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Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multi-centre, single-arm, phase 2 trial

Research output: Contribution to journalArticle

Original languageEnglish
Number of pages7
JournalThe Lancet Rheumatology
Early online date7 Feb 2020
DateAccepted/In press - 13 Jan 2020
DateE-pub ahead of print (current) - 7 Feb 2020


Uveitis associated with juvenile idiopathic arthritis (JIA) is a cause of major ocular morbidity. A significant proportion of children are refractory to systemic methotrexate (MTX) and tumour necrosis factor inhibitors. Our aim was to study the safety and efficacy of tocilizumab in children with JIAassociated uveitis refractory to both methotrexate and TNF inhibitors.

This multicentre, single-arm phase II trial was conducted following a Simon’s two-stage design. Patients aged 2 to 18 years with active JIA-associated uveitis were recruited from 7 sites across the UK. All patients had been on a stable dose of methotrexate for at least 12 weeks and had not responded to treatment with a tumor necrosis factor inhibitor. Those weighing 30 kg or more weretreated with 162 mg of subcutaneous tocilizumab every two weeks for 24 weeks, and participants weighing less than 30 kg were treated with 162 mg every three weeks for 24 weeks. The primary outcome was treatment response defined as a 2-step decrease, or decrease to zero, from baseline in the level of inflammation (anterior chamber cells) at week 12, per the Standardization of Uveitis Nomenclature criteria. The trial would be stopped for futility based on a planned interim analysis, with futility was defined as two or fewer treatment responses among ten participants. Adverse events where collected up to 30 calendar days following treatment cessation; reasons for treatment cessation included treatment non-response, withdrawing from treatment, completing 24 weeks of treatment.

Twenty-two participants were registered to the trial between December 3, 2015 and March 9, 2018, and 21 participants received treatment. One participant was determined to be ineligible immediately after registration and therefore withdrawn. Seven of 21 (median unbiased estimate of proportion 34% [95% CI 25% to 57%]) responded to treatment (p=0.11). Safety results were consistent with the known safety profile of tocilizumab.

The primary endpoint was not met, and thus the results do not support a phase III trial of tocilizumab in patients with JIA-associated uveitis. However, post-hoc analyses suggest a positive effect of tocilizumab in a subset of patients. It is important that data on use of Tocilizumab in clinical practice is now captured in national registries. Our data suggests an option for the use of Tocilizumab in children with uveitis refractory to anti TNF.



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    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Elsevier at 10.1016/S2665-9913(20)30008-4. Please refer to any applicable terms of use of the publisher.

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