Introduction

ERASURE and FIXTURE were two pivotal Phase 3 studies assessing the efficacy of secukinumab which is a fully human monoclonal antibody that selectively neutralizes IL-17A, in patients with moderate-to-severe plaque psoriasis (PsO).

Aim

To investigate PsO relapse rates upon treatment discontinuation following one year of secukinumab treatment.

Patient Profile

• Moderate-to-severe plaque PsO patients treated with secukinumab in the ERASURE and FIXTURE core studies

  Methods

• This is a post-hoc analysis of ERASURE and FIXTURE core studies
• After 52 weeks of treatment with secukinumab in the ERASURE and FIXTURE core studies, PASI75 responders at Week 52, previously treated with secukinumab 300 mg (n=120) or 150 mg (n=100), were randomised to receive placebo for a maximum of two years if relapse did not occur following treatment withdrawal, or until relapse.
• Upon relapse, patients receiving placebo were switched to their previous secukinumab dose
• Relapse rates and absolute Psoriasis Area and Severity Index (PASI) scores were assessed
• The study’s primary outcome was non-relapse rate after secukinumab withdrawal.

  Results

• After one year of secukinumab treatment, more patients with moderate-to-severe PsO who remained relapse-free for up to two years after treatment withdrawal.

  Figure 1: Proportion of patients without relapse after one- and two-years drug free, following one year of secukinumab treatment

  

• The average PASI value remained low throughout the drug-free period
  • Among patients originally treated with secukinumab 300 mg who remained relapse-free on placebo, the mean PASI score ± standard deviation (SD) was 2.8 ± 2.5 at Week 100 (one year after secukinumab 300 mg discontinuation; n = 25) and 1.7 ± 2.3 at Week 152 (two years after discontinuation; n = 14).
• The median time to first relapse in patients originally treated with secukinumab 300 mg and 150 mg for one year was 5.6 months and 4.6 months in the secukinumab 300 mg–placebo and secukinumab 150 mg–placebo groups, respectively.
• The event-free rate in the secukinumab 300 mg–placebo and secukinumab 150 mg–placebo groups was
  • 20.6% and 13.8% one year after the last dose of secukinumab
  • 14.1% and 6.9% two years after the last dose of secukinumab treatment
• Disease duration (P=0.017) and severity (P=0.022) were significantly associated with time-to-relapse in patients initially treated with secukinumab 300 mg patients with shorter disease duration and lower baseline PASI remained relapse-free for longer. (Table1)

Table 1 Association between time to relapse and baseline disease characteristics

Conclusion

Post-secukinumab treatment discontinuation a proportion of patients stayed relapse-free. Patients with shorter disease duration remained relapse-free for longer indicating, earlier treatment with secukinumab may result in long-term clinical control of moderate-to-severe PsO.

Reference

Clin Exp Dermatol. 2023 Oct 11: llad329. doi: 10.1093/ced/llad329.