Effect of Dupilumab on Lung Function Parameters in Oral Corticosteroid-Dependent Patients With Asthma Enrolled in LIBERTY ASTHMA TRAVERSE

TOPIC: Obstructive Lung Diseases TYPE: Original Investigations PURPOSE: Chronic oral corticosteroid (OCS) treatment improves asthma control but is associated with severe side effects. Dupilumab (DPL), a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4/-13, key and central drivers of type 2 inflammation in multiple diseases. In the phase 3 VENTURE study (NCT02528214), add-on DPL 300 mg every two weeks (q2w) vs placebo (PBO) significantly reduced daily OCS dose and severe asthma exacerbation rate, improving pre-bronchodilator FEV1 in patients with OCS-dependent, severe asthma. TRAVERSE (NCT02134028), a single-arm, open-label, extension study, evaluated long-term safety, tolerability, and efficacy of add-on DPL in patients who had completed a DPL study. Overall, 2,182 (96%) patients completed TRAVERSE to Week (Wk) 48 and 1,240 (54%) to Wk 96, with a cumulative study duration of 3,507 patient-years. This post hoc analysis assessed long-term improvements in lung function in patients with OCS-dependent asthma from VENTURE who enrolled in TRAVERSE. METHODS: Mean change from baseline (BL) of the VENTURE study in lung function was assessed at Wk 0, 2, and 48 in patients treated with DPL or PBO for 24 Wks in VENTURE who then enrolled in TRAVERSE and received DPL 300 mg q2w for up to 96 Wks. Treatment duration was amended from 96 to 48 Wks for some patients. RESULTS: Mean reductions in OCS dose from parent study BL (PSBL) at Wk 0 (end of VENTURE/start of TRAVERSE) were 74.2% and 45.8% in the DPL-DPL (n=90) and PBO-DPL (n=97) groups. In DPL-DPL–treated patients, FEV1 improvements in VENTURE were sustained in TRAVERSE (PSBL [SD]: 1.53 [0.50] L; mean change [SD] from PSBL: 0.29 [0.46], 0.28 [0.48], and 0.33 [0.53] L at Wk 0, 2, and 48). Improvements persisted for FEF25–75% (PSBL [SD]: 0.87 [0.49] L/s; mean change [SD] from PSBL: 0.23 [0.49], 0.23 [0.57], and 0.29 [0.66] L/s at Wk 0, 2, and 48) and FVC (PSBL [SD]: 2.59 [0.73] L; mean change [SD] from PSBL: 0.34 [0.58], 0.32 [0.48], and 0.38 [0.56]L at Wk 0, 2, and 48). In PBO-DPL–treated patients starting DPL at Wk 0, rapid improvement in lung function occurred by Wk 2 and continued through Wk 48 in FEV1 (PSBL [SD]: 1.62 [0.62] L; mean change [SD] from PSBL: −0.01 [0.50], 0.25 [0.49], and 0.31 [0.50] L at Wk 0, 2, and 48), FEF25-75% (PSBL [SD]: 0.93 [0.57] L/s; mean change [SD] from PSBL: 0.04 [0.52], 0.26 [0.56], and 0.34 [0.56] L/s at Wk 0, 2, and 48), and forced vital capacity (FVC) (PSBL [SD]: 2.74 [0.80] L; mean change [SD] from PSBL: −0.04 [0.52], 0.23 [0.50], and 0.29 [0.56] L at Wk 0, 2, and 48). There were minimal changes in the FEV1/FVC ratio, consistent with balanced improvement in FEV1 and FVC. CONCLUSIONS: Dupilumab demonstrated sustained lung function improvements in the DPL-DPL–treated group, and rapid, sustained improvements in the PBO-DPL group. CLINICAL IMPLICATIONS: Dupilumab shows long-term lung function improvements in OCS-dependent severe asthma patients who enrolled in TRAVERSE. 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