Loss of response under anti-TNF is frequent. 20% of patients with clinical relapse present an immune mediated pharmacokinetic failure. In the last AGA recommendations, switch to another anti-TNF drug is suggested with no indication of immunosuppressive agent. In a recent study, 70% of patients with an immunogenic failure to a first anti-TNF agent developed a new immunogenic failure to the second anti-TNF drug using alone.

The aim of the study in these patients with an immune mediated pharmacokinetic failure was to compare two strategies:

Switch to a second anti-TNF alone or switch to a second anti-TNF with addition of azathioprine

Comparing rates of clinical failure, rates of immunogenic failure and finally adverse events during a follow-up of 24 months

Inclusion Criteria:

• IBD Patients in clinical failure under anti-TNF (Infliximab (IFX) or Adalimumab (ADA) in monotherapy at the optimal dose) ADA: 40mg/7 days, IFX: 10mg/kg/8 weeks Active disease CD: HBI > 5 with Calprotectin > 250 µg/g stool UC: Total Mayo Score > 4 with an endoscopic subscore > 1 Anti-TNF monotherapy for at least 4 months and optimization for at least two months
• Patients with an immune mediated PK failure Undetectable rates of anti-TNF and high Ab against anti-TNFs > 20ng/mL for ATI and AAA (Elisa Theradiag) on two consecutive samples
• Patients who have agreed to and signed the consent form

Exclusion Criteria:

• Unclassified colitis
• Pregnant woman
• Crohn's disease CD with a exclusive anoperineal phenotype
• Contraindication or intolerance to azathioprine
• Primary non-responder patients To the first anti-TNF or After the switch to a - second anti-TNF
• Ostomy

open label study