APTITUDE

A phase II trial of Tocilizumab in anti-TNF refractory patients with JIA associated uveitis

Summary

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Children with JIA also are at risk of inflammation of the uvea in the eye (uveitis). 80% of all paediatric uveitis is secondary to JIA. The major risk factors for development of uveitis in JIA are oligoarticular pattern of arthritis, early onset of arthritis, and antinuclear antibody positivity. In the initial stages of mild to moderate inflammation the uveitis is entirely asymptomatic. This has led to the current practice of screening all children with JIA regularly for uveitis. Most children with mild to moderate uveitis are managed on topical steroid drops and use of systemic methotrexate (MTX) as an immunosuppressive agent. As a significant proportion of children with moderate-severe uveitis are refractory to MTX, biologicals in the form of monoclonal anti-TNF agents have been tried. The anti TNF agents are effective only in 30-60 % of the patients based on several retrospective case series. 
Tocilizumab is a biological therapy drug. If patients have rheumatoid arthritis the body overproduces a protein called IL-6, causing tiredness, anaemia, inflammation, damage to bones, cartilage and tissue.
Tocilizumab blocks the action of IL-6 and reduces these effects. Studies looking at the effect of Tocilizumab in children have looked at Rheumatology examinations and have shown positive improvements in arthritis. Data from models and in samples of eye fluid in adults show inflammation is associated with high IL-6 levels and give a strong rationale for using this approach in JIA-associated uveitis. Therefore there is good reason to target IL-6 to see if tocilizumab in uveitis and ophthalmology outcomes is efficacious. There remains a clinical need for refractory JIA-associated uveitis that have not responded to anti-TNF treatments, to undertake a study to give early indications of the clinical effectiveness of Tocilizumab in combination with MTX and to decide whether further research is justified.

Links to further information

ST001TEM01 Final Analysis Statistical Analysis Plan_APTITUDE_v3.0_191220

APTITUDE Protocol v4 0 31 05 2017

http://www.sycamoretrial.org.uk/