Secukinumab’s Efficacy and Safety in Ankylosing Spondylitis: MEASURE 5 Study

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Secukinumab Provided Significant and Sustained Improvement in the Signs and Symptoms of Ankylosing Spondylitis: Results from the 52-Week, Phase III China-Centric Study, MEASURE 5

Introduction

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by axial inflammation, structural damage to the sacroiliac joints and spine, and reduced quality of life. While tumor necrosis factor inhibitors (TNFi) are first-line biologics, up to 40% of patients exhibit inadequate responses or intolerance. Secukinumab, a monoclonal antibody targeting interleukin-17A (IL-17A), has demonstrated long-term efficacy in global Phase III trials (MEASURE 1 and 2) for AS. The MEASURE 5 study aimed to evaluate the efficacy and safety of secukinumab 150 mg in a China-centric population, including patients from China and other regions, over 52 weeks.

Study Design and Methodology

MEASURE 5 was a randomized, double-blind, placebo-controlled, multicenter Phase III trial conducted across 44 centers in China, the Czech Republic, South Korea, and the UK. Eligible patients were adults with active AS (BASDAI ≥4, spinal pain ≥40 mm on a 100 mm VAS) and inadequate response to ≥2 NSAIDs. Patients were stratified by region (China vs. non-China) and randomized 2:1 to receive subcutaneous secukinumab 150 mg or placebo. The dosing regimen included weekly injections for the first 5 weeks, followed by every 4 weeks (q4w) until Week 48. Placebo patients switched to secukinumab at Week 16.

The primary endpoint was the proportion of patients achieving ASAS20 response at Week 16. Secondary endpoints included ASAS40, changes in hsCRP, BASDAI, SF-36 Physical Component Summary (PCS), Ankylosing Spondylitis Quality of Life (ASQoL), and ASAS partial remission. Exploratory endpoints encompassed ASDAS-CRP inactive disease and MASES scores. Safety assessments included adverse events (AEs), serious AEs (SAEs), and laboratory parameters.

Patient Demographics and Disposition

Of 563 screened patients, 458 were randomized (secukinumab: 305; placebo: 153). The cohort included 327 (71.4%) Chinese patients and 131 (28.6%) non-Chinese patients. Baseline characteristics were balanced: mean age 34.4 years, 83.8% male, 80.6% Asian, and 21% TNFi-inadequate responders (TNFi-IR). Over 95% completed Week 16, and >90% completed Week 52. Discontinuation rates were low (2.9% for secukinumab, 4.7% for placebo), primarily due to patient decisions.

Efficacy Outcomes

Week 16 Results

Secukinumab demonstrated rapid and significant efficacy versus placebo:

  • ASAS20: 58.4% vs. 36.6% (P < 0.0001; odds ratio [OR] 2.45).
  • ASAS40: 43.9% vs. 17.0% (P < 0.0001; OR 3.95).
  • hsCRP: Geometric mean ratio (post-baseline/baseline) 0.39 vs. 1.05 (P < 0.0001).
  • BASDAI: Least squares (LS) mean change −2.79 vs. −1.50 (P < 0.0001).
  • ASAS partial remission: 16.7% vs. 6.5% (P < 0.01).

In the Chinese subgroup, responses were consistent:

  • ASAS20: 56.0% vs. 38.5% (P < 0.01).
  • ASAS40: 41.7% vs. 16.5% (P < 0.0001).

Week 52 Results

Efficacy improved or sustained through Week 52:

  • ASAS20: 76.1% (overall), 77.3% (Chinese).
  • ASAS40: 60.6% (overall), 60.5% (Chinese).
  • hsCRP: Sustained reduction (geometric mean ratio 0.36).
  • BASDAI: LS mean change −3.63.
  • ASDAS-CRP inactive disease: 27.2% (overall), 26.8% (Chinese).

Subgroup Analysis by Prior TNFi Use

In TNFi-naïve and TNFi-IR subgroups, secukinumab showed robust efficacy:

  • TNFi-naïve ASAS20: 58.3% vs. 36.9% (P < 0.001).
  • TNFi-IR ASAS20: 58.5% vs. 35.5% (P < 0.05).
    Responses were comparable to global MEASURE trials, with higher ASAS40 rates at Week 52 (60.6% vs. 49%–56% in MEASURE 1/2).

Safety Profile

Over 16 weeks, secukinumab exhibited a safety profile consistent with prior studies:

  • Treatment-emergent AEs: 67.8% (secukinumab) vs. 59.5% (placebo). Common AEs included upper respiratory infections (22.4%), hyperlipidemia (5.6%), and nasopharyngitis (5.3%).
  • Serious AEs: 3.3% (secukinumab) vs. 2.0% (placebo).
  • Infections: 1.3% serious infections (secukinumab), no tuberculosis or hepatitis reactivation.

Over 52 weeks (any secukinumab exposure):

  • Exposure-adjusted AE rate: 80.4/100 patient-years.
  • SAEs: 7.3%, primarily infections (2.0%).
  • Notable events: Two non-serious ulcerative colitis cases (0.45%), ten uveitis cases (2.2%; all resolved), and one non-fatal lacunar infarction.

No deaths, neutralizing antibodies, or unexpected safety signals were observed.

Discussion

MEASURE 5 confirmed secukinumab’s efficacy and safety in a predominantly Chinese AS population, aligning with global Phase III data. Key findings include:

  1. Rapid Onset: Significant ASAS20/40 improvements by Week 1–3.
  2. Sustained Response: Efficacy increased through Week 52, particularly for ASAS40 (60.6%), surpassing MEASURE 1/2 results.
  3. TNFi-IR Efficacy: Comparable responses in TNFi-naïve and TNFi-IR subgroups support secukinumab as a viable alternative after TNFi failure.
  4. Safety Consistency: No new signals, with low discontinuation rates (2.2%) and manageable AE profiles.

Limitations include the predominance of Chinese patients (71.4%), limiting non-Chinese subgroup analyses, and the absence of radiographic endpoints. However, the study’s 52-week duration and large sample size strengthen its validity.

Conclusion

Secukinumab 150 mg provided rapid, significant, and sustained improvement in AS symptoms, with efficacy and safety profiles consistent across global and Chinese populations. These results support its use as a first-line biologic or alternative to TNFi in AS management.

doi.org/10.1097/CM9.0000000000001099

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