BACKGROUND: Ankylosing spondylitis is a chronic immune-mediated inflammatory 
disease characterised by spinal inflammation, progressive spinal rigidity, and 
peripheral arthritis. Interleukin 17 (IL-17) is thought to be a key inflammatory 
cytokine in the development of ankylosing spondylitis, the prototypical form of 
spondyloarthritis. We assessed the efficacy and safety of the anti-IL-17A 
monoclonal antibody secukinumab in treating patients with active ankylosing 
spondylitis.
METHODS: We did a randomised double-blind proof-of-concept study at eight 
centres in Europe (four in Germany, two in the Netherlands, and two in the UK). 
Patients aged 18-65 years were randomly assigned (in a 4:1 ratio) to either 
intravenous secukinumab (2×10 mg/kg) or placebo, given 3 weeks apart. 
Randomisation was done with a computer-generated block randomisation list 
without a stratification process. The primary efficacy endpoint was the 
percentage of patients with a 20% response according to the Assessment of 
SpondyloArthritis international Society criteria for improvement (ASAS20) at 
week 6 (Bayesian analysis). Safety was assessed up to week 28. This study is 
registered with ClinicalTrials.gov, number NCT00809159.
FINDINGS: 37 patients with moderate-to-severe ankylosing spondylitis were 
screened, and 30 were randomly assigned to receive either intravenous 
secukinumab (n=24) or placebo (n=6). The final efficacy analysis included 23 
patients receiving secukinumab and six patients receiving placebo, and the 
safety analysis included all 30 patients. At week 6, ASAS20 response estimates 
were 59% on secukinumab versus 24% on placebo (99·8% probability that 
secukinumab is superior to placebo). One serious adverse event (subcutaneous 
abscess caused by Staphylococcus aureus) occurred in the secukinumab-treated 
group.
INTERPRETATION: Secukinumab rapidly reduced clinical or biological signs of 
active ankylosing spondylitis and was well tolerated. It is the first targeted 
therapy that we know of that is an alternative to tumour necrosis factor 
inhibition to reach its primary endpoint in a phase 2 trial.
FUNDING: Novartis.