M Desrosiers1, L P Mannent2, N Amin3, G W Canonica3, P W Hellings4, P Gevaert5, J Mullol6, S E Lee7, S Fujieda8, J K Han9, C Hopkins10, W Fokkens11, R Jankowski12, S H Cho13, X Mao14, M Zhang14, M S Rice15, A H Khan2, S Kamat3, N Patel14, N M H Graham3, M Ruddy3, C Bachert16. 1. Centre de recherche du Centre hospitalier de l’Universite de Montreal (CRCHUM), Montreal, QC, Canada. 2. Sanofi, Chilly-Mazarin, France. 3. Regeneron Pharmaceuticals, Inc. Tarrytown, NY, USA. 4. University Hospitals Leuven, Leuven, Belgium. 5. Ghent University, Ghent, Belgium. 6. Hospital Clinic, IDIBAPS, Universitat de Barcelona, CIBERES, Barcelona, Catalonia, Spain. 7. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. 8. University of Fukui, Fukui, Japan. 9. Eastern Virginia Medical School, Norfolk, VA, USA. 10. Guy's and St Thomas' Hospitals, London, UK. 11. Academic Medical Center, Amsterdam, Netherlands. 12. University Hospital of Nancy, University of Lorraine, Nancy, France. 13. University of South Florida, Tampa, FL, USA. 14. Sanofi, Bridgewater, NJ, USA. 15. Sanofi, Cambridge, MA, USA. 16. Ghent University, Ghent, Belgium; Karolinska Institutet, Stockholm, Sweden; Sun Yat-sen University, First Affiliated Hospital, Guangzhou, China.
Abstract
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 [NCT02912468]; SINUS-52 [NCT02898454]) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery. METHODOLOGY: SINUS-24 patients were randomised 1:1 to subcutaneous dupilumab 300 mg (n=143) or placebo (n=133) every 2 weeks (q2w) for 24 weeks. SINUS-52 patients were randomised 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w (n=150), 24 weeks q2w followed by 28 weeks of dupilumab 300 mg every 4 weeks (n=145) or 52 weeks of placebo q2w (n=153). RESULTS: Dupilumab reduced the number of patients undergoing sinonasal surgery (82.6%), the need for in-study SCS use (73.9%), and SCS courses (75.3%). Significant improvements were observed with dupilumab vs placebo regardless of prior sinonasal surgery or SCS use in nasal polyp, nasal congestion, Lund-MacKay, and Sinonasal Outcome Test (22-items) scores, and the University of Pennsylvania Smell Identification Test. CONCLUSIONS: Dupilumab demonstrated significant improvements in disease signs and symptoms and reduced the need for sino-nasal surgery and SCS use versus placebo in patients with severe CRSwNP, regardless of SCS use in the previous 2 years, or prior sinonasal surgery.
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 [NCT02912468]; SINUS-52 [NCT02898454]) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery. METHODOLOGY: SINUS-24 patients were randomised 1:1 to subcutaneous dupilumab 300 mg (n=143) or placebo (n=133) every 2 weeks (q2w) for 24 weeks. SINUS-52 patients were randomised 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w (n=150), 24 weeks q2w followed by 28 weeks of dupilumab 300 mg every 4 weeks (n=145) or 52 weeks of placebo q2w (n=153). RESULTS: Dupilumab reduced the number of patients undergoing sinonasal surgery (82.6%), the need for in-study SCS use (73.9%), and SCS courses (75.3%). Significant improvements were observed with dupilumab vs placebo regardless of prior sinonasal surgery or SCS use in nasal polyp, nasal congestion, Lund-MacKay, and Sinonasal Outcome Test (22-items) scores, and the University of Pennsylvania Smell Identification Test. CONCLUSIONS: Dupilumab demonstrated significant improvements in disease signs and symptoms and reduced the need for sino-nasal surgery and SCS use versus placebo in patients with severe CRSwNP, regardless of SCS use in the previous 2 years, or prior sinonasal surgery.