Dupilumab improves health related quality of life: Results from the phase 3 SINUS studies

Abstract

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2-mediated inflammatory disease with high symptom burden and reduced health-related quality of life (HRQoL). This report aimed to comprehensively understand the effects of dupilumab on domains of HRQoL, their individual elements, and health status in patients with severe CRSwNP from phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) trials.

Methods: Patients were randomized to dupilumab (n = 438) or placebo (n = 286) for 24 weeks (SINUS-24), or 52 weeks (SINUS-52). Disease-specific HRQoL using 22-item sino-nasal outcome test (SNOT-22), and health status using EuroQoL-visual analog scale (EQ-VAS) was evaluated in the pooled intention-to-treat (ITT) population (Week 24), SINUS-52 ITT (Week 52) and in the subgroups with/without asthma; non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD); and prior sinus surgery.

Results: At baseline, patients had poor disease-specific HRQoL and general health status and identified "Decreased sense of smell/taste" and "Nasal blockage" as the most important symptoms. Dupilumab significantly improved SNOT-22 total, domain (Nasal, Sleep, Function, Emotion, and Ear/facial), and 22-item scores, and EQ-VAS, at Week 24 vs placebo (all p < .0001), with continued improvements to Week 52 in SINUS-52. Improvements occurred irrespective of comorbid asthma, NSAID-ERD, or prior surgery. A significantly greater proportion of dupilumab-treated patients exceeded clinically meaningful thresholds for SNOT-22 total score and EQ-VAS vs placebo (all subgroups p < .05 except patients without surgery at Week 24).

Conclusions: Dupilumab treatment led to significant clinically meaningful improvements across all aspects of disease-specific HRQoL, and general health status in patients with severe CRSwNP.

Keywords: CRSwNP; HRQoL; SNOT-22; comorbidities; dupilumab.

Conflict of interest statement

Stella E. Lee: Allakos, AstraZeneca, GSK, Knopp Biosciences, Sanofi – clinical trial funding; AstraZeneca, Genentech, GSK, Novartis, Regeneron Pharmaceuticals, Inc., Sanofi – advisory board member. Claire Hopkins: GSK, Optinose, Sanofi‐Genzyme, Smith and Nephew – advisory board member. Joaquim Mullol: ALK, AstraZeneca, Genentech, GSK, Menarini, Mitsubishi Tanabe Pharma, MSD, Mylan‐Meda Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, Inc., Sanofi, UCB, Uriach – clinical trial funding, advisory board member, or speaker fees; Mylan‐Meda Pharmaceuticals, Uriach – research grants. Jérôme Msihid, Leda P. Mannent, Yongtao Li, Chien‐Chia Chuang, Asif H. Khan: Sanofi – employees, may hold stock and/or stock options in the company. Isabelle Guillemin: Sanofi – employee at the time of manuscript development. Nikhil Amin, Shahid Siddiqui, Siddhesh Kamat: Regeneron Pharmaceuticals, Inc. – employees and shareholders.

© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Figures

FIGURE 1

Improvement in percentage change from baseline in SNOT‐22 total score (ITT and subgroups). (A) Pooled SINUS‐24 and SINUS‐52 Week 24. (B) SINUS‐52 Week 52. *p < .0001 least squares mean difference dupilumab vs placebo. ITT, intention to treat; NP, nasal polyp; NSAID‐ERD, non‐steroidal anti‐inflammatory drug‐exacerbated respiratory disease; SNOT‐22, 22‐item sino‐nasal outcome test

FIGURE 2

Spider plot of LS mean difference between dupilumab and placebo in change from baseline in SNOT‐22 domain scores at (A) Week 24, and (B) Week 52 (ITT and subgroups). LS mean difference vs placebo in domain scores (range, 0–5) are plotted. Each of the imputed complete data were analyzed by fitting an ANCOVA model with change from baseline at the corresponding visit as the response variable, and the corresponding baseline value, treatment group, asthma/NSAID‐ERD status, prior surgery history, regions, and, for the pooled analyses, study indicator as covariates. Data collected after treatment discontinuation were included. Data post‐SCS or NP surgery were set to missing and imputed by WOCF; other missing data were imputed by multiple imputation methods. *p < .01, **p < .001, ***p < .0001; †p < .05. ANCOVA, analysis of covariance; ITT, intention to treat; LS, least squares; NP, nasal polyp; NSAID‐ERD, non‐steroidal anti‐inflammatory drug‐exacerbated respiratory disease; SCS, systemic corticosteroids; SNOT‐22, 22‐item sino‐nasal outcome test; WOCF, worst observation carried forward

FIGURE 3

LS mean difference (95% CI) between dupilumab and placebo in change from baseline at Week 24 in SNOT‐22 items (ITT n = 438). Baseline pooled for placebo and dupilumab‐treated patients. “% 5 most important” represents the percentages of patients who considered each item as one of the 5 most important items affecting their health at baseline. The 5 most frequently reported are highlighted in orange and underlined (orange numbers signify order of importance). CI, confidence interval; ITT, intention to treat; LS, least squares; PBO, placebo; SD, standard deviation; SNOT‐22, 22‐item sino‐nasal outcome test

FIGURE 4

SNOT‐22 total score responder analysis at Weeks 24 and 52 (ITT and subgroups). Treatment responder was defined as an improvement of ≥8.9 from baseline at Weeks 24 and 52 (MCID for SNOT‐22). Odds ratio with 95% confidence interval. *p < .0001, ITT, intention to treat; MCID, minimum clinically important difference; NSAID‐ERD, non‐steroidal anti‐inflammatory drug‐exacerbated respiratory disease; NP, nasal polyp; PBO, placebo; q2w, every 2 weeks; SNOT‐22, 22‐item sino‐nasal outcome test