Predictors of lack of response to methotrexate in juvenile idiopathic arthritis associated uveitis

Abstract

Objectives: To investigate clinical features associated with lack of response to MTX in juvenile idiopathic arthritis associated uveitis (JIA-U).

Methods: Clinical records of JIA-U patients were retrospectively reviewed. Differences among variables were assessed by Mann-Whitney and χ2 or Fisher's exact tests as appropriate. Association between predictors and requirement of a biological disease-modifying antirheumatic drug (bDMARD) was evaluated by univariate Cox regression analysis and Kaplan-Meier curves. A multivariable logistic model was applied to estimate strength of association, adjusting for potential confounders.

Results: Data from 99 JIA-U patients treated with MTX were analysed (82.8% female), with a mean follow up of 9.2 years and a mean age at uveitis onset of 5.7 years. In 65 patients (65.7%) at least one bDMARD to control uveitis was required. Children requiring a bDMARD for uveitis had lower age at JIA and uveitis onset, more frequent polyarticular course, higher frequency of bilateral uveitis at onset and higher prevalence of systemic steroids' use. Despite similar frequency of ocular damage at onset, MTX non-responders showed a higher percentage of ocular damage at last visit. Younger age at JIA onset, polyarticular course and a history of systemic steroids' use resulted independent factors associated to lack of response to MTX at Cox regression analysis. Kaplan-Meier curves and the multivariate model confirm the independent role of both polyarticular course and systemic steroids' use.

Conclusions: Younger age at JIA onset, polyarticular course and a history of systemic steroids' use are predictors of a worse response to MTX in JIA-U.

Keywords: biologics; juvenile idiopathic arthritis; methotrexate; uveitis.

Figure 1.

Ocular complications in patients with JIA not responsive to methotrexate treatment. (A) Anterior segment image of a 14-year-old female patient with posterior synechiae causing an irregularity of the pupil shape (left); an optical coherence tomography imaging of the macula shows cystoid edema (middle). While posterior synechiae remained stable over the years, cystoid edema resolved after introducing a biologic disease-modifying antirheumatic drug (bDMARD) (right). (B) A 12-year-old female patient showing posterior synechiae at the slit lamp examination image (left), and the presence of optic disc swelling on infrared fundus image (middle). The introduction of bDMARD resolved the optic disc swelling after three months (right)

Figure 2.

Kaplan–Meier cumulative incidence analysis and Cox regression analysis of the introduction of bDMARD in patients with JIA. (A) Sixty-five patients required a bDMARD for uveitis by the end of follow-up period (1.2 per 10 person-years). (B, C) Cumulative incidence rates differed between patients with polyarthritis and oligoarthritis (B, log-rank test: P = 0.005), and between patients with and without a history of systemic steroids’ use (C, log-rank test: P=0.011). The forest plot of hazard ratios (bottom) includes results from univariate (on the left) and multivariate (on the right) analyses and encompasses all risk factors with P-values less than 0.1 by Cox regression analysis. Both polyarticular course and history of systemic steroids’ use correlated with a higher risk of requiring a bDMARD in JIA-U