JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases.

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition of the gastrointestinal tract that requires chronic treatment and strict surveillance. Development of new monoclonal antibodies targeting one or a few single cytokines, including anti-tumor necrosis factor agents, anti-IL 12/23 inhibitors, and anti-α4ß7 integrin inhibitors, have dominated the pharmacological armamentarium in IBD in the last 20 years. Still, many patients experience incomplete or loss of response or develop serious adverse events and drug discontinuation. Janus kinase (JAK) is key to modulating the signal transduction pathway of several proinflammatory cytokines directly involved in gastrointestinal inflammation and, thus, probably IBD pathogenesis. Targeting the JAK-STAT pathway offers excellent potential for the treatment of IBD. The European Medical Agency has approved three JAK inhibitors for treating adults with moderate to severe Ulcerative Colitis when other treatments, including biological agents, have failed or no longer work or if the patient cannot take them. Although there are currently no approved JAK inhibitors for Crohn's disease, upadacitinib and filgotinib have shown increased remission rates in these patients. Other JAK inhibitors, including gut-selective molecules, are currently being studied IBD. This review will discuss the JAK-STAT pathway, its implication in the pathogenesis of IBD, and the most recent evidence from clinical trials regarding the use of JAK inhibitors and their safety in IBD patients.

Health-related quality of life decline in clinically stable inflammatory bowel disease patients during the COVID-19 outbreak.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) affects many aspects of a patient's life and impairs their health-related quality of life (HRQoL). The COVID-19 outbreak has led to important mobility restrictions and a dramatic re-adjustment of social habits and health systems. This study aimed to assess the influence of the outbreak and mobility restrictions on the HRQoL of IBD patients with stable clinical remission on biologic treatment. Their self-perceived stress scores during the outbreak were also assessed. METHODS: A prospective, observational study was performed in IBD patients on biologic treatment with stable clinical remission. Patients with both Crohn's disease and Ulcerative Colitis patients were included. Patients filled in the IBDQ9 and the Perceived stress scale (PSS) electronically. To determine any changes, the results of the IBDQ9 during the outbreak were compared with the last IBDQ9 before the outbreak. RESULTS: 106 patients in clinical remission were included, with a median age of 42 year, 42% were female and 77% had CD. Median preCOVID-19 IBDQ9 was 72.1[66.5-80.12] and decreased to 69.2 [63.1-77.10] during the outbreak (p<0.001). The median PSS score was 12 [9-19]. There was a significant negative correlation between the PSS and the outbreak IBDQ9 (r=-0.66, p< 0.001). Regression analysis showed that the PSS score was associated with a lower IBDQ-9 during the outbreak(p<0.001) Conclusion: There was a negative impact of the COVID19 outbreak on the HRQoL of IBD patients in remission, with higher self-perceived stress scores associated with a lower QoL. The COVID-19 outbreak may have long-term implications for the HRQoL in these patients.

Health-related quality of life decline in clinically stable inflammatory bowel disease patients during the COVID-19 outbreak

Background and aims: Inflammatory bowel disease (IBD) affects many aspects of a patient’s life and impairs their health-related quality of life (HRQoL). The COVID-19 outbreak has led to important mobility restrictions and a dramatic re-adjustment of social habits and health systems. This study aimed to assess the influence of the outbreak and mobility restrictions on the HRQoL of IBD patients with stable clinical remission on biologic treatment. Their self-perceived stress scores during the outbreak were also assessed. Methods: A prospective, observational study was performed in IBD patients on biologic treatment with stable clinical remission. Patients with both Crohn’s disease and Ulcerative Colitis patients were included. Patients filled in the IBDQ9 and the Perceived stress scale (PSS) electronically. To determine any changes, the results of the IBDQ9 during the outbreak were compared with the last IBDQ9 before the outbreak. Results: 106 patients in clinical remission were included, with a median age of 42 year, 42% were female and 77% had CD. Median preCOVID-19 IBDQ9 was 72.1[66.5-80.12] and decreased to 69.2 [63.1-77.10] during the outbreak (p<0.001). The median PSS score was 12 [9-19]. There was a significant negative correlation between the PSS and the outbreak IBDQ9 (r=-0.66, p< 0.001). Regression analysis showed that the PSS score was associated with a lower IBDQ-9 during the outbreak(p<0.001) Conclusion: There was a negative impact of the COVID19 outbreak on the HRQoL of IBD patients in remission, with higher self-perceived stress scores associated with a lower QoL. The COVID-19 outbreak may have long-term implications for the HRQoL in these patients (AU)

Present and Future Therapeutic Approaches to Barrier Dysfunction.

There is converging and increasing evidence, but also uncertainty, for the role of abnormal intestinal epithelial barrier function in the origin and development of a growing number of human gastrointestinal and extraintestinal inflammatory disorders, and their related complaints. Despite a vast literature addressing factors and mechanisms underlying changes in intestinal permeability in humans, and its connection to the appearance and severity of clinical symptoms, the ultimate link remains to be established in many cases. Accordingly, there are no directives or clinical guidelines related to the therapeutic management of intestinal permeability disorders that allow health professionals involved in the management of these patients to carry out a consensus treatment based on clinical evidence. Instead, there are multiple pseudoscientific approaches and commercial propaganda scattered on the internet that confuse those affected and health professionals and that often lack scientific rigor. Therefore, in this review we aim to shed light on the different therapeutic options, which include, among others, dietary management, nutraceuticals and medical devices, microbiota and drugs, and epigenetic and exosomes-manipulation, through an objective evaluation of the scientific publications in this field. Advances in the knowledge and management of intestinal permeability will sure enable better options of dealing with this group of common disorders to enhance quality of life of those affected.