Association Between Smell Loss, Disease Burden, and Dupilumab Efficacy in Chronic Rhinosinusitis with Nasal Polyps.

Objective: To evaluate the association between smell loss and other aspects of disease, and evaluate dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate or severe smell loss.
Methods: This post-hoc analysis of the SINUS-24/52 studies (NCT02912468/NCT02898454) analyzed nasal polyp score (NPS, 0-8), nasal congestion/obstruction (NC, 0-3), Lund-Mackay CT-scan score (LMK-CT, 0-24), rhinosinusitis severity visual analog scale (RS-VAS, 0-10), and 22-item Sinonasal Outcome Test (SNOT-22, 0-110) according to baseline monthly average patient-reported loss of smell scores (LoS, 0-3) of >1 to 2 (moderate) or >2 to 3 (severe) in patients randomized to dupilumab 300 mg or placebo every 2 weeks.
Results: Of 724 patients randomized, baseline LoS was severe in 601 (83%) and moderate in 106 (15%). At baseline, severe versus moderate LoS was associated with 1-point greater severity of NC (odds ratio [OR] 6.01 [95% confidence interval, (CI) 3.95, 9.15]), 5-point greater severity of LMK-CT (OR 2.19 [1.69, 2.85]), and 8.9-point greater severity of SNOT-22 (OR 1.35 [1.20, 1.49]). At Week 24, least squares mean differences (95% CI) dupilumab versus placebo in change from baseline were: NPS -1.90 (-2.56, -1.25) and -1.95 (-2.20, -1.70) in the moderate and severe baseline LoS subgroups, respectively; NC -.35 (-.64, -.06) and -1.00 (-1.13, -.87); LMK-CT -6.30 (-7.88, -4.72) and -6.22 (-6.82, -5.63); RS-VAS -1.18 (-2.20, -.16) and -3.47 (-3.90, -3.03); and SNOT-22 -7.52 (-14.55, -.48) and -21.72 (-24.63, -18.82); all nominal P  < .05 versus placebo. Improvements with dupilumab in NC, RS-VAS, and SNOT-22 were statistically greater in patients with severe versus moderate baseline LoS.
Conclusion: Significant smell impairment in severe CRSwNP is associated with significant disease (NC, RS-VAS, LMK), health-related quality of life impairment (SNOT-22), asthma, and non-steroidal anti-inflammatory drug-exacerbated respiratory disease. Dupilumab significantly improved NPS, NC, LMK-CT, RS-VAS, and SNOT-22 in subjects with moderate and severe baseline smell loss.
Competing Interests: Declaration of Conflicting InterestsThe authors declare the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Zachary M. Soler has been a consultant or advisory board member for Lyra, Novartis, Olympus, and Optinose; he has received speaker's fees from GlaxoSmithKline and Regeneron Pharmaceuticals Inc.; and held the post of medical director at Healthy Humming. Zara M. Patel has been a consultant or advisory board member for Dianosic, InfiniteMD, Mediflix, Medtronic, and Optinose and the Chief Medical Officer of Olfera Therapeutics. Joaquim Mullol has participated in a speakers’ bureau or advisory board or received a research grant from AstraZeneca, Genentech, Inc., GlaxoSmithKline, Glenmark, Menarini, Mitsubishi-Tanabe, Merck Sharp & Dohme, Viatris (Mylan-MEDA), Novartis, Procter & Gamble, Regeneron Pharmaceuticals Inc., Sanofi, and the NOUCOR/Uriach Group. Jose Mattos has no financial disclosures or conflicts of interest. Scott Nash, Changming Xia, Zhixiao Wang, Harry Sacks, and Yamo Deniz are employees of Regeneron Pharmaceuticals and may hold stock and/or stock options in the company. Kinga Borsos is a former employee of Sanofi and may hold stock and/or stock options in the company. Mark Corbett, Juby A. Jacob-Nara, and Paul Rowe are employees of Sanofi and may hold stock and/or stock options in the company. Andrew P. Lane is a member of the advisory boards of Sanofi and Regeneron Pharmaceuticals Inc.