Oral methotrexate as a steroid-sparing therapy after high-dose intravenous corticosteroid pulse therapy for refractory Vogt–Koyanagi–Harada disease

Abstract Purpose In Japan, high-dose corticosteroids serve as the first-line treatment for Vogt–Koyanagi–Harada disease (VKHD), whereas cyclosporine (CysA) and adalimumab are reserved for recurrent cases. However, some patients require prolonged corticosteroid therapy despite these immunosuppressants. Our institution generally utilizes CysA as the first-line steroid-sparing immunosuppressive agent and low-dose methotrexate (MTX; 6–8 mg/week) as a second-line or alternative therapy. We evaluated recurrence rates and treatment-related adverse effects, focusing on MTX. Study design Retrospective observational study. Methods We reviewed 64 patients with first-onset VKHD treated with systemic corticosteroids (high-dose intravenous pulse therapy followed by oral prednisolone [PSL]) between April 2017 and April 2024. Recurrence was defined as the reappearance of intraocular inflammation after initial control. Clinical data regarding recurrence patterns and subsequent treatments, including MTX and CysA, were analyzed. Results The cohort comprised 28 men and 36 women (mean age, 52.3 ± 15.4 years). Twenty-two of 64 patients (34%) experienced recurrence. Among these, 15 patients received CysA; 8 required switching to MTX because of insufficient disease control, difficulty tapering corticosteroids, or CysA-related adverse effects. After initiating MTX, six of eight patients discontinued PSL after a median of 17.5 months and remained recurrence-free during a median of 10 months. In contrast, among seven patients treated with CysA alone, five discontinued PSL after 34 months and remained recurrence-free for 24 months. No severe MTX-related adverse effects were observed. Conclusion Low-dose MTX was well tolerated and enabled discontinuation of corticosteroids in patients with recurrent VKHD, supporting its utility as a feasible steroid-sparing therapy.