SCORE1: Identification of Scores Associated With a Favorable Clinical Response With Thiopurines in IBD Patients

Sponsor

Centre Hospitalier Universitaire de Saint Etienne (Other)

Overall Status

Completed

CT.gov ID

NCT02367326

Collaborator

Apsen Farmaceutica S.A. (Industry)

400

Enrollment

Locations

Actual Duration (Months)

26.7

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Bowel Diseases	Other: data collection

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.

Study Design

Study Type:

Observational

Actual Enrollment :

400 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Identification of Composite Clinical and Lab Scores Associated With a Favorable Clinical Response With Thiopurines in Patients With IBD (Inflammatory Bowel Disease): an International Clinical Trial

Actual Study Start Date :

Jun 1, 2014

Actual Primary Completion Date :

Jun 1, 2017

Actual Study Completion Date :

Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
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	Other: data collection data collection will be carried out by the investigator during a standard hospitalization of the patient

Arm

Intervention/Treatment

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

Other: data collection

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

Outcome Measures

Primary Outcome Measures

number of patient with therapeutic failure on thiopurines [day 0 (inclusion)]
A therapeutic failure on thiopurines will be considered to be any patient with at least one of the following criteria: For Crohn's Disease: a HBI score > 4 For Ulcerative Colitis: a partial Mayo score > 2 or activity reported by the expert at the time of a visit For both disease: Corticodependence, defined according to ECCO criteria, as an impossibility to reduce the dose of Prednisolone to less than 10 mg/day (or 3 mg/day for Budesonide) in the 3 months following corticotherapy induction. Corticoresistance, defined according to ECCO criteria, as a lack of response to the dose of 0.75mg/kg of a Prednisone equivalent for 4 weeks. the need to change treatment or a surgical indication.

Secondary Outcome Measures

number of patient in clinical remission on thiopurines [day 0 (inclusion)]
A clinical remission shall be considered as any patients with at least one of the following criteria: For Crohn's Disease: a HBI score < 4 For ulcerative colitis: a partial Mayo score ≤ 2 with no subscore > 1 For both diseases, no corticotherapy for at least 3 months.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU Jean Minjoz	Besançon	France	25030
2	CHU Caen	Caen	France	14033
3	CHU Dijon	Dijon	France	21079
4	CHRU Lilles	Lilles	France	59037
5	CHU Montpellier	Montpellier	France	34295
6	CHU Nancy	Nancy	France	54511
7	CHU Nantes - Hôtel-Dieu	Nantes	France	44093
8	CHU Nice	Nice	France	06200
9	CHR Orléans	Orléans	France	45000
10	Hôpital Saint-Antoine	Paris	France	75012
11	CHU Bordeaux	Pessac	France	33604
12	CH Lyon Sud	Pierre Bénite	France	69310
13	CHU Reims	Reims	France	51092
14	CHU Rennes	Rennes	France	35033
15	CHU Saint-Etienne	Saint-Etienne	France	42055