Dupilumab (DPL) reduced the oral corticosteroid (OCS) dose needed by individuals with OCS-dependent severe asthma, regardless of their baseline OCS dosage, and maintained and improved their asthma outcomes, according to research presented at the American College of Chest Physicians (CHEST) 2022 Annual Meeting, held October 16 to 19, 2022, in Nashville, Tennessee.
Researchers conducted a post hoc analysis to evaluate DPL efficacy in patients with OCS-dependent severe asthma with differing baseline levels of asthma gauged by their OCS dose. The post hoc analysis used data from participants in the VENTURE trial (ClinicalTrials.gov Identifier: NCT02528214) who subsequently enrolled in TRAVERSE (ClinicalTrials.gov Identifier: NCT02134028).
The post hoc analysis included 187 patients with OCS-dependent asthma who received add-on DPL 300 mg or placebo every 2 weeks for 24 weeks during VENTURE and subsequently received add-on DPL 300 mg every 2 weeks for up to 96 weeks in TRAVERSE. Patients’ baseline OCS dosage in VENTURE (≤10 or >10mg/day) was used to stratify patients into cohorts for the post hoc analysis. Primary endpoints of the post hoc analysis were annualized severe asthma exacerbation rate during VENTURE and TRAVERSE; OCS dose percentage reduction from VENTURE baseline to TRAVERSE weeks 0 and 48; and pre-bronchodilator forced expiratory volume in 1 second (BD FEV1) at TRAVERSE weeks 0 and 48.
The 187 patients were stratified in 4 groups: 2 groups of patients who had used 10 or more mg/day OCS at baseline of VENTURE and had received placebo (group 1; n=61) and DPL (group 2; n=60) during VENTURE; and 2 groups of those who has used more than 10 mg/day OCS at baseline and had received placebo (group 3; n=36) and DPL (group 4; n=30) during VENTURE. All participants had gone on to receive add-on DPL 300 mg every 2 weeks during TRAVERSE. Baseline OCS dosages during VENTURE, in mg/day, for groups 1, 2, 3, and 4 were 8.1, 7.4, 17.6, and 18.1, respectively.
The investigators found that the reductions in daily OCS use seen in patients receiving DPL during VENTURE (groups 2 and 4) continued during TRAVERSE (-82.8% for group 2 and -74.7% for group 4 at TRAVERSE week 48). Participants who had received placebo in VENTURE and DPL during TRAVERSE (groups 1 and 3) also reduced their use of OCS by TRAVERSE week 48 (-49.6% for group 1 and -66.5% for group 3).
Moreover, by the end of TRAVERSE, investigators found that the proportion of participants using less than 5 mg/day of OCS by TRAVERSE week 48 in groups 1, 2, 3, and 4 were 45.1%, 87.2%, 42.3%, and 50.0%, respectively. Even with this reduced use of OCS, exacerbations declined during TRAVERSE, with 66.7% to 83.3% of patients experiencing no exacerbations. The researchers also found that VENTURE baseline pre-BD FEV1 (range, 1.50-1.63 L) improved by TRAVERSE week 48 (range, 1.8-1.9 L).
“DPL reduced OCS dose and improved and maintained clinical efficacy outcomes of asthma, regardless of baseline OCS starting dose,” the researchers concluded. “DPL demonstrated persistently high reduction in OCS use without a tapering schema of reduction in TRAVERSE.”
Gurnell M, Domingo CC, Rabe KF, et al. Dupilumab treatment leads to sustained reductions in oral corticosteroid use in patients with oral corticosteroid-dependent severe asthma. Presented at: CHEST 2022 Annual Meeting; October 16-19, 2022; Nashville, TN.