Methotrexate therapy associated with a reduced rate of new-onset uveitis in patients with biological-naïve juvenile idiopathic arthritis
Joeri W. van Straalen, Görkem Akay, Carlyn V. Kouwenberg, Sytze de Roock, Viera Kalinina Ayuso, Nico Wulffraat, Joke de Boer, Joost F. Swart
Abstract
Objective To study the effect of methotrexate (MTX) therapy on new-onset uveitis in patients with biological-naïve juvenile idiopathic arthritis (JIA). Methods In this matched case–control study, we compared MTX exposure between cases with JIA-associated chronic uveitis (JIA-U) and patients with JIA and without JIA-U at the time of matching (controls). Data were collected from electronic health records of the University Medical Centre Utrecht, the Netherlands. Cases with JIA-U were matched 1:1 to JIA control patients based on JIA diagnosis date, age at JIA diagnosis, JIA subtype, antinuclear antibodies status and disease duration. The effect of MTX on JIA-U onset was analysed using a multivariable time-varying Cox regression analysis. Results Ninety-two patients with JIA were included and characteristics were similar between cases with JIA-U (n=46) and controls (n=46). Both ever-use of MTX and exposure years were lower in cases with JIA-U than in controls. Cases with JIA-U significantly more often discontinued MTX treatment (p=0.03) and out of those who did, 50% afterwards developed uveitis within 1 year. On adjusted analysis, MTX was associated with a significantly reduced new-onset uveitis rate (HR: 0.35; 95% CI: 0.17 to 0.75). No different effect was observed between a low (<10 mg/m 2 /week) and standard MTX dose (≥10 mg/m 2 /week). Conclusion This study demonstrates an independent protective effect of MTX on new-onset uveitis in patients with biological-naïve JIA. Clinicians might consider early initiation of MTX in patients at high uveitis risk. We advocate more frequent ophthalmologic screening in the first 6–12 months after MTX discontinuation.