Identification of Scores Associated With a Favorable Clinical Response With Thiopurines in IBD Patients
Condition: Inflammatory Bowel Diseases
MeSH terms: Intestinal Diseases; Inflammatory Bowel Diseases
Study type: Observational

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.
    

Intervention name(s): data collection
Intervention type(s): Other
Intervention description(s): data collection will be carried out by the investigator during a standard hospitalization of the patient
Observational model: Cohort
Time perspective: Prospective
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
      
Keywords: score; inflammatory bowel disease; crohn's disease; ulcerative colitis; clinical response; thiopurines