Clinical trial NCT02438410: Correlation of Infliximab Levels With Outcomes in Ulcerative Colitis
Official title: Correlation of Infliximab Levels With Outcomes in Ulcerative Colitis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colitis, Ulcerative
Inflammatory Bowel Disease
IBD
Keywords: infliximab
remicade
IBD
Colitis, Ulcerative
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2015-05-08
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients must be scheduled to receive clinically indicated infliximab at the discretion of their treating physician during an acute hospitalization with a flare of moderate to severe UC. These will be inpatients at Mayo Clinic Rochester campus or be admitted in Mayo Clinic Health Systems. Endoscopic findings will be noted and those deemed to have moderate to severe disease activity based on the Mayo Scoring System for Assessment of Ulcerative Colitis Activity will be considered.

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.

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
7. Untreated latent or active tuberculosis (TB). Those with latent TB who are currently undergoing treatment can be included. Please refer to appendix 1 for more information on specific inclusion and exclusion criteria related to TB testing. Refer to 1.4.2 of appendix 1 for TB screening questions
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

Primary outcomes:
measure: Number of Participants to be Colectomy Free at 3 Months
timeFrame: 3 month
measure: Number of Participants With the Need for Colectomy Assessed by Biomarker Levels
timeFrame: 3 months
Secondary outcomes:
measure: Number of Participants to be Colectomy Free at 1 Month
timeFrame: 1 month
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Darrell S Pardi, MD
role: PRINCIPAL_INVESTIGATOR
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