Methotrexate therapy associated with a reduced rate of new-onset uveitis in patients with biological-naïve juvenile idiopathic arthritis

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/m²/week) and standard MTX dose (≥10 mg/m²/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.

Keywords: Arthritis, Juvenile; Autoimmune Diseases; Epidemiology; Methotrexate.

Figure 1

Flowchart of included patients. Patients were matched on date of JIA diagnosis, age at JIA diagnosis, JIA subtype, ANA status and JIA disease duration. ANA, antinuclear antibodies; JIA, juvenile idiopathic arthritis; JIA-U, juvenile idiopathic arthritis-associated uveitis; UMCU, University Medical Centre Utrecht.

Figure 2

Distribution of time from last MTX stop to uveitis diagnosis. The figure includes patients with juvenile idiopathic arthritis-associated uveitis who discontinued MTX and did not restart before uveitis development (n=14). MTX, methotrexate.

Figure 3

Diagram of average survival curves for new-onset uveitis in current case–control study. The separate curves for subpopulations with and without MTX use are calculated based on the adjusted time-varying Cox model, therefore they follow a similar pattern and do not represent generalisable absolute numbers of patients at risk over time. JIA, juvenile idiopathic arthritis; MTX, methotrexate.

Figure 4

Diagram of average survival curves for new-onset uveitis in current case–control study. The separate curves for subpopulations with and without low (<10 mg/m²/week) or standard dose (≥10 mg/m²/week) MTX use are calculated based on the adjusted time-varying Cox model, therefore they follow a similar pattern and do not represent generalisable absolute numbers of patients at risk over time. JIA, juvenile idiopathic arthritis; MTX, methotrexate.