Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis

Athimalaipet V Ramanan, Andrew D Dick, Ashley P Jones, Andrew McKay, Paula R Williamson, Sandrine Compeyrot-Lacassagne, Ben Hardwick, Helen Hickey, Dyfrig Hughes, Patricia Woo, Diana Benton, Clive Edelsten, Michael W Beresford, SYCAMORE Study Group

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Abstract

BACKGROUND: Adalimumab, 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.

METHODS: In 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.

RESULTS: The 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 (10.07 events per patient-year [95% CI, 9.26 to 10.89] vs. 6.51 events per patient-year [95% CI, 5.26 to 7.77]), as were serious adverse events (0.29 events per patient-year [95% CI, 0.15 to 0.43] vs. 0.19 events per patient-year [95% CI, 0.00 to 0.40]).

CONCLUSIONS: Adalimumab 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. (Funded by the NIHR Health Technology Assessment Programme and Arthritis Research UK; SYCAMORE EudraCT number, 2010-021141-41 .).

Original languageEnglish
Pages (from-to)1637-1646
Number of pages10
JournalNew England Journal of Medicine
Volume376
Issue number17
Early online date26 Apr 2017
DOIs
Publication statusPublished - 27 Apr 2017

Keywords

  • Research Support
  • Non-U.S. Gov't

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    Ramanan, A. V., Dick, A. D., Jones, A. P., McKay, A., Williamson, P. R., Compeyrot-Lacassagne, S., Hardwick, B., Hickey, H., Hughes, D., Woo, P., Benton, D., Edelsten, C., Beresford, M. W., & SYCAMORE Study Group (2017). Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis. New England Journal of Medicine, 376(17), 1637-1646. https://doi.org/10.1056/NEJMoa1614160