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

• Status: Terminated
• Trial end date: 2018-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Indiana University
• Treatments: 6-Mercaptopurine; Adalimumab; Adjuvants, Immunologic; Azathioprine; Immunologic Factors; Infliximab; Mercaptopurine; Methotrexate

Criteria

Inclusion Criteria:

• Patients with inflammatory bowel disease who on are stable doses of infliximab or adalimumab for at least 3 months who experience a secondary loss of response to the medication based on clinical symptoms.

• Presence of at least one objective marker of active disease: active disease based on endoscopy, elevated fecal calprotectin or serologic markers of inflammation (C-reactive protein or sedimentation rate).

• Crohn's patients have a Harvey Bradshaw index >5

• Ulcerative colitis patients have a Ulcerative Colitis Clinical Score > 5

• Have an undetectable or inadequate trough level of infliximab or adalimumab and detectable ATI or ADA.

• Oral corticosteroid therapy is allowed. (prednisone at a stable dose ≤30 mg/day, budesonide at a stable dose ≤9 mg/day, or equivalent steroid) provided that the dose has been stable for the 4 weeks immediately prior to enrollment if corticosteroids have recently been initiated

Exclusion Criteria:

• Previous noncompliant with medications

• < 18 years of age or >80 years of age.

• Congestive heart failure

• Abnormal liver tests alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2 × the upper limit of normal (ULN) or leucopenia WBC count <3 × 109/L

• Pregnant or planning on becoming pregnant.

• Active tuberculosis or hepatitis B infection

• Any cancer within the past 5 years. (Exception non-melanomatous skin cancer.)

• Receiving any immunomodulator therapy within the past 3 months

• Evidence of or treatment for C. difficile infection within 60 days or other intestinal pathogen within 30 days prior to enrollment

• Clinically significant extra-intestinal infection (e.g., pneumonia, pyelonephritis) within 30 days of the initial screening visit

• Any live vaccinations within 30 days prior to study drug administration except for the influenza vaccine

• Any identified congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation)

• Any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise patient safety

• Unable to give own informed consent