SAN FRANCISCO – The monoclonal antibody adalimumab was more than twice as effective as was placebo for treating methotrexate-refractory uveitis in children with idiopathic arthritis, according to early results from the largest-ever double-blind, randomized, controlled trial of the disease.
Because the difference in time to treatment failure met the prespecified efficacy endpoint, investigators halted the trial after enrolling 90 patients, said Dr. Athimalaipet V. Ramanan, professor of pediatric rheumatology at the University of Bristol (England). But adalimumab also was associated with about three times more infections and other serious adverse events, compared with placebo, he reported in a late-breaker session at the annual meeting of the American College of Rheumatology. “We will, of course, be looking at the long-term data to evaluate cost-effectiveness, as well as safety,” he added.
Amy Karon/Frontline Medical News
Dr. Athimalaipet V. Ramanan
About one in five children with juvenile idiopathic arthritis (JIA) develops uveitis, which threatens sight and is the most common type of pediatric intraocular inflammation. First-line methotrexate can substantially improve articular inflammation in JIA, but had not been studied in randomized, controlled trials of JIA-associated uveitis. Based on adalimumab’s success in treating the articular aspects of JIA, the investigators studied the biologic in patients aged 2-18 years who had active JIA-associated uveitis despite at least 12 weeks of stable methotrexate therapy. Most cases were mild to moderate, including mild flare and little vitreous haze. The average age of the patients was 9 years, about three-quarters were girls, and about half tested positive for antinuclear antibodies. All patients continued on methotrexate and were randomized 1:2 to subcutaneous, biweekly injections of placebo or weight-based adalimumab.
Patients in the adalimumab arm were about 75% less likely than were controls to fail treatment – that is, to meet Standardization of the Uveitis Nomenclature (SUN) criteria for progressive anterior segment inflammation (hazard ratio, 0.25; 95% confidence interval, 0.12-0.49; P less than .0001). The median time to treatment failure was about 20 weeks for the control arm, and nearly 60 weeks for the adalimumab arm. Specific definitions of treatment failure included a consecutive, two-step rise from baseline in the SUN cell activity score, sustained failure to improve from baseline grade 3 inflammation, persistent grade 1 or 2 inflammation after 6 months of treatment, and worsening ocular comorbidities, Dr. Ramanan said. Adalimumab also was associated with improved SUN scores, although the researchers are still analyzing those data, he added.
Serious adverse events occurred in 22% of patients who received adalimumab, Dr. Ramanan reported. These most often consisted of streptococcal disease, varicella, and other infections for which the immunomodulator has a black box warning. Although only 7% of the control group experienced serious adverse events, these included two flares of uveitis that caused patients to withdraw.
The National Institute for Health Research Health Technology Assessment Programme and Arthritis Research UK funded the study. Dr. Ramanan and one coauthor reported having received consulting fees from AbbVie, maker of Humira. AbbVie reviewed and commented on the abstract, but did not participate in trial design or data analysis.