Response to Secukinumab on Synovitis using Power Doppler Ultrasound in Psoriatic Arthritis: 12-week Results from a Phase III Study, ULTIMATE

Objectives: To investigate the dynamics of response of synovitis to interleukin (IL)-17A inhibition with secukinumab in patients with active psoriatic arthritis (PsA) using Power Doppler ultrasound. Methods: The randomised, placebo-controlled, Phase III ULTIMATE study enrolled PsA patients with active ultrasound synovitis, and clinical synovitis and enthesitis having an inadequate response to conventional disease-modifying anti-rheumatic drugs (DMARDs) and naïve to biologic DMARDs. Patients were randomly assigned to receive either weekly subcutaneous secukinumab (300 or 150 mg according to the severity of psoriasis) or placebo followed by 4-weekly dosing thereafter. The primary outcome was the mean change in the ultrasound Global European League Against Rheumatism and Outcome Measures in Rheumatoid Arthritis Clinical Trials Synovitis Score (GLOESS) from baseline to week 12. Key secondary endpoints included American College of Rheumatology 20 and 50 responses. Results: Of the 166 patients enrolled, 97% completed 12 weeks of treatment (secukinumab, 99%; placebo, 95%). The primary end point was met, and the adjusted mean change in GLOESS was higher with secukinumab than placebo (-9 [0.9] vs -6 [0.9], difference [95% CI]: -3 [-6; -1]; one-sided p = 0.004) at week 12. The difference in GLOESS between secukinumab and placebo was significant as early as one week after initiation of treatment. All key secondary endpoints were met. No new or unexpected safety findings were reported. Conclusion: This unique ultrasound study shows that apart from improving the signs and symptoms of PsA, IL-17A inhibition with secukinumab leads to a rapid and significant reduction of synovitis in PsA patients. Keywords: Clinical outcome; GLOESS; Joints; OMERACT; Power Doppler ultrasound; PsA; Responsiveness; Secukinumab; Synovitis; biological DMARDs.