JAK inhibitors Show Promise in Treating Chronic Noninfectious Uveitis

Researchers found that patients with noninfectious uveitis who don’t respond to traditional treatments (i.e., corticosteroids, antimetabolites and biologic agents) may benefit from Janus kinase inhibitor therapy. Janus kinases have been implicated in the pathogenesis of inflammatory and autoimmune conditions such as rheumatoid arthritis, psoriasis, Behçet’s disease and Crohn’s disease. These images from the study show a patient prior to initiating tofacitinib demonstrating uncontrolled vitritis (A, B), improvement at six months (C, D) and near-complete resolution of leakage and complete resolution of vitritis three years after initiation of tofacitinib (E, F). Photo: Paul M. Karpecki, OD. Click image to enlarge. Chronic noninfectious uveitis is often managed with local corticosteroids or systemic immunosuppression. Despite the availability of several steroid-sparing options, many demonstrate high failure rates, leading researchers to seek alternative treatments. Among these, Janus kinase (JAK) inhibitors—non-receptor tyrosine kinases implicated in the pathogenesis of various inflammatory and autoimmune disorders like rheumatoid arthritis and psoriasis—have gained attention. An increasing number of case reports highlight the efficacy of these agents in treating uveitis. The present study investigated two JAK inhibitors (Jakinibs), upadacitinib and tofacitinib, finding both to be well-tolerated with a low incidence of side effects in patients suffering from refractory noninfectious uveitis.Data from a total of eight patients were gathered from the Cleveland Clinic’s uveitis service between 2015 and 2022. Participants were all diagnosed with noninfectious uveitis and exhibited treatment failure with conventional immunomodulatory therapies before starting Jakinib treatment. The patients were predominantly female, with varying histories of uveitis lasting from five months to 19 years. Four patients had scleritis and one each had iritis, intermediate uveitis, retinal vasculitis and panuveitis.Patients were monitored over a median treatment duration of approximately 29.5 months. Four patients achieved stable control on tofacitinib, while one patient on upadacitinib experienced a single mild flare that was managed with corticosteroids. Among the three patients who transitioned to Jakinibs due to poor systemic disease control, two remained flare-free for up to a year after starting therapy.Importantly, side effects were minimal; gastrointestinal disturbances were noted in some taking tofacitinib, while upadacitinib had no reported side effects.“Given the promising results in this case series and the others reported, Jakinibs may have a role for refractory ocular inflammatory disease after conventional immunomodulatory therapy has been trialled,” the researchers wrote in their paper on the findings. However, they pointed out various limitations of their study, including its retrospective nature, small sample size and relatively short follow-up duration. “Until larger trials demonstrating the safety and efficacy in uveitis patients are performed, Jakinibs will likely remain a fourth or fifth-line therapy for ocular inflammatory diseases in those that are treatment refractory after corticosteroids, antimetabolites and biologic agents,” they concluded. Alongside the treatment of isolated uveitis, the researchers propose that Jakinibs may also be regarded as a fourth or fifth-line therapy for the concurrent management of rheumatologic conditions that present with both systemic and ocular symptoms. In the study, two patients started on a Jakinib primarily for systemic disease control also experienced prolonged control of ocular inflammation. The authors wrote, “All six patients with systemic manifestations of their autoimmune disease benefited from a reduced systemic disease burden with the Jakinib.”Click here for the journal source. Beckman M, Srivastava SK, Lowder CY, et al. The use of Janus kinase inhibitors to treat noninfectious uveitis. Eye. November 6, 2025. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.