A Study of the Relationship Between Infliximab Levels and the Rate of Colectomies in Patients who have Ulcerative Colitis

Overview

About this study

The purpose of this study is to assess if infliximab drug levels in patients who have Ulcerative Colitis predict the risk of needing a colectomy. Additionally, the investigators will estimate an optimal day 4 infliximab level based on the study results.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria

  • Adults, 18 years and older
  • Hospitalized, with a moderate to severe flare based on the Mayo Scoring System for Assessment of Ulcerative Colitis Activity (Mayo score of equal or greater than 6)
  • Treatment naïve to anti TNF agents
  • Initiation of infliximab, with or without immunomodulator such as azathioprine
  • Ongoing use of immunomodulators such as azathioprine or 6MP is acceptable and remains at the discretion of the treating physician

Exclusion Criteria

  • Ongoing or prior treatment with Infliximab or other anti TNF agents
    • Concomitant immunomodulator therapy is acceptable if on a stable dosing for atleast 4 weeks
    • Current medications may be continued at the discretion of the treating physician
  • Fulminant colitis or toxic megacolon requiring emergent surgery
  • Pregnancy
  • Infectious colitis, for example Clostridium difficile or CMV (cytomegalovirus) colitis
  • Active infection or abscess
  • 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
  • Active malignancy
  • Active or history of Congestive Heart failure (CHF) or those who have received treatment for CHF
  • Active or history of Multiple Sclerosis (MS), or those who have received treatment for MS
  • Prisoners, institutionalized individuals, and individuals who are not capable of giving informed consent
  • Other criteria that is the judgement of the investigator

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Darrell Pardi, M.D.

Closed for enrollment

La Crosse, Wis.

Mayo Clinic principal investigator

Michael Van Norstrand, M.D., Ph.D.

Closed for enrollment

More information

Publications

  • Crohn's disease and ulcerative colitis are chronic inflammatory disorders resulting from immune dysregulation. Patients who fail conventional medical therapy require biological treatment with monoclonal antibodies (mAbs). Although mAbs are highly effective for induction and maintenance of clinical remission, not all patients respond, and a high proportion of patients lose response over time. One factor associated with loss of response is immunogenicity, whereby the production of antidrug antibodies accelerates mAb clearance. However, other factors related to patient and disease characteristics also influence the pharmacokinetics of mAbs. These factors include gender, body size, concomitant use of immunosuppressive agents, disease type, serum albumin concentration, and the degree of systemic inflammation. Because it is important to maintain clinically effective concentrations to provide optimal clinical response and drug exposure is affected by patient factors, a better understanding of the pharmacology of mAbs will ultimately result in better patient care. Read More on PubMed
  • Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and is associated with significant morbidity. The etiology of IBD has been extensively studied during the last several decades; however, causative factors in disease pathology are not yet fully understood. IBD is thought to result from the interaction between genetic and environmental factors that influence the normal intestinal commensal flora to trigger an inappropriate mucosal immune response. Although many IBD susceptibility genes have been discovered, similar advances in defining environmental risk factors have lagged. A number of environmental risk factors have been explored, including smoking, appendectomy, oral contraceptives, diet, breastfeeding, infections/ vaccinations, antibiotics, and childhood hygiene. However, most of these factors have demonstrated inconsistent findings, thus making additional studies necessary to better understand the etiology of IBD. Read More on PubMed
  • Crohn's disease commonly recurs after intestinal resection. We evaluated whether the administration of infliximab after resective intestinal surgery for Crohn's disease reduces postoperative recurrence. Read More on PubMed
  • We performed a meta-analysis of placebo-controlled trials to evaluate safety and efficacy of tumor necrosis factor (TNF) antagonists for Crohn's disease. Read More on PubMed
  • Increased infertility in women has been reported after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis but reported infertility rates vary substantially. Read More on PubMed
  • Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality. Read More on PubMed
  • Within a lifetime, approximately 15% of ulcerative colitis (UC) patients will have a severe relapse necessitating admission to hospital. Despite intravenous steroid treatment, approximately 25% will require either surgery or ciclosporin (CsA) rescue therapy. Initial response rates to CsA have been encouraging, but remission rates have been disappointing. There is a paucity of long-term data on UC patients who have been brought into remission with CsA. Read More on PubMed
  • To evaluate in what manner ageing affects functional outcome and quality of life (QoL) in patients with chronic ulcerative colitis (CUC) after ileal pouch-anal anastomosis (IPAA). Read More on PubMed
  • Guidelines for clinical practice are intended to indicate preferred approaches to medical problems as established by scientifically valid research. Double-blind placebo-controlled studies are preferable, but compassionate use reports and expert review articles are utilized in a thorough review of the literature conducted through Medline with the National Library of Medicine. When only data that will not withstand objective scrutiny are available, a recommendation is identified as a consensus of experts. Guidelines are applicable to all physicians who address the subject without regard to the specialty training or interests and are intended to indicate the preferable but not necessarily the only acceptable approach to a specific problem. Guidelines are intended to be flexible and must be distinguished from standards of care, which are inflexible and rarely violated. Given the wide range of specifics in any health-care problem, the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. Guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Each has been extensively reviewed and revised by the Committee, other experts in the field, physicians who will use them, and specialists in the science of decision of analysis. The recommendations of each guideline are therefore considered valid at the time of their production based on the data available. New developments in medical research and practice pertinent to each guideline will be reviewed at a time established and indicated at the publication in order to assure continued validity. Read More on PubMed
  • Although the incidence and prevalence of ulcerative colitis and Crohn's disease are beginning to stabilize in high-incidence areas such as northern Europe and North America, they continue to rise in low-incidence areas such as southern Europe, Asia, and much of the developing world. As many as 1.4 million persons in the United States and 2.2 million persons in Europe suffer from these diseases. Previously noted racial and ethnic differences seem to be narrowing. Differences in incidence across age, time, and geographic region suggest that environmental factors significantly modify the expression of Crohn's disease and ulcerative colitis. The strongest environmental factors identified are cigarette smoking and appendectomy. Whether other factors such as diet, oral contraceptives, perinatal/childhood infections, or atypical mycobacterial infections play a role in expression of inflammatory bowel disease remains unclear. Additional epidemiologic studies to define better the burden of illness, explore the mechanism of association with environmental factors, and identify new risk factors are needed. Read More on PubMed
  • Primary sclerosing cholangitis (PSC), present in 5% of patients with ulcerative colitis, may be associated with pouchitis after ileal pouch-anal anastomosis. The cumulative frequency of pouchitis in patients with and without PSC who underwent ileal pouch-anal anastomosis for ulcerative colitis was determined. A total of 1097 patients who had an ileal pouch-anal anastomosis for ulcerative colitis, 54 with associated PSC, were studied. Pouchitis was defined by clinical criteria in all patients and by clinical, endoscopic, and histological criteria in 83% of PSC patients and 85% of their matched controls. PSC was defined by clinical, radiological, and pathological findings. One or more episodes of pouchitis occurred in 32% of patients without PSC and 63% of patients with PSC. The cumulative risk of pouchitis at one, two, five, and 10 years after ileal pouch-anal anastomosis was 15.5%, 22.5%, 36%, and 45.5% for the patients without PSC and 22%, 43%, 61%, and 79% for the patients with PSC. In the PSC group, the risk of pouchitis was not related to the severity of liver disease. In conclusion, the strong correlation between PSC and pouchitis suggest a common link in their pathogenesis. Read More on PubMed
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CLS-20145560

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