Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis

被引:731
作者
Wechsler, M. E. [1 ]
Akuthota, P. [2 ,3 ]
Jayne, D. [4 ]
Khoury, P. [9 ]
Klion, A. [9 ]
Langford, C. A. [10 ]
Merkel, P. A. [11 ,12 ]
Moosig, F. [15 ]
Specks, U. [16 ]
Cid, M. C. [17 ]
Luqmani, R. [5 ]
Brown, J. [6 ]
Mallett, S. [7 ]
Philipson, R. [8 ]
Yancey, S. W. [18 ]
Steinfeld, J. [13 ,14 ]
Weller, P. F. [3 ]
Gleich, G. J. [19 ,20 ]
机构
[1] Natl Jewish Hlth, Dept Med, Denver, CO USA
[2] Univ Calif San Diego, Div Pulm Crit Care & Sleep Med, La Jolla, CA 92093 USA
[3] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
[4] Univ Cambridge, Dept Med, Cambridge, MA USA
[5] Univ Oxford, Dept Orthopaed Rheumatol & Musculoskeletal Sci, Botnar Res Ctr, Oxford, England
[6] GlaxoSmithKline, Res & Dev Immunoinflammat Therapy Area Unit, Uxbridge, Middx, England
[7] GlaxoSmithKline, Res & Dev, Stat Programming & Data Stand, Uxbridge, Middx, England
[8] Trizell, Oxford, England
[9] NIAID, Human Eosinophil Sect, Lab Parasit Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[10] Cleveland Clin, Ctr Vasculitis Care & Res, Cleveland, OH 44106 USA
[11] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA
[12] Univ Penn, Dept Biostat & Clin Epidemiol, Philadelphia, PA 19104 USA
[13] GlaxoSmithKline, Resp Therapy Area Unit, Philadelphia, PA USA
[14] GlaxoSmithKline, Flexible Discovery Unit, Philadelphia, PA USA
[15] Schleswig Holstein Mitte, Rheumazentrum, Neumunster, Germany
[16] Mayo Clin, Div Pulm & Crit Care Med, Rochester, MN USA
[17] Hosp Clin Univ Barcelona, Inst Invest Biomed August Pi i Sunyer, Dept Autoimmune Dis, Vasculitis Res Unit, Barcelona, Spain
[18] GlaxoSmithKline, Resp Therapeut Area, Res Triangle Pk, NC USA
[19] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA
[20] Univ Utah, Sch Med, Dept Med, Salt Lake City, UT USA
基金
美国国家卫生研究院;
关键词
CHURG-STRAUSS-SYNDROME; TERM-FOLLOW-UP; ASTHMA CONTROL; TASK-FORCE; VASCULITIS; RECOMMENDATIONS; MANAGEMENT; OUTCOMES; PATHOGENESIS; PROGNOSIS;
D O I
10.1056/NEJMoa1702079
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND Eosinophilic granulomatosis with polyangiitis is an eosinophilic vasculitis. Mepolizumab, an anti-interleukin-5 monoclonal antibody, reduces blood eosinophil counts and may have value in the treatment of eosinophilic granulomatosis with polyangiitis. METHODS In this multicenter, double-blind, parallel-group, phase 3 trial, we randomly assigned participants with relapsing or refractory eosinophilic granulomatosis with polyangiitis who had received treatment for at least 4 weeks and were taking a stable prednisolone or prednisone dose to receive 300 mg of mepolizumab or placebo, administered subcutaneously every 4 weeks, plus standard care, for 52 weeks. The two primary end points were the accrued weeks of remission over a 52-week period, according to categorical quantification, and the proportion of participants in remission at both week 36 and week 48. Secondary end points included the time to first relapse and the average daily glucocorticoid dose (during weeks 48 through 52). The annualized relapse rate and safety were assessed. RESULTS A total of 136 participants underwent randomization, with 68 participants assigned to receive mepolizumab and 68 to receive placebo. Mepolizumab treatment led to significantly more accrued weeks of remission than placebo (28% vs. 3% of the participants had >= 24 weeks of accrued remission; odds ratio, 5.91; 95% confidence interval [CI], 2.68 to 13.03; P<0.001) and a higher percentage of participants in remission at both week 36 and week 48 (32% vs. 3%; odds ratio, 16.74; 95% CI, 3.61 to 77.56; P<0.001). Remission did not occur in 47% of the participants in the mepolizumab group versus 81% of those in the placebo group. The annualized relapse rate was 1.14 in the mepolizumab group, as compared with 2.27 in the placebo group (rate ratio, 0.50; 95% CI, 0.36 to 0.70; P<0.001). A total of 44% of the participants in the mepolizumab group, as compared with 7% of those in the placebo group, had an average daily dose of prednisolone or prednisone of 4.0 mg or less per day during weeks 48 through 52 (odds ratio, 0.20; 95% CI, 0.09 to 0.41; P<0.001). The safety profile of mepolizumab was similar to that observed in previous studies. CONCLUSIONS In participants with eosinophilic granulomatosis with polyangiitis, mepolizumab resulted in significantly more weeks in remission and a higher proportion of participants in remission than did placebo, thus allowing for reduced glucocorticoid use. Even so, only approximately half the participants treated with mepolizumab had protocol-defined remission. (Funded by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT02020889.)
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收藏
页码:1921 / 1932
页数:12
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