Safety and long-term efficacy of dupilumab in patients with moderate to severe asthma (TRAVERSE): an open label extension study



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Background

Clinical trials have shown the therapeutic benefits of dupilumab in patients with uncontrolled asthma for up to 1 year. This study aimed to assess the safety and long-term efficacy of dupilumab in patients with moderate to severe asthma, as data for prolonged treatment with dupilumab beyond one year is not available.

Methods

TRAVERSE was an open-label extension study in 362 hospitals and clinical centers in 27 countries that evaluated the safety and efficacy of dupilumab 300 mg every 2 weeks for up to 96 weeks in adults and adolescents (aged 12 at 84 years old) with severe or corticosteroid-dependent asthma by the oral route having completed a previous asthma study with dupilumab (phase 2A EXPEDITION, phase 2B DRI [P2b], phase 3 QUEST or VENTURE). The primary endpoint was the number and percentage of patients with treatment-related adverse events. Secondary endpoints included annualized exacerbation rate (AER) during treatment period and change from baseline in parental study in pre-bronchodilator FEV11, the five-item asthma monitoring questionnaire (ACQ-5), the asthma quality of life questionnaire (AQLQ), type 2 biomarkers (blood eosinophils and total serum IgE) and anti -medicines (ADA). Statistical analyzes were descriptive. We report the safety in all included patients and the efficacy in patients with oral non-corticosteroid-dependent asthma and in subgroups, including patients with type 2 inflammatory phenotype who received 148 weeks of treatment. . This study is registered with ClinicalTrials.gov, NCT02134028.

Results

Between August 5, 2014 and October 11, 2019, out of 2,302 patients assessed for eligibility, 2,282 adults and adolescents were included (median age 50, 62.1% female and 37.9% male). Safety during TRAVERSE was consistent with the known safety profile of dupilumab. The proportion of patients reporting treatment-related adverse events throughout the study period was similar to that seen in the parent studies and ranged from 76.3% to 94.7%. The most frequently reported treatment-related adverse events were nasopharyngitis (17.5–25.9%), injection site erythema (2.2–23.4%), and bronchitis (9.3– 19.0%). Serious asthma exacerbations (0.5 to 3.6%) and pneumonia (0.7 to 2.7%) were the most frequently reported serious adverse events. There were four treatment-related adverse events leading to death. Efficacy during TRAVERSE was also consistent with the results of parental studies. In patients who were not dependent on oral corticosteroids, AER remained low (0.277-0.327) across the parental study and treatment groups, prebronchodilator FEV11 improvements were maintained until the end of treatment at week 96 (mean changes from baseline in the parental study ranged from 0.22 L [SD 0·44] at 0.33 L [0·44] across the parental study and treatment groups), and improvements in ACQ-5 and AQLQ scores were maintained until the last time point assessed at week 48. Rapid improvements were seen in the Pre-bronchodilator FEV11 and sustained improvements were seen in all outcome measures for patients who received dupilumab and previously received placebo in the parental studies; further improvements in AER, asthma control and health-related quality of life were seen in patients who continued to receive dupilumab. Blood eosinophils and total serum IgE gradually decreased. ADA status had no effect on safety or efficacy. In the subgroup of patients with a type 2 inflammatory phenotype followed for 148 weeks, the AER gradually diminished and the initial improvements in lung function were maintained for 148 weeks.

Interpretation

Data show that the safety and efficacy of dupilumab in adult and adolescent patients with moderate to severe asthma are maintained when treatment is extended for up to 148 weeks. These results therefore support the long-term use of dupilumab in this patient population.

Funding

Sanofi and Regeneron Pharmaceuticals.

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