Addition of Azathioprine in IBD Patients With Immunogenic Failure (Comboswitch)

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

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.

Study Overview

• Status: Unknown
• Conditions: Clinical Failure After Switch
• Intervention / Treatment: Drug: Switch to a second anti-TNF drug alone; Drug: addition of azathioprine

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 Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: philippe vedrines, MD,PhD; Phone Number: 0608632997; Email: vedrines.philippe@wanadoo.fr
• Study Contact Backup: Name: xavier roblin, MD,PhD; Email: roblinx42@gmail.com

Study Locations

• France
  • Loire
    • Montbrison, Loire, France, 42100
      • Recruiting
      • Clinic of Montbrison
      • Contact: philippe vedrines, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: switch to anti-TNF 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.	Drug: Switch to a second anti-TNF drug alone; Switch to a second anti-TNF drug alone without addition of azathioprine
OTHER: switch to anti-TNF with 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.	Drug: addition of azathioprine; impact of addition of azathioprine after a switch of a second anti-TNF agent

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

Collaborators and Investigators

• Sponsor: Védrines, Philippe, M.D.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 23, 2018
• Primary Completion (ANTICIPATED): June 10, 2019
• Study Completion (ANTICIPATED): June 10, 2020

Study Registration Dates

• First Submitted: June 12, 2018
• First Submitted That Met QC Criteria: June 25, 2018
• First Posted (ACTUAL): July 9, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 10, 2018
• Last Update Submitted That Met QC Criteria: July 9, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Azathioprine
• Other Study ID Numbers: COMBOSWITCH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No