THU0521 The Methotrexate Treatment can Prevent Uveitis Onset in Juvenile Idiopathic Arthritis: The Experience in Cohort with Increased Proportion of Methotrexate

Abstract

BackgroundUveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA), often entirely asymptomatic but could be sight-threatening. The main predictors of uveitis in JIA are oligoarticular (OA) subtype, ANA-positivity and younger age at the JIA onset. Methotrexate (MTX) has been able to decrease the incidence of uveitis in JIA up to 2 times [1]. Treatment of JIA depends on number of active joints: NSAID and intra-articular (IAC) steroid injection are the first line-therapy for OA subtype of JIA. In Russia there is a restricted access to prolonged intra-articular steroids, such as triamcinolone hexacetamide. In the cases of relapse after short-term IAC followed by start of MTX therapy, which lead to higher proportion of patients with JIA, treated with MTX then in Europe and North America.ObjectivesTo re-evaluate the possibility of MTX to prevent the onset of uveitis in Russian JIA cohort patients with increased proportion of applying of MTX.MethodsThe clinical charts of all consecutive patients who had received a stable management for at least 2 years with or without MTX were reviewed. Patients who were given systemic medications other than MTX (except NSAID) were excluded. Patients with systemic arthritis, rheumatoid factor-positive arthritis, or enthesitis-related arthritis were also excluded. In each patient, the al least 2-year follow-up period after first visit was examined to establish whether uveitis had occurred.ResultsA total of 281 patients with a median disease duration of 3.8 year were included. One hundred and ninety one patients (68%) were treated with MTX compare to 33.9% in previous study [1]. During the at least 2-year follow-up, 64 patients (22.8%) developed uveitis, a median of 1.6 year after the disease onset. The frequency of uveitis was lower in MTX-treated than in MTX-untreated patients (11.5% vs 46.7%, respectively, OR=6.7 (95%CI:3.7-12.3), p=0.0000001). In previous study the frequency of uveitis was 10.5 in MTX-treated vs 20.2 in MTX-untreated patients [1]. Survival analysis confirmed that patients treated with MTX had a lower probability of developing uveitis (HR=4.35, p=0.000001) (Fig.). In subgroup analysis was shown that MTX more preventive in boys (HR=6.7, p=0.0007) than in girls (HR=3.6, p=0.000001); in patient with onset age more than 5 years (HR=22.2, p=0.000001) than whom disease onset less 5 years (HR=2.3, p=0.003). The data of survival analysis of MTX prevention not shown benefits depend on number of active joints: in OA (HR=4.0, p=0.000001) similar to polyarthritis (HR=3.7, p=0.02) and ANA status: ANA-positive (HR=4.4, p=0.00002) similar to ANA-negative (HR=3.6, p=0.003).ConclusionsMTX therapy may prevent the onset of uveitis in children with JIA. Further randomized controlled trial required to confirmation our results.ReferencesPapadopoulou C, Kostik M, Bohm M, Nieto-Gonzalez JC, Gonzalez-Fernandez MI, Pistorio A, Martini A, Ravelli A. Methotrexate Therapy May Prevent the Onset of Uveitis in Juvenile Idiopathic Arthritis. J Pediatr 2013;163:87...

Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept

“…It has been hypothesized that ETN may not directly cause the development of uveitis, but the discontinuation of MTX upon successful arthritis control may pose the patient at risk [38]. Recent data have shown that MTX may prevent the onset of uveitis in children with JIA [39, 40]. Nevertheless, many patients who had ETN discontinued for uveitis were likely switched to adalimumab and infliximab, which are nowadays recommended as second-line therapeutic option among patients with JIA and uveitis [41].…”

Uveitis bei juveniler idiopathischer Arthritis – leitliniengerechte Diagnostik und Therapie anhand von Kasuistiken

“…The positive effect of methotrexate on JIA uveitis has been reported in several case series and a few prospective studies 14 , 15 , 16 . As methotrexate has been shown to reduce the incidence of uveitis in JIA patients 17 , 18 , 19 , early use in JIA patients at high risk of uveitis may be considered.…”

Methotrexate Monotherapy in Juvenile Idiopathic Arthritis Associated Uveitis: Myth or Reality?

“…The majority were females, with higher frequency than in other reported cohorts. [8][9][10][11] Methotrexate is widely used in clinical practice as first csDMARD for the treatment of pediatric noninfectious uveitis and is currently recommended as the immunosuppressive drug of choice both for treatment of arthritis and uveitis in children with JIA. 4,[12][13][14][15] However, while strong evidence supports the role of MTX in the initial treatment of JIA arthritis, 14 data on its long-term efficacy in JIA-U, as monotherapy, are limited and based mostly on small observational studies that provide a mean follow-up duration of less than two years 5 which is much less than in our study (7.6 years).…”

“…Seemingly, a Russian study with similar design demonstrated that the absence of MTX treatment is a predictor for uveitis development. 11 In addition, data from a German registry showed how MTX treatment, both alone and in combination with tumor necrosis factor-α (TNF-α) inhibition, reduced uveitis incidence over time. 9 In our cohort, the difference in the two groups in the age at the time of uveitis onset seem to confirm the preventive effect of MTX: patients who were already on treatment developed uveitis almost two years later than MTX-naïve children did.…”