Safety of Janus Kinase Inhibitors in Inflammatory Bowel Diseases.

In recent years, better knowledge of the pathophysiology of inflammatory bowel diseases (IBD) has led to a relevant expansion of the therapeutic arsenal for these conditions. Janus kinase (JAK) inhibitors are a family of small molecules that block one or more of the intracellular tyrosine kinases, including JAK-1, JAK-2, JAK-3 and TYK-2. Tofacitinib, a non-selective small molecule JAK inhibitor, and upadacitinib and filgotinib, which are selective JAK-1 inhibitors, have been approved by the US Food and Drug Administration (FDA) for moderate-to-severe active ulcerative colitis. Compared to biological drugs, JAK inhibitors have a short half-life, rapid onset of action, and no immunogenicity. Both clinical trials and real-world evidence support the use of JAK inhibitors in the treatment of IBD. However, these therapies have been linked with multiple adverse events (AEs) including infection, hypercholesterolemia, venous thromboembolism, major adverse cardiovascular events, and malignancy. While early studies recognized several potential AEs, post-marketing trials have shown that tofacitinib may increase the risk of thromboembolic diseases and major cardiovascular events. The latter are seen in patients aged 50 years or older with cardiovascular risk factors. Hence, the benefits of treatment and risk stratification need to be considered when positioning tofacitinib. Novel JAK inhibitors with a more selective effect on JAK-1 have proven to be effective in both Crohn's disease and ulcerative colitis, offering a potentially safer and efficacious therapeutic option to patients, including those with previous non-response to other therapies such as biologics. Nevertheless, long-term effectiveness and safety data are required.

Current perspectives on pediatric inflammatory bowel disease focusing on transitional care management. What should we consider?

The prevalence of inflammatory bowel disease (IBD) continues to rise around the globe. Although the percentage of pediatric IBD patients seems to be increasing, rates are surprisingly heterogeneous among different populations. Although the pathogenesis of IBD is believed to be multifactorial, a genetic predisposition may be especially relevant in pediatric-onset IBD. Phenotypic characteristics can also be significantly different when comparing pediatric and adult-onset IBD. Patients that develop the disease at a younger age usually present with more extensive and more aggressive disease and develop complications faster when compared to those that develop it during adulthood. Children with IBD are found to have frequent mood disorders and have a higher risk of developing socio-economic hardship, failing to meet development milestones. Therefore, IBD management should always involve a multidisciplinary team that is not limited to medical providers. Most institutions do not have an established transition protocol and lack the resources and training for transition care. Although there is no consensus on an optimal timing to transition the patient's care to an adult team, it is usually accepted they should be eligible for adult care when most of the key transition points have been met. Management strategies should be tailored to each patient's developmental level and environment. A successful transition can improve the long-term outcomes such as sustained remission, medication adherence, mental health and social and academic performance, while decreasing healthcare utilization. Every institution that manages pediatric IBD patients should have a well-established transition protocol in order to make sure to maintain continuity of care.

An approach to acute severe ulcerative colitis.

Introduction: Despite the introduction of novel therapies and treatment strategies for ulcerative colitis (UC), many patients develop acute, severe episodes, warranting prompt care and aggressive management. There is a significant unmet need to improve outcomes in these patients. Clinicians must be able to identify those that will have worse prognosis and plan an aggressive therapy with an early/proactive adjustments in management if needed.Areas covered: The aim of this review is to evaluate the most recent evidence on the assessment and management of patients with acute severe ulcerative colitis. We searched the mainstream literature search engines for the most recent evidence on diagnosis and management of acute UC.Expert Opinion: The approach to patients with severe UC includes clinical and endoscopic assessment of disease severity and ruling out over-infections. While intravenous corticosteroids remain the first line therapy for acute severe colitis, many patients do not respond and require escalation to calcineurin inhibitors or infliximab, and may ultimately require colectomy. Even though several novel therapies are available or in development, their role in acute severe episodes of colitis is unknown.