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

Multicenter Study Evaluating the Persistence, Efficacy and Tolerability of Methotrexate in Inflammatory Bowel Disease Patients

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).

Study Overview

• Status: Completed
• Conditions: 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 Type: Observational
• Enrollment (Actual): 1282

Contacts and Locations

Study Locations

• France
  • Grand Est
    • Vandoeuvre Les Nancy, Grand Est, France, 54511
      • CHRU of Nancy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistence rate of methotrexate treatment in chronic inflammatory bowel disease patients	Persistence is measured as the time between starting treatment and stopping the drug or switching to another drug.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the effectiveness of induction therapy with methotrexate for Crohn's patient	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	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
Assess the effectiveness of induction therapy with methotrexate for Ulcerative colitis patient	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	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
Assess the safety of methotrexate therapy	Adverse reactions associated with methotrexate treatment: hematological, hepatic, pulmonary, renal toxicity, allergic reaction, abdominal pain, nausea, vomiting.	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
Describe the reasons for discontinuation of methotrexate therapy	Reasons for discontinuing methotrexate: inefficiency and intolerance	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

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Principal Investigator: Bénédicte CARON, MD, CHRU of Nancy, Hepatogastroenterology Department

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2023
• Primary Completion (Actual): January 12, 2024
• Study Completion (Actual): January 12, 2024

Study Registration Dates

• First Submitted: June 7, 2023
• First Submitted That Met QC Criteria: June 23, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Intestinal Diseases
• Other Study ID Numbers: 2023PI032

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No