Dupilumab step-down strategy to maintain remission in adult and adolescents patients with atopic dermatitis: a non-inferiority randomized trial

The primary objective of this study is to demonstrate the **non-inferiority** of a step-down dosage strategy of **dupilumab** compared to the maintenance of initial treatment in achieving long-term control of disease severity over one year in adolescents and adults with controlled **atopic dermatitis**. This is clinically relevant as it may offer a more sustainable treatment approach with potentially fewer side effects and improved patient adherence.

Secondary objectives include assessing the efficacy of a tapering dosage strategy of dupilumab compared to the standard maintenance strategy on several parameters:

• Eczema Area and Severity Index (EASI) at months 4, 8, and 12
• Investigator Global Assessment (IGA) at months 4, 8, and 12
• Itch Numerical Rating Scale at months 4, 8, and 12
• Economic efficiency through a cost-utility analysis from a collective perspective over a 1-year time horizon
• Dermatology Life Quality Index (DLQI) or Children's Dermatology Life Quality Index (CDLQI) for children under 16 at months 4, 8, and 12

The clinical trial involves **adolescents and adults** with **atopic dermatitis** who are aged 12 years and older. Both **male and female** participants are included in the study, and the population is not considered vulnerable. Participants must have moderate to severe atopic dermatitis that has been treated with **dupilumab** every two weeks for at least one year, with the condition being controlled for at least six months without tapering the dosage. The amount of topical treatment used must be stable for six months and less than 60 g per month. The sponsor has not provided information regarding the total number of participants in the trial. The study population was selected based on specific criteria, including age, treatment history, and disease control status, ensuring a focus on individuals with a stable health condition related to atopic dermatitis management.

The clinical trial is designed to evaluate the **non-inferiority** of a step-down dosage strategy of **dupilumab** in maintaining long-term control of **atopic dermatitis** severity in adolescents and adults. This is a randomized, double-blind, controlled trial with an estimated duration of three years, concluding in December 2026. Participants will be randomly assigned to either continue their current treatment regimen or transition to a reduced dosage schedule. The trial will involve multiple study visits, beginning with an inclusion visit to confirm eligibility based on criteria such as age (≥12 years), disease control, and prior treatment history. Participants must have been on a stable dose of dupilumab for at least one year and have controlled atopic dermatitis as assessed by specific clinical tools.

Following the inclusion visit, participants will attend regular follow-up visits at months 4, 8, and 12 to monitor disease control and treatment efficacy. These visits will include assessments using the Atopic Dermatitis Control Tool (ADCT), Eczema Area and Severity Index (EASI), and other relevant scales. The primary endpoint is the area under the curve of the ADCT score over one year, while secondary endpoints include changes in EASI scores, Investigator Global Assessment, and quality of life measures. The end-of-study visit will occur at the conclusion of the 12-month treatment period, where final assessments will be conducted.

Participant involvement is expected to last for the full 12-month treatment period, with conditions for early termination including significant adverse events or withdrawal of consent. The trial aims to provide valuable insights into the efficacy of a reduced dosage strategy for maintaining disease control in patients with atopic dermatitis, potentially offering a more sustainable long-term treatment approach.

The clinical trial involves the use of several treatments, including both experimental and non-experimental medications. The primary experimental medication is **Dupilumab**, marketed under the name Dupixent. Dupixent is available in two formulations: a 300 mg solution for injection in a pre-filled pen and a pre-filled syringe, as well as a 200 mg solution for injection in both a pre-filled pen and syringe. The active substance, **Dupilumab**, is a protein of other origin, with synonyms REGN668 and SAR231893. The medication is administered via **subcutaneous use**. The maximum daily dose for the 300 mg formulation is 300 mg, with a total maximum dose of 7800 mg over a 52-week period. For the 200 mg formulation, the maximum daily dose is 200 mg, with a total maximum dose of 5200 mg over the same period. The pharmaceutical form is a solution for injection, and the medication is produced by Sanofi-Aventis Groupe.

In addition to the experimental treatment, the trial includes non-experimental treatments such as **Desonide** and **Clobetasol**. Desonide is provided in a cream form for **cutaneous use**, with a maximum daily dose of 1 g and a total maximum dose of 720 g over a 12-week period. Clobetasol is available as a cutaneous foam, also for cutaneous use, with the same dosing schedule as Desonide. Both substances are of chemical origin and are used as auxiliary treatments in the trial.

Another non-experimental treatment included in the trial is **Dermafuzone**, a cream containing **Betamethasone Valerate** and **Fusidic Acid**. This treatment is also administered cutaneously, with a maximum daily dose of 1 g and a total maximum dose of 720 g over 12 weeks. The active substances in Dermafuzone are of chemical origin, and the product is manufactured by Laboratoires Bailleul SA.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed treatment regimen. The trial aims to demonstrate the non-inferiority of a step-down dosage strategy of Dupilumab compared to the maintenance of initial treatment in controlling the severity of atopic dermatitis over a one-year period.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the area under the curve of the Atopic Dermatitis Control Tool (ADCT) score, which will be measured weekly over the course of one year. This tool is designed to evaluate the control of **atopic dermatitis** in patients. Secondary endpoints include the mean difference in Eczema Area and Severity Index (EASI) score, Investigator Global Assessment, and Itch Numerical Rating Scale from baseline to months 4, 8, and 12. Additionally, the trial will assess the incremental cost-utility ratio, expressed as cost per Quality-Adjusted Life-Years (QALYs), and the mean difference in Dermatology Life Quality Index (DLQI) or Children's Dermatology Life Quality Index (CDLQI) for participants under 16 years of age, also from baseline to months 4, 8, and 12.

The collection and analysis of these efficacy parameters will be conducted at specified timepoints throughout the trial duration, ensuring a comprehensive evaluation of the treatment's impact on disease control and patient quality of life. The use of validated scales and patient-reported outcomes will facilitate a robust assessment of the therapeutic efficacy of the step-down dosage strategy of **dupilumab** compared to the maintenance of initial treatment in controlling disease severity over the long term.