Secukinumab promising for paediatric enthesitis-related arthritis and juvenile psoriatic arthritis
Treatment with the fully human anti-IL17 monoclonal antibody secukinumab resulted in fewer, and a longer time to, disease flares in children and adolescents with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA), results of the phase III JUNIPERA trial showed.
Study participants were 86 individuals aged 2 to <18 years (mean age 13.1 years, 33.7 percent female) with ERA or JPsA (n=52 and 34, respectively) for ≥6 months, active disease, and intolerance or inadequate response to ≥1 NSAID* or ≥1 DMARD*. They received open-label subcutaneous secukinumab (75 and 150 mg in patients weighing <50 and ≥50 kg, respectively) at baseline and at weeks 1, 2, 3, 4, 8, and 12 during the first treatment-period (TP1). The second treatment period (TP2) involved patients with a response (JIA ACR** ≥30 at week 12) who were then randomized double-blind to either continue secukinumab or receive placebo Q4W up to week 100 (n=37 in each group).
Mean JADAS-27*** score at baseline was 15.1, while enthesitis count was 2.6. About two-thirds of patients were on concomitant methotrexate.
At the end of TP1, 90.4 percent of patients (n=75) achieved JIA ACR 30, with 69.9 percent (n=58) achieving JIA ACR 70.
The risk of disease flare during TP2 was significantly reduced among patients who were on secukinumab compared with placebo (10 vs 21 flares; hazard ratio, 0.28, 95 percent confidence interval, 0.13–0.63; p<0.001), with a longer time to disease flare in the secukinumab group (median time to flare in the placebo group, 453 days). [EULAR 2021, abstract LB0004]
At the end of TP2 (week 104), more secukinumab than placebo recipients experienced JIA ACR 30 (89.2 percent vs 64.9 percent; p=0.014) and JIA ACR 70 (67.6 percent vs 43.2 percent; p=0.042).
“[There was a] rapid decrease in JIA disease activity with JADAS-27 improvement starting at week 1 [during TP1],” presented study author Dr Nicolino Ruperto from the IRCCS Istituto G. Gaslini, Genova, Italy, at EULAR 2021.
“[During TP2,] most disease activity reduction occurred during the initial 4 weeks of secukinumab treatment, with improvements maintained until the end of TP1 and 2,” he added.
At the end of TP1, secukinumab recipients experienced a mean -1.8 change from baseline in enthesitis count, while during TP2, the mean change from baseline in the secukinumab and placebo groups was -2.1 and -1.9, respectively. About 36 percent of secukinumab recipients had inactive disease at the end of TP1. The proportion of patients with inactive disease at the end of TP2 did not significantly differ between the secukinumab and placebo groups (47.2 percent vs 37.8 percent; p=0.500). Mean JADAS-27 score was comparable between secukinumab and placebo recipients at TP2 end (14.6 vs 13.3).
Adverse events (AEs) occurred at a comparable rate between the secukinumab and placebo groups (91.7 percent vs 92.1 percent), while non-fatal serious AEs were reported in 14.6 and 10.5 percent, respectively, throughout both the treatment periods. Eight patients discontinued treatment due to AEs, three and five in the secukinumab and placebo groups, respectively. No deaths occurred in either treatment group.
The most common (>5 percent) treatment-emergent AEs in secukinumab recipients were nasopharyngitis (33.3 percent), diarrhoea, and nausea (22.9 percent each), and in placebo recipients, nasopharyngitis (28.9 percent), upper respiratory tract infection (23.7 percent), and nausea (21.1 percent).
“Secukinumab has demonstrated efficacy and safety in adults with PsA, ankylosing spondylitis, and non-radiographic axial spondyloarthritis,” said Ruperto and co-authors.
“[The present trial showed that] in children and adolescents with ERA and JPsA, secukinumab demonstrated significantly longer time to flare and [lower] number of flares vs placebo,” said Ruperto.
“The improvement in signs and symptoms was sustained until week 104 and the safety profile was consistent with the known safety profile [of secukinumab] from trials in adults,” he concluded.