Preventing Postoperative Relapse in Crohn's Disease Patients at Risk: Azathioprine Versus Mesalazine

• endoscopic improvement at month 12, defined as ≥1 point reduction in Rutgeerts' score. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• change in CDAI score [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• adverse events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

This study aims to compare azathioprine versus mesalazine tablets for the prevention of clinical relapse in postoperative Crohn's disease (CD) patients with moderate or severe endoscopic recurrence.

• Drug: Azathioprine
  2.0-2.5mg/kg/BW azathioprine /day and mesalazine placebo tablets
  Other Name: Azafalk 50mg tablets
• Drug: Mesalazine
  4g Mesalazine tablets/day AND azathioprine placebo tablets
  Other Name: Salofalk 500mg tablets
• Drug: Azathioprine placebo
  4g Mesalazine tablets/day AND azathioprine placebo tablets
• Drug: Mesalazine placebo
  2.0-2.5mg/kg/BW azathioprine /day and mesalazine placebo tablets

• Experimental: Azathioprine
  2.0-2.5 mg/kg/BW azathioprine tablets/day AND mesalazine placebo tablets
  Interventions:

  • Drug: Azathioprine
  • Drug: Mesalazine placebo
• Active Comparator: Mesalazine
  4g mesalazine tablets/day AND azathioprine placebo tablets
  Interventions:

  • Drug: Mesalazine
  • Drug: Azathioprine placebo

Inclusion Criteria:

• Signed informed consent,
• Man or woman between 18 and 70 years of age,
• Diagnosis of Crohn's disease confirmed by endoscopic and histological, or endoscopic and radiological criteria within one year or by histopathological criteria during resection,
• Clinical remission defined as Crohn´s Disease Activity Index (CDAI) < 200, within the last two weeks. No clinical relapse due to Crohn's disease since resection,
• Moderate (i2a) or severe endoscopic recurrence (i3-i4) within 6 to 24 months after curative resection of the terminal ileum and partial colectomy with ileocolonic resection for complications of ileal Crohn´s disease and with a construction of an ileocolonic anastomosis,
• Within the neoterminal ileum at least more than 5 aphthous lesions with normal mucosa between the lesions, or skip areas of larger lesions,
• Negative pregnancy test at screening visit in females of childbearing potential,
• Use of appropriate contraceptive methods for females of childbearing potential and males with procreative capacity during treatment and at least up to 3 months after the end of treatment.

Exclusion Criteria:

• Lesions confined to the ileocolonic anastomosis (i.e., < 1 cm in length)
• Short bowel syndrome,
• Serious secondary illnesses of an acute or chronic nature, which in the opinion of the Investigator renders the patient unsuitable for inclusion into the study,
• Serum creatinine levels exceeding 1.5 mg/dL or 130 umol/L,
• Presence of an ileo-/colonic stoma,
• Genotype: thiopurine methyltransferase (TPMT) -/-,
• Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years),
• Treatment with cytostatics or immunosuppressants, methotrexate, cyclosporine, 6-MP, Azathioprine, 6-TG or anti-TFN-alpha therapy since resection; postoperative treatment with corticosteroids for more than 4 weeks or postoperative treatment with oral antibiotics (e.g., metronidazole, ciprofloxacin) for more than 4 weeks,
• Application of non-steroidal anti-inflammatory drugs (NSAIDS) within 2 weeks before Screening visit except low dose acetylsalicylic acid and except paracetamol,
• Known intolerance/hypersensitivity to study drugs or drugs of similar chemical structure or pharmacological profile,
• Scheduled or intended active immunisation with living vaccines within the next 12 months,
• Well-founded doubt about the patient's cooperation,
• Existing pregnancy, lactation, or intended pregnancy or impregnation within the next 15 months,
• Non-use of appropriate contraceptives in males with procreative capacity and females of childbearing potential (e.g. condoms for males, intrauterine device [IUD], hormonal contraception for females, or a means of contraception for a particular patient considered adequate by the responsible investigator) during treatment and within 3 months after the end of treatment,
• Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial,
• Present stricture plasty (no exclusion if the present stricture plasty was macroscopically without any relevant finding of inflammation seen during index surgery.