Identification of Scores Associated With a Favorable Clinical Response With Thiopurines in IBD Patients

NCT ID: NCT02367326

Last Updated: 2017-08-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 400 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2017-08-31

Brief Summary

Inflammatory bowel disease (IBD) groups together Crohn's Disease (CD) and ulcerative colitis (UC). Its prevalence is high representing approximately 0.4% of the population. The peak incidence for these diseases ranges between 2 and 30 years of age with a second peak for CD recently reported at 60. These diseases develop over time into complications requiring in 2/3 of cases surgical resection procedures in CD and colectomy in over 20% of cases. Cohort data has recently shown that the early use of azathioprine from the first year would decrease the need for surgery. Aside from biologics, azathioprine is the most widely used immunosuppressant in IBD management. Its metabolism is highly variable in the overall population since over 10% of patients are slow metabolizers and 15% fast metabolizers. This explains partly treatment failures and side effects with thiopurines. A lot of research has shown that metabolite measurement of azathioprine (6-TGN end methylated derivatives) could be used clinically even if these results remain controversial. In fact, their positive predicative value (PPV) in clinical response does not exceed 60%. This costly testing cannot be done everywhere, is not reimbursed by national health services, and may not be used in some countries. It is, however, key in order optimize these drugs at a time when only two anti-TNFs are possible in the event of failure on thiopurines. Older studies have shown that MCV and lymphonenia could be markers for thiopurine impregnation. Recently, an American study provided a mathematic formula enabling to achieve over 80% PPV for the clinical response on AZA but this calculation needs to be confirmed and it is, moreover, patented (costly).

Detailed Description

We suggest developing a predictive score for clinical thiopurines in IBD based on routine lab data obtained when monitoring patients on thiopurines. This initial work will enable to identify clinical and/or lab factors in order to develop a score based on an international, multicenter, cross-section study. Two hundred patients with treatment failure on thiopurines will be included and at least as many in clinical remission on thiopurines. A subsequent longitudinal study, over all recruiting centers will enable to validate the score. Finally, a prospective study will assess the clinical impact of the optimization of this score in patients sustaining a treatment failure on thiopurines. This score - if confirmed - will subsequently be at no additional cost in the management of patients on thiopurines.

Conditions

Inflammatory Bowel Diseases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with Inflammatory Bowel Disease

patients with Crohn's Disease or Ulcerative Colitis meeting clinical, endoscopic and histological criteria and on thiopurines at stable doses for at least 3 months, monotherapy or combined with corticotherapy

data collection

Intervention Type: OTHER

data collection will be carried out by the investigator during a standard hospitalization of the patient

Interventions

data collection

data collection will be carried out by the investigator during a standard hospitalization of the patient

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adult patients affiliated with or beneficiaries of a national health insurance scheme
• Male our female over 18 years of age and under 70 having given his/her informed consent to participate in this trial.
• Any patients with Crohn's Disease or Ulcerative Colitis meeting clinical, endoscopic and histological criteria.
• Patients on thiopurines at stable doses for at least 3 months, monotherapy or combined with corticotherapy using the following doses:

AZATHIOPRINE at the dose of 2 to 2.5 mg/kg/day, regular oral dosing for 3 months or PURINETHOL at the dose of 1 to 1.5 mg/kg/day, regular oral dosing for 3 months

Exclusion Criteria

• Patients with intolerance to thiopurines resulting in reduction or discontinuation of thiopurines by the referring physician.
• Post operative Crohn's Disease patients for whom thiopurines were indicated preventively or in the event of endoscopic abnormalities.
• Extensive colic resection, (sub)total colectomy.
• History of > 3 resections of the small intestine or diagnosis of a short bowel
• Crohn's Disease with a perianal lesion whether the latter is isolated or the focus of the disease
• Patient with a enterocutaneous, abdominal or pelvic fistula with abscess or fistula likely to require surgery during the study
• Ileostomy, colostomy or known intestinal stenosis
• Severe active infection
• Active neoplasia
• Known TPMPT homozygote mutation
• Patients on anti-TNF or Methotrexate in the last 3 months or during thiopurine therapy
• Patients on Allopurinol.
• Patient who expressed his/her refusal to participate in the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Apsen Farmaceutica S.A.

INDUSTRY

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xavier ROBLIN, MD

Role: PRINCIPAL_INVESTIGATOR

CHU SAINT-ETIENNE

Locations

CHU Jean Minjoz

Besançon, , France

CHU Caen

Caen, , France

CHU Dijon

Dijon, , France

CHRU Lilles

Lilles, , France

CHU Montpellier

Montpellier, , France

CHU Nancy

Nancy, , France

CHU Nantes - Hôtel-Dieu

Nantes, , France

CHU Nice

Nice, , France

CHR Orléans

Orléans, , France

Hôpital Saint-Antoine

Paris, , France

CHU Bordeaux

Pessac, , France

CH Lyon Sud

Pierre-Bénite, , France

CHU Reims

Reims, , France

CHU Rennes

Rennes, , France

CHU Saint-Etienne

Saint-Etienne, , France

Countries

France

Other Identifiers

DR-2012-589

Identifier Type: OTHER

Identifier Source: secondary_id

1208169

Identifier Type: -

Identifier Source: org_study_id