Azathioprine, Crohn Disease, Methotrexate
Conditions
Keywords
Crohn Disease, Combinations of therapy, anti-Tumor Necrosis Factor, azathioprine, methotrexate
Brief summary
Combination therapy, the association of an anti-Tumor Necrosis Factor (TNF) to an immunosuppressant, is recognized as the most effective treatment during Crohn's disease (CD). Several mechanisms have been proposed to explain the superiority of combination therapy over monotherapy, the additive effect of two effective drugs or the prevention of anti-TNF immunogenicity. As the best combination therapy is unknown, both azathioprine (AZA) and methotrexate (MTX) are used. Some retrospective studies suggest a higher effectiveness of AZA. MTX may have an advantage in terms of safety. The investigators hypothesize that AZA is more effective than MTX as combination therapy with adalimumab to improve short-term endoscopic, clinical and pharmacological outcomes in CD patients.
Interventions
DRUGAZA capsules
oral AZA capsules at a daily dose of 2.5 mg per kilogram,
DRUGMTX
MTX 25 mg SC once a week
BIOLOGICALblood sample
The lab tests are: serum albumin, C-reactive protein, thrombocytosis and haemoglobin.
Sponsors
Nantes University Hospital
AP-HP - HU BEAUJON
CHU REIMS
Centre Hospitalier Universitaire de Besancon
CHRU LILLE
University Hospital, Bordeaux
Henri Mondor University Hospital
Hospices Civils de Lyon
CHU Rennes,France
CHU ROUEN - HOPITAL DE BOIS-GUILLAUME
CHRU TOURS
University Hospital, Toulouse
University Hospital, Montpellier
CHU NICE
CHU NANCY
CHU CAEN
CHU SAINT-ETIENNE
CH TOURCOING
Hopitaux Civils de Colmar
CH COTE BASQUE
CH ROUBAIX
CHI CRETEIL
CHI TOULON LA SEYNE
CH VALENCE
CMC Ambroise Paré, Pierre Cherest, Hartmann
University Hospital, Clermont-Ferrand
Centre Hospitalier Universitaire, Amiens
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients with age \> 18 years * Crohn's disease for at least 6 weeks, * Clinically active with CDAI \> 150 * Active inflammation by endoscopy (CDEIS \> 4) at baseline * Not responder to conventional therapy or are intolerant to or have medical contraindications for such therapies and initiating treatment with adalimumab * Patient followed in a center belonging to the GETAID network * Fertile men and women of childbearing potential included in the protocol should use adequate methods of contraception according to study drug SMPCs. * Written consent
Exclusion criteria
* Short bowel syndrome, ostomy, symptomatic stricture, abscess, recent history of abdominal surgery (\<3 months) * Non-passable colonic stricture * Previous intolerance to thiopurines or MTX * Previous exposition to adalimumab * Contra-indication to immunosuppressants or anti-TNF * Others serious simultaneous illness that could interfere with study participation * Planning pregnancy, pregnancy or lactation or absence of contraception * Known substance abusers * Use of any investigational drug within 30 days * Adults protected by law
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Variation of the endoscopic response between AZA and MTX groups | 26 weeks | Variation of the endoscopic response to AZA in combination with adalimumab and to MTX in combination with adalimumab in patients with CD. The endoscopic reference score (EREFS) is used to determine severity of 5 endoscopic findings: edema, rings, exudates, furrows, and structures. The EREFS classification system rates the severity of edema (0-2), rings (0-3), exudates (0-2), furrows (0-2), and strictures (0-1) |
Countries
France
Contacts
Primary ContactMathurin Fumery, Pr
Outcome results
None listed