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, 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

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.

© 2021 Corren et al.

Figures

Figure 1
Figure 1
Study information. (A) CONSORT diagram of patient disposition and (B) study design. *NAC occurred at Week 17, after 16 weeks of treatment. †SCIT dosing regimen is detailed in Supplementary Table 1 in this article’s Online Repository at https://www.dovepress.com/.
Figure 2
Figure 2
Kaplan–Meier estimate of time to withdrawal from study treatment. Numbers below each week represent the number of patients remaining in the treatment period (16 weeks ± 1-week treatment window). Patient numbers drop after Week 15 through Week 17 due to the ±1-week treatment window at 16 weeks of study treatment. At Week 18, all subjects progressed to the follow-up period; therefore, none remained in the treatment period.
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Figure 3
Figure 3
Exploratory endpoints and changes in biomarkers. (A) LS mean percent change from baseline in PNIF AUC (0–1 h) after challenge at Week 17, LOCF method (FAS). (B) Titration SPT, early-phase reaction LS mean (SE) of percent change from pre-treatment baseline in average wheal sizes (diameter) AUC over allergen concentrations in SPT after the challenge (early-phase reaction) at Week 17, LOCF method (FAS). (C) Intradermal skin challenge test, LPR LS mean (SE) of percent change from pre-treatment baseline in wheal sizes (diameter) induced by skin TG intradermal injection 6 hours after the challenge (LPR) at Week 17, LOCF method (FAS). (D) Median (Q3-Q1) percent change in sIgE from baseline, LOCF method (FAS). (E) Median (Q3-Q1) percent change in sIgG4 from baseline, LOCF method (FAS). (F) Median (Q3-Q1) percent change in sIgG from baseline, LOCF method (FAS). (G) Median (Q3-Q1) change in log-transformed sIgG4/sIgE ratio from baseline, LOCF method (FAS). (H) Median (Q3-Q1) change in log-transformed sIgG/sIgE ratio from baseline, LOCF method (FAS). (I) Median (Q3-Q1) percent change in TARC from baseline, LOCF method (FAS).

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