Long-Term Safety of Dupilumab in Patients With Moderate-to-Severe Asthma: TRAVERSE Continuation Study.

BACKGROUND: Previous clinical trials have demonstrated dupilumab efficacy and safety in adults and adolescents with moderate to severe asthma for up to 3 years. OBJECTIVE: The TRAVERSE continuation study (NCT03620747), a single-arm, open-label study, assessed safety and tolerability of dupilumab 300 mg every 2 weeks up to an additional 144 weeks (∼3 years) in patients with moderate to severe asthma who previously completed TRAVERSE (NCT02134028). METHODS: Primary end points were incidence and event rates per 100 patient-years of treatment-emergent adverse events (TEAEs). Secondary end points included adverse events (AEs) of special interest, serious AEs, and AEs leading to study discontinuation. RESULTS: A total of 393 patients participated in the TRAVERSE continuation study (cumulative dupilumab exposure, 431.7 patient-years; median treatment duration, 309 days). A total of 29 patients (7.4%) received more than 958 days of treatment. A total of 214 (54.5%) patients reported at least 1 TEAE (event rate: 171.4); 37 (9.4%) experienced at least 1 treatment-related TEAE, none of which were considered severe; 2 patients reported 6 TEAEs of moderate intensity. A total of 22 (5.6%) patients reported serious AEs (event rate: 6.9). AEs of special interest were reported in 24 patients (6.1%; event rate: 6.0). Five (1.3%) deaths occurred (event rate: 1.2) following serious AEs of coronavirus disease 2019 (COVID-19)-related pneumonia (3 patients), pancreatitis (1 patient), and pulmonary embolism (1 patient). None of the TEAEs leading to death were considered treatment-related. CONCLUSIONS: Dupilumab treatment was well tolerated for up to an additional 3 years. Safety findings were consistent with the known safety profile of dupilumab. These findings further support the long-term use of dupilumab in patients with moderate to severe asthma.

Assessment of long-term safety and efficacy of dupilumab in children with asthma (LIBERTY ASTHMA EXCURSION): an open-label extension study.

BACKGROUND: Dupilumab efficacy and safety in children aged 6-11 years with uncontrolled, moderate-to-severe asthma were shown in the VOYAGE study-a 52-week, multinational, multicentre, phase 3 randomised, double-blind, placebo-controlled trial. We aimed to evaluate the long-term safety and efficacy of dupilumab in children with moderate-to-severe asthma who previously participated in the VOYAGE study. METHODS: 365 of 408 children with moderate-to-severe asthma from VOYAGE enrolled in EXCURSION, a 52 week, open-label extension study conducted at 70 centres across 17 countries. 240 children continued with add-on dupilumab (dosed according to bodyweight: 100 mg for those weighing ≤30 kg and 200 mg for those weighing more than 30 kg at EXCURSION baseline) once every 2 weeks administered by subcutaneous injection (dupilumab/dupilumab group) and 125 children on placebo during VOYAGE initiated dupilumab (100 or 200 mg, according to bodyweight), once every 2 weeks administered by subcutaneous injection (placebo/dupilumab group). Following a protocol amendment, for a subset of children weighing 30 kg or less, the dose was changed to 300 mg once every 4 weeks. The primary endpoint for the open-label extension study was the number and proportion of patients with any treatment-emergent adverse event (TEAE) during the 52-week study period in the overall population (defined as children aged 6-11 years old with moderate-to-severe asthma who previously completed VOYAGE). Statistical analyses were descriptive. This study is registered with ClinicalTrials.gov (NCT03560466; EXCURSION). FINDINGS: Children who completed VOYAGE were eligible to enrol in EXCURSION between June 21, 2018 and Aug 18, 2020. During EXCURSION, the safety profile and proportion of patients reporting TEAEs were consistent with those observed during the parent study (VOYAGE). In the overall population, 232 (63·6%) of 365 patients experienced at least one TEAE (dupilumab/dupilumab: 147 [61·3%]; placebo/dupilumab: 85 [68·0%]). The most frequently reported TEAEs were nasopharyngitis, pharyngitis, and upper respiratory tract infections. INTERPRETATION: In EXCURSION, long-term treatment with dupilumab was well tolerated with an acceptable safety profile. FUNDING: Sanofi and Regeneron Pharmaceuticals.