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

Crohn Disease Clinical Trial

— ADAPT  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04200547
• Other study ID #: RECHMPL19_0071
• Secondary ID: UF 7772
• Status: Recruiting
• Phase: N/A
• Start date: January 29, 2020
• Est. completion date: September 1, 2024

Study information

• Verified date: October 2022
• Source: University Hospital, Montpellier
• Contact: Lucile BOIVINEAU
• Phone: +33 467337064
• Email: l-boivineau[@]chu-montpellier.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: September 1, 2024
• Est. primary completion date: January 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 ßHCG) 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 ...)

Related Conditions & MeSH terms

• Crohn Disease

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	CHU de Montpellier	Montpellier

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Rate of adalimumab in the serum	Adalimumab levels (in µg/mL) will be measured on a blood sample	1, 3, and 6 months
Secondary	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