Personalized Medicine of Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacogenetics, Therapeutic Drug Monitoring, and Beyond

Abstract

The pharmacotherapy of inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) has experienced significant progress with the advent of monoclonal antibodies (mABs). As therapeutic proteins, mABs display peculiar pharmacokinetic characteristics that differentiate them from chemical drugs, such as aminosalicylates, antimetabolites (i.e., azathioprine, 6-mercaptopurine, and methotrexate), and immunosuppressants (corticosteroids and cyclosporine). However, clinical trials have demonstrated that biologic agents may suffer from a pharmacokinetic variability that could influence the desired clinical outcome, beyond primary resistance phenomena. Therefore, therapeutic drug monitoring (TDM) protocols have been elaborated and applied to adaptation drug doses according to the desired plasma concentrations of mABs. This activity is aimed at maximizing the beneficial effects of mABs while sparing patients from toxicities. However, some aspects of TDM are still under discussion, including time-changing therapeutic ranges, proactive and reactive approaches, the performance and availability of instrumental platforms, the widely varying individual characteristics of patients, the severity of the disease, and the coadministration of immunomodulatory drugs. Facing these issues, personalized medicine in IBD may benefit from a combined approach, made by TDM protocols and pharmacogenetic analyses in a timeline that necessarily considers the frailty of patients, the chronic administration of drugs, and the possible worsening of the disease. Therefore, the present review presents and discusses the activities of TDM protocols using mABs in light of the most recent results, with special attention on the integration of other actions aimed at exploiting the most effective and safe therapeutic effects of drugs prescribed in IBD patients.