Dupilumab Reduces Type 2 Inflammation, May Offer Clinical Benefits for Multiple Comorbid Diseases

Existing data has already proven the benefits of dupilumab, a fully human monoclonal antibody, for the treatment of atopic dermatitis (AD) but the latest research indicating its success reducing type 2 inflammation could offer expanded clinical benefits for multiple comorbid diseases, including asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and potentially eosinophilic esophagitis (not an official indication, trials are underway).¹ 

In a recent study, Boguniewicz and colleagues² sought to assess dupilumab’s impact on asthma and sinonasal conditions in adult patients with moderate to severe AD. Four randomized, double-blind, placebo-controlled trials were conducted—LIBERTY AD SOLO 1 (NCT02277743), SOLO 2 (NCT02755649), CHRONOS (NCT02260986), and CAFÉ (NCT02755649).

In each trial, participants either received a placebo or 300 mg of dupilumab every 2 weeks, or 300 mg of dupilumab weekly. Patients enrolled in the CHRONOS and CAFÉ trials also received concomitant topical corticosteroids.

This post hoc analysis assessed Asthma Control Questionnaire-5 (ACQ-5) scores in patients with asthma, Sino-Nasal Outcome Test-22 (SNOT-22) scores in patients with sinonasal conditions, and AD signs and symptoms in all patients.²

At baseline, 463 of 2444 included patients has asthmas (ACQ-5 ≥ 0.5 [19%]), 1171 had sinonasal conditions (48%); and 311 had both (13%).

According to the study’s findings, ACQ-5 scores at week 16 had improved by 0.27 (0.07) in the placebo group, 0.59 (0.08) in the 300 mg every 2 weeks group, and 0.56 (0.07) in the 300 mg weekly dose group for patients with asthma. SNOT-22 scores improved by 5.1 (0.8), 9.9 (0.9), and 10.8 (0.8), respectively, in patients with sinonasal conditions (P<.01 for all dupilumab vs placebo).

Boguniewicz and colleaguesobserved improvements in ACQ-5 and SNOT-22 in patients with both conditions and dupilumab significantly improved AD signs and symptoms among all subgroups.

“In this first analysis of patients with comorbid moderate to severe AD, asthma, and/or chronic sinonasal conditions, dupilumab improved all three diseases in a clinically meaningful and statistically significant manner (vs placebo), based on validated outcome measures,” concluded researchers.

Rabe and colleagues³ confirmed in a recent analysis that dupilumab was successful at reducing severe exacerbations and improving lung function in patients with uncontrolled, moderate-to-severe asthma with a type 2 phenotype defined by multiple parameters as per GINA guidelines. 

"In the United States and Europe, [dupilumab] is approved for patients 6 years and older with moderate-to-severe atopic dermatitis, patients 12 years and older with moderate-to-severe asthma, and in adults with uncontrolled CRSwNP," states Sanofi in a press release. "[Dupilumab] is also approved in one or more of these indications in more than 60 countries around the world and more than 200,000 patients have been treated globally."¹

Further research is being conducted to evaluate the potential of clinical remission in patients with moderate-to-severe diseases with type 2 inflammation. Additionally, clinical investigations are still underway for the use of dupilumab for eosinophilic esophagitis. 

References: 

1. New Dupixent® (dupilumab) data showcasing improvements across four type 2 inflammatory diseases to be presented at 2021 AAAAI Annual Meeting [press release published February 1, 2021]. Accessed July 14, 2021. https://www.news.sanofi.us/2021-02-01-New-Dupixent-R-dupilumab-data-showcasing-improvements-across-four-type-2-inflammatory-diseases-to-be-presented-at-2021-AAAAI-Annual-Meeting
2. Boguniewicz M, Beck LA, Sher L, et al. Dupilumab improves asthma and sinonasal outcomes in adults with moderate to severe atopic dermatitis. J Allergy Clin Immunol Pract. 2021 Mar;9(3):1212-1223.e6. doi:10.1016/j.jaip.2020.12.059.
3. Rabe K, Fitzgerald JM, Castro M, et al. Dupilumab efficacy in GINA-defined difficult-to-treat type 2 asthma patients in the LIBERTY ASTHMA QUEST study. 2021;147(2):AB59. J Allergy Clin Immunol Pract. doi:10.1016/j.jaci.2020.12.237