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

NCT02367326 | Completed

• 2 other identifiers: 1208169DR-2012-589
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 15

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).

Conditions

Inflammatory Bowel Diseases

Keywords

score; inflammatory bowel disease; crohn's disease; ulcerative colitis; clinical response; thiopurines

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• number of patient in clinical remission on thiopurines

  day 0 (inclusion)

Study Arms (1)

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

Interventions

data collection OTHER

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

Patients with Inflammatory Bowel Disease

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Apsen Farmaceutica S.A.: collaborator

Study Sites (15)

CHU Jean Minjoz

Besançon, 25030, France

Location

CHU Caen

Caen, 14033, France

Location

CHU Dijon

Dijon, 21079, France

Location

CHRU Lilles

Lilles, 59037, France

Location

CHU Montpellier

Montpellier, 34295, France

Location

CHU Nancy

Nancy, 54511, France

Location

CHU Nantes - Hôtel-Dieu

Nantes, 44093, France

Location

CHU Nice

Nice, 06200, France

Location

CHR Orléans

Orléans, 45000, France

Location

Hôpital Saint-Antoine

Paris, 75012, France

Location

CHU Bordeaux

Pessac, 33604, France

Location

CH Lyon Sud

Pierre-Bénite, 69310, France

Location

CHU Reims

Reims, 51092, France

Location

CHU Rennes

Rennes, 35033, France

Location

CHU Saint-Etienne

Saint-Etienne, 42055, France

Location

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative

Interventions

Data Collection

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Xavier ROBLIN, MD

  CHU SAINT-ETIENNE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2015
• First Posted: February 20, 2015
• Study Start: June 1, 2014
• Primary Completion: June 1, 2017
• Study Completion: August 1, 2017
• Last Updated: August 22, 2017

Record last verified: 2017-08

Locations

FR (15)