Secukinumab for the treatment of synovitis and enthesitis in psoriatic arthritis

Common features of psoriatic arthritis (PsA) include synovitis, characterized by structural damage of the peripheral joints, and enthesitis, which is inflammation at the insertion of the tendon into the bone. Treatments such as secukinumab, a monoclonal antibody that inhibits interleukin-17A, are effective and tolerable for patients receiving treatment for PsA. For example, secukinumab was shown to inhibit the progression of structural damage in PsA for up to 3 years.¹

ULTIMATE (NCT02662985) is a multicenter, randomized, phase III trial assessing the long-term impact of secukinumab on synovitis and enthesitis in PsA.

Here, we summarize the results from the ULTIMATE trial published by D’Agostino et al.¹ in Seminars in Arthritis and Rheumatism.

Study design¹

• Overall, 166 biologic-naïve patients with synovitis and clinical enthesitis were randomized to either the secukinumab cohort (n = 83) or placebo (n = 83), with 144 patients completing 52 weeks of treatment.
• The primary endpoint was reduction in synovitis with secukinumab vs placebo, as measured by power Doppler ultrasonography and the Global EULAR-OMERACT Synovitis Score composite scoring system.
• A key secondary endpoint was clinical enthesitis response, as measured by the Spondyloarthritis Research Consortium of Canada Enthesitis Index.
• The ULTIMATE trial consisted of three treatment periods:

1. 1. 1. Baseline to Week 12: subcutaneous secukinumab (150 or 300 mg) or placebo weekly until Week 4 and then once every 4 weeks until Week 12
      2. Weeks 12–24: placebo patients were switched to secukinumab; all patients now received secukinumab (150 or 300 mg)
      3. Weeks 24–52: extended open-label treatment

Key findings¹

• Between baseline and Week 12:
  • Secukinumab treatment led to a more significant reduction in power Doppler ultrasonography synovitis compared with placebo, with a Global EULAR-OMERACT Synovitis Score of −9.0 vs −6.0 (p = 0.004), respectively; and
  • There was a decrease in Spondyloarthritis Research Consortium of Canada Enthesitis Index of −2.2 in the secukinumab treatment group vs −1.6 in the placebo cohort (p = 0.03)
• After transitioning from placebo to secukinumab at Week 12, the group that switched from placebo achieved a level of power Doppler ultrasonography synovitis reduction comparable to the secukinumab group by Week 24.
• There were improvements in clinical response in all key domains of PsA in both groups by Week 52.
• No new safety signals were identified with secukinumab.

Key learnings

The ULTIMATE trial showed that treatment with secukinumab resulted in improvement in both synovitis and enthesitis amongst patients with PsA. Clinical improvements were seen in both the secukinumab-only cohort and the cohort of patients who switched from placebo to secukinumab at Week 12. Interleukin-17A inhibition is a feasible option for the sustained improvement of synovitis and enthesitis in patients with PsA.