Rapid and Continuing Improvements in Nasal Symptoms with Dupilumab in Patients with Severe CRSwNP

Abstract

Purpose

In the phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies in adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab significantly improved the co-primary endpoints of change from baseline to Week 24 in nasal polyp score (NPS) and nasal congestion/obstruction (NC) vs placebo on background intranasal corticosteroids (standard of care [SOC]). This post hoc analysis of SINUS-24/-52 investigated the direction and magnitude of within-patient change in these endpoints over time.

Methods

NPS (scale 0–8) was assessed at Weeks 4, 8, 16, 24, 40, and 52 in SINUS-52 and Weeks 8, 16, and 24 in SINUS-24. Daily patient-reported NC scores (0 [no symptoms]–3 [severe symptoms]) were averaged over 28 days. Within-patient changes from baseline were assessed through Week 24 in pooled SINUS-24/-52 (n = 438/286 dupilumab/SOC) and through Week 52 in SINUS-52 (n = 150/153).

Results

In SINUS-52, NPS improved in 70.0% of dupilumab-treated patients at Week 4 vs 31.8% with SOC (odds ratio [OR] 5.2 [95% confidence interval 3.1–8.8]) and 78.7% vs 28.2% at Week 52 (OR 10.6 [6.0–18.7]) (all p < 0.0001). NC improved in 73.3% of dupilumab-treated patients at Week 4 vs 46.7% with SOC (OR 3.2 [2.0–5.3]) and 86.9% vs 50.7% at Week 52 (OR 6.4 [3.5–11.5]) (all p < 0.0001). Clinically meaningful (≥1 point) improvements in NPS occurred in 55.7% and 72.3% of dupilumab-treated patients at Weeks 4 and 52, respectively, vs 16.9% and 16.2% with SOC. Clinically meaningful (≥1 point) improvements in NC occurred in 16.7% and 67.6% of dupilumab-treated patients at Weeks 4 and 52, respectively, vs 3.9% and 20.8% with SOC. At Week 52, NPS worsening from baseline was observed in 5.7% of dupilumab-treated patients vs 40.1% with SOC and NC worsening in 2.1% vs 20.8%, respectively.

Conclusion

Dupilumab provided rapid, continuing, and clinically relevant improvements over time in NPS and NC in most patients with severe CRSwNP in the SINUS studies.

Graphical Abstract

Keywords:

• chronic rhinosinusitis with nasal polyps
• dupilumab
• nasal polyp score
• nasal congestion

Abbreviations

CI, confidence interval; CRSwNP, chronic rhinosinusitis with nasal polyps; IL, interleukin; MFNS, mometasone furoate nasal spray; NC, nasal congestion/obstruction; NPS, nasal polyp score; OR, odds ratio; q2w, every 2 weeks; SC, subcutaneously; SOC, standard of care.

Ethics Approval and Informed Consent

The studies were conducted in accordance with the Declaration of Helsinki, approved by the local institutional review board or ethics committee at each study site (Supplementary Table 1), and all patients provided written informed consent.

Data Sharing Statement

Qualified researchers may request access to patient-level data and related study documents including clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient-level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi’s data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.vivli.org/

Acknowledgments

Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT02912468 (SINUS-24) and NCT02898454 (SINUS-52). The authors thank Nadia Daizadeh, PhD (formerly of Sanofi), for statistical analyses and Neil Anderson, PhD, of Adelphi Group, Macclesfield, UK, for medical writing/editorial assistance funded by Sanofi and Regeneron Pharmaceuticals, Inc. in accordance with Good Publications Practice.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all of these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

C.B. reports advisory board membership and/or speakers’ fees from ALK, AstraZeneca, GlaxoSmithKline, Mylan, Novartis, Sanofi, Stallergenes Greer. C.H. reports advisory board membership from AstraZeneca, GlaxoSmithKline, OptiNose, Sanofi, Smith & Nephew. M.S.B. reports consultancy from ALK, Amgen, AstraZeneca, Bellus, Covis, Merck, Pfizer, Regeneron, Sanofi, TerSera. Z.M.S. reports advisory board membership and/or consultancy from Lyra, Novartis, Olympus, OptiNose, and is medical director of Healthy Humming and Sinusonic. A.H.K., A.P., P.J.R., J.A.J.-N. are employees and may hold stock and/or stock options in Sanofi. S.N., Y.D., S.S. are employees and shareholders in Regeneron Pharmaceuticals, Inc. The authors report no other conflicts of interest in this work.

Additional information

Funding

This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.