The AIM4 Next Step study: Comparing inhaled corticosteroid dose escalation to dupilumab in patients with uncontrolled asthma and type 2 inflammation.

BACKGROUND

The Global Initiative for Asthma recommends patients with asthma uncontrolled on medium-dose inhaled corticosteroid (ICS) plus long-acting β2-agonist (LABA) therapy to first escalate their ICS dose before considering add-on biologic therapy despite acknowledging that high-dose ICS provides little additional benefit for most patients and carries an increased risk of adverse effects. Dupilumab, an IL-4Rα antagonist that inhibits signaling of IL-4 and IL-13, has demonstrated efficacy in patients with uncontrolled moderate-to-severe asthma and type 2 inflammation.

OBJECTIVE

The AIM4: Next Step study will evaluate whether earlier intervention with dupilumab provides clinical benefit compared to escalation to high-dose ICS/LABA.

METHODS

AIM4: Next Step (NCT06572228) is a randomized, double-blind, active-controlled study enrolling approximately 250 adolescents and adults with type 2 inflammatory asthma uncontrolled with medium-dose ICS/LABA treatment. Patients will be randomized 1:1 to receive dupilumab 300 mg every 2 weeks plus medium-dose ICS/LABA or placebo plus high-dose ICS/LABA.

RESULTS

The primary end point is the annualized rate of severe asthma exacerbations over 52 weeks. Key secondary end points include change from baseline in prebronchodilator forced expiratory volume in 1 second at week 12, annualized systemic corticosteroid exposure for exacerbations, and asthma control at week 12 based on 5-item Asthma Control Questionnaire.

CONCLUSION

AIM4: Next Step is the first study designed to address an important gap in asthma management by directly comparing ICS dose escalation versus early biologic intervention with dupilumab in patients with uncontrolled type 2 inflammatory asthma. Findings may inform future treatment strategies for patients whose asthma remains uncontrolled despite ICS/LABA.