Etanercept not linked to uveitis risk in real-world JIA study
medwireNews: An analysis of two UK juvenile idiopathic arthritis (JIA) registries suggests no significant difference in uveitis risk among patients treated with the tumor necrosis factor (TNF) inhibitor etanercept relative to methotrexate.
Kimme Hyrich, from The University of Manchester in the UK, and colleagues explain that etanercept “has been considered as a potential risk factor in the development of uveitis” based on previous study findings, and note that “there has been a concern that etanercept can increase the likelihood of recurrence of uveitis in patients with a preexisting history of the disease.”
To further investigate the association between etanercept use and uveitis risk, the researchers analyzed data from 2294 children and adolescents enrolled in one of two registries – the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study or the Biologics for Children with Rheumatic Diseases – who had non-systemic JIA with no history of uveitis at baseline.
In all, 45.6% of the study population received etanercept treatment, while 41.1% were taking methotrexate, 10.6% adalimumab, and 2.7% infliximab. The median age of participants ranged from 10 to 11 years across the groups.
Hyrich and team found that 44 patients received a new diagnosis of uveitis during 5456 person–years of follow-up, with crude incidence rates per 100 person–years of 0.6 for patients taking etanercept, 0.1 for those taking adalimumab or infliximab, and 1.6 for those taking methotrexate.
While rates of uveitis were numerically lower among patients taking any TNF inhibitor relative to methotrexate, there was no significant difference in risk between the etanercept and methotrexate groups in a propensity-adjusted analysis accounting for factors including age, sex, and disease activity. The investigators note that adjusted comparisons could not be carried out for the adalimumab and infliximab groups “as there were too few events.”
When the etanercept group was broken down into patients receiving the TNF inhibitor in combination with methotrexate (n=555) or as monotherapy (n=492), uveitis risk was numerically lower in the combination group, but the difference between the two groups did not reach statistical significance.
Together, these findings “do not support a causative link between etanercept and the development of uveitis,” write Hyrich and team in Rheumatology.
They note that the lower rates of uveitis among people treated with etanercept versus methotrexate in the unadjusted analysis are “likely explained by the influence of age and disease duration, whereby patients in the [methotrexate] cohort are, on average, younger and so more ‘at risk’ of developing uveitis compared with etanercept patients.”
And the team concludes that “in the absence of a sufficient comparison group, our understanding of what additional risk etanercept adds when looking at the risk of developing uveitis remains unclear.”
Talking to medwireNews about the strengths and limitations of the research, study co-lead Athimalaipet Ramanan (University of Bristol, UK) said that while “registries are important for following long-term safety of new agents (including biologics) in children, the challenge is that when we look at this data for important aspects of disease onset, course etc, the limitations of real world [studies] need to be taken into account.”
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