Precision medicine in inflammatory bowel disease: Individualizing the use of biologics and small molecule therapies

Abstract

The advent of biologics and small molecules in inflammatory bowel disease (IBD) has marked a significant turning point in the prognosis of IBD, decreasing the rates of corticosteroid dependence, hospitalizations and improving overall quality of life. The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies. Biologics do not yet represent a complete panacea: A subset of patients do not respond to first-line anti-tumor necrosis factor (TNF)-alpha agents or may subsequently demonstrate a secondary loss of response. Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics. It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents. The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease. This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.

Keywords: Precision medicine, Therapeutic ceiling, Inflammatory bowel disease, Biologics, Small molecules

Core Tip: Precision medicine and individualizing patient care has been the holy grail in the management of inflammatory bowel disease (IBD). A one-size-fits-all approach, utilizing the current armamentarium of biologics and small molecules, still yields less than ideal clinical outcomes, with significantly high non-response rates. Multiple challenges remain in breaking this therapeutic ceiling: Achieving an early diagnosis of IBD ideally even in the pre-clinical phase; accurately prognosticating the disease course; and tailoring an appropriately sequenced therapy regime to a patient’s disease severity, pharmacokinetic and pharmacodynamic profile.