Dataset Information

Secukinumab Demonstrates Sustained Efficacy and Safety in a Taiwanese Subpopulation With Active Ankylosing Spondylitis: Four-Year Results From a Phase 3 Study, MEASURE 1.

ABSTRACT:

Objectives

To present the long-term (4-year) efficacy and safety of secukinumab in Taiwanese patients with active AS in the MEASURE 1 extension study.

Methods

This post hoc analysis reports data from Taiwanese patients originally randomized to subcutaneous secukinumab 150 or 75mg or placebo every 4 weeks (following intravenous loading dose) who were invited to enter the 3-year extension study. Assessments at Week 208 included ASAS20/40 responses and other clinically relevant endpoints. Efficacy data are presented as observed. Safety analyses included all patients who received ?1 dose of secukinumab.

Results

Of the 57 Taiwanese patients in the core trial, 48 entered the extension study and 87.5% patients (42/48) completed 4 years of treatment. Thirteen Taiwanese patients (including placebo-switchers) were escalated from 75 to 150mg (approved dose) at some point starting from Week 172. ASAS20/40 responses were sustained through 4 years in the Taiwanese patients who were originally randomized to secukinumab 150mg. Clinical responses were improved in those patients who received dose-escalation from 75 to 150mg during the study. No unexpected safety signals were reported.

Conclusion

Secukinumab 150mg demonstrated sustained efficacy over 4 years in Taiwanese patients with active ankylosing spondylitis. The safety profile of secukinumab was consistent with previous reports.

Clinicaltrialsgov identifier

NCT01863732.

SUBMITTER: Tseng JC

PROVIDER: S-EPMC7725874 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Secukinumab Demonstrates Sustained Efficacy and Safety in a Taiwanese Subpopulation With Active Ankylosing Spondylitis: Four-Year Results From a Phase 3 Study, MEASURE 1.

Tseng Jui-Cheng JC Wei James Cheng-Chung JC Deodhar Atul A Martin Ruvie R Porter Brian B McCreddin Suzanne S Talloczy Zsolt Z

Frontiers in immunology 20201126

<h4>Objectives</h4>To present the long-term (4-year) efficacy and safety of secukinumab in Taiwanese patients with active AS in the MEASURE 1 extension study.<h4>Methods</h4>This <i>post hoc</i> analysis reports data from Taiwanese patients originally randomized to subcutaneous secukinumab 150 or 75mg or placebo every 4 weeks (following intravenous loading dose) who were invited to enter the 3-year extension study. Assessments at Week 208 included ASAS20/40 responses and other clinically relevan ...[more]

PMID: 33324394

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Project description:BACKGROUND:Axial spondyloarthritis including ankylosing spondylitis (AS) is characterized by chronic inflammation and new bone formation in the axial skeleton. On the other hand, bone loss, osteoporosis and an increased risk of vertebral fractures is known to frequently occur in AS. In the MEASURE 1 study, the clinically efficacious interleukin-17A inhibitor secukinumab was shown to have limited radiographic progression through 4 years in patients with active AS. Here we present a post hoc analysis to evaluate the effect of secukinumab on bone mineral density (BMD) and bone turnover biomarkers over 2 years in this study. METHODS:BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine, total hip, and femoral neck. Spinal radiographs performed at baseline and Week 104 were assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and analyzed in relation to BMD change, considering baseline syndesmophytes. Bone turnover biomarkers were assessed at baseline and at Weeks 52 or 104. RESULTS:Among 104 patients included in this analysis, 66% were male, with a mean (SD) age of 40.4 (12.3) years. In postmenopausal women and men ≥50 years of age (T-score), the proportion of patients having normal BMD at baseline and Week 104 were 54.5%/54.5% (lumbar spine), 31.6%/55.6% (total hip), and 42.1%/44.4% (femoral neck). Similarly, at baseline, the proportion of patients with osteopenia/osteoporosis was 31.8%/13.6% (lumbar spine), 57.9%/10.5% (total hip), 42.1%/15.8% (femoral neck), and 36.4%/9.1% (lumbar spine), 44.4%/0% (total hip) and 55.6%/0% (femoral neck) at Week 104, respectively. In premenopausal women and men < 50 years of age (Z-score), the proportion of patients having BMD below the expected range for age at baseline and Week 104 were 25.0%/21.2% (lumbar spine), 11.3%/17.8% (total hip), and 9.9%/8.9% (femoral neck). In relation to mSASSS change scores ≥2 over 2 years, the increase in lumbar spine BMD was not related to radiographic progression and syndesmophyte formation. No significant changes were observed in the bone turnover markers over time. CONCLUSION:The high proportion of AS patients with diminished BMD was confirmed in this study. An increase of BMD in the lumbar spine after 2 years of secukinumab treatment in patients with AS was found that was probably unrelated to radiographic progression. No relevant effects of secukinumab on bone turnover biomarkers were documented. TRIAL REGISTRATION:MEASURE 1 (post hoc analysis) Clinicaltrials.gov, NCT01358175 ; Registered, 23 May 2011.

Project description:BACKGROUND:Secukinumab, an anti-interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) in two phase 3 studies (MEASURE 1 and MEASURE 2). Here, we present 52-week results from the MEASURE 3 study assessing the efficacy and safety of secukinumab 300 and 150 mg subcutaneous maintenance dosing, following an intravenous loading regimen. METHODS:A total of 226 patients were randomized to intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous secukinumab 300 mg (IV-300 mg) or 150 mg (IV-150 mg) every 4 weeks, or matched placebo. Patients in the placebo group were re-randomized to subcutaneous secukinumab at a dose of 300 or 150 mg at week 16. The primary endpoint was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response rate at week 16 in the IV-300 mg or IV-150 mg versus placebo. Other endpoints assessed through week 52 included improvements in ASAS40, ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity Index, and ASAS partial remission responses, as well as the change from baseline in high-sensitivity C-reactive protein levels. Statistical analyses followed a predefined hierarchical hypothesis testing strategy to adjust for multiplicity of testing, with non-responder imputation used for binary variables and mixed-model repeated measures for continuous variables. RESULTS:The primary efficacy endpoint was met; the ASAS20 response rate was significantly greater at week 16 in the IV-300 mg (60.5%; P?<?0.01) and IV-150 mg (58.1%; P?<?0.05) groups versus placebo (36.8%). All secondary endpoints were met at week 16, except ASAS partial remission in the IV-150 mg group. Improvements achieved with secukinumab in all clinical endpoints at week 16 were also sustained at week 52. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period. During the entire treatment period, pooled incidence rates of Candida infections and grade 3-4 neutropenia were 1.8% for both of these adverse events in secukinumab-treated patients. CONCLUSIONS:Secukinumab (300 mg and 150 mg dose groups) provided rapid, significant and sustained improvement through 52 weeks in the signs and symptoms of patients with AS. The safety profile was consistent with previous reports, with no new or unexpected findings. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02008916 . Registered on 8 December 2013. EUDRACT 2013-001090-24. Registered on 24 October 2013). The study was not retrospectively registered.

Dataset Information

Secukinumab Demonstrates Sustained Efficacy and Safety in a Taiwanese Subpopulation With Active Ankylosing Spondylitis: Four-Year Results From a Phase 3 Study, MEASURE 1.

Objectives

Methods

Results

Conclusion

Clinicaltrialsgov identifier

Publications

Secukinumab Demonstrates Sustained Efficacy and Safety in a Taiwanese Subpopulation With Active Ankylosing Spondylitis: Four-Year Results From a Phase 3 Study, MEASURE 1.

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