Inflammatory Bowel Disease Treatments and Predictive Biomarkers of Therapeutic Response

Abstract

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with a highly heterogeneous presentation. It has a relapsing and remitting clinical course that necessitates lifelong monitoring and treatment. Although the availability of a variety of effective therapeutic options including immunomodulators and biologics (such as TNF, CAM inhibitors) has led to a paradigm shift in the treatment outcomes and clinical management of IBD patients, some patients still either fail to respond or lose their responsiveness to therapy over time. Therefore, according to the recent Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations, continuous disease monitoring from symptomatic relief to endoscopic healing along with short- and long-term therapeutic responses are critical for providing IBD patients with a tailored therapy algorithm. Moreover, considering the high unmet need for novel therapeutic approaches for IBD patients, various new modulators of cytokine signaling events (for example, JAK/TYK inhibitors), inhibitors of cytokines (for example IL-12/IL-23, IL-22, IL-36, and IL-6 inhibitors), anti-adhesion and migration strategies (for example, β7 integrin, sphingosine 1-phosphate receptors, and stem cells), as well as microbial-based therapeutics to decolonize the bed buds (for example, fecal microbiota transplantation and bacterial inhibitors) are currently being evaluated in different phases of controlled clinical trials. This review aims to offer a comprehensive overview of available treatment options and emerging therapeutic approaches for IBD patients. Furthermore, predictive biomarkers for monitoring the therapeutic response to different IBD therapies are also discussed.

Keywords: Crohn’s disease; IBD; biological treatment; biomarkers; precision medicine; ulcerative colitis.

Figure 1

STRIDE-II recommendations for disease monitoring and clinical management of inflammatory bowel disease using short- and long-term target goals.

Figure 2

Clinical management of IBD patients during disease flare and remission (a) and the market share of IBD medicines (b). Maintaining remission and prevention of disease flare that triggers signs and symptoms is the main goal of IBD treatment. This figure gives an overview of the current clinical management of IBD patients. For more details, see the main text. * Some aminosalicylates such as balsalazide and mesalamine are approved for mild-to-moderate UC patients.

Figure 3

Predictive biomarkers for different IBD treatments. The figure shows the list of different predictive biomarkers that are associated with disease severity and response to clinical therapy in patients with IBD. ^# Genetic variations in these genetic markers could predict a non-responsiveness to anti-TNF (infliximab) therapy in IBD patients. ^## Heterozygous genotype of IL12B—10993 G > C (rs3212217) positively correlated with non-responsiveness to anti-TNF therapy in UC patients. CRP: C-reactive protein; FC: fecal calprotectin; SL: stool lactoferrin; CTS: corticosteroids; IMD: immunomodulators; IFX: infliximab; VZD: vedolizumab; TNF: tumor necrosis factor; C4M: Matrix metalloproteinases-mediated degradation of type IV collagens; IL: interleukin; sTNFR2: Serum soluble tumor necrosis factor receptor-2; IFN: Interferon; FCGR3A: Fc Gamma Receptor 3a; abs: antibodies; pANCA abs: perinuclear antineutrophil cytoplasmic antibodies; Anti-OmpC abs: anti- outer-membrane protein OmpC of Escherichia coli antibodies; Fc: fragment crystallizable; NOD: nucleotide-binding and oligomerization domain; CARD 15: caspase recruitment domain-containing protein 15; ↑: increase in levels; ↓: decrease in levels.