Background/Purpose: Uveitis associated with Juvenile Idiopathic Arthritis (JIA) is a major cause of morbidity with potentially sight-threatening complications. Despite current screening and (pre-biologic) therapeutic options, 10-15% of children develop bilateral visual impairment. Tumour necrosis factor alpha plays a pathogenic role in JIA-uveitis. No controlled trials have determined the impact of biologic therapy in JIA-associated uveitis. This double blind, randomised placebo-controlled trial assessed the efficacy, safety and cost-effectiveness of adalimumab in JIA-associated uveitis.

Methods: Patients aged 2 to 18 years with active JIA-associated uveitis, despite stable methotrexate (MTX) treatment for at least 12 weeks, were randomly assigned to adalimumab or placebo in a ratio of 2:1. All patients were treated up to a maximum period of 18 months, with follow up of 2 years from randomisation. All patients received a stable dose of MTX and in addition either adalimumab (20 mg for patients weighing <30 kg or 40 mg for patients weighing ≥30 kg, subcutaneous injection every 2 weeks) or placebo.

Primary endpoint was “time to treatment failure” defined by the “Standardisation of the Uveitis Nomenclature” criteria. Ten secondary efficacy endpoints were assessed including quality of life variables and arthritis disease activity measures. Adverse events from both arms were collected. Statistical analysis of the primary outcome used the log rank test to compare treatment groups with a hazard ratio and 95% confidence interval also being reported.

Results: The trial was stopped early for efficacy after 90 patients had been randomised as interim analysis met the pre-specified statistical stopping guidelines. The final analysis of the primary outcome showed positive treatment effect in favour of adalimumab: hazard ratio (HR) 0.27 (95% CI 0.13-0.52); p<0.0001. Adverse events were experienced by 88.3% (53/60, 687 events) of patients in the adalimumab group and 90% (27/30, 144 events) of patients in the placebo group. Events were consistent with the known adalimumab profile. 15 serious adverse events (SAEs) most commonly infection (10 events) occurred in 21.7% (n=13) of the patients in the adalimumab group, 3 of these resulted in the patient being withdrawn from treatment and there were 2 SAEs (flare of uveitis) reported in 6.7% (n=2) patients in the placebo group (both patients were withdrawn from the trial).

Conclusion: This trial, the largest of its kind to be conducted in JIA-associated uveitis, provides evidence of efficacy of adalimumab treatment used in addition to methotrexate in this population. The safety profile of adalimumab was consistent with that previously reported for adalimumab.

University Hospitals Bristol NHS Foundation Trust was contracted to receive a sum under data sharing agreement.

This project was funded by the National Institute for Health Research Health Technology Assessment Programme (project 09/51/01) and Arthritis Research UK (grant reference 19612).

Adalimumab was provided by Abbvie which reviewed this abstract and provided comments for author consideration. Trial protocol design and analyses were undertaken independent of AbbVie.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomised-controlled-trial-of-the-clinical-effectiveness-safety-and-cost-effectiveness-of-adalimumab-in-combination-with-methotrexate-for-the-treatment-of-juvenile-idiopathic-arthritis-associated/