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

Inflammatory Bowel Diseases Clinical Trial

— SCORE1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02367326
• Other study ID #: 1208169
• Secondary ID: DR-2012-589
• Status: Completed
• Phase: N/A
• First received: February 12, 2015
• Last updated: August 21, 2017
• Start date: June 2014
• Est. completion date: August 2017

Study information

• Verified date: August 2017
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: August 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

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

Locations

Country	Name	City	State
France	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

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne	Apsen Farmaceutica S.A.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of patient with therapeutic failure on thiopurines	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.	day 0 (inclusion)
Secondary	number of patient in clinical remission on thiopurines	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.	day 0 (inclusion)