Withdrawal of Dupilumab in Severe Asthma

Although dupilumab is a very effective drug in severe asthma, the optimal duration of this drug is unknown. However, this is a crucial question given the high cost of dupilumab and the lack of data regarding the long-term inhibition of type 2 pathway. Studies on biologic discontinuation are scarce in severe asthma. Studies with other biologics have shown that discontinuation of these drugs is feasible particularly for patients with low exacerbation rate before stopping treatment. In a study with pooled asthma biologics, 1247 (25.1%) stopped the biologic among the 4958 biologic users (including 19.8% of dupilumab users). Among all stoppers, 10.2% failed discontinuation of the asthma biologic in the 6 months after stopping, defined as an increase of 50% or more in exacerbations. Among patients who continued the biologic, 9.5% had an increase of 50% or more in exacerbations during a 6-month period, showing a similar failing rate. Such data for dupilumab discontinuation are lacking.

In this study, we plan to include patients with controlled asthma treated with dupilumab for at least 3 years who will be randomised to stopping dupilumab or dupilumab continuation with a follow-up of 24 months.

In total, 5 visits will occur for each patient: the inclusion/randomisation visit (baseline), 3 follow-up visits at month 6, month 12, month 24 as usually done in severe asthma, and a phone call visit at 18 months for exacerbations, treatments and adverse events collection. At each onsite visit, asthma medications, concomitant treatments, nasal polyp score (if applicable), number of exacerbations, Asthma Control Questionnaire, Severe Asthma Questionnaire, Treatment Burden Questionnaire and Sino-Nasal Outcome Test-22 scores, Forced expiratory volume in one second, Forced vital capacity, Fraction exhaled nitric oxide (if available), blood eosinophil, neutrophil and lymphocyte counts, adverse events, hospital admissions, and unscheduled medical visits will be recorded.

• Change in asthma control test score [Срок оценки: 6, 12 and 24 months]
• Resumption of dupilumab [Срок оценки: 6, 12 and 24 months]
• Adverse events or serious adverse events [Срок оценки: 24 months]
• Time to loss of control [Срок оценки: 24 months]
• First exacerbation [Срок оценки: 24 months]
• Number of exacerbations [Срок оценки: 24 months]
• Proportion of patients with ≥ 1 exacerbation(s) [Срок оценки: 6, 12 and 24 months]
• Change in quality of life [Срок оценки: 6, 12 and 24 months]
• Change in lung function [Срок оценки: 6, 12 and 24 months]
• Change in the daily dose of oral corticosteroids [Срок оценки: 6, 12 and 24 months]
• Change in the daily dose of inhaled corticosteroids [Срок оценки: 6, 12 and 24 months]
• Effect on nasal polyposis [Срок оценки: 6, 12 and 24 months]