Introduction

Treatment options for patients with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are limited. Conventional synthetic disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and non-steroidal anti-inflammatory drugs offer only modest efficacy and raise safety concerns with long-term use. While biologic DMARDs (bDMARDs), anti-TNF agents have demonstrated effectiveness in ERA and JPsA, many patients experience uncontrolled disease or adverse effects from treatment.

Aim

The aim of this trial was to assess the efficacy and safety of secukinumab in individuals with active enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) who did not respond adequately to conventional treatment.

Patient Profile

Biologic-naïve patients (aged 2 to <18 years) with active disease ERA and JPsA

Table 1: Baseline demographics and clinical characteristics of patients

Methods

• Double-blind, randomised, placebo- controlled, event-driven treatment withdrawal phase 3 study.
  

  Endpoints

• Primary endpoint was time to disease flare in TP2
• Secondary efficacy end points included
  • Juvenile Arthritis Disease Activity Score (JADAS)-27-C reactive protein and total enthesitis and dactylitis counts at week 12 in TP1, and JIA ACR30/50/70/90/100 responses and JIA ACR-ID status at the end of TP2
• Safety assessments included all AEs coded , serious AEs (SAEs), treatment-emergent AEs (TEAEs), injection site reactions & antisecukinumab antibody development (immunogenicity)

Results

 Primary Endpoint results

• Statistically significant prolongation in the time to disease flare in TP2 for the combined JIA categories of ERA and JPsA in the secukinumab group when compared to the placebo group (HR, 0.28, p<0.001). (Table 1)
• Subgroup analysis based on JIA category indicated that the time to disease flare extended with secukinumab treatment compared to placebo for both ERA and JPsA (Table 1)

  Table 1: Time to disease flare in overall JIA population and  Flare risk reduction  in JIA subcategories of (ERA & JPsA) in TP2

  	Overall JIA Patients		Flare risk reduction
  	Flare events occurred in	Time to flare	Overall JIA Patients (HR; P value)	ERA (HR; P value)	JPsA (HR; P value)
  Secukinumab Group	27 %	Not reached	72% (28; <0.001)	55% (0.45; p=0.075	85% (0.15; p<0.00)
  Placebo Group	55%	453 days	-	-	-

  Figure 1: Probability of remaining free of disease flares after 1 year 

  

  Secondary Endpoint results

• Improvements in JIA American College of Rheumatology (ACR) responses, JIA ACR-inactive disease, JIA ACR core set components, Juvenile Arthritis Disease Activity Score were reported in patients treated with secukinumab up to 12 weeks

  Figure 2: JIA American College of Rheumatology (ACR) Responses at Week 12

  

• During TP2, a greater percentage of patients treated with secukinumab achieved JIA ACR30/50/70/90/100 responses and met the JIA ACR-ID criteria at the conclusion of TP2 compared to those assigned to placebo

  Figure 2: JIA American College of Rheumatology (ACR) Responses at  end of TP2 ( At week 100)

  

   

• In the overall JIA population receiving secukinumab, a significant decrease in the mean JADAS-27 score was noted up to week 12, resulting in moderate disease activity. By TP2, both the secukinumab and placebo groups achieved minimal disease activity.

Safety Results

• The exposure-adjusted incidence rates for all patients in the overall JIA population were 290.7 per 100 patient-years (ranging from 230.2 to 362.3) for adverse events, and 8.2 per 100 patient-years (ranging from 4.1 to 14.6) for serious adverse events.
• No new safety signals were reported with secukinumab for up to 2 years

 Table 2 : Safety results

Secukinumab and placebo in TP2 groups have not been compared as the study design and the exposure times for these groups were different over the entire TP. In addition, it cannot be ruled-out that events occurring in TP2 under placebo are due to a spill-over effect by the previous secukinumab treatment in TP1. AE, adverse event; IR, incidence rate per 100 subject years; PT, preferred term; SAE, serious adverse event; SOC, primary system organ class; TEAEs, treatment emergent AEs; TP, treatment period.

Conclusion

• Secukinumab exhibited both efficacy and safety within the categories of ERA and JPsA.
• The observed significant prolongation in the time to disease flare in TP2, along with improvements in disease activity, supports the positioning of secukinumab as a viable therapeutic option for patients with ERA and JPsA.

Reference

Ann Rheum Dis 2023;82:154–160