A new study using a nationwide database shows that early use of methotrexate and tumor necrosis factor (TNF) inhibitors in patients with juvenile idiopathic arthritis (JIA) can significantly reduce their risk of developing uveitis.
While not particularly surprising, this large study provides further confirmation of previous observations in JIA-related uveitis which show that early treatment is effective and that methotrexate combined with TNF inhibitors provides even better protection.
The authors evaluated records for 3,512 children, about half of whom tested positive for antinuclear antibodies (ANA). One hundred and eighty patients (5.1%) developed uveitis within 1 year of arthritis onset, while an additional 251 patients (7.1%) developed the condition after the first year.
The risk factors for developing uveitis were similar to previous reports: oligoarthritis, ANA positive, young age (less than 3 years) and high disease activity (by clinical examination as well as ESR over 35 mm/hour).
Both methotrexate (HR 0.63, P=0.022) and TNF inhibitors (HR 0.56, P<0.001) were found to lower risk of uveitis. But methotrexate therapy delivered within the first year of diagnosis was even more effective (HR 0.29, P<0.001). As may be expected, the combination therapy of methotrexate and a TNF inhibitors resulted in even more protection (HR 0.10, P<0.001). The authors suggest that those at higher risk might benefit from an immunosuppressive treatment, even if the arthritis is stable.
Interestingly, etanercept was used in the majority of patients on TNF inhibitors, while less than 10% used adalimumab and none received infliximab. It has been the impression of many uveitis specialists that etanercept is not very effective in treating ocular inflammatory disease. Indeed, there are reports of ocular inflammatory disease appearing to be precipitated (or at least not prevented) by TNF inhibitors and certainly here they were not completely effective, although it is unclear if it is specific to etanercept.
Other inhibitors have been associated with extra-articular disease in a seemingly paradoxical fashion as well. In fact, a 2010 review of etanercept trials for ankylosing spondylitis found that etanercept was superior to placebo for preventing uveitis. However, uveitis rates for etanercept was similar to sulfasalazine, an agent long used to prevent recurrences but not to treat acute anterior uveitis. That is not to say that etanercept is as effective as adalimumab or infliximab as therapy for uveitis, but rather that it may be easier to treat than prevent disease.