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

Phase 3

Recruiting

• Conditions: Azathioprine; Crohn Disease; Methotrexate
• Interventions: Drug: AZA capsules; Drug: MTX; Biological: blood sample

• Registration Number: NCT05040464
• Lead Sponsor: Centre Hospitalier Universitaire, Amiens

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-08-26
• Study First Submitted: 2021-08-26
• Study First Submitted QC: 2021-09-07
• Study First Posted: 2021-09-10
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-07
• Last Update Posted: 2023-02-08
• Primary Completion: 2023-08
• Study Completion: 2024-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 166

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AZA group	AZA capsules	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
AZA group	blood sample	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
MTX group	blood sample	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
MTX group	MTX	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

Primary Outcome Measures

Name	Time	Method
Variation of the endoscopic response between AZA and MTX groups	26 weeks	Variation of the endoscopic response to AZA in combination with adalimumab and to MTX in combination with adalimumab in patients with CD.; The endoscopic reference score (EREFS) is used to determine severity of 5 endoscopic findings: edema, rings, exudates, furrows, and structures. The EREFS classification system rates the severity of edema (0-2), rings (0-3), exudates (0-2), furrows (0-2), and strictures (0-1)

Trial Locations

Locations (1)

CHU Amiens; 🇫🇷 Amiens, France