Withdrawal of Dupilumab in Severe Asthma (WIDUSA)

Toulouse University Hospital

Status and phase: Not yet enrolling; Phase 4

Conditions: Severe Asthma

Treatments: Drug: Stopping dupilumab

Study type: Interventional

Funder types: Other

Identifiers

NCT06818019

RC31/24/0325

2024-516789-13-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

Asthma management has been revolutionised by the development of biological therapies. Dupilumab is an anti-interleukin4 receptor marketed in 2020 for severe asthmatic patients with 2 exacerbations or more within the last 12 months. Although data showed that safety and efficacy of dupilumab are sustained when treatment is extended up to 3 years, no study has emerged regarding dupilumab discontinuation. This study aims to demonstrate the non-inferiority regarding strategy failure at 24 months of stopping dupilumab (intervention group) compared with its continuation (control group) in controlled asthma patients receiving this drug for at least 3 years.

Full description

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.

Enrollment: 205 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients ≥ 18 years old
• Treated with dupilumab for at least 36 months for severe asthma
• Well controlled asthma defined by an Asthma Control Questionnaire score ≥ 18 and 0 or 1 exacerbation within the year prior to the inclusion visit

Exclusion criteria

• Patients who refuse to discontinue dupilumab, for any reason
• Patients with Forced expiratory volume in one second ≤ 30% of predicted values
• Patients treated by an oral corticosteroid dose ≥ 10 mg/day (in prednisone equivalent)
• Patients who have to discontinue dupilumab for a reason other than controlled asthma, such as an adverse drug reaction, a planned or current pregnancy, or a planned switch to another biologic indicated in severe asthma
• Patients who have to continue dupilumab for the treatment of comorbidities apart from nasal polyposis
• Active smoking
• Pregnancy or breastfeeding

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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205 participants in 2 patient groups

Stopping dupilumab

Experimental group

Description:

The experimental strategy comprises stopping dupilumab with no dose-reducing or interval of time-increasing strategy from the day of inclusion/randomisation

Treatment:

Drug: Stopping dupilumab

Dupilumab continuation

No Intervention group

Description:

Dupilumab continuation at the same dose and same interval as baseline