MILAN, Italy; ZURICH, Switzerland; and HAMBURG, Germany—Of patients with JIA (juvenile idiopathic arthritis)-associated uveitis,13% to 20% had a generally good long-term outcome despite a high rate of complications, and responded better to infliximab (Remicade®) than to etanercept (Enbrel®) when topical and second-line agents failed.1-3
Uveitis prevalence varies with type of JIA
Dr. Grassi and colleagues reviewed medical records of 309 JIA patients for uveitis occurrence and complications and type of JIA (oligoarticular onset, polyarticular onset, or systemic onset). They report that uveitis developed in 62 patients (20.1%) over a mean follow-up period of 7.6 years. Uveitis was asymptomatic in 56 of 62 cases and was most common in patients with oligoarticular-onset JIA, in early age at disease onset, and in the presence of antinuclear antibodies (ANA). Most cases of uveitis (77.4%) developed within the first 2 years after arthritis onset.
"Forty-four of the 62 patients experienced relapses of uveitis; in 20/62 relapses were concomitant to arthritis relapses; in 24/62 relapses presented without active arthritis," Dr. Grassi et al write. Uveitis complications developed in 35.5% of the patients, leaving 13/62 of them (21%) visually impaired, four of whom became blind.
"Oligoarticular-onset JIA patients with early onset disease who are ANA-positive may benefit from closer ophthalmologic follow-up, particularly during flares of the articular disease for the first 4 years of the disease, as recommended by current guidelines," Dr. Grassi recommends.
Similar data on uveitis were reported by Rotraud K. Saurenmann, MD, with the department of pediatrics at University Children's Hospital, in Zurich, Switzerland, and colleagues.2 They conducted a long-term follow-up study of an inception cohort of 1081 JIA patients, 13.1% of whom had developed uveitis after a mean follow-up of 6.9 years. As in the Grassi study, the main risk factors were young age at diagnosis, ANA positivity, and oligoarticular-onset JIA. Female gender was also a risk factor in this study.
Dr. Saurenmann et al report that uveitis complications developed in 37.3% of patients (4.9% of the total cohort), but only 9.1% of patients had impaired vision.
"Our results suggest that routine ophthalmologic follow-up examination with close collaboration of ophthalmologists and pediatric rheumatologists leads to excellent visual outcomes. In addition, we suggest that it is likely that early aggressive immunosuppressive treatment, which may include anti-TNFα agents, may further improve visual outcome and decrease complications by preventing prolonged intraocular inflammation," Dr. Saurenmann concludes.
Infliximab better than etanercept for refractor uveitis-associated JIA
Ivan Foeldvari, MD, head of pediatric rheumatology at the Hamburg Center for Child and Adolescent Rheumatology at Eilbek Clinic, in Hamburg, Germany, and colleagues surveyed 33 pediatric rheumatology centers on use and efficacy of TNF inhibitors in 884 patients with JIA-associated uveitis.3 Dr. Foeldvari found that 15 of these centers (following 404 patients) were using TNF inhibitors for this indication. "The mean duration from onset of uveitis to start of anti-TNF treatment was 45.1 months," Dr. Foeldvari et al write.
The centers in this study had used etanercept in 34 cases, infliximab in 25 cases, and adalimumab (Humira®) in three. Responses were rated as good in 53% of patients treated with etanercept, in 70% of patients treated with infliximab, and in all three patients treated with adalimumab.
"Infliximab was statistically significantly more efficacious for the treatment of JIA-associated uveitis than etanercept (chi-square P = .004)," Dr. Foeldvari reports.
Whom and how to screen for JIA-associated uveitis
Pirjo Tynjälä, MD, a specialist in pediatric rheumatology at Helsinki University's Hospital for Children and Adolescents, in Finland, discussed with CIAOMed the clinical management of JIA-associated uveitis.
Dr. Tynjälä said that JIA patients younger than 7 years of age are screened for uveitis every 3-to-4 months; patients 7-to-12 years old are screened every 6 months; and patients older than 12 years are screened every 1-to-2 years. The screening is done by an experienced ophthalmologist with expertise in pediatric rheumatology and includes the slit-lamp examination, and measurements of ocular pressure and visual acuity.
"Usually at the same visit and at the same outpatient clinic, the patient and parents meet the pediatric rheumatologist as well," Dr. Tynjälä said. "If a ‘fresh' uveitis is found or uveitis is more active, the information is transferred immediately to the pediatric rheumatologist, who initiates at least methotrexate (if the patient is not yet on MTX) or some other option is discussed. Usually we initiate infliximab before we start on systemic steroids if the uveitis is not very soon controlled by topical steroids plus methotrexate."
The Helsinki clinicians agree with Foeldvari and use TNF-modulators early, avoiding the use of systemic steroids if possible. "High-dose systemic steroids are used very seldom (only if there is an ophthalmologic crisis), and the need of low-dose steroids is diminishing alongside the increased use of TNF-modulators. If we reach no remission in uveitis with a methotrexate dose up to 15mg/m2 and topical steroids, or the compliance of the patient is not good enough, we usually initiate infliximab," Dr. Tynjälä said.
Egla Rabinovich, MD, co-chief of pediatrics at the division of rheumatology, at Duke University Medical Center, in Nashville, Tennessee, told CIAOMed that there are currently two major efforts under way to study uveitis in children with JIA. "One is a result of collaboration between the pediatric rheumatology community (CARRA, the Childhood Arthritis and Rheumatology Research Alliance) and the pediatric ophthalmology community (PEDIG, the Pediatric Eye Disease Investigator Group). In addition, CARRA has funded a prospective registry of infliximab use in pediatric uveitis for which I am the primary investigator," Dr. Rabinovich said.
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References
1. Grassi A, Corona F, Casellato A, et al. Prevalence and outcome of juvenile idiopathic arthritis-associated uveitis and relation to articular disease. J Rheumatol. 2007 Mar 1; [Epub ahead of print].
2. Saurenmann RK ,Levin AV, Feldman BM, et al. Prevalence, risk factors, and outcome of uveitis in juvenile idiopathic arthritis. A long-term followup study. Arthritis Rheum. 2007;56:647-657.
3. Foeldvari I, Nielsen S, Kümmerle-Deschner J, et al. Tumor necrosis factor-α blocker in treatment of juvenile idiopathic arthritis-associated uveitis refractory to second-line agents: results of a multinational survey. J Rheumatol. 2007 Mar 1; [Epub ahead of print].
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