SNOWMASS, COLO. – Abatacept may be a safe and effective therapy for patients with juvenile idiopathic arthritis and severe uveitis that is refractory to anti–tumor necrosis factor agents.

Dr. Alexei Grom

Findings from a series of abatacept-treated patients recently reported by Italian investigators are encouraging because uveitis is an important source of morbidity in patients with JIA, and roughly 20% of affected patients do not respond to infliximab and adalimumab, Dr. Alexei A. Grom said at a symposium sponsored by the American College of Rheumatology.

The Italian series included seven patients with a mean uveitis duration of 11.6 years when they went on abatacept (Orencia) at 10 mg/kg per month. All had previously failed immunosuppressive therapy and two or more anti-TNF agents. All responded to abatacept, and six maintained a clinical remission after a mean of 9.2 months of therapy at 10 mg/kg per month.

The mean frequency of uveitis flares in the 6 months immediately prior to introducing abatacept was 3.7 episodes. In the first 6 months on the T-cell costimulation modulator, the mean frequency of flares was 0.7 episodes. There were no new ocular complications and no deterioration of preexistent ones. One patient withdrew from the study because of an arthritis flare and oral mycosis (Arthritis Care Res. 2010;62:821-5). The same investigators subsequently reported on two additional abatacept-treated patients with uveitis (Arthritis Care Res. 2011;63:308).

Up to one-quarter of all JIA patients will develop uveitis. Roughly 90% of cases occur in patients with oligoarticular-onset JIA. About 80% of uveitis cases are asymptomatic, but this complication can nonetheless be damaging. In one Midwestern case series, 30% of affected JIA patients had cataracts, 24% had band keratopathy, 27% had glaucoma, and 33% had permanently diminished vision.

"So, in most cases of JIA, what determines how we treat them is not the arthritis itself, but whether they have this complication or not," according to Dr. Grom of Children’s Hospital Medical Center, Cincinnati.

Treatment typically begins with steroid eyedrops, but they shouldn’t be used alone for longer than 3 months. Even low-grade inflammation at 3 months is intolerable; if present, it’s time to add systemic therapy, typically methotrexate. If that doesn’t clear the inflammation, anti-TNF therapy is warranted, he continued.

There are no good clinical trials of anti-TNF therapy for JIA uveitis, only relatively small uncontrolled case series akin to the Italian abatacept report, but the clinical experience indicates that about 50% of patients will respond to etanercept (Enbrel), albeit with frequent flares.

The response rate to the anti-TNF monoclonal antibodies seems to be significantly better. About 80% of patients respond to infliximab (Remicade), although many require relatively high doses of 10-20 mg/kg and infusions every 4 weeks. Similarly, about 80% of patients respond to adalimumab (Humira), although weekly injections may be required, at least initially, Dr. Grom said.

He declared having no relevant financial relationships.

02/16/11