Tofacitinib in uveitis and scleritis

Abstract:

Janus kinases (JAKs) are a family of intracellular, non-receptor tyrosine kinases that play a crucial role in the JAK signaling pathway involved in the inflammatory process. Over the years, this pathway has garnered significant interest among researchers, leading to the development of various therapeutic agents aimed at blocking the pathway, thereby contributing to remarkable progress in the management of inflammatory diseases across multiple medical specialties. Although the use of JAK inhibitors in ophthalmology is still limited, evidence is gradually emerging on their role in managing uveitis and scleritis. One such agent is tofacitinib, a small-molecule pan-JAK inhibitor. Its therapeutic profile differs from that of biologics due to its partial and reversible inhibition of cytokines. Additionally, owing to its smaller molecular size, the drug is available in an oral formulation. In recent years, there has been a growing interest in JAK inhibitors, particularly tofacitinib, as a potential therapeutic option for refractory uveitis and scleritis in both adult and pediatric populations. Tofacitinib, either as monotherapy or in combination, has shown effectiveness in managing various uveitis cases that were unresponsive to conventional immunosuppressive therapies. It has also been explored in treatment-resistant scleritis. However, concerns persist regarding the potential adverse effects of tofacitinib, including cardiovascular events, thromboembolism, malignancies, and infections. This review aims to provide a comprehensive update on the role of tofacitinib in ocular inflammation, with particular emphasis on its clinical efficacy, safety profile, and the emerging literature surrounding its risks and side effects.