MADULO

The MADULO project is a Hospital Clinical Research Program (PHRC) funded by the Direction Générale de l'Offre de Soins (DGOS).

The project is promoted and coordinated by the Nantes University Hospital, under the responsibility of Dr Hélène Aubert, dermatologist.

The primary objective of the clinical trial is to demonstrate the non-inferiority of a step down dosage strategy (injection spacing) of dupilumab (DUPIXENT®) as compared with maintenance of initial treatment, on long-term control of the disease severity at one year in adolescents and adults patients with controlled AD.

The first-line treatment of atopic dermatitis is based on the application of corticosteroid-based creams combined with the application of emollient creams or creams containing immunomodulators. In cases of moderate to severe atopic dermatitis not controlled by creams (about 10% of patients), oral treatment can be proposed. Recent treatments using monoclonal antibodies (biotherapies) are available, including Dupilumab. It has been authorised in Europe and France since 2017 for the treatment of moderate to severe atopic dermatitis in adults and children. Dupilumab is administered every 14 days by subcutaneous injection (using a syringe or an injection pen) by a nurse or by the patient himself. This treatment improves eczema in a majority of patients. It has a good tolerance profile and can be taken over a long period of time.

In practice, it has been observed that some patients with well-controlled atopic dermatitis can space out Dupilumab injections without worsening their atopic dermatitis. However, few studies are available regarding the necessary dose of Dupilumab over the long term in patients who are good responders to treatment.

The MADULO research proposes to study a strategy of spacing Dupixent® injections compared to maintaining injections every 14 days in patients who are good responders to treatment.

The MADULO study is a national multicentre research study that plans to include 256 patients (adults and adolescents from 12 years of age) in 29 investigation centres.

Patients will be divided into two groups, one with the classic injection schedule (every 14 days), the other with spaced injections. This is an open-label study, i.e. the doctor and the patient know in which group the patient is included.

In the control arm: the prescribed dose of Dupixent® will be 300 mg every 14 days for adults and adolescents aged 12 to 17 years weighing more than 60kg and 200 mg every 14 days for adolescents aged 12 to 17 years weighing less than 60kg.

In the experimental arm: Dupixent® injections will be spaced :

• Every 3 weeks between M0 and M4 (i.e. between the first month and the fourth),
• Then every 4 weeks between M4 and M8 (i.e. between the fourth month and the eighth month),
• Then every 5 weeks until the end of the research (M12 or month 12

Dose intervals will be maintained only if efficacy is maintained, i.e. if the eczema does not worsen. Efficacy will be measured by a self-assessment questionnaire that evaluates the control of the dermatitis: the ADCT questionnaire.

In current practice, AD patients who respond well to dupilumab treatment often express the wish to reduce the treatment, and often do so on their own, with or without agreement from the prescriber (Jendoubi F et al. oral communication, Journées Dermatologiques de Paris 2021)

The expected benefits of a dupilumab tapering strategy compared to a standard maintenance strategy are:

• a better long-term benefit/risk ratio,
• improved patient satisfaction / reduced disease burden due to less injections

The benefits to the community could be: 

• Improved management of long-term systemic therapies in patients with moderate to severe chronic AD,
• Improved knowledge of long-term strategies for dupilumab in responder patients,
• a decrease in the cost of systemic treatments for health insurance,
• improved cost-effectiveness of AD treatment.