TY - JOUR
T1 - Benralizumab for the Prevention of COPD Exacerbations
AU - Criner, Gerard J.
AU - Celli, Bartolome R.
AU - Brightling, Christopher E.
AU - Agusti, Alvar
AU - Papi, Alberto
AU - Singh, Dave
AU - Sin, Don D.
AU - Vogelmeier, Claus F.
AU - Sciurba, Frank C.
AU - Bafadhel, Mona
AU - Backer, Vibeke
AU - Kato, Motokazu
AU - Ramírez-venegas, Alejandra
AU - Wei, Yu-feng
AU - Bjermer, Leif
AU - Shih, Vivian H.
AU - Jison, Maria
AU - O’quinn, Sean
AU - Makulova, Natalya
AU - Newbold, Paul
AU - Goldman, Mitchell
AU - Martin, Ubaldo J.
PY - 2019/5/20
Y1 - 2019/5/20
N2 - 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
AB - 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
KW - anti–IL-5Rα
KW - benralizumab
KW - chronic obstructive pulmonary disease
KW - COPD
KW - Phase III
KW - randomized controlled trial
U2 - 10.1056/NEJMoa1905248
DO - 10.1056/NEJMoa1905248
M3 - Article
SN - 0028-4793
VL - 381
SP - 1023
EP - 1034
JO - New England Journal Of Medicine
JF - New England Journal Of Medicine
ER -