Dupilumab Reduces OCS Dosage, Improves Lung Function for Asthma, CRSwNP

Dupilumab was associated with reductions in exacerbations and oral corticosteroid (OCS) dosage, as well as improved lung function, in patients with OCS-dependent asthma with and without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP). Findings were reported recently at the 2022 American Thoracic Society (ATS) International Conference.

More frequent exacerbations and airway obstructions have been observed in patients with severe asthma who do not respond to standard therapies, and these populations account for a majority of health care resource usage and significantly high costs.

Although long-term use of OCS is common in patients with severe asthma, researchers note that such usage is associated with negative side effects, such as infections, bone and muscle disease, atrial fibrillation, and hypertension.

“Comorbid severe CRSwNP increases the disease burden and may pose additional treatment challenges,” they added.

Use of biologic therapies in patients with OCS-dependent asthma have shown promise in reducing OCS dosage, OCS pharmacy claims, and asthma exacerbations leading to hospitalization.

Further efficacy has been demonstrated with the use of dupilumab, a fully human monoclonal antibody that blocks 2 key and central drivers of type 2 inflammation (interleukin [IL]-4 and IL-13), among patients with OCS-dependent asthma in the VENTURE study (NCT02528214). Outcomes were then sustained in this population in the open-label TRAVERSE study (NCT02134028).

Researchers conducted a post hoc analysis to further investigate long-term efficacy of dupilumab in patients with OCS-dependent asthma with and without CRSwNP.

“Patients with OCS-dependent asthma received add-on dupilumab 300 mg every 2 weeks (q2w) or placebo for 24 weeks during VENTURE (parent study), followed by add-on dupilumab 300 mg q2w for up to 96 weeks in TRAVERSE (dupilumab/dupilumab and placebo/dupilumab groups, respectively),” explained researchers.

Patients with comorbid CRSwNP (n = 61) and without (n = 126) who participated in VENTURE and TRAVERSE were evaluated on their unadjusted annualized severe asthma exacerbation rate (AER) during the 96-week treatment period, mean change from parent study baseline (PSBL) in pre-bronchodilator forced expiratory volume in 1 second (FEV₁), and mean OCS dose at weeks 0, 48, and 96.

Sustained improvement in clinical endpoints over the evaluated time period in TRAVERSE were shown in both patients with and without CRSwNP, with those initially placed on placebo demonstrating rapid improvement in lung function upon initiating dupilumab:

• AERs were comparable between dupilumab/dupilumab-treated patients with and without comorbid CRS/NP (0.353 vs 0.407)
• AERs were low in both placebo/dupilumab-treated patients with and without CRSwNP, but reduced further in the nonCRSwNP cohort (0.449 vs 0.211)
• dupilumab/dupilumab-treated patients with and without CRSwNP demonstrated improvements from PSBL in pre-bronchodilator FEV₁ during VENTURE, and these were maintained up to week 96 in TRAVERSE
• placebo/dupilumab-treated patients also showed rapid improvements from PSBL in pre-bronchodilator FEV₁ from week 2 onwards in TRAVERSE, and these were sustained up to week 96
• mean OCS doses were stable or decreased over the course of TRAVERSE in patients with and without CRSwNP of both the placebo/dupilumab-treated and dupilumab/dupilumab-treated groups
  

“In patients with OCS-dependent asthma who participated in VENTURE and TRAVERSE, dupilumab led to sustained reduction in exacerbations, improvements in lung function, and reductions in OCS dose,” concluded the study authors. “These clinical effects were observed both in patients with and without CRSwNP.”

Reference

Berger P, Menzies-Gow A, Peters AT, et al. Long-term efficacy of dupilumab in patients with oral corticosteroid-dependent asthma with and without comorbid chronic rhinosinusitis and/or nasal polyps. Presented at 2022 ATS International Conference. Abstract: C101.