The following article is a part of conference coverage from the American Academy of Allergy, Asthma & Immunology Virtual Annual Meeting, being held virtually from February 26 to March 1, 2021. The team at Pulmonology Advisor will be reporting on the latest news and research conducted by leading experts in the field. Check back for more from the AAAAI 2021 Virtual Annual Meeting.
Disease-specific health-related quality of life (HRQoL) and symptom burden were both improved in adolescent and adult patients with eosinophilic esophagitis with weekly dupilumab treatment, according to findings presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Virtual Annual Meeting, held February 26 to March 1, 2021.
Researchers evaluated the efficacy and safety of weekly dupilumab 300 mg vs placebo in part A of this 3-part phase 3 study (ClinicalTrials.gov Identifier: NCT03633617). The coprimary endpoints included obtaining peak esophageal intraepithelial eosinophil counts of 6 or less eosinophil/high powered field (eos/hpf) and change from baseline in Dysphagia Symptom Questionnaire scores at week 24; both of which were achieved and treatment was well tolerated.
In this analysis of secondary and exploratory endpoints, researchers included 81 patients (dupilumab=42; placebo=39) to assess dupilumab’s effect on disease-specific HRQoL and symptom burden. Disease-specific HRQoL was assessed via an 11-item EoE Impact Questionnaire (EoE-IQ; score range: 1-5), which measured emotional, social, productivity, and sleep-related effects of EoE.
Meanwhile, symptom burden was assessed by the 5-item EoE Symptom Questionnaire (EoE-SQ-Frequency; score range, 5-25), which measured the frequency of symptoms other than dysphagia or swallowing pain, including chest pain, stomach pain, heartburn, regurgitation, and vomiting. Higher EoE-IQ and EoE-SQ-Frequency scores indicated a greater effect on HRQoL and symptom burden. Some patients who reported dysphagia improvement on the Patient Global Impression of Change (PGIC) were also evaluated.
At baseline, the mean EoE-IQ scores were 2.0 and 2.4, and the mean EoE-SQ-Frequency scores were 10.1 and 11.5 in the dupilumab and placebo groups, respectively. The mean least-squares mean change from baseline difference for dupilumab vs placebo at week 24 was -0.4 for EoE-IQ (95% CI, -0.6 to -0.1; nominal P =.008) and -1.7 for EoE-SQ-Frequency (95% CI, -2.9 to -0.5; nominal P =.005).
A total of 47.2% patients treated with dupilumab reported their dysphagia as “very much better” compared with baseline on the PGIC vs 10.7% of patients who received placebo. In addition, 30.6% of patients treated with dupilumab vs 14.3% of patients who received placebo reported their dysphagia as “moderately better.”
Overall, weekly dupilumab treatment improved disease-specific HRQoL and reduced symptom burden in both adolescent and adult patients with EoE.
We interviewed lead investigator, Evan S. Dellon, MD, professor in the Department of Medicine, Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine in Chapel Hill, to learn more about what these findings could mean for patients with EoE.
Editor’s Note: This interview has been edited for length and clarity.
Given the HRQoL improvements seen with dupilumab, do you think we are 1 step closer to having an FDA-approved treatment for EoE?
Dr Dellon: These data are promising, along with the positive primary and key secondary endpoints that were presented at meetings last year, in showing the potential impact that dupilumab treatment could have for patients with EoE.
In part A of the phase 3 trial, more dupilumab-treated patients reported their dysphagia as “very much better” or “moderately better” compared with baseline on the PGIC (67% vs 18% placebo). Patients treated with dupilumab also reported improvement in multiple aspects of their quality of life including relationships, work or school and sleep, which is very encouraging for adults and adolescents living with this chronic, progressive disease. These data are very supportive to and consistent with the coprimary and key secondary endpoints.
Were there any adverse events related to treatment?
Dr Dellon: The trial demonstrated similar safety results to the known safety profile of dupilumab in its approved indications. Adverse events that were more commonly observed with dupilumab included injection site reactions and upper respiratory-tract infections. Overall, the treatment was well tolerated in the EoE population.
What are the next steps for research in this patient population?
Dr Dellon: The phase 3 trial of dupilumab for adult and adolescent patients with EoE is designed in 3 parts. Part A gave us important information on treating patients living with EoE with dupilumab over an initial 24 weeks. Other parts of the phase 3 trial are ongoing, with additional patients enrolling in part B to evaluate alternative dosing regimens.
When patients in parts A and B complete the double-blind period, they may then enter a 28-week extended active treatment period (part C) so that we can assess the longer term effects of the medication, including whether the initial response is sustained. This trial has already given us important information about the disease itself, showing that inhibiting interleukin-4 and interleukin-13 with dupilumab can significantly improve multiple disease measures, including molecular measures, and we hope to learn more from the other parts of the phase 3 study.
Dellon E, Rothenberg M, Hirano I, et al. Dupilumab improves health-related quality of life (HRQol) and reduces symptom burden in patients with eosinophilic esophagitis (EoE): results from part A of a randomized, placebo-controlled three-part phase 3 study. Presented at: the American Academy of Allergy, Asthma & Immunology (AAAAI) Virtual Annual Meeting; February 26-March 1, 2021. Abstract 290.
Visit Pulmonology Advisor’s conference section for complete coverage of AAAAI 2021 Virtual Annual Meeting.