Clinical Efficacy among Patients with Chronic Rhinosinusitis with Nasal Polyps and Clinical Features of Obstructive Lung Disease: Post Hoc Analysis of the Phase III SINUS-24 and SINUS-52 Studies

Abstract

Jorge F Maspero,1 Claus Bachert,2,3 Fernando J Martinez,4 Nicola A Hanania,5 Benjamin Ortiz,6 Naimish Patel,7 Leda P Mannent,8 Amy Praestgaard,7 Nami Pandit-Abid,9 Shahid Siddiqui,6 Megan Hardin7 1Allergy and Respiratory Research Unit, Fundación CIDEA, Buenos Aires, Argentina; 2Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium; 3Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden; 4Division of Pulmonary and Critical Care, Weill Cornell Medical College, New York, NY, USA; 5Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA; 6Immunology and Allergy Medical Affairs, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 7Immunology and Inflammation, Sanofi, Cambridge, MA, USA; 8Global Clinical Development, Sanofi, Chilly-Mazarin, France; 9Immunology and Inflammation, Sanofi, Bridgewater, NJ, USACorrespondence: Jorge F Maspero, Allergy and Respiratory Research Unit, Fundación CIDEA, Paraguay 2035, Buenos Aires, C1121ABE, Argentina, Tel [phone], Email [email protected]: To provide a descriptive summary of clinical efficacy and health-related quality of life (HRQoL) measures in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and clinical features of obstructive lung disease in the Phase III dupilumab studies SINUS-24 and SINUS-52 (NCT02912468, NCT02898454).Patients and Methods: Patients met a “broad” definition of having clinical features of obstructive lung disease with any of 3 criteria: (i) pre-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) 10 pack-years’ smoking history. A “narrow” definition including criteria (i) or (ii) was also analyzed. CRSwNP and HRQoL measures were evaluated in all patients and lung function (FEV1; FEV1/FVC ratio) was captured and analyzed only in those patients who had a self-reported history of asthma.Results: Across both studies, 131 patients met the “broad” definition, of whom 90 also had asthma, and 115 patients met the “narrow” definition, of whom 74 had asthma. CRSwNP outcomes and HRQoL were improved with dupilumab vs placebo in both the broad and narrow subgroups. Among the 90 patients who met the broad definition and had asthma, dupilumab improved pre-bronchodilator FEV1 and FEV1/FVC ratio at Week 16 (least squares mean differences vs placebo: 0.38 L [95% confidence interval: 0.17, 0.59; p = 0.0004] and 4.8% [1.7%, 7.9%; p = 0.0024], respectively) sustained through Week 24. Similar results were seen in the “narrow” subgroup with asthma.Conclusion: In a population of patients with CRSwNP and clinical features of obstructive lung disease, dupilumab improved CRSwNP and HRQoL outcomes, and, among those with a history of asthma, also improved lung function. These results support further analyses of dupilumab in patients with evidence of type 2 inflammation and obstructive lung disease such as COPD.Keywords: obstructive lung disease, chronic obstructive pulmonary disease, dupilumab, type 2 inflammation, interleukin-4, interleukin-13

Keywords

• obstructive lung disease
• chronic obstructive pulmonary disease
• dupilumab
• type 2 inflammation
• interleukin-4
• interleukin-13