Background Children with severe uveitis or those who have not responded to anti-tumour necrosis factor agents and methotrexate (MTX) are at significant risk of sight loss1-3. Evidence on alternative therapies is needed.
Objectives To evaluate the clinical response to Tocilizumab with MTX in children with Juvenile Idiopathic Arthritis (JIA)-associated uveitis who failed anti-TNF therapy to determine the need for further research.
Methods Multi-centre, open label, single arm trial using a two-stage Simon design4.
Setting: 7 UK sites
Participants: Children aged 2-18 years with JIA-associated uveitis defined as "2 readings of cellular infiltrate in anterior chamber of SUN criteria grade ≤1+ or more during the preceding 6 weeks, the latest reading must be at the time of screening."
Intervention: Treatment with MTX and those weighing ≤30 kg treated with 162 mg of Tocilizumab every 2 weeks and those weighing <30 kg every 3 weeks.
Main Outcome Measures: Primary outcome was treatment response at 12 weeks defined as per SUN criteria as a 2 step decrease in the level of inflammation or decrease to 0 between baseline and 12 weeks of treatment. Data on safety, topical corticosteroid usage, tolerability, compliance, optic and ocular measurements, American College of Rheumatology Pedi core set criteria measurements, changes in biologic/Disease-modifying anti-rheumatic drugs therapy and flares of arthritis collected.
Results 22 participants were registered; 1 was removed as found to be ineligible soon after registration. A total of 7 were classified as a pre-specified treatment response, the median unbiased estimate of proportion was 34% 95% CI (25% to 57%), p=0.11. 4 had macular oedema at baseline and this was resolved in 3 participants. Post-hoc analysis showed that there were 4 (19%) who were classified as a non-treatment response but had at least a one-step improvement at 3 months, leaving 10 (48%) showing no response, the mean (SD) number of steroid drops at baseline was 4.48 (3.11) and which reduced to 4.33 (2.29) at 12 weeks. Safety results were consistent with the known safety profile of Tocilizumab; no SAEs were reported.
Conclusion Whilst this study did not pass the pre-specified criterion, the data shows almost a half of the participants including 7 (33%) with a 2-step improvement, and a further 3 (14%) with 1-step improvement, responded to Tocilizumab.
References  Foeldvari I, Wierk A. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis. J Rheumatol 2005;32:362-365.
 Weiss AH, Wallace CA, Sherry DD. Methotrexate for resistant chronic uveitis in children with juvenile rheumatoid arthritis. J Pediatr 1998;133:266-8.
 Yu EN, Meniconi ME, Tufail F, Baltatzis S, Foster CS. Outcomes of treatment with immunomodulatory therapy in patients with corticosteroid-resistant juvenile idiopathic arthritis-associated chronic iridocyclitis. Ocul Immunol Inflamm 2005;13:353-60.
 Simon R. Optimal Two-Stage Designs for Phase II Clinical Trials. Control Clin Trials 1989;10:1-10.
Acknowledgement This trial is funded by Versus Arthritis (project reference number 20659)
Disclosure of Interests Athimalaipet Ramanan Consultant for: AbbVie, UCB, Sobi, Eli Lilly, Speakers bureau: Speaker fees/ honoraria from Abbvie, SOBI, Eli Lilly and UCB, AbbVie, UCB, Sobi, Eli Lilly, Andrew Dick: None declared, Ashley Jones: None declared, Andrew McKay: None declared, Catherine Guly: None declared, Ben Hardwick: None declared, Richard Lee: None declared, Matthew Smyth: None declared, Michael Beresford: None declared
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