Ixekizumab may offer additional treatment option for juvenile idiopathic arthritis

medwireNews: Patients with juvenile idiopathic arthritis (JIA) who are candidates for biologic disease-modifying antirheumatic drugs (DMARDs) experience reductions in disease activity with the interleukin (IL)-17 inhibitor ixekizumab, indicates a phase 3, noncomparative study.

“Ixekizumab showed promising results as a new treatment option for children with enthesitis-related arthritis and juvenile psoriatic arthritis,” write Athimalaipet Ramanan (University of Bristol, UK) and colleagues in The Lancet Rheumatology.

Ixekizumab is a high-affinity monoclonal antibody that selectively targets IL-17A and has been used for the treatment of psoriatic arthritis and axial spondyloarthritis in adults, and pediatric psoriasis.

To investigate its potential for JIA, the researchers conducted COSPIRIT-JIA, an ongoing multicenter, open-label, Bayesian study in patients with a bodyweight of at least 10 kg who had enthesitis-related arthritis (aged 6 to <18 years) or juvenile psoriatic arthritis (aged 2 to <18 years).

No restriction on previous DMARD exposure

Participants were required to have swelling or limited motion and pain in at least three peripheral joints and the primary endpoint was a JIA American College of Rheumatology 30 (ACR30) response, defined as improvement from baseline in three of any six core outcome variables of at least 30%, with no more than one of the remaining variables worsening by more than 30%.

The first 40 patients who enrolled in the study were naïve to biologic DMARDs and were randomly assigned to receive treatment with ixekizumab or the biologic DMARD adalimumab. A further 61 patients were given ixekizumab irrespective of biologic DMARD experience.

Ixekizumab was given as a subcutaneous injection once every 4 weeks, at a dose of 80 mg for participants weighing more than 50 kg, 40 mg for those weighing 25–50 kg, and 20 mg for those weighing 10 to less than 25 kg. Subcutaneous adalimumab was given once every 2 weeks, at a dose of 40 mg for patients weighing 30 kg or more, and 20 mg for those weighing 10–29 kg.

The participants could continue with chronic stable use of oral glucocorticoids (≤10 mg/day or ≤0.2 mg/kg per day prednisone equivalent), conventional synthetic DMARDs (methotrexate and sulfasalazine), nonsteroidal anti-inflammatory drugs, and analgesics.

The median age of the patients was 14.0 years, while 56% were boys, and 85% were White.

Ixekizumab is effective and well tolerated

At week 16, 89% of the 81 patients treated with ixekizumab had a JIA-ACR30 response, as did 95% of the 20 patients given adalimumab. Among ixekizumab-treated patients, a JIA-ACR30 response was observed in 90% of those who were biologic DMARD-naïve, while 86% of biologic DMARD-experienced patients had a response. The rate of response to ixekizumab was the same for patients with enthesitis-related arthritis or juvenile psoriatic arthritis.

Ixekizumab was also associated with a reduction from baseline to week 16 in Juvenile Arthritis Disease Activity Score-27 (14.7 to 4.6 points), as well as the Leeds Enthesitis Index (LEI) for participants with enthesitis (2.1 to 0.5 points), and the Psoriasis Area and Severity Index (4.6 to 0.8 points) for those with psoriasis.

The reduction in LEI scores reached the minimal disease activity threshold of tender entheseal points of 1 point or below, and “was considered a clinically meaningful improvement,” the researchers write.

Treatment-related AEs were experienced by 81% of patients treated with ixekizumab versus 80% of those given adalimumab, with 82% versus 65% of events deemed mild or moderate in nature. Serious AEs were experienced by 4% versus 15% of patients.

The most common treatment-emergent AEs were infections (52 vs 45%), allergic reactions or hypersensitivities (31 vs 30%), and injection site reactions (32 vs 10%). Among patients receiving ixekizumab, 4% experienced cytopenia, 2% depression-related adverse events, and 1% a mild and transient hepatic adverse event.

Exploratory post-hoc analysis indicated only a 53% probability that ixekizumab was noninferior to adalimumab.

Further investigation required

In an accompanying editorial, Matthew Stoll and Maria Danila, both from the University of Alabama at Birmingham, USA, say the study “demonstrates the efficacy of ixekizumab in children with spondyloarthritis, positioning it as an additional therapeutic option in the management of juvenile spondyloarthritis.”

However, they note that there was a “missed opportunity” to report axial outcomes, and the serious AE rate with adalimumab appears to “contradict long-term safety data of adalimumab in the paediatric population,” and does not reflect previous comparative studies in adults.

This, Stoll and Danila write, “could reflect differences in the population or perhaps differential reporting.”

They therefore conclude: “These findings, as well as the differences in the safety events, warrant further investigation, and more studies on axial endpoints in children with spondyloarthritis are desperately needed.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2026 Springer Healthcare Ltd, part of Springer Nature

Lancet Rheumatol 2026; doi:10.1016/S2665-9913(25)00346-7
Lancet Rheumatol 2026; doi:10.1016/S2665-9913(26)00043-3