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

Study Overview
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Brief Summary
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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.

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

Conditions
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Crohn Disease, Azathioprine, Methotrexate

Intervention / Treatment
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* Drug: AZA capsules
* Drug: MTX
* Biological: blood sample


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZA group<br>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 | Drug: AZA capsules<br>* oral AZA capsules at a daily dose of 2.5 mg per kilogram,<br>Biological: blood sample<br>* The lab tests are: serum albumin, C-reactive protein, thrombocytosis and haemoglobin.<br>|
| Experimental: MTX group<br>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 | Drug: MTX<br>* MTX 25 mg SC once a week<br>Biological: blood sample<br>* The lab tests are: serum albumin, C-reactive protein, thrombocytosis and haemoglobin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation of the endoscopic response between AZA and MTX groups | 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) | 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn Disease, Combinations of therapy, anti-Tumor Necrosis Factor, azathioprine, methotrexate