Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis

Abstract

BACKGROUNDAdalimumab, a fully human anti-tumor necrosis factor α monoclonal antibody, is effective in the treatment of juvenile idiopathic arthritis (JIA). We tested the efficacy of adalimumab in the treatment of JIA-associated uveitis. METHODSIn this multicenter, double-blind, randomized, placebo-controlled trial, we assessed the efficacy and safety of adalimumab in children and adolescents 2 years of age or older who had active JIA-associated uveitis. Patients who were taking a stable dose of methotrexate were randomly assigned in a 2:1 ratio to receive either adalimumab (at a dose of 20 mg or 40 mg, according to body weight) or placebo, administered subcutaneously every 2 weeks. Patients continued the trial regimen until treatment failure or until 18 months had elapsed. They were followed for up to 2 years after randomization. The primary end point was the time to treatment failure, defined according to a multicomponent intraocular inflammation score that was based on the Standardization of Uveitis Nomenclature criteria. RESULTSThe prespecified stopping criteria were met after the enrollment of 90 of 114 patients. We observed 16 treatment failures in 60 patients (27%) in the adalimumab group versus 18 treatment failures in 30 patients (60%) in the placebo group (hazard ratio, 0.25; 95% confidence interval [CI], 0.12 to 0.49; P<0.0001 [the prespecified stopping boundary]). Adverse events were reported more frequently in patients receiving adalimumab than in those receiving placebo ( CONCLUSIONSAdalimumab therapy controlled inflammation and was associated with a lower rate of treatment failure than placebo among children and adolescents with active JIA-associated uveitis who were taking a stable dose of methotrexate. Patients who received adalimumab had a much higher incidence of adverse events and serious adverse events than those who received placebo.

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis

“…In this registry, however, all JIA subtypes with various comorbidities are included and this may explain the difference. In agreement with previous studies, infections represented the most frequent AE for both ADA and IFX 6,12,15 .…”

“…The results showed efficacy of ADA in controlling ocular inflammation, with a treatment failure of 27% at 18 months' followup in 60 patients with JIA-associated uveitis, which was significantly lower than in the placebo group (30 patients) treated with just MTX, where the treatment failure was 60% 12 . Although the uveitis duration at treatment start was not reported and the followup was 6 months shorter than in our study, the results obtained are very close to ours, confirming the overall efficacy of ADA in JIA-associated uveitis.…”

“…The first double-blind randomized controlled trial investigating the effect of ADA in the treatment of JIA-associated uveitis in 90 patients has recently been published 12 . The results showed efficacy of ADA in controlling ocular inflammation, with a treatment failure of 27% at 18 months' followup in 60 patients with JIA-associated uveitis, which was significantly lower than in the placebo group (30 patients) treated with just MTX, where the treatment failure was 60% 12 .…”

ADJUVITE: a double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis

“…While the SYCAMORE trial aimed to demonstrate that adalimumab could prevent treatment failure, and indeed demonstrated in a double-blind randomised fashion in a large number of patients that adalimumab was superior to placebo in either reducing inflammation or avoid uveitis worsening within 3 months and well tolerated over 12 months,26 ADJUVITE aimed to demonstrate early uveitis improvement on adalimumab. In addition to conforming the results of SYCAMORE on several common outcome measures, ADJUVITE showed that LFP assessment, which detects inflammation even in patients with low-grade inflammation and sometimes no cells on SL examination as shown by response to maximised therapy,33 enables an earlier documentation of improvement on adalimumab therapy.…”

“…In patients with JIA-associated uveitis and an inadequate response to MTX and topical steroids, several uncontrolled studies are in favour of using adalimumab 14–25. In such patients, the randomised placebo-controlled SYCAMORE trial recently demonstrated that adding adalimumab to MTX was effective in preventing treatment failure 26. The assessment of ocular inflammation was based on grading the cellularity of the anterior chamber of the eye by slit lamp (SL), using definitions of improvement or worsening according to the Standardised Uveitis Nomenclature (SUN) classification 27.…”