Secukinumab shows sustained efficacy and low structural progression in ankylosing spondylitis: 4-year results from the MEASURE 1 study

Abstract

Objective: To evaluate the effect of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, on efficacy, imaging outcomes, and safety through 4 years (208 weeks) in patients with ankylosing spondylitis.

Methods: Patients opting to enrol had completed 2 years' treatment in the MEASURE 1 core study with subcutaneous secukinumab 150 or 75 mg every 4 weeks (q4Wk), following intravenous loading to Week (Wk) 4, or placebo treatment to Wk16/24. Up-titration from secukinumab 75-150 mg q4Wk was permitted following a protocol amendment. Efficacy is reported for patients originally randomized to secukinumab. Radiographic changes were assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and changes in MRI measures of inflammation using the Berlin scoring method. Safety and tolerability were evaluated.

Results: Among 274 extension study participants, 89.7% (78/87) and 93.0% (93/100) originally randomized to secukinumab 150 and 75 mg, respectively, completed 208Wk. Through Wk208, Assessment of Spondyloarthritis International Society 20/40 (observed) were 79.7%/60.8% (150 mg), 71.0%/43.5% (75 mg) and 80.0%/76% (up-titrators; n = 25). Mean (s.d.) changes in mSASSS were 1.2 (3.91) (150 mg), 1.8 (4.32) (75 mg) and 1.6 (5.67) (up-titrators). No radiographic progression (mSASSS change from Baseline < 2) was observed in 79% of patients receiving either secukinumab dose. Exposure-adjusted incidence rates per 100 patient-years were: serious infections (1.0), Candida infections (0.4), Crohn's disease (0.6), ulcerative colitis (0.2), and malignant/unspecified tumours (0.5), with no new safety signals.

Conclusion: Through 4 years, secukinumab provided sustained efficacy on signs and symptoms, and MRI outcomes, a low rate of radiographic progression and a consistent safety profile.

Trial registration: NCT01863732.

Keywords: MEASURE 1; ankylosing spondylitis; radiographic progression; secukinumab.

Fig. 1

(A) ASAS20, (B) ASAS40 responses and (C) mean change from baseline in BASDAI through Wk208 Data are presented for patients originally randomized to secukinumab IV-150 mg. ASAS 20/40 are reported as observed and using multiple imputation. For BASDAI, mean change from baseline is reported as observed data and as least-square mean change (MMRM analysis). ASAS: Assessment of Spondyloarthritis International Society; IV: intravenous; MMRM: mixed model repeated measures; n: number of evaluable patients; N: total number of patients initially randomized to secukinumab 150 mg at baseline; Obs: observed data; Wk: week.

Fig. 2

Cumulative probability plot for change from baseline in the mSASSS through Wk208 *Includes 23 patients whose dose was up-titrated from secukinumab 75 mg to 150 mg at various timepoints starting at Wk168, in accordance with a protocol amendment at the discretion of investigators. Data shown as observed. mSASSS: modified Stoke Ankylosing Spondylitis Spine Score; IV: intravenous; n: number of patients with evaluable paired X-rays at Baseline and Wk208; Wk: week.

Fig. 3

Change in mSASSS between (A) Baseline to Wk104, (B) Wk104 to Wk208, (C) Baseline to Wk208 *Includes 23 patients (22 patients of whom had X-ray data at baseline, Wk104 and Wk208) whose dose was up-titrated from secukinumab 75 mg to 150 mg at various timepoints starting at Wk168. mSASSS score ranges from 0–72; higher scores indicate greater radiographic damage. Δ represents mean (s.d.) difference in mSASSS between timepoints. Baseline and Wk104 X-rays were re-read with Wk208 X-rays to minimize longitudinal variability. BL: baseline; IV: intravenous; mSASSS: modified Stoke Ankylosing Spondylitis Spine Score; n: number of patients with assessments at both timepoints; Wk: week.