Study Investigating Tailored Treatment With Infliximab for Active Crohn's Disease (TAILORIX)

• Clinical remission [ Time Frame: week 14 after inclusion ] [ Designated as safety issue: No ]
  Clinical remission (CDAI <150) at each visit and the whole study period
• Endoscopic evaluation [ Time Frame: week 0, week 12 and week 54 ] [ Designated as safety issue: No ]
  • percentage of patients in each group with absence of ulcers;
  • percentage of patients in each group with >50% improvement in CDEIS (Crohn's Disease Endoscopic Index Score

To investigate whether sustained trough levels of IFX can be achieved using IFX (Infliximab) trough level measurements and adjustment of dosing based upon these levels by means of two different standardized algorithms in comparison with 'standard of care' IFX treatment and its effects on clinical and endoscopic outcomes.

• Drug: Infliximab
  Perfusion of IFX 5mg/kg to be increased to 10 mg/kg based on clinical symptoms
  Other Name: IFX
• Drug: Infliximab
  Perfusion of IFX 5mg/kg or 10 mg/kg if dose increase criteria are met (biological)
  Other Name: IFX
• Drug: Infliximab
  Perfusion of IFX 5mg/kg or 7,5 mg/kg if dose increase criteria are met (biological)and 10mg/kg if dose increase criteria are met for a second time
  Other Name: IFX

• Placebo Comparator: Cohort 1 =Control Group
  the dose of IFX will be increased by 5 mg/kg (maximally 1 time) based on symptom relapse (usual clinical practice) Dose will be kept stable ofr the rest of the trial Dose decreases will not be allowed.
  Intervention: Drug: Infliximab
• Active Comparator: Cohort 2
  Dose of IFX will be increased by 2.5 mg/kg (maximally 2 times) if the following criteria are met A dose increase is maintained for the following infusions
  Intervention: Drug: Infliximab
• Active Comparator: Cohort 3
  Dose of IFX will be increased by 5 mg/kg (maximally 1 time) if the following criteria are met A dose increase is maintained for the following infusions
  Intervention: Drug: Infliximab

• Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P; ACCENT I Study Group. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002 May 4;359(9317):1541-9.
• Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med. 2004 Feb 26;350(9):876-85.
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• D'Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, De Vos M, van Deventer S, Stitt L, Donner A, Vermeire S, Van de Mierop FJ, Coche JC, van der Woude J, Ochsenkühn T, van Bodegraven AA, Van Hootegem PP, Lambrecht GL, Mana F, Rutgeerts P, Feagan BG, Hommes D; Belgian Inflammatory Bowel Disease Research Group; North-Holland Gut Club. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet. 2008 Feb 23;371(9613):660-7.
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Inclusion Criteria:

• Age > 18 years
• Active CD (CDAI>220) and signs of active inflammation as evidenced by elevated serum hsCRP levels (>5 mg/L) and/or elevated fecal calprotectin levels (>250 µg/g) and endoscopically visible ulcers.
• Patients must be naïve to biologics with indication for starting anti-TNF therapy in accordance with national reimbursement criteria.
• Patients must be naïve to thiopurines or have failed therapy with thiopurines (in which case AZA will be continued).
• Ongoing steroids are allowed if at stable dose for at least 2 weeks and at a maximum of prednisone 40 mg/d or budesonide 9 mg/day.
• Patients who consent to receiving Infliximab 5 mg/kg at week 0, 2 and 6 and further on every 8 weeks in conjunction with azathioprine (2,5 mg/kg/day). Patients who develop AZA intolerance during the trial are continued in the trial without AZA (ie IFX monotherapy).

Exclusion Criteria:

• Absence of endoscopically visible ulcers
• Prior exposure to infliximab (other biologics allowed)
• Ongoing steroid therapy at doses > 40 mg/d prednisolone equivalent
• Previous intolerance to azathioprine leading to drug discontinuation
• Ongoing infections
• Positive tuberculosis screen per local guidelines
• Serious other diseases including cancer in the 5 years prior to inclusion excluding non-melanoma skin cancer
• Indication for immediate surgery
• Pregnant or breast-feeding woman.
• Positive fecal culture for Salmonella, Shigella, Yersinia and Campylobacter and/or presence of Clostridium difficile B toxin in the stools
• Active tuberculosis
• Untreated latent tuberculosis (see national recommendations. Appendix 2).
• Non-compliant subjects.
• Participation in another therapeutic study.