Dupilumab reduces exacerbations and improves FEV1 in uncontrolled, moderate-to-severe asthma

A recent study found that in patients having uncontrolled, moderate-to-severe asthma Dupilumab showed sustained, long-term reduction in exacerbations and improved FEV1 regardless of the prior exacerbation history. 

Asthma affects millions of populations worldwide characterized by airway inflammation and acute exacerbations. Multiple drugs are used for the management of Asthma-like corticosteroids, beta2 agonists, and immunoglobulins. Recent data shows that Dupilumab which is a fully human monoclonal antibody blocks the shared receptor component for interleukin (IL)-4/IL-13, key and central drivers of type 2 inflammation in multiple diseases. Add-on dupilumab significantly reduced exacerbations and improved lung function in patients with uncontrolled, moderate-to-severe asthma in the phase 3 LIBERTY ASTHMA QUEST study. The long-term safety, tolerability, and efficacy of dupilumab in patients from the previous dupilumab asthma study were evaluated by the LIBERTY ASTHMA TRAVERSE open-label extension study. Dupilumab safety during TRAVERSE was consistent with the known safety profile. The present study assessed dupilumab efficacy in QUEST patients enrolled in TRAVERSE with blood eosinophils ≥ 150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥ 20 parts per billion (ppb) at parent study baseline, and ≥ 1, ≥ 2, or ≥ 3 exacerbations in the year before QUEST. 

Patients who received placebo or dupilumab in QUEST received dupilumab 300 mg every 2 weeks in TRAVERSE (placebo/dupilumab and dupilumab/dupilumab groups) for up to 48 or 96 weeks. Unadjusted annualized severe asthma exacerbation rate (AER) and mean change from the parent study baseline in forced expiratory volume in 1 second (FEV1) were assessed. 

RESULTS:

• Dupilumab vs placebo reduced AER in patients with ≥ 1 (0.458 vs 1.107), ≥ 2 (0.528 vs 1.483), or ≥ 3 (0.617 vs 1.915) prior exacerbations in QUEST.
• Patients in dupilumab/dupilumab vs. placebo/dupilumab groups with ≥ one (0.314 vs. 0.368), ≥ two (0.403 vs. 0.453), or ≥ three (0.445 vs. 0.545) previous exacerbations experienced further AER reductions in TRAVERSE from weeks 0–48.
• The same trend repeated in patients with ≥ 1 (0.229 vs 0.250), ≥ 2 (0.285 vs 0.235), or ≥ 3 (0.268 vs 0.186) prior exacerbations in TRAVERSE from weeks 48–96.
• In addition, mean change from parent study baseline in FEV1 (placebo/dupilumab vs dupilumab/dupilumab) was 0.34 vs 0.37, 0.36 vs 0.42, and 0.41 vs 0.47 at Week 2 of TRAVERSE in patients with ≥ 1, ≥ 2, or ≥ 3 prior exacerbations, respectively, and 0.37 vs 0.34, 0.44 vs 0.37, and 0.49 vs 0.45 at Week 96 of TRAVERSE. 

Thus, in patients with uncontrolled, moderate-to-severe asthma and blood eosinophils 150 cells/L or FeNO 20 ppb at parent study baseline, regardless of prior exacerbation history, showed sustained, long-term reductions in exacerbations and improved FEV1 with Dupilumab. 

Further reading: https://doi.org/10.1016/j.chest.2022.08.1603 

CORREN J, CASTRO M, F MASPERO J, et al. DUPILUMAB REDUCED EXACERBATIONS AND IMPROVED LUNG FUNCTIONS IN PATIENTS WITH MODERATE-TO-SEVERE ASTHMA AND PRIOR EXACERBATIONS: LIBERTY ASTHMA TRAVERSE STUDY. Chest. 2022;162(4): A1936-A1938. doi:10.1016/j.chest.2022.08.1603