Early-onset Dupilumab Effects in CRSwNP

Summary

While it is known that Dupilumab has profound effects in patients with CRSwNP, these are often seen months later after treatment initiation; however, in practice, patients often endorse feeling significantly better within days of their first injection. No studies have investigated the molecular basis for such an acute change. This study proposes that specific cytokine changes in phenotype in addition to microbiome and oscillometry effects play a synergistic role in producing this effect.

Timeline

Start

2024-06-01

Primary completion

2026-06-01

Completion

2027-06-01

Publications

• Background Bachert C, Han JK, Desrosiers M, Hellings PW, Amin N, Lee SE, Mullol J, Greos LS, Bosso JV, Laidlaw TM, Cervin AU, Maspero JF, Hopkins C, Olze H, Canonica GW, Paggiaro P, Cho SH, Fokkens WJ, Fujieda S, Zhang M, Lu X, Fan C, Draikiwicz S, Kamat SA, Khan A, Pirozzi G, Patel N, Graham NMH, Ruddy M, Staudinger H, Weinreich D, Stahl N, Yancopoulos GD, Mannent LP. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019 Nov 2;394(10209):1638-1650. doi: 10.1016/S0140-6736(19)31881-1. Epub 2019 Sep 19.
• Background Canonica GW, Bourdin A, Peters AT, Desrosiers M, Bachert C, Weidinger S, Simpson EL, Daizadeh N, Chen Z, Kamat S, Khan AH, Chao J, Graham NMH, Laws E, Rossi AB, Ardeleanu M, Mannent LP, Amin N, Ortiz B, Deniz Y, Djandji M, Rowe PJ. Dupilumab Demonstrates Rapid Onset of Response Across Three Type 2 Inflammatory Diseases. J Allergy Clin Immunol Pract. 2022 Jun;10(6):1515-1526. doi: 10.1016/j.jaip.2022.02.026. Epub 2022 Mar 6.
• Background Fokkens W, Van Der Lans R, Reitsma S. Dupilumab for the treatment of chronic rhinosinusitis with nasal polyposis. Expert Opin Biol Ther. 2021 May;21(5):575-585. doi: 10.1080/14712598.2021.1901881. Epub 2021 Apr 1.
• Background Jonstam K, Swanson BN, Mannent LP, Cardell LO, Tian N, Wang Y, Zhang D, Fan C, Holtappels G, Hamilton JD, Grabher A, Graham NMH, Pirozzi G, Bachert C. Dupilumab reduces local type 2 pro-inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis. Allergy. 2019 Apr;74(4):743-752. doi: 10.1111/all.13685. Epub 2019 Jan 21.
• Background Mimmi S, Lombardo N, Maisano D, Piazzetta G, Pelaia C, Pelaia G, Greco M, Foti D, Dattilo V, Iaccino E. Spotlight on a Short-Time Treatment with the IL-4/IL-13 Receptor Blocker in Patients with CRSwNP: microRNAs Modulations and Preliminary Clinical Evidence. Genes (Basel). 2022 Dec 15;13(12):2366. doi: 10.3390/genes13122366.
• Background Beck L, Boguniewicz M, Hata T, Fuxench ZC, Simpson E, De Benedetto A, et al. Effect of Dupilumab on the Host-Microbe Interface in Atopic Dermatitis. Journal of Allergy and Clinical Immunology. 2022;149:AB150. https://doi.org/10.1016/j.jaci.2021.12.503
• Background Watelet JB, Gevaert P, Holtappels G, Van Cauwenberge P, Bachert C. Collection of nasal secretions for immunological analysis. Eur Arch Otorhinolaryngol. 2004 May;261(5):242-6. doi: 10.1007/s00405-003-0691-y. Epub 2003 Oct 9.

Drugs

Indications