Longer Time to Flare With Secukinumab in Enthesitis-Related Arthritis and PsA in Children

In children with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA), time to disease flare was significantly longer with secukinumab compared with placebo, according to study findings published in Annals of the Rheumatic Diseases.

Researchers at the Paediatric Rheumatology International Trials Organization (PRINTO) and Pediatric Rheumatology Collaborative Study Group (PRCSG) conducted a 2-year, randomized, double-blind, placebo-controlled, phase 3 trial (ClinicalTrials.gov Identifier: NCT03031782) to study the safety and efficacy of secukinumab in pediatric patients with ERA and JPsA.

Patients received 75 or 150 mg open-label subcutaneous secukinumab, depending on their weight, through week 12 during phase 1 of the trial. During phase 2, responders were randomly assigned 1:1 to receive secukinumab or placebo through week 100, and those who experienced a flare proceeded to phase 3 of the trial. In phase 3, patients received open-label secukinumab through week 104.

Treatment response was defined as at least 30% improvement in 3 or more Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) core set values (CRVs), with no CRV worsening by more than 30%.

The primary study outcome was time to disease flare, defined as greater than 30% worsening from baseline in at least 3 CRVs, with no more than 1 CRV with at least a 30% improvement.

Patients with ERA (n=52) and JPsA (n=34) were aged a mean of 13.7 (SD, 2.6) years and 12.2 (SD, 3.7) years; 78.8% and 47.1% were boys; and mean Juvenile Arthritis Disease Activity Scores (JADAS) were 14.8 (SD, 6.7) and 15.5 (SD, 7.8) points, respectively.

In phase 2, treatment response was observed among 44 patients with ERA and 31 with JPsA.

A total of 31 flares occurred among secukinumab (27%) and placebo (55%) recipients. The median time to flare was 453 days in the placebo cohort and not reached in the secukinumab cohort.

These data indicated that, overall, secukinumab was favored over placebo for prolonging time to disease flare (hazard ratio [HR], 0.28; 95% CI, 0.13-0.63; P <.001), as well as among patients with ERA (HR, 0.45; 95% CI, 0.16-1.28) and JPsA (HR, 0.15; 95% CI, 0.04-0.57).

Using Kaplan-Meier estimation, the probability of remaining free from flares at 1 year was 76.7% with secukinumab compared with 54.3% with placebo.

Any adverse event occurred among 65.1% to 91.9% of participants and serious adverse events among 2.3% to 13.5% of participants with use of secukinumab.

The most common treatment-emergent adverse events included nasopharyngitis (31.4%), nausea (22.1%), upper respiratory tract infection (22.1%), and diarrhea (19.8%).

The study may have been limited by the fact that efficacy was based on time to flare and not objective improvements in symptoms.

The study authors concluded, “Secukinumab demonstrated efficacy and safety in the JIA categories of ERA and JPsA. The significantly longer time to disease flare in treatment period [2] and improvement in disease activity observed establish secukinumab as a candidate in the treatment of patients with ERA and JPsA.”

Disclosure: This research was supported by Novartis Pharma. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.