Evaluate if Response to Infliximab or Adalimumab May be Regained With an Immunomodulator
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|ClinicalTrials.gov Identifier: NCT02413047|
Recruitment Status : Terminated (physician decision to stop study early due to low enrollment)
First Posted : April 9, 2015
Results First Posted : November 4, 2019
Last Update Posted : November 4, 2019
|Condition or disease||Intervention/treatment||Phase|
|Inflammatory Bowel Disease Ulcerative Colitis Crohn's Disease||Drug: Azathioprine Drug: 6 mercaptopurine Drug: Methotrexate||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study to Evaluate if Response to Infliximab or Adalimumab May be Regained With the Addition of an Immunomodulator|
|Actual Study Start Date :||May 2015|
|Actual Primary Completion Date :||February 2018|
|Actual Study Completion Date :||February 2018|
Azathioprine, 6 mercaptopurine or methotrexate.
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.
Other Name: Imuran
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
Medication will be given in subcutaneous injection form once a week if the patient cannot take imuran or 6 mercaptopurine.
- Harvey Bradshaw Index HBI: Decrease >3 Points or Remission Score<5 [ Time Frame: 4 months ]
The Harvey-Bradshaw index (HBI) is a simplified version of the CDAI to foster a systematic collection of clinical data related to Crohn's disease.
The index considers five parameters, exclusively clinical; patient well-being, abdominal pain, number of liquid or soft stools, abdominal mass, and complications.
- Therapeutic Trough Level for Infliximab is Defined as >3 and as > 5 for Adalimumab. [ Time Frame: 4 months ]Trough level is the lowest level of drug detected in a subject prior to next dose of medication
- Ulcerative Colitis Clinical Score UCCS Decrease >3 Points or Remission Score <3 [ Time Frame: 4 months ]UCCS is the ulcerative colitis clinical score which is based on disease activity. The score is based on bowel movements, blood in stool, overall well being, and global assessment.
- Change Inflammatory Bowel Disease Questionnaire SIBDQ [ Time Frame: 4 months ]SIBDQ is the short inflammatory bowel disease questionnaire which is a health-related quality of life tool measuring physical, social, and emotional status.
- Eliminate Antibodies: Threshold Levels for ATI is < 3.1and is < 1.7 for ADA. [ Time Frame: 4 months ]unwanted immunogenicity is an immune response by an organism against a therapeutic antigen. This reaction leads to production of anti-drug antibodies inactivating the therapeutic effects of the treatment.
- Improvement or Normalization of Mayo Endoscopy Score for UC Patients [ Time Frame: 4 months ]Mayo endoscopy score is scoring completed during the endoscopy to evaluate disease activity. Scoring is based on stool frequency, rectal bleeding, mucosal appearance at endoscopy, and physician rating of disease activity
- Improvement or Normalization of C-reactive Protein, Sedimentation Rate and Fecal Calprotectin [ Time Frame: 4 months ]c-reactive protein, sedimentation rate, and fecal calprotectin were collected to monitor the level of inflammation in the subject. Improvement was determined if inflammation level was reduced.
- Improvement or Normalization of the Simple Endoscopic Score-Crohn's Disease (SES-CD) [ Time Frame: 4 months ]SESCD is the simple endoscopic score for crohn's disease patients scored during endoscopy. The scoring is based on appearance of ulcers/sizing, % of ulcerative surface, % of affected surface, and if there were any narrowings or strictures found.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02413047
|United States, Indiana|
|Indiana University Hospital|
|Indianapolis, Indiana, United States, 46062|
|Principal Investigator:||Matthew Bohm, DO||IndianaU IRB|