Background/Purpose: In the MEASURE 1 trial (NCT01358175), secukinumab significantly improved
the signs and symptoms of patients (pts) with active ankylosing spondylitis
(AS) over 52 weeks (wks).¹ Here, we report the effects of secukinumab on radiographic progression up to 104 wks.

Methods:
In MEASURE
1, 371 pts with active AS were randomized to secukinumab or placebo (pbo). Pts
on secukinumab received a 10 mg/kg i.v. loading dose at baseline (BL), Wks 2
and 4, and then 150 mg s.c. (IV→150 mg) or 75 mg s.c. (IV→75 mg)
every 4 wks from Wk 8. Pbo was given on the same schedule. Pbo pts were
re-randomized to secukinumab 150 or 75 mg s.c. based on ASAS20 response at Wk
16 (non-responders switched at Wk 16 and responders at Wk 24). Lateral radiographs
of the cervical and lumbar spine performed at BL and Wk 104 were read centrally applying the modified Stoke Ankylosing
Spondylitis Spinal Score (mSASSS). Two
independent readers, blinded to treatment arm and radiograph sequence, scored the
digitized images. Pts initially randomized to secukinumab, who had x-rays
available at BL and Wk 104 (n=168), were included in this analysis. Only observed
data are shown.

Results: Secukinumab
data were pooled as there were no major differences between the two doses. Data
from pts randomized to secukinumab at BL and those who switched from pbo were
analyzed separately. At BL in the secukinumab only group, 104/168 (62%) pts had
syndesmophytes, 105/168 (63%) had elevated (>5 mg/L) C-reactive protein (CRP)
levels, 42/168 (25%) were smokers, and 123/168 (73%) were men. The mean (±SD)
mSASSS at BL was 10.22±16.62; mean change from BL at Wk 104 was 0.30±2.53. There
were no major differences between the secukinumab only and pbo→secukinumab
groups in terms of mSASSS change through Wk 104. Approximately 80% of pts
randomized to secukinumab at BL showed no radiographic progression (mSASSS
change ≤0) (Figure). At Wk 104 in the secukinumab only group, new
syndesmophytes were found in 3/64 (5%) pts who were without syndesmophytes at BL.
Overall, BL mSASSS and mean mSASSS change at Wk 104 in the secukinumab only
group were higher in males (mean change 0.38±2.79 vs 0.08±1.58 in females), those
with BL syndesmophytes (0.47±3.20 vs 0.02±0.26 in pts with no BL syndesmophytes),
or elevated CRP levels at BL (0.47±2.66 vs 0.02±2.27 in pts with normal CRP
levels).  

Conclusion: The mean change in mSASSS
was only 0.30±2.53 in the secukinumab only group, with no major difference
between doses. Changes were higher in pts who were male, had BL syndesmophytes,
or elevated BL CRP. No radiographic progression was observed in ~80% of the pts
receiving secukinumab over 104 wks. This is the first report of interleukin-17A inhibition on
structural changes in patients with AS. The changes in mSASSS through 2 years
reported here may be lower than those reported in earlier observational and
interventional studies in AS.

Reference

1.    Baeten et al. Arthritis Rheumatol
2014; 66 (11Suppl):S360