock/stock options and has received travel expenses from ImmunePharm. J. Sheikh has received grants and travel support from and has consultant arrangements with GlaxoSmithKline. D. N. Templeton is employed by and has stock/stock options in GlaxoSmithKline. A. E. Haig is employed by and has stock/stock options in GlaxoSmithKline. A. D. Klion has received research support from GlaxoSmithKline. H. G. Ortega is an employee of GlaxoSmithKline. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 2
P. 461 - février 2013 Retour au numéro
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