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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Crohn Disease
• Intervention / Treatment: Other: Immunomonitoring-based follow-up; Other: Standard follow-up

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Montpellier, France
    • CHU de Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 ...)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immunomonitoring-based follow-up; 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; 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.
Active Comparator: Standard follow-up; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Lucile BOIVINEAU, Montpellier University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2020
• Primary Completion (Actual): June 29, 2024
• Study Completion (Actual): June 29, 2024

Study Registration Dates

• First Submitted: December 12, 2019
• First Submitted That Met QC Criteria: December 13, 2019
• First Posted (Actual): December 16, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 17, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: RECHMPL19_0071; UF 7772 (Other Identifier: UH Montpellier)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No