NCT02413047

Evaluate if Response to Infliximab or Adalimumab May be Regained With an Immunomodulator

A Pilot Study to Evaluate if Response to Infliximab or Adalimumab May be Regained With the Addition of an Immunomodulator

• Status: Terminated
• Phase: N/A
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: Indiana University · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The immunogenicity of anti-tumor necrosis factor alpha (anti-TNF) therapy in inflammatory bowel disease (IBD) is an important cause of loss of response to therapy that may lead to escalation of dose or discontinuation of therapy. Antibodies may develop to infliximab (ATI) or to adalimumab (ATA) and cause this loss of response, also known as a secondary loss of response. An alternative approach is the addition of immunomodulator (IM) therapy to counteract the antibody response and regain efficacy of the biologic medication. The investigators' goal is to treat patients' who have lost response to adalimumab or infliximab with an immunomodulator with the goal of eliminating the circulating antibodies to the anti-TNF and restoring efficacy.

Detailed description

The immunogenicity of anti-tumor necrosis factor alpha (anti-TNF) therapy in inflammatory bowel disease (IBD) is an important cause of loss of response to therapy that may lead to escalation of dose or discontinuation of therapy. Antibodies may develop to infliximab (ATI) or to adalimumab (ATA) and cause this loss of response, also known as a secondary loss of response. In an attempt to overcome these antibodies, dose escalation can be accomplished either by increasing the dose or shortening the interval between doses. The ability of dose escalation to overcome loss of response due to the presence of ATI or ATA remains controversial. Escalation of dose increases the cost of therapy substantially. If the decision is made to discontinue therapy after a secondary loss of response, a clinician may choose to switch to an alternate anti-TNF therapy of which there are currently only four. Loss of response to one agent predicts a lesser response to other anti-TNF agents and with a limited number of therapeutic options the goal should be to optimize therapy rather than to discontinue therapy. An alternative approach is the addition of immunomodulator (IM) therapy to counteract the antibody response and regain efficacy of the biologic medication. Three such IMs known to be effective in the treatment of IBD are azathioprine (AZA), 6-mercaptopurine (6MP) and methotrexate (MTX). The SONIC trial showed that patients on infliximab and azathioprine only developed antibodies at 4% of the time as opposed to those on infliximab monotherapy who formed ATI at 13%. The same principal was shown during the COMMIT trial in which patients on infliximab alone had ATI at a rate of 20% versus 4% on methotrexate plus infliximab. Ben-Horin et al. reported five patients treated initially with infliximab monotherapy whom had secondary loss of response based on clinical symptoms. These patients had ATI and all had undetectable troughs of infliximab. In all five patients ATI became undetectable, an adequate trough level was restored and the patients regained clinical response with the addition of an immunomodulator. Combination therapy with azathioprine and infliximab has led to a higher percentage of patients in steroid free remission than either drug alone. Our goal is to treat patients' who have lost response to adalimumab or infliximab with an immunomodulator with the goal of eliminating the circulating antibodies to the anti-TNF and restoring efficacy.

Conditions

• Inflammatory Bowel Disease
• Ulcerative Colitis
• Crohn's Disease

Interventions

Type	Name	Description
DRUG	Azathioprine	Medication will be given in pill form to patients to take daily as long as the patient has not been intolerant to it in the past.
DRUG	6 mercaptopurine	Medication will be given in pill form to patients to take daily as long as the patient has not been intolerant to it in the past as an alternative to imuran
DRUG	Methotrexate	Medication will be given in subcutaneous injection form once a week if the patient cannot take imuran or 6 mercaptopurine.

Timeline

• Start date: 2015-05-01
• Primary completion: 2018-02-01
• Completion: 2018-02-01
• First posted: 2015-04-09
• Last updated: 2019-11-04
• Results posted: 2019-11-04

Locations

1 site across 1 country: United States