Control Crohn Safe Trial

Study Overview
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Brief Summary
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Crohn's disease (CD) is a chronic disease with a heterogeneous clinical presentation, relapse rate and treatment response. Insufficient control of mucosal inflammation results in irreversible bowel damage and complications and at present no markers are available to predict such a complicated disease course at diagnosis. Therefore, to prevent overtreatment of low risk patients, step-up treatment with subsequent introduction of corticosteroids, thiopurines maintenance and TNF-blockers if a previous category fails is standard care. Combination treatment with thiopurines and a TNF-blocker is more effective than monotherapy but associated with a higher risk for infectious complications. Landmark studies convincingly showed an improved long-term outcome if the TNF-blocker infliximab is introduced early after diagnosis. The standard step-care approach thus prolongs steroid exposure and delays start of disease modifying biologicals in high risks patients. Given the higher efficacy of combination therapy with a thiopurine of infliximab and potential allergic reactions and lower response rates after re-initiation of this chimeric biological, temporary monotherapy with this TNF-blocker has not been studied as first line treatment before. Adalimumab is a humanised monoclonal antibody and subsequently, combination therapy of adalimumab + thiopurines has only a marginal effect on anti-drug anti-body formation. Furthermore, combination therapy with adalimumab does not enhance the clinical response. Therefore, periodic treatment with adalimumab in combination with close monitoring after drug-discontinuation, in newly diagnosed CD might improve outcome, reduce drug-related side effects while still preventing overtreatment. The aim of this study is to compare the long-term efficacy and safety of periodic adalimumab as initial treatment in newly diagnosed CD patients compared to standard step-care with corticosteroid/budesonide as the initial treatment

Official Title
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Control Crohn Safe With Episodic Adalimumab Monotherapy as First Line Treatment Study.

Conditions
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Crohn Disease, Inflammatory Bowel Diseases

Intervention / Treatment
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* Drug: Adalimumab
* Drug: standard step-up care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed CD patients or CD patients with a flare, visiting the outpatient clinic or endoscopy ward of the participating centres CD diagnosis according to ECCO-guidelines + complete ileo-colonoscopy + complete small bowel imaging at diagnosis (MRI or CT-enterography ) Naïve to biologicals Sufficient knowledge of Dutch language 18 years old ≤ 70 years old Smartphone with internet access Use of myIBDcoach or willingness to start using myIBDcoach Exclusion Criteria: Use of prednisone for longer than 4 weeks in the year before screening Use of budesonide (≥6 mg daily) for a duration longer than 3 months in the year before screening Use of thiopurines in the 3 years before screening Indication for primary treatment with biologicals or surgery Malignancy in 5 years before treatment. Exception is adequately treated non-melanoma skin cancer Contra-indication for TNF-blockers or immunosuppressive agents Contra-indication for MRI- and CT-enterography Patients with short bowel syndrome or an ostomy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter randomised controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Adalimumab<br>Episodic adalimumab monotherapy as first line treatment for 6 months | Drug: Adalimumab<br>* episodic treatment with subcutaneous adalimumab for 6 months<br>* Other names: Humira;|
| Active Comparator: Standard step-up care<br>Step-up care as first line treatment, starting with corticosteroids. | Drug: standard step-up care<br>* conventional step-up care starting with corticosteroids<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of yearly-quarters of corticosteroid free remission as a measure of treatment efficacy | Remission is defined as combined clinical (MIAH scores (≤3)) and biochemical (C-reactive protein ≤5 mg/L (i.e. within normal range) and fecal calprotectin ≤ 200 μg/g) remission. | at week 96 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative structural bowel damage as a measure of disease progression | Disease progression on MRI-enterography based on the Lémann score (Crohn's Disease Digestive Damage Score); the Lémann score is an instrument to measure cumulative structural bowel damage in Crohn's disease. The score takes into account the damage location (upper digestive tract, small bowel, colon/rectum and anal/perianal), extent and severity. Grades 0 (normal) to 3 (maximal) are given to each segment of the digestive tract, with grade 3 representing the most damage, or resection/bypass. | at week 96 | 
| Incidence of drug related serious adverse events | Drug related serious adverse events | at week 24, 48 and 96 | 
| Incidence of serious disease related adverse events | Crohn disease related hospitalisation and surgery | at week 24, 48 and 96 | 
| Integer amount of direct health care costs (in €) | Direct costs include expenses for medication, diagnostic procedures, number of outpatient clinic visits, hospitalisations and surgeries. Direct costs will be combined with indirect costs to report total health care costs. | at week 96 | 
| Integer amount of indirect health care costs (in €) | Indirect costs consist of costs due to presenteeism and absenteeism and are assessed by questionnaires in the telemedicine tool myIBDcoach used for monitoring of IBD patients. Indirect costs will be combined with direct costs to report total health care costs. | at week 96 | 
| Corticosteroid use | Cumulative corticosteroid dose | at week 24, 48 and 96 | 
| Endoscopic remission as assessed by SES-CD | Proportion of endoscopic remission based on SES-CD (simple endoscopic score for CD). Endoscopic remission is defined as a score below 3 and the absence of ulcers. | at week 24 | 
| Time to remission | Time to remission | at week 96 | 
| Quality of life as assessed by QoL EQ-5D-5L questionnaire | Quality of life as assessed by the QoL EQ-5D-5L questionnaire in which the level of severity is chosen for five domains (mobility, self-care, usual activities, pain, anxiety/depression). A higher level (maximal 5) indicates more severe problems in that particular domain. | at week 24, 48 and 96 |