title: Addition of an immunomodulator to infliximab therapy eliminates antidrug antibodies in serum and restores clinical response of patients with inflammatory bowel disease.
abstract: There are few therapeutic options for patients with inflammatory bowel disease who lose response to infliximab because they produced antibodies against the drug. We performed a retrospective analysis to investigate whether administration of immune modulators to 5 patients who developed antibodies to infliximab (ATI) restored response to this drug; 3 patients were given azathioprine/6-mercaptopurine and 2 patients were given methotrexate. Concentrations of infliximab and ATIs, and antitumor necrosis factor (TNF) activity, were analyzed using enzyme-linked immunosorbent assay-based competition assays of serum samples collected before and after patients were given the immunomodulator. In all patients, levels of ATIs gradually decreased and trough levels of infliximab increased; clinical responses were restored to all patients. In competition assays, immunomodulator-induced elimination of ATIs was associated with increased anti-TNF activity in serum. The addition of immunomodulators to therapy might be helpful to patients who have lost response to anti-TNF agents owing to formation of antidrug antibodies.
authors.affiliation: Department of Gastroenterology, Sheba Medical Center & Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. sben-horin@013.net.il
authors.forename: Shomron
authors.initials: S
authors.lastname: Ben-Horin
authors.forename: Matti
authors.initials: M
authors.lastname: Waterman
authors.forename: Uri
authors.initials: U
authors.lastname: Kopylov
authors.forename: Miri
authors.initials: M
authors.lastname: Yavzori
authors.forename: Orit
authors.initials: O
authors.lastname: Picard
authors.forename: Ella
authors.initials: E
authors.lastname: Fudim
authors.forename: Halim
authors.initials: H
authors.lastname: Awadie
authors.forename: Batia
authors.initials: B
authors.lastname: Weiss
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Chowers
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology*; D001379:Azathioprine / Q000008:administration & dosage; D004359:Drug Therapy, Combination / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D012189:Retrospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D015122:Mercaptopurine; D001379:Azathioprine; D008727:Methotrexate