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

Tracking Information

• First Submitted Date: June 7, 2023
• First Posted Date: July 3, 2023
• Last Update Posted Date: March 15, 2024
• Actual Study Start Date: July 21, 2023
• Actual Primary Completion Date: January 12, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 23, 2023)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 23, 2023)

• 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
• 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
• 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.
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Evaluating the Persistence, Efficacy and Tolerability of Methotrexate in Inflammatory Bowel Disease Patients
• Official Title: Multicenter Study Evaluating the Persistence, Efficacy and Tolerability of Methotrexate in Inflammatory Bowel Disease Patients

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).

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
• Study Design: Observational Model: Cohort; Time Perspective: Retrospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: All patients followed for IBD treated with methotrexate between 01/01/2015 and 12/31/2022.

Condition

• Inflammatory Bowel Diseases
• Crohn Disease
• Ulcerative Colitis

• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 12, 2024): 1282
• Original Estimated Enrollment (submitted: June 23, 2023): 1000
• Actual Study Completion Date: January 12, 2024
• Actual Primary Completion Date: January 12, 2024 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Not Provided
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT05927064
• Other Study ID Numbers: 2023PI032
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: CARON Bénédicte, Central Hospital, Nancy, France
• Original Responsible Party: Same as current
• Current Study Sponsor: Central Hospital, Nancy, France
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Central Hospital, Nancy, France
• Verification Date: March 2024