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

Védrines, Philippe, M.D.

Status and phase: Unknown; Phase 4

Conditions: Clinical Failure After Switch

Treatments: Drug: Switch to a second anti-TNF drug alone; Drug: addition of azathioprine

Study type: Interventional

Identifiers

NCT03580876

COMBOSWITCH

Details and patient eligibility

About

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.

Full 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

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

switch to anti-TNF alone

Other group

Description:

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.

Treatment:

Drug: Switch to a second anti-TNF drug alone

switch to anti-TNF with addition of azathioprine

Other group

Description:

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.

Treatment:

Drug: addition of azathioprine