Although the current treatment strategies for children with juvenile idiopathic arthritis help to relieve pain symptoms, these medications provide limited efficacy on the underlying disease.
Pediatric patients with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) receiving treatment with secukinumab reported significantly longer time to disease flare when compared with placebo. Additionally, the safety profile was consistent with adult indications of psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to a study published in Annals of the Rheumatic Diseases.1
“Non-steroidal anti-inflammatory drugs (NSAIDs) and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) are considered first-line agents in JPsA, while NSAIDs and sulphasalazine are considered for ERA,” investigators explained. “Although the current treatment strategies for ERA and JPsA help to relieve pain, these medications often provide limited efficacy on the underlying disease. This necessitates initiation of more intensive therapy, including the introduction of biologic (b)DMARDs, of which very few are approved for ERA and JPsA treatments.”
The phase 3, randomized, double-blind, placebo-controlled, treatment-withdrawal trial compared biologic-naïve pediatric patients with active disease treated with either open-label subcutaneous secukinumab or placebo during 3 treatment periods. Patients received secukinumab (75/150 mg in patients <50/≥50 kg) in treatment period 1 (TP1) up to week 12. Juvenile idiopathic arthritis (JIA) American College of Rheumatology 30 (ACR30) responders at week 12 were then randomized 1:1 to receive secukinumab or placebo up to 100 weeks. Patients who flared in the treatment period 2 (TP2) were entered open-label secukinumab treatment period 3 (TP3), which lasted up to week 104. The primary endpoint was measuring time to disease flare in TP2.
Eligible patients were aged ≥2 to <18 years, had a disease duration of 6 or more months with inadequate response to 1 or more csDMARDs or NSAIDs, had active disease, were bDMARD-naïve, and were classified according to the International League of Associations for Rheumatology JIA classification criteria as either ERA or JPsA.
In total, 86 patients (52 patients [60.5%] diagnosed with ERA and 34 [39.5%] with JPsA) were entered into open-label secukinumab TP1. The median age was 14 years, 78.8% were male in the ERA cohort, and 52.9% were female in the JPsA group.
Most (87.2%) of patients achieved a JIA ACR30 response at the end of TP1 and were able to enter TP2. During TP2, responders received secukinumab or placebo (ERA, 44/52; JPsA, 31/34). A statistically significant longer time to disease flare was reported in TP2 for patients with ERA and JPsA receiving secukinumab when compared with placebo (27% vs 55%, HR, 0.28; 95% CI 0.13 to 0.63; p<0.001).
The majority (n = 79, 91.1%) reported 1 AE, 8 patients (9.3%) discontinued the study due to AEs, and 11 patients (12.8%) reported SAEs. The most frequent treatment-emergent AEs (TEAEs) were nasopharyngitis (31.4%), nausea (22.1%), upper respiratory tract infection (22.1%), and diarrhea (19.8%).
Although the trial population was small and mostly White, it was comparable to previous JIA trials. However, these limitations hindered the ability to detect rare AEs. Additionally, secukinumab efficacy was indirectly determined via JIA flares. Lastly, while there was a lack of data on skin manifestations, secukinumab has demonstrated efficacy across skin outcomes in other randomized trials evaluating pediatric patients with psoriasis (PsO).
“We consider secukinumab an important new treatment option for children with ERA and JPsA as secukinumab resulted in a rapid and profound improvement of signs and symptoms of both ERA and JPsA in this study, including the resolution of dactylitis and enthesitis,” investigators concluded.
Brunner HI, Foeldvari I, Alexeeva E, et al. Secukinumab in enthesitis-related arthritis and juvenile psoriatic arthritis: a randomised, double-blind, placebo-controlled, treatment withdrawal, phase 3 trial [published online ahead of print, 2022 Aug 12]. Ann Rheum Dis. 2022;annrheumdis-2022-222849. doi:10.1136/ard-2022-222849