Treatment Strategies in Inflammatory Bowel Diseases

Abstract

Background: The prevalence of inflammatory bowel disease (IBD) is rising globally. In Germany, these conditions affect 0.7% of the population, or approximately 600 000 patients. Treatment strategies have become more diversified as a result of an improved understanding of disease pathogenesis. It remains unclear how the currently available drugs should best be used in each individual patient.

Methods: This review is based on pertinent publications retrieved by a selective search in PubMed, with special attention to phase III and IV trials and to the German and European guidelines on the treatment of IBD.

Results: An improved understanding of the immunological mechanisms of disease underlies the current treatment strategies in patients with IBD. For those with a complex clinical course, monoclonal antibodies against pro-inflammatory cytokines (TNF, IL-12/IL-23, IL-23) and cell adhesion molecules (α4β7) are of established therapeutic value, along with "small molecules" such as JAK inhibitors and sphingosine-1-phosphate receptor modulators. The numerous studies that have been performed, only a few of which have been head-to-head comparison trials, and the (network) meta-analyses that have been published to date do not imply that any single one of these drugs can be considered the universal, primary treatment for all patients with IBD. In this review, we discuss the available substances and certain important differential-therapeutic aspects of the treatment of IBD.

Conclusion: The treatment of a patient with IBD must take his or her prior treatment(s) and comorbidities into account, along with individual patient characteristics and treatment goals. Rational decision-making is required on the basis of the mechanism of action and the side-effect profile of the various drugs that are now available for use.

Figure

The immune pathogenesis of inflammatory bowel disease The impaired integrity of the epithelial barrier enables an increased translocation of microorganisms into the intestinal wall. This leads to aberrant activation of innate immune cells, with increased production of pro-inflammatory cytokines by intestinal macrophages and effector T cells (T helper 1 [TH1], TH2 and TH17). After the cytokines bind to their membrane receptor on the corresponding target cells, the intracellular, pro-inflammatory Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is activated. The excessive immune response is further promoted by the increased migration of immune cells. The recirculation of T cells from the tissue into the blood is mediated by an S1P gradient; T cells migrate from the lymphatic tissue into the efferent lymphatic vessels and onward into the systemic circulation. There, T cells that express integrins (e.g., α4β7) on their surface can interact with ligands expressed on endothelial cells (e.g., mucosal addressin cell adhesion molecule-1“ (MAdCAM-1), and this leads to the migration of T cells into the intestine and further perpetuation of inflammation. The illustration was created with BioRender.