Comparison of the Effects of Secukinumab and Adalimumab Biosimilar on Radiographic Progression in Patients with Ankylosing Spondylitis: Design of a Randomized, Phase IIIb Study (SURPASS).

BACKGROUND AND

objectiveSecukinumab, an anti-interleukin (IL)-17A monoclonal antibody, has demonstrated low radiographic progression over 4 years in patients with ankylosing spondylitis (AS). An adalimumab (tumor necrosis factor [TNF] inhibitor) biosimilar, GP2017 (SDZ-ADL; Sandoz), has been approved by the European Medicines Agency (July 2018) for use in all same indications as adalimumab, including AS. Adalimumab has also shown low long-term radiographic progression in patients with AS. Direct comparison of radiographic progression in AS between IL-17A and TNF inhibitors has not been studied. SURPASS is the first head-to-head, Phase IIIb, randomized, biologic-controlled study in AS to compare effects of secukinumab versus SDZ-ADL on spinal radiographic progression.

methodsOverall, 858 biologic-naïve patients with AS with elevated high-sensitivity C-reactive protein (≥ 5 mg/L) and/or at least one syndesmophyte in the cervical/lumbar spine at baseline (without total ankylosis) were randomized (1:1:1) to subcutaneous (sc) secukinumab (300 or 150 mg) or SDZ-ADL (40 mg). Secukinumab will be administered at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 100. SDZ-ADL will be administered every 2 weeks from baseline until week 102. Patients and investigators will be unblinded to drug but blinded to secukinumab doses. Spinal X-rays will be obtained at baseline, and weeks 52 and 104, sacroiliac joint (SIJ) X-rays at baseline and week 104, and magnetic resonance imaging (MRI) of SIJs and spine at baseline, weeks 16, 52, and 104. The primary endpoint is to demonstrate superiority of secukinumab (300 or 150 mg) treatment versus SDZ-ADL regarding proportion of patients with no radiographic progression (change from baseline in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤ 0.5) at week 104. Secondary endpoints include change from baseline in mSASSS, proportion of patients with syndesmophyte at baseline who develop no new syndesmophytes, reduction of osteitis on MRI of SIJs and spine (Berlin method). Assessment of SpondyloArthritis International Society (ASAS) 20/40 responses, ASAS partial remission, and AS Disease Activity Score (ASDAS) inactive disease (ASDAS < 1.3) in secukinumab- versus SDZ-ADL-treated patients at week 104.

conclusionThis is the first study designed to evaluate superiority of an IL-17A inhibitor, secukinumab, over a TNF inhibitor, SDZ-ADL, in reducing spinal radiographic progression in AS. STUDY REGISTRATION: ClinicalTrials.gov, NCT03259074.