title: Clinical impact of concomitant immunomodulators on biologic therapy: Pharmacokinetics, immunogenicity, efficacy and safety.
abstract: Immune-mediated inflammatory diseases encompass a variety of different clinical syndromes, manifesting as either common diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and psoriasis, or rare diseases such as cryopyrin-associated periodic syndromes. The therapy for these diseases often involves the use of a wide range of drugs including nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, immunomodulators, and biologic therapies. Due to the abundance of relevant clinical data, this article provides a general overview on the clinical impact of the concomitant use of immunomodulators and biologic therapies, with a focus on anti-tumor necrosis factor-α agents (anti-TNFα), for the treatment of RA and Crohn's disease (CD). Compared to biologic monotherapy, concomitant use of immunomodulators (methotrexate, azathioprine, and 6-mercaptopurine) often increases the systemic exposure of the anti-TNFα agent and decreases the formation of antibodies to the anti-TNFα agent, consequently enhancing clinical efficacy. Nevertheless, long-term combination therapy with immunomodulators and anti-TNFα agents may be associated with increased risks of serious infections and malignancies. Therefore, the determination whether combination therapy is suitable for a patient should always be based on an individualized benefit-risk evaluation. More research should be undertaken to identify and validate prognostic markers for predicting patients who would benefit the most and those who are at greater risk from combination therapy with immunomodulators and anti-TNFα agents.
authors.affiliation: Janssen Research and Development, LLC., Spring House, PA, USA.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Xu
authors.forename: Hugh M
authors.initials: HM
authors.lastname: Davis
authors.forename: Honghui
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001688:Biological Products / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001688:Biological Products; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha
keywords: 6-mercaptopurine; Crohn's disease; azathioprine; biologic therapy; drug-drug interaction; immunogenicity; immunomodulator; immunosuppression; inflammatory disease; metabolism; methotrexate; monoclonal antibody; pharmacokinetics; rheumatoid arthritis; safety; tumor necrosis factor blocker