Optimizing Biologic Agents in Ulcerative Colitis and Crohn’s Disease

Abstract

The goals of therapy in inflammatory bowel disease (IBD) are the induction and maintenance of clinical and biological remission. Mucosal healing is desirable to prevent complications and reduce the need for surgery, hospitalizations, and steroid exposure. Therapeutic monoclonal antibodies (biologic agents) have revolutionized the treatment of IBD. The initial magnitude of the clinical/biologic response to these agents has been associated with a number of underlying phenotypic features in the recipient. In addition, the durability of the initial response often declines over time. This can occur due to low drug serum drug levels, anti-drug antibodies, and a shift to alternative inflammatory pathways. This review discusses strategies that may optimize the initial response to biologics and sustain this to improve patient outcomes.

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

“…While the subsequent Tailored Treatment With Infliximab for Active Luminal Crohn's Disease (TAILORIX) study found no additional benefit of proactive TDM‐guided dose intensification after induction therapy compared with usual care for the combined primary endpoint of steroid‐free clinical and endoscopic remission . However, a retrospective observational study found significantly lower rates of discontinuing infliximab in IBD patients who had proactive TDM compared to those who had reactive TDM (10% vs 31%, P = .009) . There was, however, potential for confounders in this study.…”

“…Data on benefits of proactive TDM over empiric dosing or reactive TDM are mixed, making recommending a regular interval for repeating TDM among patients who maintain response difficult . The TAXIT study compared TDM‐guided dosing to maintain infliximab levels within a therapeutic range, to dosing based on clinical symptoms and CRP, among infliximab responders following an initial dose optimisation phase .…”

Proactive therapeutic drug monitoring of infliximab: a comparative study of a new point‐of‐care quantitative test with two established ELISA assays

“…The benefits of optimising the IFX therapy in IBD and other inflammatory diseases’ treatment are amply acknowledged in the literature. In fact, adjusting the IFX doses (either escalating or de‐escalating) and the infusion intervals has been proved to be a clinically powerful tool and a cost‐effective strategy . For those reasons, a serious effort of the medical and research community has been recently applied to the development of novel point‐of‐care assays concerning the IBD patients monitoring .…”

“…Despite the underlying reasons for this variability, monitoring of serum IFX concentrations and of the formation of anti‐drug antibodies during therapy (Therapeutic Drug Monitoring, TDM) is a powerful tool to aid physicians in the therapeutic decision‐making process in the case of loss or of suboptimal response . Moreover, TDM may also support IFX de‐escalation in case of supratherapeutic serum concentrations, enhancing the cost‐effectiveness of the therapeutic process and avoiding unnecessary side effects …”

Host-Microbiota Interactions Shape Local and Systemic Inflammatory Diseases

“…Additionally, monoclonal antibodies have been developed to block cytokine pathways implicated in chronic inflammation. For instance, blockade of the Th1 and Th17 cell pathways by targeting the shared anti-p40 subunit of IL-12/IL-23 with the monoclonal antibody Ustekinumab is rapidly advancing through clinical trials as a novel treatment for moderate-to-severe CD (101, 102). ILCs have also received increasing attention as novel targets for the treatment of inflammatory diseases given some of their analogous signaling pathways with T cells (103).…”