Claire Hopkins1, Martin Wagenmann2, Claus Bachert3,4,5, Martin Desrosiers6, Joseph K Han7, Peter W Hellings8, Stella E Lee9, Jérôme Msihid10, Amr Radwan11, Paul Rowe12, Nikhil Amin13, Yamo Deniz13, Benjamin Ortiz13, Leda P Mannent10, Rajesh Rout14. 1. ENT Department, Guy's and St Thomas' Hospitals, London, UK. 2. Department of Otorhinolaryngology, Düsseldorf University Hospital (UKD), Düsseldorf, Germany. 3. Department of Otorhinolaryngology, Ghent University, Ghent, Belgium. 4. Division of ENT diseases, Karolinska Institutet, Stockholm, Sweden. 5. First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 6. Department of Otorhinolaryngology, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada. 7. Division of Allergy, Rhinology and Skull Base Surgery, Eastern Virginia Medical School, Norfolk, VA, USA. 8. Department of Otorhinolaryngology, University Hospitals Leuven, Leuven, Belgium. 9. Department of Otorhinolaryngology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. 10. Sanofi, Chilly-Mazarin, France. 11. Regeneron Pharmaceuticals, Inc., Uxbridge, London, UK. 12. Sanofi, Bridgewater, NJ, USA. 13. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. 14. Sanofi Genzyme, Reading, UK.
Abstract
BACKGROUND:Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease treated with sinus surgery when refractory to medical intervention. However, recurrence postsurgery is common. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor for interleukin 4 (IL-4) and IL-13, key and central drivers of type 2 inflammation. We report the efficacy of dupilumab in patients with CRSwNP from the SINUS-24/SINUS-52 trials (NCT02912468/NCT02898454), by number of prior surgeries and time since last surgery. METHODS: Patients were randomized to placebo or dupilumab 300 mg every 2 weeks. Post hoc subgroup analyses were performed for patients with 0, ≥1, 1/2, or ≥3 prior surgeries, and for patients who had surgery within <3, 3 to <5, 5 to <10, or ≥10 years. Efficacy outcomes at 24 weeks included co-primary endpoints nasal polyp score (NPS) and nasal congestion (NC), and Lund-Mackay (LMK), 22-item Sino-Nasal Outcome Test (SNOT-22), and smell scores. RESULTS: Of 724 patients randomized, 459 (63.4%) had ≥1 prior surgery. Baseline sinus disease (NPS, NC, LMK) and olfactory dysfunction (University of Pennsylvania Smell Identification Test [UPSIT] and loss of smell) scores were worse for patients with ≥3 prior surgeries vs no surgery. Baseline NPS and LMK were worse in patients with <3 years since last surgery than in patients with ≥5 years since last surgery. Dupilumab significantly improved all outcome measures vs placebo in all subgroups by number of surgeries and by time since last surgery. Improvements in NPS and LMK were greater in patients with <3 years since last surgery than patients with ≥5 years. Safety results were consistent with the known dupilumab safety profile. CONCLUSION:Dupilumab improved CRSwNP outcomes irrespective of surgery history, with greater improvements in endoscopic outcomes in patients with shorter duration since last surgery.
RCT Entities:
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease treated with sinus surgery when refractory to medical intervention. However, recurrence postsurgery is common. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor for interleukin 4 (IL-4) and IL-13, key and central drivers of type 2 inflammation. We report the efficacy of dupilumab in patients with CRSwNP from the SINUS-24/SINUS-52 trials (NCT02912468/NCT02898454), by number of prior surgeries and time since last surgery. METHODS:Patients were randomized to placebo or dupilumab 300 mg every 2 weeks. Post hoc subgroup analyses were performed for patients with 0, ≥1, 1/2, or ≥3 prior surgeries, and for patients who had surgery within <3, 3 to <5, 5 to <10, or ≥10 years. Efficacy outcomes at 24 weeks included co-primary endpoints nasal polyp score (NPS) and nasal congestion (NC), and Lund-Mackay (LMK), 22-item Sino-Nasal Outcome Test (SNOT-22), and smell scores. RESULTS: Of 724 patients randomized, 459 (63.4%) had ≥1 prior surgery. Baseline sinus disease (NPS, NC, LMK) and olfactory dysfunction (University of Pennsylvania Smell Identification Test [UPSIT] and loss of smell) scores were worse for patients with ≥3 prior surgeries vs no surgery. Baseline NPS and LMK were worse in patients with <3 years since last surgery than in patients with ≥5 years since last surgery. Dupilumab significantly improved all outcome measures vs placebo in all subgroups by number of surgeries and by time since last surgery. Improvements in NPS and LMK were greater in patients with <3 years since last surgery than patients with ≥5 years. Safety results were consistent with the known dupilumab safety profile. CONCLUSION:Dupilumab improved CRSwNP outcomes irrespective of surgery history, with greater improvements in endoscopic outcomes in patients with shorter duration since last surgery.