INTERLEUKIN-4/13 VERSUS INTERLEUKIN-5 BIOLOGICS AND RISK OF ASTHMA EXACERBATIONS: A REAL-WORLD COHORT STUDY
Author(s)
Chanakan Jenjai, PharmD, MS1, Shao-Hsuan Chang, BS, MS1, James G. Krings, MD, MSc2, Mario Castro, MD3, Kathryn Blake, PharmD4, Haesuk Park, PhD1;
1University of Florida College of Pharmacy, Pharmaceutical Outcomes and Policy, Gainesville, FL, USA, 2Washington University in St. Louis School of Medicine, St. Louis, MO, USA, 3University of Kansas, KU Medical Center, Kansas City, KS, USA, 4Nemours Children’s Health, Center for Pharmacogenomics and Translational Research, Jacksonville, FL, USA
1University of Florida College of Pharmacy, Pharmaceutical Outcomes and Policy, Gainesville, FL, USA, 2Washington University in St. Louis School of Medicine, St. Louis, MO, USA, 3University of Kansas, KU Medical Center, Kansas City, KS, USA, 4Nemours Children’s Health, Center for Pharmacogenomics and Translational Research, Jacksonville, FL, USA
OBJECTIVES: Biologics targeting type 2 inflammation via the interleukin-4/interleukin-13 (IL-4/IL-13) pathway or the interleukin-5 (IL-5) pathway are widely used for severe asthma, but comparative real-world effectiveness remains limited. We compared asthma exacerbation risk among patients initiating IL-4/IL-13 versus IL-5 biologics.
METHODS: We conducted a retrospective cohort study using the Merative MarketScan Commercial and Medicare Supplemental databases (2016-2023). Patients aged 6 years and older with uncontrolled asthma who initiated an IL-4/IL-13 pathway biologic (dupilumab) or an IL-5 pathway biologic (benralizumab or mepolizumab) were included. The primary outcome was time to first asthma exacerbation, defined as an emergency department (ED) visit or hospitalization with a primary or secondary asthma exacerbation diagnosis. The index date was the first biologic prescription. Follow-up continued until first exacerbation, treatment discontinuation, insurance disenrollment, or study end. After 1:1 propensity score matching, Cox proportional hazards regression models compared exacerbation risk. Sensitivity analyses were restricted to asthma exacerbations identified using a primary diagnosis only.
RESULTS: After matching, 7,590 patients were included in each group with well-balanced baseline characteristics (IL-4/IL-13: mean age 49.9 [SD 15.7] years, 61.7% female; IL-5: mean age 51.4 [SD 14.7] years, 63.6% female). Crude exacerbation rates were 16.8 and 33.5 per 100 person-years in the IL-4/IL-13 and IL-5 groups, respectively, over a mean follow-up of 474 and 452 days, respectively; > 95% of events were ED visits. In Cox regression analyses, IL-4/IL-13 initiation was associated with significantly lower exacerbation risk compared to IL-5 (adjusted hazard ratio [aHR] 0.49; 95% CI 0.47-0.53). Results were consistent in sensitivity analyses limited to primary diagnoses (aHR 0.51; 95% CI 0.48-0.54).
CONCLUSIONS: In this real-world matched cohort, IL-4/IL-13 biologic therapy was associated with lower risk of asthma exacerbations compared to IL-5 biologics in patients with severe asthma.
METHODS: We conducted a retrospective cohort study using the Merative MarketScan Commercial and Medicare Supplemental databases (2016-2023). Patients aged 6 years and older with uncontrolled asthma who initiated an IL-4/IL-13 pathway biologic (dupilumab) or an IL-5 pathway biologic (benralizumab or mepolizumab) were included. The primary outcome was time to first asthma exacerbation, defined as an emergency department (ED) visit or hospitalization with a primary or secondary asthma exacerbation diagnosis. The index date was the first biologic prescription. Follow-up continued until first exacerbation, treatment discontinuation, insurance disenrollment, or study end. After 1:1 propensity score matching, Cox proportional hazards regression models compared exacerbation risk. Sensitivity analyses were restricted to asthma exacerbations identified using a primary diagnosis only.
RESULTS: After matching, 7,590 patients were included in each group with well-balanced baseline characteristics (IL-4/IL-13: mean age 49.9 [SD 15.7] years, 61.7% female; IL-5: mean age 51.4 [SD 14.7] years, 63.6% female). Crude exacerbation rates were 16.8 and 33.5 per 100 person-years in the IL-4/IL-13 and IL-5 groups, respectively, over a mean follow-up of 474 and 452 days, respectively; > 95% of events were ED visits. In Cox regression analyses, IL-4/IL-13 initiation was associated with significantly lower exacerbation risk compared to IL-5 (adjusted hazard ratio [aHR] 0.49; 95% CI 0.47-0.53). Results were consistent in sensitivity analyses limited to primary diagnoses (aHR 0.51; 95% CI 0.48-0.54).
CONCLUSIONS: In this real-world matched cohort, IL-4/IL-13 biologic therapy was associated with lower risk of asthma exacerbations compared to IL-5 biologics in patients with severe asthma.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO33
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment, Comparative Effectiveness or Efficacy
Disease
SDC: Respiratory-Related Disorders (Allergy, Asthma, Smoking, Other Respiratory), STA: Biologics & Biosimilars