title: Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms.
abstract: Crohn's disease and ulcerative colitis are chronic inflammatory disorders resulting from immune dysregulation. Patients who fail conventional medical therapy require biological treatment with monoclonal antibodies (mAbs). Although mAbs are highly effective for induction and maintenance of clinical remission, not all patients respond, and a high proportion of patients lose response over time. One factor associated with loss of response is immunogenicity, whereby the production of antidrug antibodies accelerates mAb clearance. However, other factors related to patient and disease characteristics also influence the pharmacokinetics of mAbs. These factors include gender, body size, concomitant use of immunosuppressive agents, disease type, serum albumin concentration, and the degree of systemic inflammation. Because it is important to maintain clinically effective concentrations to provide optimal clinical response and drug exposure is affected by patient factors, a better understanding of the pharmacology of mAbs will ultimately result in better patient care.
authors.affiliation: Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Ordás
authors.forename: Diane R
authors.initials: DR
authors.lastname: Mould
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics; D004306:Dose-Response Relationship, Immunologic; D004359:Drug Therapy, Combination; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D000069285:Infliximab; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab