Switching From Adalimumab to Infliximab

Inclusion criteria

• Diagnosis of Crohn's disease confirmed by radiological, endoscopical or histological evidence.
• Moderately to severely active Crohn's disease: Crohn's Disease Activity Index (CDAI) ≥ 220 ≤ 450, scored during the screening period.
• Primary non-response to Adalimumab induction (160mg at week 0, 80 mg at week 2, then 40 mg every 2 weeks: q2w), defined as CDAI ≥ 220 in combination with C-Reactive Protein (CRP) ≥ 0.5mg/dl or endoscopic or radiological evidence of disease activity and evaluated 2 weeks after 6 injections (q2w) of Adalimumab (injections week 0 to week 10, evaluation week 12). OR Loss of response to Adalimumab, defined as CDAI ≥ 220 in combination with CRP ≥ 0.5mg/dl or endoscopic or radiological evidence of disease activity and after at least 4 weeks of weekly injections of Adalimumab (40mg).
• Male or female aged 18-75 years old.
• No history, signs or symptoms of active or latent, untreated tuberculosis (TB).
• Having laboratory results as follows:

Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels not exceeding 2 times the upper limit of normal for the central laboratory conducting the test Serum creatinine not exceeding 1.7 mg/dl. Platelets ≥ 100 x 103 cells/µl. Neutrophils ≥ 1.5 x 103 cells/µl.

• Having met all concomitant medication criteria:

Capable of providing informed consent, prior to any study related procedure.

Exclusion criteria

• Exclusively fistulising Crohn's disease or exclusive involvement of the upper gastrointestinal (GI) tract.
• Subject with abscess or suspicion of abscess.
• Subject with obstructive fibrotic strictures (with prestenotic dilatation).
• Subject with short bowel syndrome.
• Subject who has had a surgical bowel resection within the past 6 months or planning of any resection at the time while enrolled in the study.
• Subject with Ulcerative Colitis or Indeterminant Colitis.
• Subject with ostomy or ileoanal pouch.
• Subject who is currently receiving total parenteral nutrition.
• Subject who has previously been treated with Infliximab or Certolizumab Pegol.
• Subject with positive stool cultures for enteric pathogens or positive C. difficile toxins during screening period.
• Subject who has received any investigational drug within 12 weeks prior to screening.
• Subject with a history of drug or alcohol abuse within the past 3 years.
• Females who are pregnant or breast feeding.
• Females of child bearing age not practicing effective birth control.
• Subject with a history of malignancy irrespective of time (except carcinoma- in situ of cervix or basal cell carcinoma or squamous cell carcinoma that was successfully treated).
• Subject with a history or symptoms of lymphoproliferative disease.
• Subject with a history of Human Immunodeficiency Virus (HIV), chronic or active Hepatitis B.
• History of Congestive Heart Failure (CHF), including medically controlled asymptomatic CHF.
• Subject who currently has or had an opportunistic infection (e.g. cytomegalovirus (CMV), pneumocystis carinii, aspergillosis, histoplasmosis, coccidioidomycosis) within 6 months prior to screening.
• Subject who currently has an active infection.
• Subject who has a transplanted organ (except for corneal transplant).
• History of known demyelinating disease such as optic neuritis or multiple sclerosis.
• Signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, psychiatric or cerebral disease.

CONCOMITANT MEDICATION

• Corticosteroids (prednisone, (methyl)prednisolone, budesonide):

stable dose for 2 weeks prior to baseline, then tapering at the discretion of the investigator.

• Immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate):

patients taking this medication prior to baseline: stable dose for 8 weeks prior to baseline, then stable dose until week 26 of the study. Starting or restarting of immunosuppressants is allowed until week 2, then stable dose until week 26 of the study.

• 5-ASA analogues (sulphasalazine, mesalazine): stable dose for 4 weeks prior to baseline, stable dose until week 26 of the study.
• Antibiotics (e.g. quinolone, metronidazole): stable dose for 2 weeks prior to baseline.
• Adalimumab: at least 2 week washout period prior to first Infliximab infusion.

Starting or increasing the dose of other medication for Crohn's disease than Infliximab during the study will be considered as "treatment failure". (except for immunosuppressants as described above under 2.)