Early Serum Infliximab Levels in Severe Ulcerative Colitis.

NCT01971814 | Completed Phase 1 DMC

• 1 other identifier: UCSF
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to a.) evaluate whether early serum infliximab levels are predictive of avoidance of colectomy, b) evaluate whether serum albumin levels correlate with serum infliximab levels, and c) evaluate whether serum tumor necrosis factor levels are inversely correlated with serum infliximab levels. In patients hospitalized for severe ulcerative colitis and treated with high-dose infliximab, we predict that early serum infliximab levels (24, 48, and 72 hour) will be positively associated with clinical response and avoidance of colectomy.

Conditions

Ulcerative Colitis (UC); Inflammatory Bowel Disease

Outcome Measures

Primary Outcomes (1)

• serum infliximab level

  2 weeks

Secondary Outcomes (2)

• serum tumor necrosis factor alpha level

  2 weeks

• Colectomy

  Up to 10 days after infliximab infusion (post-treatment)

Study Arms (1)

Early infliximab monitoring group.

EXPERIMENTAL

A consecutive sample of patients hospitalized with severe ulcerative colitis who are eligible to receive infliximab at 10mg/kg IV.

Drug: Infliximab

Interventions

Infliximab DRUG

All patients meeting inclusion criteria will receive the infliximab 10mg/kg IV as part of standard care of the hospitalized patient with severe ulcerative colitis at UCSF Medical Center.

Also known as: Infliximab (generic), Remicade (brand name), National Drug Codes - 57894-0030

Early infliximab monitoring group.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \> 18 yrs.
• Admitted with a primary diagnosis of ulcerative colitis.
• Ulcerative colitis disease activity index score 6-12 (scale, 0-12).
• Mayo endoscopic subscore of 2 or greater.
• No prior treatment with infliximab.
• Patients with prior or ongoing exposure to non-infliximab biologic therapies, regardless of drug washout.

You may not qualify if:

• \< 18 yrs.
• Other inflammatory bowel disease including Crohn's disease, indeterminate colitis, and microscopic colitis.
• Prior treatment with infliximab therapy.
• Contraindication to anti-TNF therapy.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California at San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (15)

• Clark M, Colombel JF, Feagan BC, Fedorak RN, Hanauer SB, Kamm MA, Mayer L, Regueiro C, Rutgeerts P, Sandborn WJ, Sands BE, Schreiber S, Targan S, Travis S, Vermeire S. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23, 2006. Gastroenterology. 2007 Jul;133(1):312-39. doi: 10.1053/j.gastro.2007.05.006.

  PMID: 17631151 BACKGROUND

• 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. doi: 10.1056/NEJMoa050516.

  PMID: 16339095 BACKGROUND

• Colombel JF, Rutgeerts P, Reinisch W, Esser D, Wang Y, Lang Y, Marano CW, Strauss R, Oddens BJ, Feagan BG, Hanauer SB, Lichtenstein GR, Present D, Sands BE, Sandborn WJ. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology. 2011 Oct;141(4):1194-201. doi: 10.1053/j.gastro.2011.06.054. Epub 2011 Jun 30.

  PMID: 21723220 BACKGROUND

• Jarnerot G, Hertervig E, Friis-Liby I, Blomquist L, Karlen P, Granno C, Vilien M, Strom M, Danielsson A, Verbaan H, Hellstrom 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. doi: 10.1053/j.gastro.2005.03.003.

  PMID: 15940615 BACKGROUND

• Van Assche G, Vermeire S, Rutgeerts P. Treatment of severe steroid refractory ulcerative colitis. World J Gastroenterol. 2008 Sep 28;14(36):5508-11. doi: 10.3748/wjg.14.5508.

  PMID: 18810767 BACKGROUND

• Halpin SJ, Hamlin PJ, Greer DP, Warren L, Ford AC. Efficacy of infliximab in acute severe ulcerative colitis: a single-centre experience. World J Gastroenterol. 2013 Feb 21;19(7):1091-7. doi: 10.3748/wjg.v19.i7.1091.

  PMID: 23467174 BACKGROUND

• Sandborn WJ, Rutgeerts P, Feagan BG, Reinisch W, Olson A, Johanns J, Lu J, Horgan K, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Gastroenterology. 2009 Oct;137(4):1250-60; quiz 1520. doi: 10.1053/j.gastro.2009.06.061. Epub 2009 Jul 28.

  PMID: 19596014 BACKGROUND

• Nanda KS, Cheifetz AS, Moss AC. Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (IBD): a meta-analysis. Am J Gastroenterol. 2013 Jan;108(1):40-7; quiz 48. doi: 10.1038/ajg.2012.363. Epub 2012 Nov 13.

  PMID: 23147525 BACKGROUND

• Katz L, Gisbert JP, Manoogian B, Lin K, Steenholdt C, Mantzaris GJ, Atreja A, Ron Y, Swaminath A, Shah S, Hart A, Lakatos PL, Ellul P, Israeli E, Svendsen MN, van der Woude CJ, Katsanos KH, Yun L, Tsianos EV, Nathan T, Abreu M, Dotan I, Lashner B, Brynskov J, Terdiman JP, Higgins PD, Chaparro M, Ben-Horin S. Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response. Inflamm Bowel Dis. 2012 Nov;18(11):2026-33. doi: 10.1002/ibd.22902. Epub 2012 Jan 31.

  PMID: 22294554 BACKGROUND

• Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D'Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P; SONIC Study Group. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010 Apr 15;362(15):1383-95. doi: 10.1056/NEJMoa0904492.

  PMID: 20393175 BACKGROUND

• Ordas I, Feagan BG, Sandborn WJ. Therapeutic drug monitoring of tumor necrosis factor antagonists in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2012 Oct;10(10):1079-87; quiz e85-6. doi: 10.1016/j.cgh.2012.06.032. Epub 2012 Jul 17.

  PMID: 22813440 BACKGROUND

• Fasanmade AA, Adedokun OJ, Olson A, Strauss R, Davis HM. Serum albumin concentration: a predictive factor of infliximab pharmacokinetics and clinical response in patients with ulcerative colitis. Int J Clin Pharmacol Ther. 2010 May;48(5):297-308. doi: 10.5414/cpp48297.

  PMID: 20420786 BACKGROUND

• Martinez-Borra J, Lopez-Larrea C, Gonzalez S, Fuentes D, Dieguez A, Deschamps EM, Perez-Pariente JM, Lopez-Vazquez A, de Francisco R, Rodrigo L. High serum tumor necrosis factor-alpha levels are associated with lack of response to infliximab in fistulizing Crohn's disease. Am J Gastroenterol. 2002 Sep;97(9):2350-6. doi: 10.1111/j.1572-0241.2002.05990.x.

  PMID: 12358255 BACKGROUND

• Takeuchi T, Miyasaka N, Tatsuki Y, Yano T, Yoshinari T, Abe T, Koike T. Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis. Ann Rheum Dis. 2011 Jul;70(7):1208-15. doi: 10.1136/ard.2011.153023. Epub 2011 Apr 8.

  PMID: 21478189 BACKGROUND

• Seow CH, Newman A, Irwin SP, Steinhart AH, Silverberg MS, Greenberg GR. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010 Jan;59(1):49-54. doi: 10.1136/gut.2009.183095.

  PMID: 19651627 BACKGROUND

MeSH Terms

Conditions

Colitis, Ulcerative; Inflammatory Bowel Diseases

Interventions

Infliximab; Drugs, Generic

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pharmaceutical Preparations

Study Officials

• Uma Mahadevan, MD

  University of California at San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2013
• First Posted: October 29, 2013
• Study Start: November 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: May 29, 2015

Record last verified: 2015-05

Locations

US (1)