Interest of the Dosage of Adalimumab Serum Levels in Crohn's Disease Patients for Prevention of Postoperative Recurrence

Study Overview
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Brief Summary
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Study comparing 2 modalities of Crohn's disease patients postoperative follow-up treated with adalimumab (Humira® or biosimilar) : immunomonitoring of adalimumab serum levels versus standard follow-up, which is based on the clinical and biological activity of the disease.

Detailed Description
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Patients in the experimental arm will have a post-operative follow-up based on the immunomonitoring of serum levels of adalimumab. After ileocolic resection surgery, patients will have a therapeutic optimization of their adalimumab (Humira® or biosimilar) treatment, based on their serum residual rate of adalimumab. Patients in the control group will receive a standard post-operative follow-up, which is based on clinical and biological recurrence.

Official Title
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Prospective, Controlled, Randomized, Multicentered, Open-label Study, Comparing 2 Modalities of Follow-up of Patients With Crohn's Disease, Postoperatively Treated With Adalimumab (Immunomonitoring vs Standard Follow-up)

Conditions
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Crohn Disease

Intervention / Treatment
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* Other: Immunomonitoring-based follow-up
* Other: Standard follow-up


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient between the ages of 18 and 75 Use of an effective method of contraception during treatment with adalimumab for women of childbearing age Crohn's disease diagnosed according to the criteria defined by the national and international recommendations for at least 3 months IIeocolic resection with ileocolic anastomosis and absence of residual macroscopic lesion, or ileocolic resection with transient ostomy and restoration of continuity For anti-TNF-naive patients: negative pre-anti TNF balance Indication of postoperative treatment for the prevention of recurrence of Crohn's disease (with at least 1 risk factor for recidivism): active smoking (≥ 1 cigarette / day at the time of surgery) hail resection> 50 cm second intestinal resection presence of anoperineal lesions Penetrating impairment (B3 of the Montreal Classification) Biotherapy treatment for more than 6 months before the surgery Written and signed consent by the participant and the investigator Affiliated person or beneficiary of the social security system. Exclusion Criteria: Intolerance or allergy to adalimumab (Humira® or biosimilar) Patients to whom adalimumab (Humira® or biosimilar) is contraindicated Intestinal stoma without restoration of continuity Pregnant woman (dosage of positive βHCG) or breastfeeding according to article L1121-5 of the french public health law. Contraindication or refusal of ileocolonoscopy at 6 months Patient who could not be followed regularly for psychological, social or geographical reasons Vulnerable people according to article L1121-6 of the french public health law Persons subject to legal protection (guardianship, trusteeship) or unable to express their consent according to Article L1121-8 of the french public health law or under the protection of justice according to article L1122.2 of the CSP Concomitant participation of the patient in another research involving the human person. Patient not affiliated to the social security system (Article L.1121-11). Patient unable to sign the consent form Immunized patients (with anti-adalimumab antibodies > 10ng / mL and undetectable adalimumab levels, Elisa drug sensitive technique used) for patients already treated with adalimumab (Humira® or biosimilar) before surgery Patients in combination therapy with azathioprine, 6-mercaptopurine or methotrexate Post-operative, or treated by another biotherapy (infliximab, vedolizumab, ustekinumab ...)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a multicenter, interregional, open-label, prospective comparative PHASE III, randomized with a ratio (1:1), with 2 parallel groups (experimental group called immunomonitoring and control group called standard strategy based on clinical and biological activity).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunomonitoring-based follow-up<br>Post-operative follow-up of Crohn's disease patients will be done through the measurement of the residual rate of the drug adalimumab in the serum. | Other: Immunomonitoring-based follow-up<br>* Post-operative follow-up of Crohn's disease patients will be done through the measurement of the residual rate of the drug adalimumab in the serum. Patients will receive adalimumab treatment every other week, starting 1 month after the surgery. 3 months after the surgery, serum levels of adalimumab will be measured: If the level is below 5ug/mL, adalimumab treatment will be increased to every other week until the end of the study. If adalimumab level in the serum is above 5ug/mL, the treatment's frequency will be maintained until the end of the study.<br>|
| Active Comparator: Standard follow-up<br>Post-operative follow-up of Crohn's disease patients will be based on clinical and biological parameters. This strategy is the standard strategy for post-operative follow-up of Crohn's disease patients. | Other: Standard follow-up<br>* Post-operative follow-up of Crohn's disease patients will be based on clinical and biological parameters. Patients will receive adalimumab treatment every other week, starting 1 month after the surgery. If clinical relapse (CDAI > 220 together with an increase of 70 points) and biological relapse (CRP > 10mg/mL and fecal calprotectin > 100 ug/g) occur, frequency of adalimumab treatment will be increased to once a week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with a Rutgeerts score ≥ i2 | The primary endpoint will be measured by ileocolonoscopy under general anesthesia after standard preparation by PEG with video recording of the examination, carried out by one of the investigators of the study in each center. An ileocolonoscopy 6 months after intestinal resection remains the reference examination for the endoscopic diagnosis of recurrence according to the endoscopic Rutgeerts score (endoscopic recurrence if Rutgeerts score ≥ i2) and allows the adaptation or the introduction of a treatment to limit clinical recurrence at 18 months. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with clinical recurrence | Evaluation of the clinical recurrence after surgery . Evaluation based on the CDAI. (clinical recurrence if CDAI ≥ 220 and ≥70 points increase from baseline CDAI), CRP (> 10mg/L) and fecal calprotectin (> 100μg/ g). | 3 and 6 months | 
| Percentage of patients with biological recurrence | Biological recurrence will be evaluated based on CRP and fecal calprotectin: CRP: 10 mg / L threshold to define a biological recurrence. Fecal Calprotectin: 100 μg / g threshold to define a biological recurrence | 3 and 6 months | 
| Percentage of patients with adverse effects | The practitioner will assess (through a questionnaire) the presence or absence : of joint pain, allergic reactions, autoimmune reaction, complications at the puncture wound, infections, hospitalization . | 3 and 6 months | 
| Rate of adalimumab in the serum | Adalimumab levels (in μg/mL) will be measured on a blood sample | 1, 3, and 6 months | 
| Rate of anti-adalimumab antibodies in the serum | Anti-adalimumab antibodies (ng/mL) will be measured on a blood sample only in cases of undetectable adalimumabemia (Elisa Drug-sensitive technique) | 1, 3, and 6 months |