Biomaterial Database

Factors Influencing Drug Disposition of Monoclonal Antibodies in Inflammatory Bowel Disease: Implications for Personalized Medicine. 2019

Pavine L C Lefevre, and Lisa M Shackelton, and Niels Vande Casteele

Robarts Clinical Trials, Inc., London, ON, Canada.

Monoclonal antibody (mAb) therapies have revolutionized the treatment of several chronic inflammatory diseases, including the inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis. While efficacious, responses to these therapies vary considerably from patient to patient, due in part to inter- and intra-individual variability in pharmacokinetics (PK) and drug exposure. The concept of personalized medicine to monitor drug exposure and to adjust dosing in individual patients is consequently gaining acceptance as a powerful tool to optimize mAb therapy for improved outcomes in IBD. This review provides a brief overview of the different mAbs currently approved or in development for the treatment of IBD, including their presumed mechanisms of action and PK properties. Specifically described are (1) the factors known to affect mAb PK and drug exposure in patients with IBD, (2) the value of population PK/pharmacodynamic (PD) modeling to identify and understand the influence of these factors on drug exposure and effect, and (3) the clinical evidence for the potential of therapeutic drug monitoring (TDM) to improve IBD outcomes in response to mAb-based therapy. Incorporation of PK/PD parameters into clinical decision support tools has the potential to guide therapeutic decision making and aid implementation of personalized medicine strategies in patients with IBD.

UI	MeSH Term	Description	Entries
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000911	Antibodies, Monoclonal	Antibodies produced by a single clone of cells.	Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D014409	Tumor Necrosis Factor-alpha	Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.	Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D015212	Inflammatory Bowel Diseases	Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.	Bowel Diseases, Inflammatory,Inflammatory Bowel Disease
D016023	Integrins	A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors (RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.	Integrin
D016896	Treatment Outcome	Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.	Rehabilitation Outcome,Treatment Effectiveness,Clinical Effectiveness,Clinical Efficacy,Patient-Relevant Outcome,Treatment Efficacy,Effectiveness, Clinical,Effectiveness, Treatment,Efficacy, Clinical,Efficacy, Treatment,Outcome, Patient-Relevant,Outcome, Rehabilitation,Outcome, Treatment,Outcomes, Patient-Relevant,Patient Relevant Outcome,Patient-Relevant Outcomes
D016903	Drug Monitoring	The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically.	Monitoring, Drug,Therapeutic Drug Monitoring,Drug Monitoring, Therapeutic,Monitoring, Therapeutic Drug
D057285	Precision Medicine	Clinical, therapeutic and diagnostic approaches to optimal disease management based on individual variations in a patient's genetic profile.	Individualized Medicine,Predictive Medicine,P Health,P-Health,Personalized Medicine,Theranostics,Medicine, Individualized,Medicine, Personalized,Medicine, Precision,Medicine, Predictive,Theranostic
D058990	Molecular Targeted Therapy	Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease.	Targeted Molecular Therapy,Molecular Targeted Therapies,Molecular Therapy, Targeted,Targeted Molecular Therapies,Targeted Therapy, Molecular,Therapy, Molecular Targeted,Therapy, Targeted Molecular