Evaluation of Adalimumab Monotherapy Versus Corticosteroid-Based Step-Up Therapy in Newly Diagnosed Crohn's Disease Patients

The primary objective of this study is to evaluate the long-term **efficacy** and **safety** of periodic **adalimumab** as an initial treatment in patients newly diagnosed with **Crohn's disease**. This is compared to the standard step-up care approach, which utilizes corticosteroids or budesonide as the initial treatment. The clinical relevance of this objective lies in determining whether adalimumab can provide a more effective and safer first-line treatment option for Crohn's disease, potentially altering current treatment protocols and improving patient outcomes.

The clinical trial focuses on individuals diagnosed with **Crohn's disease**, specifically targeting newly diagnosed patients or those experiencing a flare. The study population includes both male and female participants, aged between 18 and 70 years. Participants are required to have a confirmed diagnosis of Crohn's disease according to ECCO guidelines, with recent complete ileocolonoscopy and small bowel imaging. The trial does not involve a vulnerable population. Participants must be naïve to biological treatments and possess sufficient knowledge of the Dutch language. Additionally, they should have a smartphone with internet access and either use or be willing to start using myIBDcoach. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the long-term efficacy and safety of periodic **adalimumab** as an initial treatment in patients newly diagnosed with **Crohn's disease**. This study is a randomized, double-blind, controlled trial comparing adalimumab monotherapy to standard step-up care with corticosteroids or budesonide. The trial is expected to last until September 2027, with recruitment having started in September 2019. Participants will be involved in the study for a duration of 96 weeks, during which they will undergo a series of study visits.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as a recent diagnosis of Crohn's disease, age between 18 and 70 years, and naivety to biological treatments. Participants must also have sufficient knowledge of the Dutch language and access to a smartphone with internet. Following the screening, participants will attend regular follow-up visits to monitor their response to treatment and any adverse events. The primary endpoint is the difference in the number of yearly-quarters of corticosteroid-free clinical and biochemical remission at week 96. Secondary endpoints include total healthcare costs, cumulative corticosteroid dose, and patient-reported outcomes on quality of life and treatment tolerability.

The end-of-study visit will occur at week 96, where final assessments will be conducted to evaluate the primary and secondary endpoints. Conditions that may lead to early termination from the study include significant disease progression, drug-related adverse events, or serious adverse events such as hospitalizations or surgeries. Participants will receive **Hyrimoz 40 mg solution for injection** via subcutaneous injection, with a maximum daily dose of 160 mg. The trial is categorized as a phase IV integrated clinical trial, focusing on the real-world application of adalimumab in managing Crohn's disease.

The clinical trial involves the administration of **Hyrimoz**, a 40 mg solution for injection in a pre-filled syringe, containing the active substance **adalimumab**. This medication is classified as a **solution for injection** and is administered via **subcutaneous injection**. The maximum daily dose is 160 mg, with a total maximum dose of 160 mg over the treatment period. The treatment is not formulated specifically for pediatric use. The pharmaceutical form is a solution for injection in a pre-filled syringe, ensuring ease of administration and accurate dosing. The active substance, adalimumab, is a protein of other origin, and it is utilized in this study to evaluate its efficacy and safety as a first-line treatment for newly diagnosed Crohn's disease patients.

In addition to the experimental treatment, the study includes a comparator treatment involving standard step-up care with corticosteroids or budesonide as the initial treatment. This non-experimental treatment serves as a control to assess the relative efficacy and safety of adalimumab monotherapy. The dosing schedules for the comparator treatments are consistent with standard-of-care practices for Crohn's disease management. Participant compliance with the dosing regimen is monitored throughout the study to ensure adherence and to accurately assess the outcomes of the treatment interventions.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the difference in the number of yearly-quarters of corticosteroid-free clinical and biochemical remission at week 96. Safety outcomes will also be monitored, including disease progression at week 96, drug-related adverse events, and disease-related serious adverse events such as hospitalizations and surgeries. Secondary outcomes include total healthcare costs, cumulative corticosteroid dose, the proportion of patients achieving endoscopic remission at week 24, drug-related side effects, and patient-reported outcome measures on quality of life, work disability, and treatment tolerability. These efficacy parameters will be collected and analyzed at specified time points throughout the study duration, ensuring a comprehensive evaluation of the treatment's impact on patients with **Crohn's disease**. The study aims to compare the long-term efficacy and safety of periodic adalimumab as an initial treatment in newly diagnosed Crohn's disease patients against standard step-up care with corticosteroids or budesonide.