A Comprehensive Literature Review and Expert Consensus Statement on Therapeutic Drug Monitoring of Biologics in Inflammatory Bowel Disease

• Published in: The American journal of gastroenterology Vol. 116; no. 10; pp. 2014 - 2025
• Main Authors: Cheifetz, Adam S., Abreu, Maria T., Afif, Waqqas, Cross, Raymond K., Dubinsky, Marla C., Loftus, Edward V., Osterman, Mark T., Saroufim, Ariana, Siegel, Corey A., Yarur, Andres J., Melmed, Gil Y., Papamichael, Konstantinos
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer 01.10.2021; Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subjects: Antibodies; Attitude of Health Personnel; Biological products; Biological Products - therapeutic use; Clinical medicine; Consensus; Crohn's disease; Delphi Technique; Drug dosages; Drug Monitoring; Drug withdrawal; Gastroenterology; Humans; Inflammatory bowel disease; Inflammatory Bowel Diseases - drug therapy; Literature reviews; Monoclonal antibodies; Optimization; Patients; Pediatrics; Practice Patterns, Physicians; Remission (Medicine); Steroids; Therapeutic drug monitoring; Tumor necrosis factor-TNF
• ISSN: 0002-9270; 1572-0241; 1572-0241
• DOI: 10.14309/ajg.0000000000001396

Therapeutic drug monitoring (TDM) of biologics is a rapidly evolving field. We aimed to provide a consensus statement regarding the clinical utility of TDM for biologics in inflammatory bowel disease (IBD). A modified Delphi method was applied to develop consensus statements. A comprehensive literature review was performed regarding TDM of biologic therapies in IBD, and 45 statements were subsequently formulated on the potential application of TDM in IBD. The statements, along with literature, were then presented to a panel of 10 gastroenterologists with expertise in IBD and TDM who anonymously rated them on a scale of 1–10 (1 = strongly disagree and 10 = strongly agree). An expert consensus development meeting was held virtually to review, discuss, refine, and reformulate statements that did not meet criteria for agreement or that were ambiguous. During the meeting, additional statements were proposed. Panelists then confidentially revoted, and statements rated ≥7 by 80% or more of the participants were accepted. During the virtual meeting, 8 statements were reworded, 7 new statements were proposed, and 19 statements were rerated. Consensus was finally reached in 48/49 statements. The panel agreed that reactive TDM should be used for all biologics for both primary nonresponse and secondary loss of response. It was recommended that treatment discontinuation should not be considered for infliximab or adalimumab until a drug concentration of at least 10–15 μg/mL was achieved. Consensus was also achieved regarding the utility of proactive TDM for anti–tumor necrosis factor therapy. It was recommended to perform proactive TDM after induction and at least once during maintenance. Consensus was achieved in most cases regarding the utility of TDM of biologics in IBD, specifically for reactive and proactive TDM of anti–tumor necrosis factors.