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Dupilumab Improves Sense of Smell in Patients With Chronic Rhinosinusitis With Nasal Polyps Regardless of Sinonasal Surgery History – Pooled Results From SINUS-24 and SINUS-52 Phase 3 Trials
Rationale Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden, with loss of smell a particularly troublesome symptom that is generally refractory to nasal corticosteroids and may not improve after sinonasal surgery. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation. We report dupilumab effect on sense of smell in the pooled intent-to-treat (ITT) population with severe CRSwNP from SINUS-24/SINUS‑52 studies (NCT02912468/NCT02898454) and in those with/without a history of sinonasal surgery.
Methods Patients were treated with dupilumab 300mg or placebo every 2 weeks in SINUS-24 (n = 276) and SINUS-52 (n = 448). Sense of smell was analyzed using the University of Pennsylvania Smell Identification Test (UPSIT; 0–40) and daily self-reported loss of smell (0–3) scores.
Results 459 (63.4 %) patients had a history of sinonasal surgery. At baseline, sense of smell was greatly impaired (mean scores for ITT/with surgery/without surgery: UPSIT, 13.98/12.80/16.02; loss of smell, 2.74/2.79/2.65), and 77.6 % of the ITT population were anosmic (UPSIT score ≤18). At Week 24, this decreased to 28.0 % with dupilumab but was unchanged (77.1 %) with placebo. Dupilumab improved sense of smell at Week 24 regardless of sinonasal surgery history (least squares mean difference vs placebo for ITT/with surgery/without surgery: UPSIT 10.57/10.57/10.45, loss of smell –1.04/–1.07/–0.96; all nominal P<0.0001) with improvements in UPSIT score seen as early as Week 2 (5.53/4.82/6.70; nominal P<0.0001).
Conclusions Dupilumab markedly and rapidly improved sense of smell in patients with CRSwNP regardless of sinonasal surgery history and was well tolerated.
Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT02912468 (SINUS-24) and NCT02898454 (SINUS-52). Medical writing/editorial assistance provided by Sinéad Holland, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc.
Article published online:
10 June 2020
© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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