Drugs最新文献

Donanemab (donanemab-azbt; Kisunla^TM) is an amyloid β-directed antibody developed by Eli Lilly and Company for the treatment of Alzheimer's disease. Donanemab recently received approval in the USA for the treatment of adults with early symptomatic Alzheimer's disease (patients with mild cognitive impairment or mild dementia stage of disease). This article summarizes the milestones in the development of donanemab leading to this first approval for Alzheimer's disease.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) are chronic immune-mediated diseases which primarily target the intestines. In recent years, the development and regulatory approval of various immunotherapies, both biological agents and small molecules, that target specific pathways of the IBD-associated inflammatory cascade have revolutionized the treatment of IBD. Small molecules offer the advantages of oral administration and short wash-out times. Sphingosine-1-phosphate (S1P) is a bioactive metabolite of ceramide, which exerts its functions after binding to five G-protein-coupled receptors (S1PR1-S1PR5). Concerning IBD, S1P participates in the egress of lymphocytes from the secondary lymphoid tissue and their re-circulation to sites of inflammation, mainly through S1PR1 binding. In addition, this system facilitates the differentiation of T-helper cells towards proinflammatory immunophenotypes. Recently, S1P modulators have offered a valuable addition to the IBD treatment armamentarium. They exert their anti-inflammatory function via sequestration of T cell subsets in the lymphoid tissues and prevention of gut homing. In this review, we revisit the role of the S1P/S1PR axis in the pathogenesis of IBD and discuss efficacy and safety data from clinical trials and real-world reports on the two S1PR modulators, ozanimod and etrasimod, that are currently approved for IBD treatment, and comment on their potential positioning in the IBD day-to-day management. We also present recent data on emerging S1P modulators. Finally, based on the successes and failures of S1PR modulators in IBD, we discuss future avenues of IBD treatments targeting the S1P/S1PR axis.

The nuanced landscape of anticoagulation therapy in patients with chronic kidney disease (CKD) presents a formidable challenge, intricately balancing the dual hazards of hemorrhage and thrombosis. These patients find themselves in a precarious position, teetering on the edge of these risks due to compromised platelet functionality and systemic disturbances within their coagulation frameworks. The management of such patients necessitates a meticulous approach to dosing adjustments and vigilant monitoring to navigate the perilous waters of anticoagulant therapy. This is especially critical considering the altered pharmacokinetics in CKD, where the clearance of drugs is significantly impeded, heightening the risk of accumulation and adverse effects. In the evolving narrative of anticoagulation therapy, the introduction of direct oral anticoagulants (DOACs) has heralded a new era, offering a glimmer of hope for those navigating the complexities of CKD. These agents, with their promise of easier management and a reduced need for monitoring, have begun to reshape the contours of care, particularly for patients not yet on dialysis. However, this is not without its caveats. The application of DOACs in the context of advanced CKD remains a largely uncharted territory, necessitating a cautious exploration to unearth their true potential and limitations. Moreover, the advent of innovative strategies such as left atrial appendage occlusion (LAAO) underscores the dynamic nature of anticoagulation therapy, potentially offering a tailored solution for those at the intersection of CKD and elevated stroke risk. Yet the journey toward integrating such advancements into standard practice is laden with unanswered questions, demanding rigorous investigation to illuminate their efficacy and safety across the spectrum of kidney disease. In summary, the management of anticoagulation in CKD is a delicate dance, requiring a harmonious blend of precision, caution, and innovation. As we venture further into this complex domain, we must build upon our current understanding, embracing both emerging therapies and the need for ongoing research. Only then can we hope to offer our patients a path that navigates the narrow strait between bleeding and clotting, toward safer and more effective care.

Asthma and cardiovascular disease (CVD) often co-exist. When a patient has both conditions, management requires an approach that addresses the unique challenges of each condition separately, while also considering their potential interactions. However, specific guidance on the management of asthma in patients with CVD and on the management of CVD in patients with asthma is still lacking. Nevertheless, health care providers need to adopt a comprehensive approach that includes both respiratory and CVD health. The management of CVD in patients with asthma requires a delicate balance between controlling respiratory symptoms and minimising potential cardiovascular (CV) risks. In the absence of specific guidelines for the management of patients with both conditions, the most prudent approach would be to follow established guidelines for each condition independently. Careful selection of asthma medications is essential to avoid exacerbation of CV symptoms. In addition, optimal management of CV risk factors is essential. However, close monitoring of these patients is important as there is evidence that some asthma medications may have adverse effects on CVD and, conversely, that some CVD medications may worsen asthma symptoms. On the other hand, there is also increasing evidence of the potential beneficial effects of asthma medications on CVD and, conversely, that some CVD medications may reduce the severity of asthma symptoms. We aim to elucidate the potential risks and benefits associated with the use of asthma medications in patients with CVD, and the potential pulmonary risks and benefits for patients with asthma who are prescribed CVD medications.

Vorasidenib (VORANIGO^®; Servier) is an orally administered, first-in-class, highly brain-penetrant dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 (IDH1/2) enzymes being developed for use in IDH-mutant diffuse glioma. Vorasidenib received its first approval on 6 August 2024, in the USA, for the treatment of adult and pediatric patients aged 12 years and older with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation following surgery, including biopsy, sub-total resection, or gross total resection. Approval was based on results from the multinational phase III INDIGO trial, in which vorasidenib significantly improved progression-free survival and time to the next anticancer intervention relative to placebo. In the EU and other countries worldwide, regulatory review of vorasidenib in IDH-mutant glioma is currently underway. This article summarizes the milestones in the development of vorasidenib leading to this first approval for glioma.