New Therapeutic Options for Inflammatory Bowel Disease: An Integrative Review

Review Article

Austin J Gastroenterol. 2024; 11(1): 1130.

New Therapeutic Options for Inflammatory Bowel Disease: An Integrative Review

Davi Vieira Ferreira¹*; Ythay Amerson Tavares Saraiva²

1Residente Doctor at Hospital Regional do Cariri, Brazil

2Routine Physician at Hospital Regional do Cariri, Brazil

*Corresponding author: Davi Vieira Ferriera Residente Doctor at Hospital Regional do Cariri, Brazil. Email: davivieiraferreira@gmail.com

Received: January 02, 2024 Accepted: February 07, 2024 Published: February 14, 2024

Abstract

Inflammatory Bowel Diseases (IBD) are chronic inflammatory disorders of the gastrointestinal system that affect thousands of people worldwide. It is an inflammatory condition characterized by changes in mucosal structure, changes in gut microbial composition, and biochemical abnormalities. The main symptoms are systemic inflammatory signs, diarrhea, abdominal pain, rectal bleeding, and weight loss. Despite advances in the treatment of IBD, conventional therapies are still used, which are generally ineffective, as they do not prevent relapses or mucosal healing. Thus, there was a need for new therapeutic means, because a large number of patients undergoing conventional treatment require surgical intervention due to the worsening of the disease later on. However, the new treatment options have been little explored in the literature, with the need for scientific studies on the subject. Thus, this study aims to present new therapeutic options for inflammatory bowel disease and an update on the current status in the clinical development of these new therapeutic classes in IBD. It has been found that new therapeutic options for inflammatory bowel disease offer hope and improved quality of life for patients. As research continues to advance and more effective therapies are developed, the outlook for the treatment of IBD is increasingly positive. However, more clinical trials and investment in research are needed to further improve the available therapeutic options, providing a better life for individuals affected by this debilitating condition.

Keywords: Inflammatory Bowel Diseases; Crohn’s Disease; Ulcerative Colonitis; Management

Introduction

Inflammatory Bowel Disease (IBD) is part of a group of chronic autoimmune diseases. Its etiology is unknown, however, it is characterized by intestinal inflammation and divided into Crohn's Disease (CD), which presents a discontinuous, transmural inflammation affecting the gastrointestinal tract and Ulcerative Colitis (UC), which is restricted to the intestinal mucosa [23,28]. The pathogenesis of CD and UC involves a dysregulated immune response to the commensal microbiota in genetically susceptible individuals [12]. Both disorders are conditions characterized by chronic histological inflammation and impaired quality of life, as CD and UC symptoms include inflammation, diarrhea, abdominal pain, rectal bleeding, and weight loss. The diseases can occur in adolescents and adults, in addition to affecting all sexes [11,25]. CD involves the terminal ileum, cecum, perianal area, and colon, however, it can affect other regions of the intestine and UC affects the rectum and part or all of the colon. The cause of the diseases is still unknown, however, recent studies present evidence that pathogenesis is related to genetic susceptibility, gut microbiota, environmental factors, and immune abnormalities [10]. There are multiple possibilities involved in the pathogenesis of IBD, however, only part of the heritability has been explained by genetic studies [20]. Furthermore, it is worth noting that the growing understanding of the immunopathogenesis of Inflammatory Bowel Disease (IBD) has opened new avenues for the development of more effective therapies than traditional ones. These advances in treatment options targeting different mechanisms of action offer new hope for the proper management of the disease [7]. Cambui and Natali (2015) state that conventional treatments are, for the most part, ineffective, given that they do not prevent recurrent crises, nor the cure of the disease. Thus, there is a need for new therapeutic means, since most patients submitted to conventional treatment require surgical intervention due to the worsening of the disease later. Therefore, there is a need to innovate with the development of new treatments to alter the clinical course of IBD, including fewer clinical relapses, hospitalizations, surgeries, and better quality of life for the patient. Unfortunately, the new treatment options have been little explored in the literature, and there is a need for scientific studies on the subject. Therefore, this research seeks to present an update on the current status in the clinical development of these new therapeutic classes of Inflammatory Bowel Disease.

The general objective of this study is to present the new therapeutic options available for the treatment of inflammatory bowel diseases. The specific objectives are: to present the traditional management that involves the use of sulfasalazine, corticosteroids, antibiotics and immunosuppressants; discuss the therapeutic approach by biological agents of the disease and analyze the benefits of the use of stem cells in the treatment of the disease.

Theoretical Framework

Inflammatory Bowel Diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal system that affect thousands of people worldwide. It is a chronic inflammatory condition characterized by changes in mucosal structure, change in gut microbial composition, and biochemical abnormalities [27.

IBDs have two main clinical forms, Ulcerative Colitis (UC) and Crohn's Disease (CD), which are distinguished by the different clinical manifestations of intestinal inflammation and location. Both diseases are more commonly found in urban areas compared to rural areas and both have different side effects [25].

UC is an inflammation and sores (ulcers) along the lining of the large intestine (colon) and rectum. CD, as far as it is concerned, is characterized by inflammation of the lining of the digestive tract, which can usually involve the deeper layers of the digestive tract, affecting the small and large intestine, as well as, in rare cases, the upper gastrointestinal tract [13].

In addition, CD can affect any part of the gastrointestinal tract. It usually affects the portion of the small intestine before the large intestine/colon. The areas impacted by the disease are manifested through spots that are next to areas of healthy tissue, and can reach through the multiple layers of the walls of the gastrointestinal tract. In UC, the damaged areas are continuous, starting in the rectum and spreading to the colon, being present only in the innermost layer of the colon lining [9].

Several factors are attributed to the prevalence of CD and UC, such as: geographic location, diet, genetics and inadequate immune response. However, the hypothesis most widely regarded by researchers in the scientific community suggests that IBD is the result of an exaggerated immune response, triggered by environmental factors in relation to altered gut microbiota or pathogenic microorganisms in a genetically prone host. Alteration of the gut microbiota in IBD pathology is a possibility; however, it is unclear whether such an alteration is the cause of intestinal inflammation or a consequence of it, and the way in which these bacteria contribute to the pathogenesis of IBD [13].

Regarding genetic factors, Maranhão, Vieira and Campos (2015) complement by stating that 163 gene loci related to IBD were found, in which 110 are associated with both diseases, demonstrating the sharing of common genetic bases and, thus, similar mechanisms in their development, while 30 were associated only with CD and 23 with UC.

The main clinical features of IBDs are: diarrhoea, abdominal pain and, in the case of ulcerative colitis, bleeding. CD is characterized by symptoms of diarrhea, abdominal pain, weight loss, malaise, anorexia, weight loss, and fever. UC has the following specific manifestations: bloody diarrhea, bladder tenesmus, mucus elimination, abdominal cramps, and urgency to evacuate [22].

The diagnosis of IBD is made through the evaluation of the patient's clinical condition, in line with imaging, laboratory and histopathological tests. It should be performed, first, through an interview conducted by the health professional with the patient, in order to verify symptoms, perform a physical examination and family history (SOUSA, 2017).

Likewise, the use of laboratory diagnostic tools is highlighted, such as: complete blood count, C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), serum albumin biochemical parameter, iron deficiency screening, as well as a test that seeks to identify microorganisms that may be related to gastrointestinal changes (coproscopy and stool culture), aiming to exclude other diagnostic possibilities (BARROS et al., 2020).

Barros et al. (2020) complement by presenting the importance of ileo-colonoscopic examination and biopsy, which define the severity and extent of the disease. Histological examination reveals the loss of structure of undifferentiated cell mixtures of all cell types and the presence of inflammatory cells in the lamina propria.

Laboratory tests may show anemia, due to the difficulty of assimilation or blood loss, with an increase in the number of white blood cells, per volume of circulating blood; lower than normal blood potassium concentration in cases of severe diarrhea and a gradual increase in Erythrocyte Sedimentation Rate (ESR), in addition to an increase in C-Reactive Protein (CRP), indicating the presence of inflammation or infection [22].

Treatment of IBD varies depending on the type and symptoms. The purpose of IBD treatment is to reduce inflammation, which can lead not only to symptom relief, but also to a reduction in the risk of complications [2]. It usually involves drug therapy or surgery. The improvement of symptoms, prevention of recurrences, induction of remission in patients and healing of fistulas involves a pharmacological approach that is not so simple, in view of the lack of understanding of the nature of the agents responsible for the inflammatory process, the variations in the pharmacokinetics of the drugs and the unique characteristics of each patient [5].

Thus, there are different approaches to treatment, such as: conventional treatment, which involves [5,30]:

• Use of anti-inflammatory drugs Sulfasalazine, Mesalamine. They work by minimizing irritation in the intestines;

• Use of corticosteroids (prednisone). Keeps the immune system under control and manages flare-ups;

• Use of antibiotics, such as ciprofloxacin and metronidazole , as they treat infections and abscesses);

• Use of immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate, and tacrolimus);

Currently, treatment mediated by biological agents stands out. It is a recent therapy, in which it is targeted to neutralize proteins in the body that are causing inflammation. Some are administered through intravenous (IV) infusions and others are intramuscular injections. The most commonly used are: Infliximab, Adalimumab, Golimunab and Certolizumab [5,30].

Methodology

Study Design

This is an exploratory, descriptive study with a qualitative approach. The main purpose of exploratory searches is to clarify concepts and ideas, providing an overview of a given fact. In this way, it makes it possible to broaden the researcher's experience on the problem in question, deepening his study within the limits of a specific reality. Therefore, it has the plan to obtain the desired results, based on contact with a certain population, and can be used to raise possible problem issues [19].

Descriptive research aims to address the particularities of a target audience. The problem of this study is highlighted by identifying, recording and analyzing the characteristics or factors involved with the phenomenon, without interference from the researcher, as they involve standardized data collection techniques (BRUCH&Ecicr;Z, 2018).

Regarding data collection procedures, this is an integrative literature review. For Roman and Friedlander (2018, p. 109), this type of research "is a method that aims to synthesize results obtained in research on a delimited theme or issue, in a systematic and orderly manner, with the aim of contributing to the knowledge of that theme or issue".

Methodological Procedures

The research was carried out through publications in the form of scientific articles on Inflammatory Bowel Diseases (IBD), using scientific works available in the Virtual Health Library (VHL), which is an online information network coordinated by the Latin American Center for Health Sciences Information (BIREME).

The LILACS, SciELO, BDENF and PubMed databases were used, using the DeSC descriptors in Portuguese and English, such as "Inflammatory Bowel Diseases AND Crohn's Disease", "Inflammatory Bowel Diseases and Ulcerative Colitis" and "Inflammatory Bowel Diseases And Therapeutic Adherence".

The selected articles were those that responded to the objectives of the study, published in the last 5 years, available in Portuguese and English, and that were not repeated, were not monographs, dissertations, theses, review articles, news articles, texts in reviews, non-indexed articles, opinions, editorials or manuals.

Data analysis was performed through Thematic Content Analysis, which consists of three stages: pre-analysis, exploration of the material or coding, and treatment of the results obtained/interpretation. During the pre-analysis stage, hypotheses or assumptions were formulated and reformulated, and the corpus was constituted.

In the stage of exploration of the material, categories were found that were organized according to the expressions or words that were significant. From there, inferences and interpretations were proposed, interrelating them with the theoretical framework initially drawn or opening other avenues around new theoretical and interpretative dimensions.

Through the methodology used in this integrative review, 1457 publications were initially identified. After filtering, a total of 35 articles were obtained. An exploratory reading of these articles was carried out, and subsequently, 27 of them were excluded because they did not meet the established criteria or because they were repeated.

Thus, a total of 8 articles were incorporated into this research. The procedure was divided into stages to ensure a better systematization of knowledge on the topic addressed. Initially, the descriptors were searched in the databases, followed by the reading of the abstracts and objectives of the selected articles. Finally, a complete reading of the articles that met the inclusion criteria established for this review was performed.

Data analysis was performed by reading and interpreting the information obtained from the articles.

The selected studies were organized in a table, presenting the profile of the publications: title, authors, year, objective, method, results obtained, database and scientific journal. The academic findings were analyzed in descriptive and interpretative form.

Results

Description of Selected Studies

An analytical reading of the selected articles was carried out, which allowed the subjects to be organized in order of importance and to synthesize the essential ideas to achieve the objective of the research. Graph 1 shows the distribution of articles according to the databases used.

Graph 1 shows that the database with the highest number of articles selected for this study was Scopus (6 articles), followed by PubMed (2 articles). The studies selected according to methodological approach and language are shown in Table 1.