Asthma exacerbations drop with medium-dose ICS to biologic switch

Efficacy of Direct Escalation to Biologic Therapy vs High-Dose Inhaled Corticosteroids in Asthma Management

Importance: Current Global Initiative for Asthma (GINA) guidelines generally recommend escalating patients from medium-dose inhaled corticosteroids (ICS) to high-dose ICS before initiating biologic therapies. However, recent real-world data suggests that bypassing high-dose ICS and escalating directly to a biologic may yield superior clinical outcomes, particularly in reducing exacerbations and oral corticosteroid dependence.                      

Objective: To evaluate the impact of escalating from medium-dose ICS to either high-dose ICS or biologic therapy on the rates of asthma exacerbations and systemic corticosteroid prescriptions.

Design, Setting, and Participants: This retrospective cohort study utilized administrative claims data from the Optum Clinformatics Data Mart between 2016 and 2023. The study, presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in Philadelphia, included patients aged 12 years and older with asthma who escalated their treatment from a medium-dose ICS.

The cohort was divided into patients escalating to a high-dose ICS (n = 11,198) and those escalating directly to a biologic agent (n = 984). The biologic group was further stratified into those initiating dupilumab (n = 350), omalizumab (n = 258), and anti-IL-5 biologics (n = 376).

Table 1. Baseline Clinical and Demographic Characteristics

 Main Outcomes and Results: The primary endpoints evaluated were the number of exacerbation episodes per person per year and systemic corticosteroid prescription fills per person per year, comparing the 12 months prior to the treatment change (baseline) to the 12 months following the change (follow-up).

As noted by Joe Yang, PhD, director of health economics and outcomes research at Regeneron Pharmaceuticals: “Currently, the GINA guideline recommends escalating medium-dose ICS to high-dose ICS, but we’re showing that sometimes skipping high-dose ICS and going straight to biologics could be beneficial for patients. If a patient has a high burden of type 2 comorbidities or severe asthma, the data suggest doctors could consider escalating straight to biologics.”

Patients escalating to biologics experienced profound, statistically significant reductions in exacerbation episodes compared to the moderate reduction seen in the high-dose ICS cohort.

Table 2. Exacerbation Episodes per Person per Year (Baseline vs. 12-Month Follow-Up)

Similarly, biologic initiation correlated with drastic reductions in systemic corticosteroid prescription fills. While all biologic cohorts saw significant decreases, the high-dose ICS group saw a negligible and non-significant reduction.

Table 3. Systemic Corticosteroid Fills per Person per Year (Baseline vs. 12-Month Follow-Up)

An alternative analysis utilizing a different index date (the first date when a cumulative 56 days of supply was reached within the initial 90 days) corroborated the primary findings, showing even greater reductions in exacerbations (Dupilumab: 67%; Anti-IL-5: 52%; Omalizumab: 40%; High-Dose ICS: 24%) and corticosteroid fills.

Conclusions and Relevance:

Direct escalation from medium-dose ICS to biologic therapy is associated with significantly greater reductions in asthma exacerbations and systemic corticosteroid reliance compared to the traditional step-up to high-dose ICS.

However, Dr. Yang cautioned against direct cross-biologic efficacy comparisons based solely on these raw data due to baseline variances in disease severity. “In the different biologic categories, there is a different size of reduction,” Yang stated. “Even though we see that dupilumab seems to have the largest size of reduction among the biologics, we cannot draw the conclusion that it is necessarily better than the others because the baseline characteristics are not consistent. We need to do some adjustments to the analysis to make it more comparable before we can reach a conclusion, so that could be a next step.”