Background/Purpose: In MEASURE
2 (NCT01649375), subcutaneous (s.c.) secukinumab, an anti–interleukin-17A antibody, improved the
signs and symptoms of ankylosing spondylitis (AS) through 16 weeks (wks) of therapy.¹ Here we report the long-term
(52 wk) efficacy and safety of secukinumab
in this study.

Methods: 219 patients (pts) with
active AS, classified by modified New York criteria, despite
therapy
with NSAIDs, were randomized to s.c.
secukinumab 150 or 75 mg or placebo (PBO) at
baseline, Wks 1, 2, and 3, and every 4 wks from Wk 4. At Wk 16,
PBO-treated pts were re-randomized to receive secukinumab
150 or 75 mg s.c. every 4
wks. The primary endpoint was the proportion of pts achieving an ASAS20
response at Wk 16. The secondary endpoints were ASAS40,
hsCRP, ASAS 5/6, BASDAI, SF-36 PCS, ASQoL, and ASAS partial remission. Primary and
secondary endpoints were assessed through Wk 52 using
a non-responder imputation (binary variables) and mixed-model repeated measures
analysis (continuous variables). A predefined hierarchical hypothesis testing
strategy was used in statistical analyses at Wk 16 to
adjust for multiplicity of testing.

Results: Overall, 181
pts (82.6%) completed 52 wks of treatment. ASAS20
response rates at Wk 16 were 61.1% with secukinumab 150 mg vs 28.4% with PBO (P=0.0001). Secukinumab 150 mg also significantly improved ASAS40, hsCRP, ASAS 5/6, BASDAI, SF-36 PCS, and ASQoL
at Wk 16 vs PBO. Clinical responses with secukinumab 75 mg did not reach statistical significance
for any of the pre-specified endpoints based on hierarchical testing.
Improvements with secukinumab 150 mg were sustained
through Wk 52 (Table). Using a more conservative
estimate of efficacy with non-responder imputation, ASAS20/40 response rates
with secukinumab 150 mg at Wk
52 were 62.5/48.6%; rates with observed data were 73.8/57.4%. ASAS20/40
response rates in pts originally randomized to PBO who received secukinumab 150 mg at week 16 (n=34) were 70.6%/52.9% at Wk
52 (non-responder imputation). Over the entire study period, exposure-adjusted
SAE rates (mean
secukinumab exposure: 425.8 days; mean PBO exposure:
107.6 days) were 6.6, 7.7, and 14.0. per 100 pt-years with secukinumab 150 mg,
75 mg, and PBO, respectively. The most common SAEs were infections; no pt discontinued therapy due to an infection. Three pts on secukinumab had a Candida infection (1 on 150 mg and 2 on
75 mg), 1 had a fatal myocardial infarction (75 mg), 2 had AEs of Crohn’s
disease (1 on 150 mg [de novo] and 1 on 75 mg [flare]), and 1 had an AE of uveitis
(150 mg). There were no
suicidality-related AEs with secukinumab.

Conclusion: Secukinumab
150 mg s.c. provided
sustained improvements over 52 weeks in the signs and symptoms of AS, reducing
inflammation, and improving physical function and health-related quality of
life. Secukinumab was well tolerated; safety findings were consistent with
previous reports.

References:

1.   Sieper
J, et al. Arthritis Rheumatol.
2014;66(11Suppl):S232