A multicenter, randomized control study published in the New England Journal of Medicine shows that adding adalimumab to methotrexate therapy for juvenile idiopathic arthritis (JIA)-associated uveitis greatly increases the duration of disease remission.
Subjects included 90 children and adolescents 2 years of age or older with active JIA-associated uveitis who had been on a stable weekly dose of methotrexate for at least 12 weeks. Patients were randomized 2:1 to receive either 20 mg or 40 mg of adalimumab (depending on body weight) or placebo, administered subcutaneously every 2 weeks until month 18 or treatment failure. Patients maintained their methotrexate dose during the study period.
The primary outcome measure was time to treatment failure, defined according to a multicomponent intraocular inflammation score.
During the second interim analysis of the study period, the adalimumab group exhibited significantly lower risk of treatment failure than the placebo group. The monitoring committee decided that participants in the placebo group should cease the trial protocol and enter the 6-month follow-up period, and that treatment subjects should continue receiving adalimumab and then complete the follow-up phase. All participants who received at least one dose of adalimumab or placebo were included in the safety analysis.
Analysis of data up to the stopping point revealed that patients who added adalimumab showed significant delays in time to treatment failure compared with placebo (hazard ratio, 0.25; P<0.0001), and these patients also had a significantly lower rate of failure (27% vs. 60%; P=0.002). In addition, adalimumab patients had a mean duration of inactive disease (zero anterior chamber cells) that was remarkably longer than control patients (mean 179 vs. 14.5 days), with an estimated treatment effect of 164.8 days of remission gained (P<0.0001).
Furthermore, a significantly greater number of patients in the adalimumab group discontinued topical glucocorticoids (hazard ratio, 3.58; P=0.02).
An increase in adverse events (AEs) was of concern, however. Incidences of both minor and serious adverse events (AEs) were higher in the adalimumab group at 10.07 events per patient-year in the adalimumab group compared with 6.51 in the control group. The most common AEs were minor infections, respiratory disorders and gastrointestinal disorders.
The authors conclude that the combination of methotrexate and adalimumab is an effective therapy for JIA-associated uveitis, but that a greater risk of side effects should be anticipated.
While the treatment effect is possibly underestimated as many patients remained in remission past the end of follow-up, the short follow-up period may have also masked any serious long-term complications from medication, such as cancers and demyelinating events. An open-label extension of the trial is ongoing, which should provide more insight into long-term outcomes.