Therapeutic Advances in Gastroenterology

Capsule endoscopy first captivated the medical world when it provided a means to visualize the small bowel, which was previously out of endoscopic reach. In the subsequent decade and a half we continue to learn of the true potential that capsule endoscopy has to offer. Of particular current interest is whether capsule endoscopy has any reliable investigative role in the upper gastrointestinal tract. Much research has already been dedicated to enhancing the diagnostic and indeed therapeutic properties of capsule endoscopy. Specific modifications to tackle the challenges of the gut have already been described in the current literature. In the upper gastrointestinal tract, the capacious anatomy of the stomach represents one of many challenges that capsule endoscopy must overcome. One solution to improving diagnostic yield is to utilize external magnetic steering of a magnetically receptive capsule endoscope. Notionally this would provide a navigation system to direct the capsule to different areas of the stomach and allow complete gastric mucosal examination. To date, several studies have presented promising data to support the feasibility of this endeavour. However the jury is still out as to whether this system will surpass conventional gastroscopy, which remains the gold standard diagnostic tool in the foregut. Nevertheless, a minimally invasive and patient-friendly alternative to gastroscopy remains irresistibly appealing, warranting further studies to test the potential of magnetically assisted capsule endoscopy. In this article the authors would like to share the current state of magnetically assisted capsule endoscopy and anticipate what is yet to come.

Many reference biological therapies have now reached or are near to patent expiry, and therefore a number of biosimilars have been or will be developed. The term biosimilar can be defined as a biotherapeutic product that is similar in efficacy, safety and quality to the licensed reference product. Biosimilars may lead to a reduced price and significant cost savings for the health community and hopefully more patients globally will have easier access to biological therapy when indicated. CT-P13, which is a TNF-alfa inhibitor, is the first monoclonal antibody biosimilar being used in clinical practice. The drug is approved for all indications as an innovator product although clinical efficacy has only been demonstrated in rheumatic diseases. Until now the number of patients with inflammatory bowel disease (IBD) treated with CT-P13 is confined, but experience is continuously growing. Based on current data, CT-P13 seems to be efficacious and generally well tolerated in IBD especially in patients who are naïve to biological therapy. Knowledge with regard to interchangeability between CT-P13 and the originator infliximab is however, still rather sparse and more data are desired. Immunogenicity and long-term safety related to CT-P13 are other areas of great importance and good and reliable postmarketing pharmacovigilance is therefore required in the coming years.

Vedolizumab, an α4β7-integrin antagonist, is the first gut-selective monoclonal antibody that has been approved for the treatment of moderate-to-severe ulcerative colitis and Crohn’s disease in many countries in the world. However, questions still remain regarding its appropriate use and placement in current treatment algorithms. Therefore, we sought out to evaluate the existing literature on the use of vedolizumab in inflammatory bowel disease. From inception to 21 June 2015 we searched MEDLINE for phase III randomized control trials assessing the utility of vedolizumab in inflammatory bowel disease, of which three were identified. The GEMINI trials demonstrate that vedolizumab is an effective and safe treatment for patients suffering from moderate-to-severe ulcerative colitis (GEMINI I) and Crohn’s disease (GEMINI II and III). However, further studies are needed comparing its efficacy directly with anti-tumor necrosis factor therapies to allow for further delineation of current treatment algorithms as well as ensuring its long-term safety profile.

The gut and the brain communicate bidirectionally through anatomic and humoral pathways, establishing what is known as the gut–brain axis. Therefore, interventions affecting one system will impact on the other, giving the opportunity to investigate and develop future therapeutic strategies that target both systems. Alterations in the gut–brain axis may arise as a consequence of changes in microbiota composition (dysbiosis), modifications in intestinal barrier function, impairment of enteric nervous system, unbalanced local immune response and exaggerated responses to stress, to mention a few. In this review we analyze and discuss several novel pharmacological targets within the gut–brain axis, with potential applications to improve intestinal and mental health.

Irritable bowel syndrome is a functional bowel disorder with gastrointestinal symptoms (e.g. abdominal pain, straining, urgency, incomplete evacuation, nausea, and bloating) that occur alongside bowel function alterations (i.e. constipation, diarrhea, or both). Patients with irritable bowel syndrome may also experience comorbid anxiety and depression. Irritable bowel syndrome is common, with a prevalence estimated between 3% and 28%, affecting patient health and quality of life. Patients with moderate or severe irritable bowel syndrome generally seek medical care, whereas those with milder symptoms may choose self-management. Most patients with irritable bowel syndrome receive outpatient care, but irritable bowel syndrome-related hospitalizations do occur. The pathophysiology of irritable bowel syndrome is multifactorial (i.e. genetics, immune components, changes in the gut microbiota, disturbances in physiologic stress response systems, and psychosocial factors). Management of irritable bowel syndrome can include lifestyle changes, dietary interventions, counseling, psychologic medication, and agents that affect gastrointestinal motility. A number of therapies have emerged in recent years with clinical trial data demonstrating efficacy and safety for patients with irritable bowel syndrome, including agents that target gastrointestinal motility (i.e. linaclotide), gastrointestinal opioid receptors (i.e. asimadoline, eluxadoline), and gut microbiota (i.e. rifaximin). Linaclotide has been shown to significantly improve stool frequency and abdominal pain compared with placebo in constipation-predominant irritable bowel syndrome (number needed to treat, 5.1). Asimadoline shows efficacy in patients with moderate-to-severe irritable bowel syndrome-related pain. Rifaximin provided adequate relief of global irritable bowel syndrome symptoms versus placebo for a significantly greater percentage of patients with diarrhea-predominant irritable bowel syndrome (p < 0.001). Management that encompasses all aspects of irritable bowel syndrome (gastrointestinal symptoms) and comorbid psychologic symptoms (e.g. anxiety or depression) is important for improving overall patient health and well-being.

Recent developments in understanding the role of bile acids (BAs) as signalling molecules in human metabolism and inflammation have opened new avenues in the field of hepatology research. BAs are no longer considered as simple molecules helping in fat digestion but as agents with real therapeutic value in treating complex autoimmune and metabolic liver diseases. BAs and their receptors such as farnesoid X receptor, transmembrane G protein-coupled receptor 5 and peroxisome proliferator-activated receptor have been identified as novel targets for drug development. Some of these novel pharmaceuticals are already in clinical evaluation with the most advanced drugs having reached phase III trials. Chronic liver diseases such as primary biliary cholangitis, primary sclerosing cholangitis and nonalcoholic fatty liver disease, for which there is no or limited pharmacotherapy, are most likely to gain from these developments. In this review we discuss recent and the most relevant basic and clinical research findings related to BAs and their implications for novel therapy for chronic liver diseases.

Nonalcoholic fatty liver disease (NAFLD) is emerging as a major public health problem because of its association with increased cardiovascular and liver-related morbidity and mortality. Both genetic factors and lifestyle contribute to the pathogenesis of NAFLD. Lifestyle, including dietary habits and physical activity, is a modifiable risk factor and thus represents the main target for the prevention and treatment of NAFLD. In this review, we summarize the evidence regarding nutritional aspects (i.e. total energy intake, saturated fat and carbohydrates intake, certain foods or drinks and dietary patterns as a whole) in the treatment of NAFLD. In addition, we analyze the evidence concerning the independent effect of physical activity, including aerobic and resistance training, in the treatment of NAFLD. A therapeutic algorithm according to results from intervention trials is also provided for clinicians and other healthcare professionals involved in the management of NAFLD.

Advanced imaging techniques used in the management of Barrett’s esophagus include electronic imaging enhancement (e.g. narrow band imaging, flexible spectral imaging color enhancement, and i-Scan), chromoendoscopy, and confocal laser endomicroscopy. Electronic imaging enhancement is used frequently in daily practice, but use of the other advanced technologies is not routine. High-definition white light endoscopy and random four quadrant biopsy remain the standard of care for evaluation of Barrett’s esophagus; this is largely due to the value of advanced imaging technologies not having been validated in large studies or in everyday practice. A new advanced imaging technology called volumetric laser endomicroscopy is commercially available in the United States. Its ease of use and rapid acquisition of high-resolution images make this technology very promising for widespread application. In this article we review the technology and its potential for advanced imaging in Barrett’s esophagus.