Comparison of Azathioprine to Methotrexate in Combination Therapy With Adalimumab in Crohn's Disease: an Open-label Randomized Controlled Trial (COMET)

Centre Hospitalier Universitaire, Amiens

Status and phase: Enrolling; Phase 3

Conditions: Methotrexate; Azathioprine; Crohn Disease

Treatments: Drug: MTX; Biological: blood sample; Drug: AZA capsules

Study type: Interventional

Funder types: Other

Identifiers

NCT05040464

PI2021_843_0080

Details and patient eligibility

About

Combination therapy, the association of an anti-Tumor Necrosis Factor (TNF) to an immunosuppressant, is recognized as the most effective treatment during Crohn's disease (CD). Several mechanisms have been proposed to explain the superiority of combination therapy over monotherapy, the additive effect of two effective drugs or the prevention of anti-TNF immunogenicity. As the best combination therapy is unknown, both azathioprine (AZA) and methotrexate (MTX) are used. Some retrospective studies suggest a higher effectiveness of AZA. MTX may have an advantage in terms of safety.

The investigators hypothesize that AZA is more effective than MTX as combination therapy with adalimumab to improve short-term endoscopic, clinical and pharmacological outcomes in CD patients.

Enrollment: 166 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female patients with age > 18 years
• Crohn's disease for at least 6 weeks,
• Clinically active with CDAI > 150
• Active inflammation by endoscopy (CDEIS > 4) at baseline
• Not responder to conventional therapy or are intolerant to or have medical contraindications for such therapies and initiating treatment with adalimumab
• Patient followed in a center belonging to the GETAID network
• Fertile men and women of childbearing potential included in the protocol should use adequate methods of contraception according to study drug SMPCs.
• Written consent

Exclusion criteria

• Short bowel syndrome, ostomy, symptomatic stricture, abscess, recent history of abdominal surgery (<3 months)
• Non-passable colonic stricture
• Previous intolerance to thiopurines or MTX
• Previous exposition to adalimumab
• Contra-indication to immunosuppressants or anti-TNF
• Others serious simultaneous illness that could interfere with study participation
• Planning pregnancy, pregnancy or lactation or absence of contraception
• Known substance abusers
• Use of any investigational drug within 30 days
• Adults protected by law

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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166 participants in 2 patient groups

AZA group

Experimental group

Description:

Combination of sub-cutaneous administration of adalimumab at a dose of 160mg(W0)-80mg(W2)-40mg(W6) and then 40mg EOW and oral AZA capsules at a daily dose of 2.5 mg/kg

Treatment:

Drug: AZA capsules

Biological: blood sample

MTX group

Experimental group

Description:

Combination of sub-cutaneous administration of adalimumab at a dose of 160mg (week (W) 0)-80mg(W2)-40mg(W6) and then 40mg EOW and sub-cutaneous MTX 25mg once a week

Treatment:

Drug: MTX

Biological: blood sample