Trial Boosts Cosentyx for Juvenile Arthritis

A 2-year randomized trial demonstrated that secukinumab (Cosentyx) was effective in reducing disease flares in young patients with different forms of juvenile idiopathic arthritis (JIA), researchers said.

Flares occurred in 27% of patients receiving secukinumab in the phase III JUNIPERA study, compared with 55% of those assigned to placebo during the trial’s double-blind phase, reported Hermine I. Brunner, MD, of the University of Cincinnati, and colleagues in Annals of the Rheumatic Diseases.

By day 450, half the placebo group had experienced a flare. In the patients receiving secukinumab, the median had not been reached at the end of follow-up, approximately day 660, at which point only 30% had had flares.

Secukinumab appeared about equally effective in both JIA subtypes — enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) — considered in the trial. About 30% in each of these subgroups had flares during follow-up with secukinumab.

But flare risk differed markedly between JIA subtypes for the placebo recipients. Only about 45% of ERA patients experienced flares by day 660, whereas more than 70% did in the JPsA subgroup.

Safety findings were unremarkable, Brunner and colleagues indicated, with adverse event types and rates similar to those seen in adult patients with spondyloarthritis and psoriatic arthritis.

“The significantly longer time to disease flare in [the randomized double-blind phase] and improvement in disease activity observed establish secukinumab as a candidate in the treatment of patients with ERA and JPsA,” the researchers concluded.

JUNIPERA underpinned secukinumab’s approval last December for these indications, in children as young as 2 years with active JPsA and in those 4 and older with ERA. Secukinumab was first approved in 2015 for plaque psoriasis in adults.

The trial was divided into three phases: first, with open-label secukinumab given for up to 8 weeks; second, the randomized double-blind phase lasting up to 104 weeks; and finally, another open-label treatment period with secukinumab followed by withdrawal of the drug and additional follow-up.

Patients were included in the second phase only if they had achieved ACR30 responses (30% improvement by American College of Rheumatology criteria) during the initial open-label phase. Patients entered the third phase immediately after experiencing a flare during the randomized double-blind portion or at week 104 if they had not had a flare.

Eighty-six patients entered the first phase, including 52 with ERA and the rest with JPsA; 11 failed to achieve ACR30 responses, leaving 75 (44 ERA, 31 JPsA) for the second phase with randomized blinded assignments. A total of 32 entered the third phase and 26 completed it. Among those entering phase 2, adverse events were the main reason for discontinuing prematurely.

Mean patient age was 13 overall, with the ERA subgroup slightly older (by 1.5 years) on average. Boys accounted for 79% of the ERA group and 47% of the JPsA patients. Nearly all patients in the trial were white.

Mean affected-joint counts at baseline were 6.1 with ERA and 10.0 with JPsA. Total enthesitis counts averaged 2.7 with ERA and 2.3 with JPsA; mean total dactylitis counts for these subtypes were 0.4 and 1.8, respectively. About two-thirds of patients in both groups came into the study on methotrexate.

Time to disease flare was the primary outcome measure. Secondary endpoints included ACR30/50/70/90/100 responses, achievement of inactive disease, and change in 27-joint Juvenile Arthritis Disease Activity Score (JADAS-27).

Secukinumab led to greater proportions of patients achieving each of these ACR response levels relative to placebo at the end of the randomized phase. Patients on the active drug showed rates ranging from 89% for ACR30 to 43% for ACR100. Rates in the placebo group ranged from 65% to 38%. JADAS-27 scores fell from a mean of 15.2 at baseline to 4.9 at the end of phase 1, and stayed low throughout phase 2 with both placebo and secukinumab.

Rates of adverse events were somewhat higher with secukinumab versus placebo (92% vs 76% for events overall), and noticeably so for serious events (14% vs 0%). On the other hand, discontinuations due to adverse events were more common with placebo (13% vs 5%), largely because some manifestations of inefficacy were counted as adverse events and these were more frequent in the placebo group. Gastrointestinal complaints, nasopharyngitis, and fever were the main types of adverse events that were more common with secukinumab.

Limitations to the study cited by Brunner and colleagues included the small, overwhelmingly white, sample and lack of data on skin manifestations, “especially in JPsA patients.”