Addition of Azathioprine in IBD Patients With Immunogenic Failure

Phase 4

• Conditions: Clinical Failure After Switch
• Interventions: Drug: addition of azathioprine; Drug: Switch to a second anti-TNF drug alone

• Registration Number: NCT03580876
• Lead Sponsor: Védrines, Philippe, M.D.

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

Study Timeline

• Study First Submitted: 2018-06-12
• Study First Submitted QC: 2018-06-25
• Status Verified: 2018-07
• Study First Posted: 2018-07-09
• Last Update Submitted: 2018-07-09
• Last Update Posted: 2018-07-10
• Study Start: 2018-07-23
• Primary Completion: 2019-06-10
• Study Completion: 2020-06-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 90

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
switch to anti-TNF with addition of azathioprine	addition of azathioprine	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.
switch to anti-TNF alone	Switch to a second anti-TNF drug alone	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.

Primary Outcome Measures

Name	Time	Method
clinical failure	24 months	clinical relapse or serious adverse event requiring stopping treatment during follow up

Trial Locations

Locations (1)

Clinic of Montbrison; 🇫🇷 Montbrison, Loire, France