• Surya P Bhatt, Klaus F Rabe, Nicola A Hanania, Claus F Vogelmeier, Mona Bafadhel, Stephanie A Christenson, Alberto Papi, Dave Singh, Elizabeth Laws, Naimish Patel, George D Yancopoulos, Bolanle Akinlade, Jennifer Maloney, Xin Lu, Deborah Bauer, Ashish Bansal, Raolat M Abdulai, Lacey B Robinson, and NOTUS Study Investigators.
• From the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.P.B.); LungenClinic Grosshansdorf (member of the German Center for Lung Research [DZL]), Airway Research Center North (ARCN), Grosshansdorf (K.F.R.), Christian-Albrechts University, DZL, ARCN, Kiel (K.F.R.), and the Department of Medicine, Pulmonary and Critical Care Medicine, University of Marburg, DZL, Marburg (C.F.V.) - all in Germany; the Section on Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston (N.A.H.); King's Centre for Lung Health, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London (M.B.), and the Medicines Evaluation Unit, Manchester University NHS Foundation Trust, University of Manchester, Manchester (D.S.) - both in the United Kingdom; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, San Francisco (S.A.C.); the Respiratory Medicine Unit, University of Ferrara, S. Anna University Hospital, Ferrara, Italy (A.P.); Sanofi, Bridgewater, NJ (E.L., X.L., D.B.); Sanofi, Cambridge, MA (N.P., R.M.A., L.B.R.); and Regeneron Pharmaceuticals, Tarrytown, NY (G.D.Y., B.A., J.M., A.B.).
• N. Engl. J. Med. 2024 Jun 27; 390 (24): 227422832274-2283.

BackgroundDupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation, has shown efficacy and safety in a phase 3 trial involving patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation and an elevated risk of exacerbation. Whether the findings would be confirmed in a second phase 3 trial was unclear.MethodsIn a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of 300 cells per microliter or higher to receive subcutaneous dupilumab (300 mg) or placebo every 2 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Key secondary end points, analyzed in a hierarchical manner to adjust for multiplicity, included the changes from baseline in the prebronchodilator forced expiratory volume in 1 second (FEV1) at weeks 12 and 52 and in the St. George's Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better quality of life) total score at week 52.ResultsA total of 935 patients underwent randomization: 470 were assigned to the dupilumab group and 465 to the placebo group. As prespecified, the primary analysis was performed after a positive interim analysis and included all available data for the 935 participants, 721 of whom were included in the analysis at week 52. The annualized rate of moderate or severe exacerbations was 0.86 (95% confidence interval [CI], 0.70 to 1.06) with dupilumab and 1.30 (95% CI, 1.05 to 1.60) with placebo; the rate ratio as compared with placebo was 0.66 (95% CI, 0.54 to 0.82; P<0.001). The prebronchodilator FEV1 increased from baseline to week 12 with dupilumab (least-squares mean change, 139 ml [95% CI, 105 to 173]) as compared with placebo (least-squares mean change, 57 ml [95% CI, 23 to 91]), with a significant least-squares mean difference at week 12 of 82 ml (P<0.001) and at week 52 of 62 ml (P = 0.02). No significant between-group difference was observed in the change in SGRQ scores from baseline to 52 weeks. The incidence of adverse events was similar in the two groups and consistent with the established profile of dupilumab.ConclusionsIn patients with COPD and type 2 inflammation as indicated by elevated blood eosinophil counts, dupilumab was associated with fewer exacerbations and better lung function than placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; NOTUS ClinicalTrials.gov number, NCT04456673.).Copyright © 2024 Massachusetts Medical Society.

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