Addition of Azathioprine in IBD Patients With Immunogenic Failure

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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

Official Title
-----------------
Addition of Azathioprine to the Switch of Anti-TNF Drug in IBD Patients in Clinical Relapse With Undectectable Anti-TNF Trough Levels and Anti-drug Antibodies : a Prospective Randomized Trial

Conditions
-----------------
Clinical Failure After Switch

Intervention / Treatment
-----------------
* Drug: addition of azathioprine
* Drug: Switch to a second anti-TNF drug alone


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: two strategies
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: switch to anti-TNF alone<br>Switch to the second anti-TNF drug alone (infliximab or adalimumab) Loss of response under Infliximab: 10 mg/kg IV every 8 weeks Randomization to: Adalimumab: induction 160/80 mg SC and Maintenance 40 mg EOW SC OR Loss of response under Adalimumab: 40mg EW SC Randomization to: Infliximab: 5mg/kg IV at W0, W2, W6 and every 8 weeks. | Drug: Switch to a second anti-TNF drug alone<br>* Switch to a second anti-TNF drug alone without addition of azathioprine<br>|
| Other: switch to anti-TNF with addition of azathioprine<br>Switch to anti-TNF (infliximab or adalimumab) with addition of azathioprine Loss of response under Infliximab: 10 mg/kg IV every 8 weeks Randomization to: Adalimumab: induction 160/80 mg SC and Maintenance 40 mg EOW SC with azathioprine 2.5 mg/kg/day OR Loss of response under Adalimumab: 40mg EW SC Randomization to: Infliximab: 5mg/kg IV at W0, W2, W6 and every 8 weeks with azathioprine 2.5 mg/kg/day. | Drug: addition of azathioprine<br>* impact of addition of azathioprine after a switch of a second anti-TNF agent<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical failure | clinical relapse or serious adverse event requiring stopping treatment during follow up | 24 months |