Colitis, Ulcerative, IBD, Inflammatory Bowel Disease
Conditions
Keywords
infliximab, remicade, IBD, Colitis, Ulcerative
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.
Interventions
None listed
Sponsors
Mayo Clinic
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants to be Colectomy Free at 3 Months | 3 month | Total number of participants to be colectomy free at 3 months |
| Number of Participants With the Need for Colectomy Assessed by Biomarker Levels | 3 months | Biomarkers markers ESR, CRP, TNF levels, and hemoglobin will be collected to assess relationships between colectomy an other potential biomarkers |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants to be Colectomy Free at 1 Month | 1 month | Total number of participants to be colectomy free at 1 month |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hospitalized Patients Receiving Infliximab Patients hospitalized and scheduled to receive clinically indicated infliximab due to flare of moderate to severe UC. | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Hospitalized Patients Receiving Infliximab | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 13 Participants | — |
| Age, Continuous | 34 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 13 participants | — |
| Sex: Female, Male Female | 4 Participants | — |
| Sex: Female, Male Male | 9 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Number of Participants to be Colectomy Free at 3 Months
Total number of participants to be colectomy free at 3 months
Time frame: 3 month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hospitalized Patients Receiving Infliximab | Number of Participants to be Colectomy Free at 3 Months | 6 Participants |
Primary
Number of Participants With the Need for Colectomy Assessed by Biomarker Levels
Biomarkers markers ESR, CRP, TNF levels, and hemoglobin will be collected to assess relationships between colectomy an other potential biomarkers
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hospitalized Patients Receiving Infliximab | Number of Participants With the Need for Colectomy Assessed by Biomarker Levels | 13 Participants |
Secondary
Number of Participants to be Colectomy Free at 1 Month
Total number of participants to be colectomy free at 1 month
Time frame: 1 month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hospitalized Patients Receiving Infliximab | Number of Participants to be Colectomy Free at 1 Month | 11 Participants |