Benralizumab for the Prevention of COPD Exacerbations

Gerard J. Criner, Bartolome R. Celli, Christopher E. Brightling, Alvar Agusti, Alberto Papi, Dave Singh, Don D. Sin, Claus F. Vogelmeier, Frank C. Sciurba, Mona Bafadhel, Vibeke Backer, Motokazu Kato, Alejandra Ramírez-venegas, Yu-feng Wei, Leif Bjermer, Vivian H. Shih, Maria Jison, Sean O’quinn, Natalya Makulova, Paul NewboldMitchell Goldman, Ubaldo J. Martin

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Abstract

BACKGROUND The efficacy and safety of benralizumab, an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known. METHODS In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. <220 per cubic millimeter]) who had frequent exacerbations despite receiving guideline-based inhaled treatment. Patients were randomly assigned to receive benralizumab (30 or 100 mg in GALATHEA; 10, 30, or 100 mg in TERRANOVA) every 8 weeks (every 4 weeks for the first three doses) or placebo. The primary end point was the treatment effect of benralizumab, measured as the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56 in patients with baseline blood eosinophil counts of 220 per cubic millimeter or greater. Safety was also assessed. RESULTS In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P=0.65) and 0.83 for 100 mg of benralizumab (P=0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P=0.06), 1.04 (P=0.66), and 0.93 (P=0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo. CONCLUSIONS Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater
Original languageEnglish
Pages (from-to)1023-1034
JournalNew England Journal Of Medicine
Volume381
Early online date20 May 2019
DOIs
Publication statusPublished - 20 May 2019

Keywords

  • anti–IL-5Rα
  • benralizumab
  • chronic obstructive pulmonary disease
  • COPD
  • Phase III
  • randomized controlled trial

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