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.

The Increase of miR-195-5p Reduces Intestinal Permeability in Ulcerative Colitis, Modulating Tight Junctions’ Expression

“…TNF-α causes an alteration of the TJ-mediated barrier and intestinal permeability, as well as inducing IECs apoptosis [ 40 , 41 ] that precludes the redistribution of TJ and prevents the sealing of the left gaps. Anti-TNF-α, an antibody commonly used in IBD therapy, can ameliorate intestinal permeability but their efficacy depends on the patient’s response [ 42 ]. In this context, new therapeutic strategies are needed.…”

Inflammasome-targeting natural compounds in inflammatory bowel disease: Mechanisms and therapeutic potential

“…However, antibody-based therapies are challenged by their high cost due to the high biologic dosage used in treatment and maintenance of diseases, which lead to a high economic burden to the patients ( 9 ). Moreover, the side effects of antibody-based therapies in treatment of IBD, such as serious infection and malignancy after administration of anti-TNF antibody, has long been observed and are still significant concerns of current IBD clinicians, which may limit the application of this type of therapies ( 26 , 27 ). Thus, other alternative therapeutic strategies need to be developed for the intervention of IBD.…”

Current Strategies and Potential Prospects of Nanomedicine-Mediated Therapy in Inflammatory Bowel Disease

“… 45 One of the vital biological treatments in IBD is monoclonal antibodies (mABs). 46 The mABs against pro-inflammation cytokines such as TNF-α and IFN-γ would target crosstalk among IL-23, IL-6, IL-17, IL-13, and TGF-β. The mABs against adhesion molecules like ICAM-1 could inhibit the recruitment of effector T cells.…”