To the Editor:

This letter represents an update of an article by my group published in Arthritis & Rheumatism in June 2001 (Reiff A, Takei S, Sadeghi S, Stout A, Shaham B, Bernstein B, et al. Etanercept therapy in children with treatment-resistant uveitis. Arthritis Rheum 2001;44:1411–5). In that article we reported that etanercept injected subcutaneously twice weekly had a beneficial effect in 10 children (18 eyes) with treatment-resistant chronic uveitis. Within 3 months, 10 of 16 affected eyes (63%; P = 0.017) showed a rapid decrease in anterior chamber cell density, with remission achieved in 4 eyes. Among children with a visual acuity of <20/25, 4 of 10 eyes (40%) improved. An exacerbation of uveitis during treatment with etanercept occurred in only 1 child (1 of 14 eyes) (7%). Other ocular outcome parameters, such as intraoccular pressure, synechiae formation, and lens clarity, remained unchanged. An increase in the dosage of etanercept to an average of 1.1 mg/kg after 3 months in 7 children failed to produce further improvement after 6 months of treatment.

Since the completion of our original data accumulation, 2 years have passed. In the meantime, multiple studies describing the use of tumor necrosis factor antagonists in uveitis treatment have been published. Of particular interest are the results of a small double-blind placebo-controlled trial of etanercept in the treatment of pediatric uveitis, reported as an abstract at the 2002 American College of Rheumatology Annual Scientific Meeting (Smith JA, Smith S, Whitcup SM, Suhler E, Clarke G, Thompson D, et al. The treatment of JRA-associated uveitis with etanercept [abstract]. Arthritis Rheum 2002;46 Suppl 9:S482). In that study 12 children (mean age 11 years) were treated with either etanercept 0.4 mg/kg (maximum dosage 25 mg twice weekly) or placebo. After 6 months the authors were unable to detect any improvement in anterior chamber cell density in either patient group. In contrast, the beneficial effect of the treatment has been maintained in a majority of our patients. Of the 10 children originally enrolled, 2 withdrew within the first 6 months for reasons unrelated to the study drug. Both children had initially improved, and had flares after etanercept was discontinued. Four children did not respond to treatment, and 3 of them discontinued etanercept within 12 months. One child continues to have uncontrolled uveitis but still takes etanercept for control of his arthritis.

Of the 4 children with sustained improvement, 1 girl continued to show improvement for 18 months, and her vision normalized. The family has since moved and the child was lost to followup. One girl who initially had a favorable response discontinued etanercept after 14 months of treatment when she experienced a grand mal seizure. Results of a diagnostic evaluation, including magnetic resonance imaging of the brain, lumbar puncture, and electroencephalography, were inconclusive for demyelinating disease. She was diagnosed as having benign childhood epilepsy (rolandic seizures) and started on gabapentin treatment. One month after discontinuation of etanercept she experienced a severe uveitis flare in both eyes. Etanercept was restarted 3 months later, and the uveitis again improved. She still has occasional mild seizure activity, while the uveitis in her left eye remains fully controlled and her right eye has minor inflammation. One girl continued to show improvement and had minimal uveitis but chose to discontinue etanercept after 22 months. She experienced a significant disease flare 2 months later. She was initially unable to restart etanercept due to a worldwide shortage of the drug. However, she was able to resume etanercept therapy after 15 months, and her uveitis has improved significantly ever since. Lastly, one girl continues to improve, currently has no active uveitis, and her vision has significantly improved.

In summary, in 6 of 10 children enrolled in this small, prospective open-label trial, etanercept had a beneficial effect for at least 3 months, and 4 children exhibited sustained benefit for at least 1 year. Etanercept may represent a viable alternative for children with active uveitis who have been treated unsuccessfully with traditional disease-modifying antirheumatic drugs.

Andreas Reiff MD*, * University of Southern California Childrens Hospital Los Angeles Los Angeles, CA.