%0 Journal Article
%A Bhatt, P.
%A Puente Maestu, Luis
%A Abdulai, R.M.
%T Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts
%D 2023
%U https://hdl.handle.net/20.500.14352/129898
%X BACKGROUNDIn some patients with chronic obstructive pulmonary disease (COPD), type 2 inflammationmay increase exacerbation risk and may be indicated by elevated blood eosinophilcounts. Dupilumab, a fully human monoclonal antibody, blocks the shared receptorcomponent for interleukin-4 and interleukin-13, key drivers of type 2 inflammation.METHODSIn a phase 3, double-blind, randomized trial, we assigned patients with COPD whohad a blood eosinophil count of at least 300 per microliter and an elevated exacerbationrisk despite the use of standard triple therapy to receive dupilumab (300 mg) orplacebo subcutaneously once every 2 weeks. The primary end point was the annualizedrate of moderate or severe exacerbations of COPD. Key secondary and other endpoints that were corrected for multiplicity were the change in the prebronchodilatorforced expiratory volume in 1 second (FEV1) and in the scores on the St. George’sRespiratory Questionnaire (SGRQ; range, 0 to 100, with lower scores indicating abetter quality of life) and the Evaluating Respiratory Symptoms in COPD (E-RS–COPD; range, 0 to 40, with lower scores indicating less severe symptoms).RESULTSA total of 939 patients underwent randomization: 468 to the dupilumab group and471 to the placebo group. The annualized rate of moderate or severe exacerbationswas 0.78 (95% confidence interval [CI], 0.64 to 0.93) with dupilumab and 1.10 (95%CI, 0.93 to 1.30) with placebo (rate ratio, 0.70; 95% CI, 0.58 to 0.86; P<0.001). Theprebronchodilator FEV1 increased from baseline to week 12 by a least-squares (LS)mean of 160 ml (95% CI, 126 to 195) with dupilumab and 77 ml (95% CI, 42 to 112)with placebo (LS mean difference, 83 ml; 95% CI, 42 to 125; P<0.001), a differencethat was sustained through week 52. At week 52, the SGRQ score had improved byan LS mean of −9.7 (95% CI, −11.3 to −8.1) with dupilumab and −6.4 (95% CI, −8.0to −4.8) with placebo (LS mean difference, −3.4; 95% CI, −5.5 to −1.3; P = 0.002). TheE-RS–COPD score at week 52 had improved by an LS mean of −2.7 (95% CI, −3.2 to−2.2) with dupilumab and −1.6 (95% CI, −2.1 to −1.1) with placebo (LS mean difference,−1.1; 95% CI, −1.8 to −0.4; P = 0.001). The numbers of patients with adverseevents that led to discontinuation of dupilumab or placebo, serious adverse events,and adverse events that led to death were balanced in the two groups.CONCLUSIONSAmong patients with COPD who had type 2 inflammation as indicated by elevatedblood eosinophil counts, those who received dupilumab had fewer exacerbations,better lung function and quality of life, and less severe respiratory symptoms thanthose who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals;BOREAS ClinicalTrials.gov number, NCT03930732.)
%~