Background/Purpose:

Previous data indicate that interleukin (IL)-17, a key pro-inflammatory cytokine, might play a role in the pathogenesis of ankylosing spondylitis (AS). We assessed the efficacy and safety of two different doses of secukinumab, a fully human anti–IL-17A monoclonal antibody, in a randomized, multicenter, double-blind, placebo (PBO)-controlled, phase 3 trial in patients with AS (MEASURE 2; NCT01649375).

Methods: Adults with active AS fulfilling modified New York Criteria and a BASDAI ≥ 4, despite adequate NSAID therapy, were randomized to receive weekly subcutaneous (s.c.) secukinumab 75 mg, 150 mg, or PBO for 4 weeks followed by dosing every 4 weeks. Subjects naïve to anti-TNF agents (61.6%) and subjects with prior intolerance or inadequate response to anti-TNF agents (TNF-IR; 38.4%) were included. The primary endpoint was the proportion of subjects achieving an ASAS20 response at Week 16. Secondary endpoints included ASAS40, hsCRP, BASDAI, ASAS 5/6, SF-36, ASQoL, and ASAS partial remission. Statistical analyses used non-responder imputation and followed a pre-defined hierarchical hypothesis testing strategy to adjust for multiplicity.

Results: 219 subjects were randomized. Demographics and baseline disease characteristics were comparable between study arms: mean age 43.3 years, mean time since diagnosis 6.2 years and mean BASDAI 6.65. The primary endpoint was met with secukinumab 150 mg at Week 16: ASAS20 response rate was 61.1% vs. 27.0% with PBO (P < 0.001; Figure), with significant improvements seen as early as Week 1. Secukinumab 150 mg also significantly improved hsCRP, ASAS40, ASAS 5/6, BASDAI, SF-36 PCS and ASQoL compared with PBO. Efficacy of secukinumab 150 mg vs. PBO was observed in both TNF-naïve and TNF-IR subjects for ASAS20 (68.9% vs. 31.1% and 48.1% vs. 20.7%, respectively; both P < 0.05) and ASAS40 (44.4% vs. 17.8% and 22.2% vs. 0%, respectively; both P < 0.05). Secukinumab 75 mg provided numerically greater responses than PBO at Week 16, but these did not reach statistical significance for any of the pre-specified primary or secondary endpoints based on hierarchical testing. Similar adverse event (AE) rates were reported up to Week 16 for secukinumab 75 mg (57.5%), 150 mg (62.5%), and PBO (63.5%). Serious AEs were reported in 5.5% of subjects in the secukinumab 75 mg group, compared with 5.6% in the secukinumab 150 mg group and 4.1% in the PBO group.

Conclusion:

Secukinumab 150 mg s.c. was effective at rapidly reducing the signs and symptoms of disease and improving health-related quality of life in subjects with active AS, regardless of prior anti-TNF exposure. Secukinumab was well tolerated, with no unexpected safety findings.