Successful treatment of tofacitinib-refractory scleritis associated with multiple systemic inflammatory diseases using upadacitinib

Scleritis is often associated with systemic inflammatory diseases, and a subset of patients remains refractory to conventional therapies, including corticosteroids, immunosuppressants, and tumor necrosis factor inhibitors (TNFi). Janus kinase inhibitors (JAKi) exert anti-inflammatory effects by broadly suppressing downstream cytokine signaling and have been increasingly applied in the management of systemic inflammatory conditions. Recently, more selective JAKi have been developed to minimize adverse effects while preserving therapeutic efficacy. However, clinical experience comparing the efficacy of non-selective versus selective JAKi remains limited. We report a case of highly refractory scleritis positive for proteinase 3-antineutrophil cytoplasmic antibody and suffered from rheumatoid arthritis (RA), and ulcerative colitis (UC). While RA and UC were controlled with TNFi, scleritis remained active and difficult to manage. Following the initiation of tofacitinib, a pan-JAKi, the scleritis rapidly entered remission. However, after tapering and discontinuation of methotrexate and corticosteroids, the scleritis relapsed, suggesting that control was not maintained with tofacitinib and became refractory to treatment. A subsequent switch to upadacitinib, a selective JAK1 inhibitor, resulted in renewed remission and sustained control of ocular inflammation. This case highlights the potential of JAKi as a treatment option for refractory scleritis, particularly in patients unresponsive to conventional therapies, and the possibility of transitioning to a selective JAK1 inhibitor in cases of pan-JAKi resistance.