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Precision medicine in inflammatory bowel disease: Individualizing the use of biologics and small molecule therapies.

ABSTRACT: The advent of biologics and small molecules in inflammatory bowel disease (IBD) has marked a significant turning point in the prognosis of IBD, decreasing the rates of corticosteroid dependence, hospitalizations and improving overall quality of life. The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies. Biologics do not yet represent a complete panacea: A subset of patients do not respond to first-line anti-tumor necrosis factor (TNF)-alpha agents or may subsequently demonstrate a secondary loss of response. Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics. It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents. The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease. This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.

SUBMITTER: Cheah E

PROVIDER: S-EPMC10037250 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Precision medicine in inflammatory bowel disease: Individualizing the use of biologics and small molecule therapies.

Cheah Eric E Huang James Guoxian JG

World journal of gastroenterology 20230301 10

The advent of biologics and small molecules in inflammatory bowel disease (IBD) has marked a significant turning point in the prognosis of IBD, decreasing the rates of corticosteroid dependence, hospitalizations and improving overall quality of life. The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies. Biologics do not yet represent a complete panacea: A subset of patients do not respond to first-line anti-tumor necros ...[more]

PMID: 36970587

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Project description:IntroductionInflammatory Bowel Disease (IBD), encompassing Crohn's disease and ulcerative colitis, presents significant clinical challenges due to its heterogeneous nature and complex etiology. Recent advancements in biomedical research have enhanced our understanding of IBD's genetic, microbial, and biochemical aspects. However, persistent issues in clinical management, including treatment non-response, surgical interventions, and diagnostic uncertainties, underscore the need for more targeted approaches. This review examines the convergence of artificial intelligence (AI) and precision medicine (PM) in IBD management. By leveraging AI's capacity to analyze complex, multi-dimensional datasets, this emerging field offers promising applications in improving diagnostic accuracy, predicting treatment responses, and forecasting disease progression, potentially transforming IBD patient care.MethodThe systematic review (SR) was conducted by searching the following databases: PubMed, PubMed PMC, BVS, Scopus, Web of Science, Embase, Cochrane, and ProQuest up to February 2024. Studies that employed AI in IBD applied to precision medicine were included.Results139 studies on applying AI in precision medicine for IBD were identified. Most studies (>70%) were published after 2020, indicating a recent surge in interest. The AI applications primarily focused on diagnosis, treatment response prediction, and prognosis. Machine learning algorithms were predominantly used, particularly random forest, logistic regression, and support vector machines. Omics data were frequently employed as predictors, especially transcriptomics and microbiome analyses. Studies demonstrated good predictive performance across all three areas, with median AUC values ranging from 0.85 to 0.90.ConclusionAI applications in IBD show promising potential to enhance clinical practice, particularly in disease prognosis and predicting treatment response. However, clinical implementation requires further validation through prospective studies. Future research should focus on standardizing protocols, defining clinically significant outcomes, and evaluating the efficacy of these tools.

Project description:Inflammatory bowel diseases (IBD) encompass two main entities including ulcerative colitis and Crohn's disease. Although having a common global pathophysiological mechanism, IBD patients are characterized by a significant interindividual heterogeneity and may differ by their disease type, disease locations, disease behaviours, disease manifestations, disease course as well as treatment needs. Indeed, although the therapeutic armamentarium for these diseases has expanded rapidly in recent years, a proportion of patients remains with a suboptimal response to medical treatment due to primary non-response, secondary loss of response or intolerance to currently available drugs. Identifying, prior to treatment initiation, which patients are likely to respond to a specific drug would improve the disease management, avoid unnecessary side effects and reduce the healthcare expenses. Precision medicine classifies individuals into subpopulations according to clinical and molecular characteristics with the objective to tailor preventative and therapeutic interventions to the characteristics of each patient. Interventions would thus be performed only on those who will benefit, sparing side effects and expense for those who will not. This review aims to summarize clinical factors, biomarkers (genetic, transcriptomic, proteomic, metabolic, radiomic or from the microbiota) and tools that could predict disease progression to guide towards a step-up or top-down strategy. Predictive factors of response or non-response to treatment will then be reviewed, followed by a discussion about the optimal dose of drug required for patients. The time at which these treatments should be administered (or rather can be stopped in case of a deep remission or in the aftermath of a surgery) will also be addressed. IBD remain biologically complex, with multifactorial etiopathology, clinical heterogeneity as well as temporal and therapeutic variabilities, which makes precision medicine especially challenging in this area. Although applied for many years in oncology, it remains an unmet medical need in IBD.

Project description:Although initially described as an anti-tumor mediator, tumor necrosis factor-alpha (TNF) is generally considered as the master pro-inflammatory cytokine. It plays a crucial role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease, ankylosing spondylitis (AS), and psoriasis. Consequently, anti-TNF therapy has become mainstay treatment for autoimmune diseases. Historically, anti-inflammatory agents were developed before the identification of TNF. Salicylates, the active components of Willow spp., were identified in the mid-19th century for the alleviation of pain, fever, and inflammatory responses. Study of this naturally occurring compound led to the discovery of aspirin, which was followed by the development of non-steroidal anti-inflammatory drugs (NSAIDs) due to the chemical advances in the 19th-20th centuries. Initially, the most of NSAIDs were organic acid, but the non-acidic compounds were also identified as NSAIDs. Although effective in the treatment of inflammatory diseases, NSAIDs have some undesirable and adverse effect, such as ulcers, kidney injury, and bleeding in the gastrointestinal tract. In the past two decades, anti-TNF biologics were developed. Drugs belong to this class include soluble TNF receptor 2 fusion protein and anti-TNF antibodies. The introduction of anti-TNF therapeutics has revolutionized the management of autoimmune diseases, such as RA, psoriatic arthritis (PsA), plaque psoriasis (PP), AS, CD and ulcerative colitis (UC). Nevertheless, up to 40% of patients have no response to anti-TNF treatment. Furthermore, this treatment is associated with some adverse effects such as increased risk of infection, and even triggered the de novo development of autoimmune diseases. Such harmful effect of anti-TNF treatment is likely caused by the global inhibition of TNF biological functions. Therefore, specific inhibition of TNF receptor (TNFR1 or TNFR2) may represent a safer and more effective treatment, as proposed by some recent studies. In this review article, the historical development of anti-inflammatory drugs after World War II as briefly described above will be reviewed and analyzed. The future trend in the development of novel TNF receptor-targeting therapeutics will be discussed in the context of latest progress in the research of TNF biology.

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Precision medicine in inflammatory bowel disease: Individualizing the use of biologics and small molecule therapies.

Publications

Precision medicine in inflammatory bowel disease: Individualizing the use of biologics and small molecule therapies.

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