Correlation of Infliximab Levels With Outcomes in Ulcerative Colitis
Condition: Colitis, Ulcerative; Inflammatory Bowel Disease; IBD
MeSH terms: Colitis; Colitis, Ulcerative; Inflammatory Bowel Diseases; Ulcer
Study type: Observational

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.
    

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.
      
Biospecimen description: 
      Stool and blood laboratory data such as CBC with differential, creatinine, TNF levels,
      albumin, fecal calprotectin, ESR, CRP, infliximab and antibodies to infliximab levels will be
      obtained.
    
Keywords: infliximab; remicade; IBD; Colitis, Ulcerative