Reslizumab for Inadequately Controlled Asthma With Elevated Blood Eosinophil Levels A Randomized Phase 3 Study

被引:320
作者
Bjermer, Leif [1 ]
Lemiere, Catherine [2 ]
Maspero, Jorge [3 ]
Weiss, Sivan [4 ]
Zangrilli, James [5 ]
Germinaro, Matthew [5 ]
机构
[1] Lund Univ, Skane Univ Hosp, Lund, Sweden
[2] Univ Montreal, Sacre Coeur Hosp, Montreal, PQ, Canada
[3] CIDEA, Allergy Resp Res, Buenos Aires, DF, Argentina
[4] Teva Pharmaceut, Netanya, Israel
[5] Teva Pharmaceut, Frazer, PA USA
关键词
asthma; eosinophil; phase; 3; reslizumab; QUALITY-OF-LIFE; HUMAN INTERLEUKIN-5; MONOCLONAL-ANTIBODY; QUESTIONNAIRE; INFLAMMATION; MEPOLIZUMAB; PLACEBO; VALIDATION; IL-5;
D O I
10.1016/j.chest.2016.03.032
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
BACKGROUND: This phase 3 study further characterizes the efficacy and safety of reslizumab a humanized anti-IL-5 monoclonal antibody) in patients aged 12 to 75 years with asthma inadequately controlled by at least a medium-dose inhaled corticosteroid and with a blood eosinophil count >= 400 cells/mu L. METHODS: Patients were randomized to receive reslizumab 0.3 or 3.0 mg/kg or placebo administered once every 4 weeks for 16 weeks total four doses). The primary end point was change from baseline in pre-bronchodilator FEV1 over 16 weeks. Secondary end points included FVC, forced expiratory flow at 25% to 75% of FVC FEF25%-75%), patient-reported control of asthma symptoms, short-acting beta-agonist SABA) use, blood eosinophil levels, and safety. RESULTS: Reslizumab significantly improved FEV1 difference vs placebo [reslizumab 0.3 and 3.0 mg/kg], 115 mL [95% CI, 16-215; P =.0237] and 160 mL [95% CI, 60-259; P =.0018]). Clinically meaningful increases in FVC 130 mL) and FEF25%-75% 233 mL/s) were observed with reslizumab 3.0 mg/kg. Reslizumab improved scores on the Asthma Control Questionnaire ACQ) and Asthma Quality of Life Questionnaire AQLQ) vs placebo greater effects seen with 3.0 mg/kg; P <.05). The minimally important difference was reached for the AQLQ reslizumab 3.0 mg/kg) but not on the ACQ. Scores on the Asthma Symptom Utility Index and SABA use were improved with reslizumab. The most common adverse events were worsening of asthma, headache, and nasopharyngitis; most events were mild to moderate in severity. CONCLUSIONS: Reslizumab improved lung function, asthma control and symptoms, and quality of life. It was well tolerated in patients with inadequately controlled asthma despite standard therapy) and elevated blood eosinophil levels. Overall, the 3.0-mg/kg dose of reslizumab provided greater improvements in asthma outcomes vs the 0.3-mg/kg dose, with comparable safety.
引用
收藏
页码:789 / 798
页数:10
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