Correlation of Infliximab Levels With Outcomes in Ulcerative Colitis

NCT ID: NCT02438410

Last Updated: 2022-05-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 13 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2019-12-04

Brief Summary

To assess if infliximab drug levels in subjects with Ulcerative Colitis predict risk of colectomy rate. Additionally, the investigators will estimate an optimal day 4 infliximab level based on the study results.

Detailed Description

Infliximab is approved for induction and maintenance of clinical remission and mucosal healing in patients with moderate to severe active ulcerative colitis, in those who have an inadequate response to conventional therapy such as IV steroids. It is typically dosed at 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter. The alternative to rescue medical therapy with infliximab is proctocolectomy with ileal pouch anastomosis, which carries risks including pouchitis, fecal incontinence, pouch failure requiring further surgical procedures and female infertility, or proctocolectomy with permanent end-ileostomy, which many patients wish to avoid. The induction regimen of 3 doses of Infliximab followed by a maintenance dose every 8 weeks is used to achieve response in hopes of avoiding colectomy. Unfortunately, a large proportion of patients are unable to achieve or sustain a clinical response over time and end up getting a colectomy.

Potential implicated pathways in non-responders include fecal wasting of infliximab and factors that accelerate drug clearance such as a large TNF (tumor necrosis factor) or CRP (C reactive protein) burden, anti-infliximab antibodies (ATI), low serum albumin, male sex and larger body size. Patients with severe ulcerative colitis who fail corticosteroids and standard dosing with infliximab usually proceed to proctocolectomy. Optimizing early infliximab blood levels in patients with moderate-severe ulcerative colitis by administering the second dose of infliximab before week 2 could improve the efficacy and further reduce the need for colectomy. However, there is a paucity in the literature as this is a relatively new school of thought. Our study will address this deficit by evaluating the relationship between early drug levels of infliximab in ulcerative colitis and colectomy rates at one and three months.

Conditions

Colitis, Ulcerative; Inflammatory Bowel Disease; IBD

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

1. Adults, ages 18-65 years

2. Hospitalized, with a moderate -severe flare. Based on the Mayo Scoring System for Assessment of Ulcerative Colitis Activity (Mayo score of equal or greater than 6)

3. Treatment naïve to anti TNF agents

4. Initiation of infliximab, with or without immunomodulator such as azathioprine

5. Ongoing use of immunomodulators such as azathioprine or 6MP is acceptable. Their initiation or continuation remains at the discretion of the treating physician

Exclusion Criteria

1. Ongoing or prior treatment with Infliximab or other anti TNF agents

2. Ongoing or recent (with in 1 month) administration of rescue cyclosporine

3. Fulminant colitis requiring emergent surgery or toxic megacolon

4. Pregnancy

5. Infectious colitis, for example Clostridium difficile or CMV (cytomegalovirus) colitis

6. Active infection or abscess

8. Active malignancy

9. Active or history of Congestive Heart failure (CHF) or those who have received treatment for CHF

10. Active or history of Multiple Sclerosis (MS), or those who have received treatment for MS

11. Prisoners, institutionalized individuals, and individuals who are not capable of giving informed consent

12. Judgement of investigator

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Darrell S. Pardi, M.D.

PI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Darrell S Pardi, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

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Provided Documents

Document Type: Study Protocol

View Document

Related Links

https://www.mayo.edu/research/clinical-trials

Mayo Clinic Clinical Trials

Other Identifiers

14-005723

Identifier Type: -

Identifier Source: org_study_id