Ramanan, AV;
Dick, AD;
Jones, AP;
Guly, C;
Hardwick, B;
Hickey, H;
Lee, R;
... APTITUDE Trial Management Group, .; + view all
(2018)
A phase II trial protocol of Tocilizumab in anti-TNF refractory patients with JIA-associated uveitis (the APTITUDE trial).
BMC Rheumatology
, 2
, Article 4. 10.1186/s41927-018-0010-2.
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A phase II trial protocol of Tocilizumab in anti-TNF refractory patients with JIA-associated uveitis (the APTITUDE trial).pdf - Published Version Download (832kB) | Preview |
Abstract
Background: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Children with JIA are at risk of intraocular inflammation (uveitis). In the initial stages of mild-moderate inflammation uveitis is asymptomatic. Most children with mild-moderate uveitis are managed on topical steroid drops with or without systemic methotrexate (MTX). When children with moderate-severe uveitis are refractory to MTX, monoclonal anti-tumour necrosis factor agents have been trialled, interim analysis data showed positive results. However, several children with severe recalcitrant disease or non-responsive to anti-tumour necrosis factor agents remain and are at greater risk of significant ocular complications and visual loss. Further evidence of alternative therapies is needed with evidence of a potential role of anti-interleukin-6 agents in the management of severe refractory uveitis. Methods: The trial will be conducted following a two-stage Simon design. The trial will register at least 22 patients aged 2 to 18 years with active JIA-associated uveitis, who have taken MTX for at least 12 weeks and have failed an anti-TNF agent. It will take place in 7 centres across the UK. All participants will be treated for 6 months, with follow up of 9 months from registration. Participants will receive a stable dose of MTX and those weighing ≥30 kg will be dosed with 162 mg of Tocilizumab every 2 weeks and participants weighing < 30 kg dosed with 162 mg of Tocilizumab every 3 weeks. Primary outcome is treatment response at 12 weeks. Adverse events will be collected up to 30 calendar days following treatment cessation. Discussion: This is a novel adaptive design study of subcutaneous IL-6 inhibition in anti-TNF refractory JIA associated uveitis which will be able to determine if further research should be conducted. This is the first trial to look at ophthalmology outcomes in the efficacy of Tocilizumab in uveitis.This is the first paediatric clinical trial to assess the clinical effectiveness and safety of tocilizumab with MTX in JIA associated uveitis.
| Type: | Article |
|---|---|
| Title: | A phase II trial protocol of Tocilizumab in anti-TNF refractory patients with JIA-associated uveitis (the APTITUDE trial) |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s41927-018-0010-2 |
| Publisher version: | https://doi.org/10.1186/s41927-018-0010-2 |
| Language: | English |
| Additional information: | © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creative commons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Keywords: | Juvenile Idiopathic Arthritis, Methotrexate, Ophthalmology, Paediatric, Rheumatology, Safety, Tocilizumab, Uveitis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10072175 |
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