Correlation of Infliximab Levels With Outcomes in Ulcerative Colitis

Inflammatory Bowel Disease Clinical Trial

Official title:

Correlation of Infliximab Levels With Outcomes in Ulcerative Colitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02438410
• Other study ID #: 14-005723
• Status: Completed
• Start date: May 2015
• Est. completion date: December 4, 2019

Study information

• Verified date: April 2022
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: December 4, 2019
• Est. primary completion date: December 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• IBD
• Inflammatory Bowel Disease
• Inflammatory Bowel Diseases
• Ulcer

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

References & Publications (16)

Brandse J.F. MWM, de Bruyn J., Wolbink GJ., Lowenberg M., Ponsioen C., van den Brink G.R., D'Haens G.R. Fecal Loss of Infliximab As a Cause of Lack of Response in Severe Inflammatory Bowel Disease. Gastroenterology May 2013;144:S-36.

Campbell S, Travis S, Jewell D. Ciclosporin use in acute ulcerative colitis: a long-term experience. Eur J Gastroenterol Hepatol. 2005 Jan;17(1):79-84. — View Citation

Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med. 2011 Nov 3;365(18):1713-25. doi: 10.1056/NEJMra1102942. Review. — View Citation

Gibson DJ, Heetun ZS, Redmond CE, Nanda KS, Keegan D, Byrne K, Mulcahy HE, Cullen G, Doherty GA. An accelerated infliximab induction regimen reduces the need for early colectomy in patients with acute severe ulcerative colitis. Clin Gastroenterol Hepatol. 2015 Feb;13(2):330-335.e1. doi: 10.1016/j.cgh.2014.07.041. Epub 2014 Jul 30. — View Citation

Hahnloser D, Pemberton JH, Wolff BG, Larson DR, Crownhart BS, Dozois RR. The effect of ageing on function and quality of life in ileal pouch patients: a single cohort experience of 409 patients with chronic ulcerative colitis. Ann Surg. 2004 Oct;240(4):615-21; discussion 621-3. — View Citation

Järnerot G, Hertervig E, Friis-Liby I, Blomquist L, Karlén P, Grännö C, Vilien M, Ström M, Danielsson A, Verbaan H, Hellström PM, Magnuson A, Curman B. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology. 2005 Jun;128(7):1805-11. — View Citation

Kornbluth A, Sachar DB; Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2004 Jul;99(7):1371-85. — View Citation

Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology. 2004 May;126(6):1504-17. — View Citation

Molodecky NA, Kaplan GG. Environmental risk factors for inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2010 May;6(5):339-46. — View Citation

Ordás I, Mould DR, Feagan BG, Sandborn WJ. Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms. Clin Pharmacol Ther. 2012 Apr;91(4):635-46. doi: 10.1038/clpt.2011.328. Epub 2012 Feb 22. Review. — View Citation

Penna C, Dozois R, Tremaine W, Sandborn W, LaRusso N, Schleck C, Ilstrup D. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis. Gut. 1996 Feb;38(2):234-9. — View Citation

Peyrin-Biroulet L, Deltenre P, de Suray N, Branche J, Sandborn WJ, Colombel JF. Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol. 2008 Jun;6(6):644-53. doi: 10.1016/j.cgh.2008.03.014. — View Citation

Regueiro M, Schraut W, Baidoo L, Kip KE, Sepulveda AR, Pesci M, Harrison J, Plevy SE. Infliximab prevents Crohn's disease recurrence after ileal resection. Gastroenterology. 2009 Feb;136(2):441-50.e1; quiz 716. doi: 10.1053/j.gastro.2008.10.051. Epub 2008 Oct 31. — View Citation

Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. Erratum in: N Engl J Med. 2006 May 18;354(20):2200. — View Citation

Sandborn WJ. A critical review of cyclosporine therapy in inflammatory bowel disease. Inflammatory Bowel Diseases 1995;1:48-63.

Waljee A, Waljee J, Morris AM, Higgins PD. Threefold increased risk of infertility: a meta-analysis of infertility after ileal pouch anal anastomosis in ulcerative colitis. Gut. 2006 Nov;55(11):1575-80. Epub 2006 Jun 13. Review. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants to be Colectomy Free at 3 Months	Total number of participants to be colectomy free at 3 months	3 month
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	3 months
Secondary	Number of Participants to be Colectomy Free at 1 Month	Total number of participants to be colectomy free at 1 month	1 month

External Links

•   Mayo Clinic Clinical Trials