Short-Term Subcutaneous Allergy Immunotherapy and Dupilumab are Well Tolerated in Allergic Rhinitis: A Randomized Trial

Jonathan Corren; Sarbjit S Saini; Remi Gagnon; Mark H Moss; Gordon Sussman; Joshua Jacobs; Elizabeth Laws; Elinore S Chung; Tatiana Constant; Yiping Sun; Jennifer Maloney; Jennifer D Hamilton; Marcella Ruddy; Claire Q Wang; Meagan P O'Brien

doi:10.2147/JAA.S318892

Short-Term Subcutaneous Allergy Immunotherapy and Dupilumab are Well Tolerated in Allergic Rhinitis: A Randomized Trial

J Asthma Allergy. 2021 Aug 16:14:1045-1063. doi: 10.2147/JAA.S318892. eCollection 2021.

Authors

Affiliations

¹ Departments of Medicine and Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
² Department of Internal Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA.
³ Clinique Spécialisée en Allergie de la Capitale, Québec, QC, Canada.
⁴ Departments of Medicine and Pediatrics, Division of Allergy, Pulmonary and Critical Care, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁵ Department of Medicine, University of Toronto, Toronto, ON, Canada.
⁶ Allergy and Asthma Clinical Research, Inc, Walnut Creek, CA, USA.
⁷ Sanofi, Bridgewater, NJ, USA.
⁸ Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.

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.

Associated data

ClinicalTrials.gov/NCT03558997

Grants and funding

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.