Study Evaluating the Persistence, Efficacy and Tolerability of Methotrexate in Inflammatory Bowel Disease Patients (MICI-METHO)

• ClinicalTrials.gov Identifier: NCT05927064
• Recruitment Status: Completed
• First Posted: July 3, 2023
• Last Update Posted: March 15, 2024
• Sponsor: Central Hospital, Nancy, France
• Information provided by (Responsible Party): CARON Bénédicte, Central Hospital, Nancy, France

Study Description

Brief Summary:

Methotrexate is one of the immunosuppressants used in chronic inflammatory bowel disease (IBD). It is indicated as monotherapy for induction and maintenance treatment of Crohn's disease (CD), or in combination with anti-tumor necrosis factor (TNF) agents for prevention of immunization.

The main objective is to assess the persistence rate of methotrexate treatment in patients followed for chronic inflammatory bowel disease (IBD).

Condition or disease
Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis

Detailed Description:

Methotrexate is one of the immunosuppressants used in chronic inflammatory bowel disease (IBD). It is indicated as monotherapy for induction and maintenance treatment of Crohn's disease (CD), or in combination with anti-tumor necrosis factor (TNF) agents for prevention of immunization Thiopurines are the most commonly used immunosuppressants in IBD, which contrasts with rheumatology data where methotrexate is the first-line immunosuppressant. Thiopurines and methotrexate have equivalent efficacy in CD 4.

Methotrexate is available in injectable (intramuscular (IM) or subcutaneous (SC)) or tablet form. In IBD, only parenteral administration has been shown to be effective. There is no consensus on the optimal maintenance dosage.

Tolerance problems remain an obstacle to its use, even if the side effects are not severe.

In this context, the objectives of this study are to describe the use of methotrexate in current practice in patients followed for IBD, its persistence, compliance, tolerance, as well as the factors associated with the persistence of treatment.

Study Design

• Study Type: Observational
• Actual Enrollment: 1282 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Multicenter Study Evaluating the Persistence, Efficacy and Tolerability of Methotrexate in Inflammatory Bowel Disease Patients
• Actual Study Start Date: July 21, 2023
• Actual Primary Completion Date: January 12, 2024
• Actual Study Completion Date: January 12, 2024

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Persistence rate of methotrexate treatment in chronic inflammatory bowel disease patients [ Time Frame: minimum follow-up of 6 months post-induction of treatment and maximum on the date of cessation of treatment or date of last news 12/31/2022 ]
   Persistence is measured as the time between starting treatment and stopping the drug or switching to another drug.

Secondary Outcome Measures :

1. Assess the effectiveness of induction therapy with methotrexate for Crohn's patient [ Time Frame: minimum follow-up of 6 months post-induction of treatment and maximum on the date of cessation of treatment or date of last news 12/31/2022 ]

   Clinical response defined as a decrease of at least 3 points in the Harvey-Bradshaw Index (HBI) for CD assessed at 6 months of methotrexate therapy.

   The Harvey-Bradshaw Index consists of a few questions (n=5) to quickly categorize the severity of Crohn's disease and detect remission.

   Harvey-Bradshaw Index Score:

   Remission: <5 Mild Disease: 5 to 7 Moderate Disease: 8 to 16 Severe Disease: >16

2. Assess the effectiveness of induction therapy with methotrexate for Ulcerative colitis patient [ Time Frame: minimum follow-up of 6 months post-induction of treatment and maximum on the date of cessation of treatment or date of last news 12/31/2022 ]

   Clinical response defined as a decrease of at least 3 points in the partial Mayo score for Ulcerative colitis (UC) assessed at 6 months of methotrexate therapy

   Mayo score composed by 4 items: stool frequency; rectal bleeding, mucosal appearance at endoscopy and physician rating of disease activity.

   Mayo score:

   Score <2 : no activity Score between 3 and 5: mild activity Score between 6 and 10 :moderate activity Score >11 : severe activity

3. Assess the safety of methotrexate therapy [ Time Frame: minimum follow-up of 6 months post-induction of treatment and maximum on the date of cessation of treatment or date of last news 12/31/2022 ]
   Adverse reactions associated with methotrexate treatment: hematological, hepatic, pulmonary, renal toxicity, allergic reaction, abdominal pain, nausea, vomiting.
4. Describe the reasons for discontinuation of methotrexate therapy [ Time Frame: minimum follow-up of 6 months post-induction of treatment and maximum on the date of cessation of treatment or date of last news 12/31/2022 ]
   Reasons for discontinuing methotrexate: inefficiency and intolerance

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Sampling Method: Non-Probability Sample

Study Population

All patients followed for IBD treated with methotrexate between 01/01/2015 and 12/31/2022.

Criteria

Inclusion Criteria:

1. Person who has received full information on the organization of the research and has not objected to the use of this data
2. Age ≥18 years
3. Certain diagnosis of IBD (European Crohn's Colitis Organization criteria)
4. Introduction of methotrexate mono- or combination therapy between January 1, 2015 and December 31, 2022
5. Minimum 6-month follow-up after initiation of methotrexate therapy
6. Person affiliated with a social security plan or beneficiary of such a plan

Exclusion Criteria:

1. Age <18 years

2. Person referred to in articles L. 1121-5, L. 1121-7 and L1121-8 of the public health code

   • Pregnant woman, parturient or nursing mother
   • Minor (not emancipated)
   • Adult person subject to a legal protection measure (guardianship, curatorship, safeguard of justice)
   • A person of full age who is unable to give consent
3. Persons deprived of liberty by a judicial or administrative decision, persons under psychiatric care by virtue of articles L. 3212-1 and L. 3213-1

Contacts and Locations

Locations

France

CHRU of Nancy

Vandoeuvre Les Nancy, Grand Est, France, 54511

Sponsors and Collaborators

Central Hospital, Nancy, France

Investigators

• Principal Investigator: Bénédicte CARON, MD; CHRU of Nancy, Hepatogastroenterology Department

More Information

Publications of Results:

Feagan BG, Rochon J, Fedorak RN, Irvine EJ, Wild G, Sutherland L, Steinhart AH, Greenberg GR, Gillies R, Hopkins M, et al. Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators. N Engl J Med. 1995 Feb 2;332(5):292-7. doi: 10.1056/NEJM199502023320503.

Mate-Jimenez J, Hermida C, Cantero-Perona J, Moreno-Otero R. 6-mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroid-dependent inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2000 Nov;12(11):1227-33. doi: 10.1097/00042737-200012110-00010.

Nielsen OH, Ainsworth MA, Steenholdt C. Methotrexate for inflammatory bowel disease: time for reconsideration. Expert Rev Gastroenterol Hepatol. 2019 May;13(5):407-409. doi: 10.1080/17474124.2019.1596797. Epub 2019 Mar 21. No abstract available.

Ardizzone S, Bollani S, Manzionna G, Imbesi V, Colombo E, Bianchi Porro G. Comparison between methotrexate and azathioprine in the treatment of chronic active Crohn's disease: a randomised, investigator-blind study. Dig Liver Dis. 2003 Sep;35(9):619-27. doi: 10.1016/s1590-8658(03)00372-4.

• Responsible Party: CARON Bénédicte, Doctor, Central Hospital, Nancy, France
• ClinicalTrials.gov Identifier: NCT05927064
• Other Study ID Numbers: 2023PI032
• First Posted: July 3, 2023
• Last Update Posted: March 15, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Crohn Disease; Intestinal Diseases; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases