Outcomes of Upadacitinib Use in Non-Infectious Uveitis: Novel Report of 12 Cases and Summary of Published Reports

PURPOSE: Treatment‑refractory uveitis can lead to vision‑threatening sequelae if not adequately controlled. We present a summary of previously published cases and describe the response and progression of 12 novel patients after starting off-label upadacitinib (UPA) (JAK-1 inhibitor) as a second- or third-line treatment for various uncontrolled non-infectious uveitides. METHODS: Retrospective case series from a rheumatology clinic within a single Canadian city. Control of ocular inflammation, as determined by the amount of additional systemic and topical immunomodulators required to achieve quiescence, frequency of flares, or severity of inflammation, is described herein. RESULTS: Ten of the 12 participants were women (83.3%), and the sample had a mean age of 48.3 years (range 31.0-75.0 years). Five patients (41.7%) achieved complete control of inflammation, two of whom were able to discontinue all other systemic and topical immunomodulatory therapies for ocular inflammation and continue UPA use as of publication. An additional three patients (25.0%) achieved only partial control of ocular inflammation. The final four patients (33.3%) completely failed to respond to the medication (no change in uveitis). Ultimately, four patients (33.3%) had to discontinue UPA: two whose uveitis did not respond, and two despite good ophthalmic results. CONCLUSION: The use of UPA off-label can be transformative for the management of ocular inflammation in only select cases. We are the first to document treatment failure. A prospective, comparative, blinded trial is required to draw reliable conclusions about the perfect candidate for therapy initiation. Our observations may help providers and patients anticipate potential treatment outcomes.