Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Psoriatic Arthritis: Final 5-year Results from the Phase 3 FUTURE 1 Study.
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SUBMITTER: Mease PJ
PROVIDER: S-EPMC6957920 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPain is one of the most important domains affecting health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). Secukinumab has demonstrated rapid and sustained improvements in signs and symptoms, including HRQoL, among patients with active PsA. This analysis evaluates the effect of secukinumab on patient-reported pain in PsA through 104 weeks of treatment.MethodsPain was assessed through week 104 using clinically relevant measures, including change from baseline in a pain visual analog scale (VAS) and Short Form-36 (SF-36) bodily domain scores; proportion of patients reporting improvements equal to or better than minimum clinically meaningful differences in the pain VAS and SF-36 bodily pain domain scores; and proportion of patients with no, moderate, or extreme pain/discomfort measured by the EuroQoL 5-Dimension 3-Level Questionnaire (EQ-5D-3 L) pain item scores. Correlations of pain measures were analyzed using Pearson's correlation coefficient. Pre-specified analyses of TNF-naïve patients and patients who stopped TNF-inhibitors (TNFis) due to inadequate responses or safety/tolerability (TNF-IR patients) were performed using "as-observed data."ResultsMean improvements from baseline in pain VAS scores were greater with secukinumab versus placebo by week 3 (- 16.9; P < 0.0001 with secukinumab 300 mg and - 12.6; P < 0.05 with secukinumab 150 mg) and sustained through week 104. SF-36 bodily pain domain scores were significantly greater with 300 mg secukinumab and secukinumab 150 mg versus placebo by week 4 (16.2 and 16.3, respectively; P < 0.0001 for both), and these changes were maintained through week 104. With both secukinumab 300 mg and secukinumab 150 mg, improvements equal to or better than the minimum clinically meaningful differences in pain VAS and SF-36 bodily pain were significant versus placebo at week 3 and week 4, respectively. At week 4, 15%, 9%, and 5% of patients receiving secukinumab 300 mg, secukinumab 150 mg, and placebo, respectively, reported "no pain/discomfort" measured by EQ-5D-3 L; these proportions increased to week 104 with both secukinumab doses. Similarly, improvements in pain measures were significant in both TNF-naïve and TNF-IR patients.ConclusionSecukinumab provided rapid and sustained pain relief in PsA over 2 years of treatment. Improvements in pain were reported regardless of prior exposure to TNFis.Trial registrationClinicalTrials.gov, NCT01752634 . Registered on 19 December 2012.
| S-EPMC5992664 | biostudies-literature
Project description:To assess long-term efficacy, safety and tolerability of secukinumab up to 104 weeks in patients with active PsA.Patients with PsA (n = 397) were randomized to s.c. secukinumab 300, 150 or 75 mg or placebo at baseline, weeks 1, 2, 3 and 4 and every 4 weeks thereafter. Placebo-treated patients were re-randomized to receive secukinumab 300 or 150 mg s.c. from week 16 (placebo non-responders) or week 24 (placebo responders). Exploratory endpoints at week 104 included 20, 50 and 70% improvement in ACR criteria (ACR20, 50, 70); 75 and 90% improvement in the Psoriasis Area Severity Index, 28-joint DAS with CRP, presence of dactylitis and enthesitis and other patient-reported outcomes. For binary variables, missing values were imputed; continuous variables were analysed by a mixed-effects model for repeated measures.A total of 86/100 (86%), 76/100 (76%) and 65/99 (66%) patients in the secukinumab 300, 150 and 75 mg groups, respectively, completed 104 weeks. At week 104, ACR20 response rates after multiple imputation in the 300, 150 and 75 mg groups were 69.4, 64.4 and 50.3%, respectively. Sustained clinical improvements were observed through week 104 with secukinumab across other clinically important domains of PsA. Responses were sustained through week 104 regardless of prior anti-TNF-? use. Over the entire treatment period the incidence, type and severity of adverse events were consistent with those reported previously.Secukinumab provided sustained improvements in signs and symptoms and multiple clinical domains in patients of active PsA through 2 years of therapy. Secukinumab was well tolerated, with a safety profile consistent with that reported previously.ClinicalTrials.gov (https://clinicaltrials.gov), NCT01752634.
| S-EPMC5850284 | biostudies-literature
Project description:ObjectiveTo evaluate the effect of secukinumab on radiographic progression through 52 weeks in patients with PsA from the FUTURE 5 study.MethodsPatients with active PsA, stratified by prior anti-TNF use (naïve or inadequate response), were randomized to s.c. secukinumab 300 mg load (300 mg), 150 mg load (150 mg), 150 mg no load regimens or placebo at baseline, at weeks 1, 2 and 3 and every 4 weeks starting at week 4. Radiographic progression was assessed by change in van der Heijde-modified total Sharp score (vdH-mTSS; mean of two readers). Statistical analysis used a linear mixed-effects model (random slope) at weeks 24 and 52, and observed data at week 52. Assessments at week 52 included additional efficacy endpoints (non-responders imputation and mixed-effects models for repeated measures) and safety.ResultsThe majority (86.6%) of patients completed 52 weeks of treatment. The proportion of patients with no radiographic progression (change from baseline in vdH-mTSS ⩽0.5) was 91.8, 85.2 and 87.2% in 300, 150 and 150 mg no load groups, respectively, at week 52. The change in vdH-mTSS from baseline to week 52 using random slope [mean change (s.e.)] was -0.18 (0.17), 0.11 (0.18) and -0.20 (0.18) in 300, 150 and 150 mg no load groups, respectively; the corresponding observed data [mean change (s.d.)] was -0.09 (1.02), 0.13 (1.39) and 0.21 (1.15). Clinical efficacy endpoints were sustained, and no new or unexpected safety signals were reported through 52 weeks.ConclusionSecukinumab 300 and 150 mg with or without s.c. loading regimen provided sustained low rates of radiographic progression through 52 weeks of treatment.Trial registrationClinicalTrials.gov, http://clinicaltrials.gov, NCT02404350.
| S-EPMC7244782 | biostudies-literature
Project description:OBJECTIVE:Secukinumab 150 mg has demonstrated significant improvement in signs and symptoms of ankylosing spondylitis (AS), with response rates sustained for up to 5 years. Here, we report end-of-study 3-year efficacy and safety results of secukinumab 150 and 300 mg from the MEASURE 3 study. METHODS:A total of 226 patients was randomized to intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous (s.c.) secukinumab 300/150 mg every 4 weeks or a matched placebo. At week 16, placebo patients were re-randomized to s.c. secukinumab 300/150 mg. Analysis at week 156 included patients initially randomized to secukinumab and those who switched from placebo to secukinumab at week 16 (any secukinumab 300/150 mg). Outcome measures at week 156 included Assessment of Spondyloarthritis International Society (ASAS) 20/40, Bath Ankylosing Spondylitis Disease Activity Index, ASAS partial remission (PR), ASAS 5/6, and Ankylosing Spondylitis Disease Activity Score-C-reactive protein inactive disease. RESULTS:The retention rates from weeks 16 to 156 were 80.5% and 80.9% in secukinumab 300 and 150 mg, respectively. ASAS 20/40 response rates at week 156 were 75.0%/56.5% and 68.2%/47.7% for secukinumab 300 and 150 mg, respectively. At week 156, response rates on more stringent clinical end points (eg, ASAS 40, ASAS-PR) were higher with the 300-mg dose, particularly in tumor necrosis factor (TNF)-inadequate responder (IR) patients. No new safety findings were observed. CONCLUSION:Secukinumab (300 and 150 mg) provided sustained improvements through 3 years in the signs and symptoms of active AS. Improvements with secukinumab 300 mg were numerically higher compared with the 150-mg dose for some higher hurdle end points and in TNF-IR patients. The safety profile of secukinumab was consistent with previous reports.
| S-EPMC7011421 | biostudies-literature
Project description:To assess whether secukinumab treatment in patients with active psoriatic arthritis (PsA) is associated with sustained inhibition of radiographic progression.In this phase III, double-blind, placebo-controlled study, 606 patients with PsA were randomized to receive intravenous (IV) secukinumab at a dose of 10 mg/kg (weeks 0, 2, 4) followed by subcutaneous secukinumab at a dose of 150 mg or 75 mg (the IV?150 mg and IV?75 mg groups, respectively) or placebo. Patients were stratified according to prior anti-tumor necrosis factor (anti-TNF) exposure (71% were anti-TNF naive). At week 16, placebo-treated patients who had at least a 20% reduction in the tender and swollen joint counts (responders) continued to receive placebo until week 24; nonresponders were re-randomized to receive secukinumab at a dose of 150 mg or 75 mg. The modified total Sharp/van der Heijde score (SHS) was determined at baseline, week 16 or 24, and week 52.In the overall population, radiographic progression was inhibited through 52 weeks; efficacy was demonstrated for both erosion and joint space narrowing scores and in patients who switched from placebo to secukinumab at week 24. Subgroup analyses showed that secukinumab reduced radiographic progression at week 24, regardless of previous anti-TNF treatment. Among anti-TNF-naive patients, the mean changes from baseline to week 24 in the modified total SHS were 0.05 in the pooled secukinumab group and 0.57 in the placebo group; among patients with an inadequate response or intolerance to anti-TNF treatment, the mean changes were 0.16 and 0.58, respectively. Anti-TNF-naive patients showed negligible progression through week 52. Inhibition of structural damage was observed through week 52 irrespective of concomitant methotrexate use. A high proportion of patients receiving secukinumab showed no progression (change in SHS of ??0.5) from baseline to week 24 (82.3% of the IV?150 mg group and 92.3% of the IV?75 mg group) and from week 24 to week 52 (85.7% of the IV?150 mg group and 85.8% of the IV?75 mg group).Secukinumab inhibited radiographic progression over 52 weeks of treatment in patients with active PsA.
| S-EPMC5129532 | biostudies-literature
Project description:Secukinumab (Cosentyx®) is a fully human monoclonal antibody that selectively targets interleukin (IL)-17A, a proinflammatory cytokine involved in the pathogenesis of psoriatic arthritis (PsA). Administered subcutaneously, the first-in-class anti-IL-17 agent is approved in numerous countries worldwide for the treatment of adults with active PsA. In the phase III FUTURE trials, secukinumab 150 or 300 mg improved the clinical signs and symptoms of PsA versus placebo in patients with active disease despite previous treatment with NSAIDs, biological disease-modifying anti-rheumatic drugs (bDMARDs) and/or tumour necrosis factor inhibitors (TNFi). The benefits of secukinumab were seen regardless of whether or not patients had received previous TNFi therapy, and were maintained during longer term (up to 5 years) treatment. In FUTURE 1 and 5, secukinumab inhibited structural joint damage and was associated with sustained low rates of radiographic progression through 1-3 years of treatment. Treatment with secukinumab improved physical function and health-related quality of life (HR-QOL) and was generally well tolerated, both in the short- and longer-term. In the head-to-head EXCEED trial, secukinumab did not quite attain statistical significance for superiority versus adalimumab in the joint domain. In conclusion, secukinumab is effective across all key PsA domains and is generally well tolerated, and thus represents a useful treatment alternative to TNFi and other bDMARDs in adult patients with active PsA.
| S-EPMC8049904 | biostudies-literature
Project description:BACKGROUND:Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2?years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2?years among patients with PsA in the FUTURE 2 study. METHODS:PASDAS (cut-off scores: remission ??1.9; LDA >?1.9 and?<?3.2; Moderate Disease Activity ??3.2 and?<?5.4; and high disease activity [HDA]???5.4) was assessed in the overall population (tumour necrosis factor inhibitor [TNFi]-naïve and TNFi-experienced), in patients stratified by prior TNFi use and by disease duration at weeks 16, 52 and 104. The impact of secukinumab on individual PASDAS core components and on the relationship between PASDAS states and patient-reported outcomes (PROs), including physical function, health-related quality of life (HRQoL) and work productivity, were also assessed. Data for the approved doses of secukinumab (300 and 150?mg) are reported. PASDAS scores and core components were reported as observed, and PROs were analysed using mixed models for repeated measures. RESULTS:In the overall population, PASDAS remission and LDA were achieved in 15.6% and 22.9%, respectively, of patients treated with secukinumab 300?mg and in 15.2% and 19.2%, respectively, in the secukinumab 150?mg group versus 2.3% and 13.8%, respectively, with placebo at week 16. In the TNFi-naïve group, a higher proportion of patients achieved remission?+?LDA at week 16 with secukinumab 300 and 150?mg (46.2% and 42.9%, respectively) versus placebo (17.5%), with corresponding responses in TNFi-experienced patients being 22.6% and 19.4% versus 13.3%. Remission/LDA responses with secukinumab were sustained through 2?years. Patients achieving remission/LDA reported greater improvements in PROs than patients in HDA through 2?years. CONCLUSIONS:Secukinumab-treated patients achieved higher PASDAS-defined remissions or LDA compared with placebo at week 16, which were sustained through 2?years. Remission/LDA was achieved by both TNFi-naïve and TNFi-experienced patients treated with secukinumab, with higher rates in TNFi-naïve patients. Secukinumab-treated patients achieving remission/LDA reported significantly greater improvements in PROs, including physical function and different dimensions of health-related quality of life and work, than patients in HDA. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01752634 . Registered on December 19, 2012. EUDRACT, 2012-004439-22 . Registered on December 12, 2012.
| S-EPMC6286532 | biostudies-literature
Project description:The treatment of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) positively changed since the introduction of anti-TNF? drugs. These treatments were shown to reduce the symptoms and signs of the diseases and improve the quality of life. However, a variable percentage of patients do not respond to anti-TNF? or can exhibit a loss of response and, furthermore, despite anti-TNF? drugs' proven efficacy in reducing peripheral radiographic progression in PsA, the impact in reducing radiographic damage in AS is still debated. Recently, the discovery of new pathogenic mechanisms paved the way to the development of new drugs that target other pro-inflammatory cytokines. In particular, the inhibition of interleukin (IL)-17, which is the principal cytokine produced by Th17 lymphocytes, a pro-inflammatory subset involved in both inflammation and new bone formation in AS and PsA, demonstrated promising results. The new molecule secukinumab, an IL-17A inhibitor, showed its efficacy and safety in phase III randomized clinical trials in AS and PsA and is the first non-anti-TNF? biologic approved for the treatment of AS, providing a useful alternative treatment strategy in both diseases. The aim of this article was to review the pathophysiological basis, the efficacy and the safety of secukinumab treatment in AS and PsA patients.
| S-EPMC5085310 | biostudies-literature
Project description:OBJECTIVES:To evaluate the effect of subcutaneous (s.c.) secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic progression in patients with psoriatic arthritis (PsA). METHODS:Adults (n=996) with active PsA were randomised 2:2:2:3 to s.c. secukinumab 300 mg or 150 mg with loading dose (LD), 150 mg without LD or placebo. All groups received secukinumab or placebo at baseline, weeks 1, 2 and 3 and then every 4 weeks from week 4. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 16. RESULTS:Significantly more patients achieved an ACR20 response at week 16 with secukinumab 300 mg with LD (62.6%), 150 mg with LD (55.5%) or 150 mg without LD (59.5%) than placebo (27.4%) (p<0.0001 for all; non-responder imputation). Radiographic progression, as measured by van der Heijde-modified total Sharp score, was significantly inhibited at week 24 in all secukinumab arms versus placebo (p<0.01 for 300 mg with LD and 150 mg without LD and p<0.05 for 150 mg with LD; linear extrapolation). Adverse event rates at week 24 were similar across treatment arms: 63.1% (300 mg with LD), 62.7% (150 mg with LD), 61.1% (150 mg without LD) and 62.0% (placebo). No deaths or new safety signals were reported. CONCLUSION:S.c. secukinumab 300 mg and 150 mg with and without LD significantly improved clinical signs and symptoms and inhibited radiographic structural progression versus placebo at week 24 in patients with PsA. TRIAL REGISTRATION NUMBER:NCT02404350; Results.
| S-EPMC5965348 | biostudies-literature
Project description:IntroductionPsoriatic arthritis (PsA) is an immune-mediated chronic inflammatory arthropathy associated with impaired physical function and reduced quality of life. Biologic therapies that target tumor necrosis factor (anti-TNF) have significantly improved clinical outcomes. Partial, non- and transient responses remain common comprising significant unmet clinical need. New therapies with novel modes of action are urgently required.ObjectivesThe interleukin (IL)-17 pathway has recently been attributed a critical role in the pathogenesis of spondyloarthritides. Herein, we review data from clinical studies with secukinumab, a novel fully human IgG1κ anti-IL-17A monoclonal antibody (mAb), in patients with active PsA.ResultsAcross two pivotal phase 3 studies, secukinumab provided significant and sustained reductions in the signs and symptoms of PsA, inhibition of radiographic progression, and improved patient-reported outcomes and measures of quality of life. The primary efficacy endpoint, a ≥20% improvement from baseline according to the American College of Rheumatology 20 (ACR20) response at Week 24, was significantly higher in patients treated with secukinumab compared with placebo, with improvements sustained through at least 52 weeks. Clinical benefits were seen with secukinumab regardless of concomitant methotrexate treatment and in patients who were either anti-TNF-naïve or who were inadequate responders to anti-TNF therapy. Secukinumab was well-tolerated, with a safety profile consistent with that previously reported in psoriasis trials. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and headache.ConclusionSecukinumab offers an effective new addition to the available treatment options for PsA. Regulatory submissions have been filed worldwide, with the first approvals recently obtained in Japan and Europe. Future studies are required to define the optimal timing and strategic use of this novel treatment modality.FundingNovartis Pharma.
| S-EPMC4999581 | biostudies-literature