Data Show Novartis’ Secukinumab Leads to Early Synovitis Reduction in Patients With PsA

New results from ULTIMATE, the first phase 3 study of its kind, show Novartis’ Cosentyx (secukinumab) demonstrated significant treatment response on synovitis (joint lining inflammation) in patients with active psoriatic arthritis (PsA) compared with placebo. The 12-week double-blind treatment period results were presented at the American College of Rheumatology’s (ACR) All-Virtual Annual Meeting, taking place November 5-9, 2020.

Secukinumab has already received FDA approvals for the treatment of nonradiographic axial spondyloarthritis, moderate to severe plaque psoriasis, active PsA, and active ankylosing spondylitis.

The study was primarily designed to assess the time course of response to subcutaneous secukinumab on joint synovitis using Power Doppler ultrasonography, a sensitive noninvasive imaging technology, in patients with PsA. Specifically, a standardized ultrasound synovitis score (GLOESS) was the study’s primary end point, which showed differences in mean change from baseline to week 12 between treatment and placebo. GLOESS was determined with mixed-effect model repeated measures analysis.

“Psoriatic arthritis can have a significant impact on a patient’s joints. Joint lining inflammation, also known as synovitis, if left untreated, can cause pain to worsen, joint damage, and may decrease physical function,” said Maria A. D’Agostino, MD, PhD, a lead researcher of the study. “These data are highly encouraging, showing Cosentyx can significantly reduce synovitis at week 12 versus placebo, with results seen as early as week 1, and that ultrasound is a sensitive and objective tool to monitor joint inflammation in PsA patients.”

A total of 166 biologic-naïve patients were included in the trial, and 96% (n = 160) completed the 12-week treatment phase (secukinumab: 99% [82/83] and placebo: 94% [78/83]). The study included the initial treatment phase, a 12-week open-label phase, and a 6-month open-label extension. Both demographic and baseline clinical characteristics were comparable across treatment groups.

The researchers found:

• Mean (SD) GLOESS was 24 (16) for secukinumab and 27 (17) for placebo
• Mean baseline Spondyloarthritis Research Consortium of Canada enthesitis index was 4.2 (2.9) for secukinumab and 4.4 (3.3) for placebo
• Adjusted mean change in GLOESS was significantly higher with secukinumab vs placebo (–9.0 vs –5.8; P = .004) at week 12, with statistical significance observed as early as week 1
• Treatment with secukinumab also significantly improved key secondary end points vs placebo, including ACR20 (68% vs 34%, respectively) and ACR50 (46% vs 9%, respectively)
• No new or unexpected safety signals were reported
  
  

Since launch, over 400,000 patients have been treated with secukinumab across moderate to severe psoriasis, PsA, ankylosing spondylitis, and nonradiographic axial spondyloarthritis. Novartis expects to release full 24-week data from ULTIMATE in 2021.

“As a strong believer in the diagnostic and treatment monitoring benefits of ultrasound, this first large randomized double-blind placebo-controlled clinical trial in PsA with an ultrasonographic primary end point is incredibly exciting,” said Catherine Bakewell, MD, another study investigator. “The ability to use a sensitive imaging technique to assess synovitis and enthesitis in PsA represents a breakthrough in how we conceptualize treatment goals.”

Reference

D’Agostino MA, Schett G, López-Rdz A, et al. Secukinumab significantly decreased joint synovitis measured by power doppler ultrasonography in biologic-naïve patients with active psoriatic arthritis: primary (12-week) results from a randomized, placebo-controlled phase III study. Presented at: American College of Rheumatology All-Virtual Annual Meeting; November 5-9, 2020. Abstract 1361.