THE INFLUENCE OF IMMUNOBIOLOGICALS AND SMALL MOLECULES ON THE MANAGEMENT OF CROHN'S DISEASE

• DOI: https://doi.org/10.22533/at.ed.1595202524044

• Palavras-chave: Crohn's Disease; Immunobiologicals; Inflammatory Bowel Disease; Crohn's Disease Therapeutic Targets; Basic Immunology; Applied Immunology.

• Keywords: Crohn's Disease; Immunobiologicals; Inflammatory Bowel Disease; Crohn's Disease Therapeutic Targets; Basic Immunology; Applied Immunology.

• Abstract:

  Introduction: Crohn's disease (CD) is a chronic inflammatory bowel disease that mainly affects adolescents and young adults, affecting the entire gastrointestinal tract, with specific foci of greater inflammation. In addition, there may be extra-intestinal manifestations in the joints, eyes, skin and liver. The pathogenesis is multifactorial, including genetic and environmental factors such as eating habits and previous infections. Polymorphisms in genes that encode inflammatory cytokines, adhesion molecules and influence the production of intestinal mucus are fundamental in the pathogenesis and are therapeutic targets. CD is diagnosed using laboratory, imaging and endoscopic tests, with endoscopy being fundamental for diagnosis, predicting severity and controlling the disease. Treatment involves a series of medications aimed at controlling tissue inflammation, such as corticosteroids, immunosuppressants and immunobiologicals. The main classes of immunobiologicals that will be discussed are: Anti-TNF-alpha, Anti-integrins and p40 inhibitors. Methodology: Qualitative review of articles on CD, more specifically on the importance of immunobiologicals and small molecules and the need for more in-depth research on this aspect. The terms "Crohn's Disease"; "Immunobiologicals"; "Inflammatory Bowel Disease"; "Therapeutic Targets for CD" were used as descriptors for the search on the PubMed and Google Scholar platforms. Discussion: CD is an autoimmune inflammatory disease characterized by inflammation of all intestinal histological layers. The pathophysiology of Crohn's disease is explained by hypersensitivity to symbiont bacteria in the GIT, characterized by a predominantly Th1 immune response. This autoimmunity is caused by mutations with gain of function in lymphocyte adhesion proteins, cytokines such as TNF-α and IL-2, as well as decreased mucin production in the mucosa. The therapeutic goal of CD is to achieve a state of clinical and laboratory remission, requiring behavioral and drug treatment, involving therapies with immunomodulators and immunobiologicals, the focus of this review. Tumor necrosis factor (TNF) antagonists, Infliximab and Adalimumab, act by inhibiting TNF-alpha, reducing the intestinal pro-inflammatory state. Currently, Infliximab is a chimeric antibody and Adalimumab is a fully humanized antibody. Natalizumab and Vedolizumab are monoclonal antibodies that act by inhibiting the role of integrins. Ustekinumab, an inhibitor of the p40 subunit common to IL-12 and IL-23, acts by blocking the chronic inflammatory response in CD, interfering with the functions of these cytokines in the inflammatory pathways. Conclusion: Immunobiological therapy with small molecules can improve the prognosis of patients with CD, being a conservative treatment with the aim of inducing remission of the disease, reducing the need for surgical interventions. However, patients tend to lose their response to immunobiologicals over time. Immunotherapy with monoclonal antibodies is a vast field of research in high demand. Finally, the search for an understanding of the loss of response to immunobiologicals, the variety of drugs and the reduction of adverse effects is necessary.