The commission based its decision on SYCAMORE2, a double-masked, randomised, placebo-controlled clinical trial. The results showed that adalimumab combined with methotrexate significantly delayed the time to treatment failure compared with methotrexate plus placebo in children 2 years of age and older with active juvenile idiopathic arthritis-associated uveitis.
"These results demonstrate adalimumab has the potential to help many children who have failed standard treatments," said Dr Athimalaipet Ramanan, paediatric rheumatologist at University Hospitals Bristol NHS Trust and principal investigator of the SYCAMORE study, in a press release.
SYCAMORE2 was sponsored by the University Hospitals Bristol NHS Foundation Trust and coordinated by the Clinical Trials Research Centre at the University of Liverpool.
Investigators assigned patients who were taking a stable dose of methotrexate in a 2:1 ratio to receive either adalimumab (at a dose of 20 mg or 40 mg, according to body weight) or placebo, administered subcutaneously every two weeks.
Patients continued the trial regimen until treatment failure or until 18 months had elapsed. The researchers followed them for up to 2 years, including 6 months off the study drug.
The primary endpoint was the time to treatment failure, defined as meeting at least one of the following criteria: multiple components of intraocular inflammation, worsening or development of ocular comorbidities, use of concomitant medications that were not allowed or that did not follow pre-specified criteria, and suspension of treatment for an extended period of time.
The Independent Data Safety and Monitoring Committee (IDSMC) recommended unmasking the trial early after seeing that adalimumab combined with methotrexate controlled ocular inflammation better and was associated with a lower rate of treatment failure in 90 patients than the combination of methotrexate and placebo.
The pre-specified stopping criteria were met after the enrolment of 90 of 114 patients. Researchers observed 16 treatment failures in 60 patients (27%) in the adalimumab group versus 18 treatment failures in 30 patients (60%) in the placebo group (hazard ratio, 0.25; 95% confidence interval [CI], 0.12 to 0.49; (P<0.0001). This was the pre-specified stopping boundary.
Patients taking adalimumab experienced 10.7 (95% CI 9.26 to 10.89) adverse events per patient-year, compared with 6.51 (95% CI, 5.26 to 7.77) for patients taking the placebo.
A higher proportion of these adverse events were serious in the patients taking adalimumab. These patients suffered 0.29 events per patient-year (95% CI 0.15 to 0.43) versus 0.19 events per patient-year for the patients taking placebo (95% CI 0.00 to 0.40).