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Efficacy and Safety of Secukinumab 150 mg with and Without Loading Regimen in Ankylosing Spondylitis: 104-week Results from MEASURE 4 Study.

ABSTRACT: INTRODUCTION:To evaluate the efficacy and safety of secukinumab 150 mg, with or without a loading regimen, using a self-administered prefilled syringe in patients with ankylosing spondylitis (AS) over 104 weeks from the MEASURE 4 study. METHODS:Patients (N = 350) with active AS were randomized (1:1:1) to receive subcutaneous secukinumab 150 mg with loading dose (150 mg), without loading dose (150 mg no load), or placebo. All patients received secukinumab or placebo at baseline, weeks 1, 2, and 3 and every 4 weeks starting at week 4. The primary endpoint was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) at week 16. RESULTS:A total of 96.9% of patients (339/350) completed 16 weeks and 82.6% (289/350) completed 104 weeks of treatment. The ASAS20 response rate at week 16 was 59.5% and 61.5% with 150 and 150 mg no load groups, respectively, versus placebo (47%; P = 0.057 and 0.054, respectively); the primary endpoint was not met. Increases in response rates achieved with secukinumab for ASAS20 at week 16 were sustained through week 104. The safety profile of secukinumab 150 mg, with or without a loading regimen, showed no new or unexpected safety signals. CONCLUSIONS:Secukinumab 150 mg, with or without loading regimen, provided rapid and sustained decreases in the signs and symptoms of patients with AS, but the differences were not statistically significant at week 16 due to higher than expected placebo responses. The responses and safety profile were consistent with previous phase 3 studies and sustained through 2 years. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT02159053. FUNDING:Novartis Pharma AG, Basel, Switzerland.

SUBMITTER: Kivitz AJ

PROVIDER: S-EPMC6251842 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionTo assess the efficacy and safety of the subcutaneous (s.c.) secukinumab 150 mg with loading (150 mg) or without loading (150 mg no-load) regimen through 104 weeks in patients with active psoriatic arthritis (PsA) in the FUTURE 4 (NCT02294227) study.MethodsPatients with PsA (N = 341) were randomized to s.c. secukinumab 150 mg, 150 mg no-load or placebo at baseline, weeks 1, 2, 3 and every 4 weeks thereafter. All placebo patients were reassigned to secukinumab 150 mg no-load at either week 16 (non-responders) or week 24 (responders). The primary end point was ACR20 at week 16. Patients could have their dose escalated from 150 to 300 mg based on their physician's decision starting at week 36. Pre- and post-escalation ACR and PASI responses were also assessed.ResultsA total of 95.6% (326/341), 84.5% (288/341) and 79.8% (272/341) patients completed 16, 52 and 104 weeks of treatment, respectively. The primary end point was met; ACR20 response rate at week 16 was 41.2% and 39.8% with the 150 mg and 150 mg no-load groups, respectively, versus placebo (18.4%; adjusted P value = 0.0003 for both treatment arms). Efficacy responses observed at week 16 in both treatment regimens were sustained up to week 52 and 104, with many patients continuing to show improvements up to week 104. After dose escalation to 300 mg, the proportion of patients with non-/low-level ACR/PASI response decreased with increasing proportions of patients having higher ACR/PASI responses. No new or unexpected safety signals were reported.ConclusionThe secukinumab 150 mg or 150 mg no-load regimen demonstrated significant and sustained improvements in the signs and symptoms of psoriatic arthritis through 104 weeks; the loading regimen was associated with numerically higher and earlier responses for some high-hurdle end points. Improved efficacy was observed upon dose escalation from 150 to 300 mg. The safety profile was consistent with previous reports.Trial registrationClinicalTrials.gov identifier, NCT02294227.FundingNovartis Pharma AG, Basel, Switzerland.

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.

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Efficacy and Safety of Secukinumab 150 mg with and Without Loading Regimen in Ankylosing Spondylitis: 104-week Results from MEASURE 4 Study.

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