@article{3bf78cce81d3461c90b7d00e6a6161f5,
title = "Short-term subcutaneous allergy immunotherapy and dupilumab are well tolerated in allergic rhinitis: A randomized trial",
abstract = "Background: Subcutaneous immunotherapy (SCIT) has been proven as an effective therapy against some allergens for seasonal allergic rhinitis (SAR) patients unresponsive to intranasal corticosteroids and/or antihistamines but carries risk of systemic allergic reactions. Dupilumab blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation in multiple diseases. Objective: To evaluate the efficacy and safety of SCIT+dupilumab vs SCIT alone. Methods: This phase 2a, multicenter, double-blind, placebo-controlled parallel-group study conducted in 103 adults with grass pollen-induced SAR (NCT03558997) randomized patients 1:1:1:1 to SCIT, dupilumab (300 mg every 2 weeks), SCIT+dupilumab, or placebo. SCIT was administered using an 8-week cluster protocol followed by 8 weeks of maintenance injections. Primary endpoint was change from pre-treatment baseline in area under the curve (AUC) in total nasal symptom score (TNSS) 0–1 h following nasal allergen challenge (NAC) with timothy grass extract at Week 17. Results: Although 16 weeks of treatment with SCIT+dupilumab did not significantly improve TNSS AUC (0–1 h) following NAC at Week 17 vs SCIT (least squares mean −56.76% vs −52.03%), a higher proportion of SCIT+dupilumab-treated patients (61.5%) achieved SCIT maintenance dose vs SCIT (46.2%). A lower proportion of SCIT+dupilumab-treated patients (7.7%) required epinephrine rescue treatment vs SCIT (19.2%). There were significantly fewer withdrawals in the SCIT+dupilumab group than in the SCIT group (n = 2 [7.7%] vs n = 8 [30.8%]; P = 0.0216); the majority of SCIT group withdrawals were due to SCIT-related intolerability, compared with no discontinuations from the SCIT+dupilumab group. Conclusion: In SAR patients, 16 weeks of SCIT+dupilumab may improve SCIT tolerability but did not incrementally reduce post-allergen challenge nasal symptoms compared with SCIT alone. Clinical Study Number: NCT03558997.",
keywords = "Dupilumab, Nasal allergen responses, Seasonal allergic rhinitis, Subcutaneous immunotherapy",
author = "Jonathan Corren and Saini, {Sarbjit S.} and Remi Gagnon and Moss, {Mark H.} and Gordon Sussman and Joshua Jacobs and Elizabeth Laws and Chung, {Elinore S.} and Tatiana Constant and Yiping Sun and Jennifer Maloney and Hamilton, {Jennifer D.} and Marcella Ruddy and Wang, {Claire Q.} and O{\textquoteright}brien, {Meagan P.}",
note = "Funding Information: JC reports research grants from and consultancy for AstraZeneca, Genentech, Novartis, Regeneron Pharmaceuticals, Inc., and Sanofi; and speaker fees from AstraZeneca, Genentech, Novartis, Optinose, and Teva. SSS reports research grants from NIH, Novartis, and Regeneron Pharmaceuticals, Inc.; and consultancy for Allakos, Gbio, Genentech, GI Innovations, MedImmune, Novartis, Ono Pharma, and Regeneron Pharmaceuticals, Inc. RG reports research grants from ALK, AstraZeneca, BioCryst, DBV Technologies, Genentech, GreenCross, Novartis, Regeneron Pharmaceuticals, Inc., Sanofi, and Shire; consultancy for ALK, AstraZeneca, Pfizer, and Sanofi; and speaker fees from Novartis. MHM reports advisory board membership for Regeneron Pharmaceuticals, Inc. GS reports personal fees from Pfizer, Anaphylaxis Canada, Allergy, Asthma, and Immunology Society of Ontario, and Canadian Hereditary Angioedema Network; research grants from Aimmune, DBV Technologies, Genentech, AstraZeneca, CSL Behring, Merck, Leo Pharma Inc, Stallergens, ALK, Pfizer, Novartis, Regeneron Pharmaceuticals, Inc., and Sanofi; and consultancy from Amgen, Genentech, Novartis, Nuvo Pharmaceuticals, and Sanofi. JJ reports contracted research, consultant fees, and speaker fees from AstraZeneca, Allakos, Biocryst, CSL Behring, Genentech, Novartis, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Takeda, and Teva. EL is an employee and may hold stock and/or stock options in Sanofi Genzyme. ESC, TC, YS, JM, JDH, MR, CQW, and MPO are employees and shareholders of Regeneron Pharmaceuticals, Inc and have a pending patent application on this study. The patent application number is PCT/US2020/044958. It is in the name of Regeneron Pharmaceuticals, Inc. and Sanofi Biotechnology. The authors report no other conflicts of interest in this work. Funding Information: This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing and editorial assistance provided by Julian J. Freen-van Heeren, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Funding Information: This work was supported by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifier: NCT03558997. Medical writing/editorial assistance was provided by Julian J. Freen-van Heeren, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Publisher Copyright: {\textcopyright} 2021 Corren et al. This work is published and licensed by Dove Medical Press Limited.",
year = "2021",
doi = "10.2147/JAA.S318892",
language = "English (US)",
volume = "14",
pages = "1045--1063",
journal = "Journal of Asthma and Allergy",
issn = "1178-6965",
publisher = "Dove Medical Press Ltd.",
}