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Secukinumab provides sustained low rates of radiographic progression in psoriatic arthritis: 52-week results from a phase 3 study, FUTURE 5.

ABSTRACT: OBJECTIVE:To evaluate the effect of secukinumab on radiographic progression through 52 weeks in patients with PsA from the FUTURE 5 study. METHODS:Patients 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. RESULTS:The 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. CONCLUSION:Secukinumab 300 and 150 mg with or without s.c. loading regimen provided sustained low rates of radiographic progression through 52 weeks of treatment. TRIAL REGISTRATION:ClinicalTrials.gov, http://clinicaltrials.gov, NCT02404350.

SUBMITTER: van der Heijde D

PROVIDER: S-EPMC7244782 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Secukinumab provides sustained low rates of radiographic progression in psoriatic arthritis: 52-week results from a phase 3 study, FUTURE 5.

van der Heijde Désirée D Mease Philip J PJ Landewé Robert B M RBM Rahman Proton P Tahir Hasan H Singhal Atul A Boettcher Elke E Navarra Sandra S Zhu Xuan X Ligozio Gregory G Readie Aimee A Mpofu Shephard S Pricop Luminita L

Rheumatology (Oxford, England) 20200601 6

<h4>Objective</h4>To evaluate the effect of secukinumab on radiographic progression through 52 weeks in patients with PsA from the FUTURE 5 study.<h4>Methods</h4>Patients 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 He ...[more]

PMID: 31586420

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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.

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.

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.

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.

Project description:IntroductionA previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other treatments for patients with radiographic axial spondyloarthritis (r-axSpA; i.e., ankylosing spondylitis), including the IL-17A inhibitors secukinumab and ixekizumab. This matching-adjusted indirect comparison (MAIC) assessed 52-week relative efficacy of bimekizumab versus secukinumab and ixekizumab.MethodsIndividual patient data from BE MOBILE 2 (bimekizumab 160 mg; N = 220) were matched to pooled summary data from MEASURE 1/2/3/4 (secukinumab 150 mg), MEASURE 3 (secukinumab 300 mg; escalated dose for inadequate responders), COAST-V (ixekizumab) and COAST-V/-W (ixekizumab). BE MOBILE 2 patients were reweighted using propensity score weights based on age, sex, ethnicity, tumor necrosis factor inhibitor (TNFi) exposure, weight, baseline ASDAS and BASFI (secukinumab) and baseline BASDAI (ixekizumab), and 52-week efficacy outcomes from the trial recalculated. Odds ratios (OR) or mean difference for unanchored comparisons are reported with 95% confidence intervals (CI).ResultsAt week 52, MAIC demonstrated that patients may have higher likelihood of improvement in key efficacy outcomes with bimekizumab versus secukinumab 150 mg (e.g., ASAS40: [OR (95% CI): 1.48 (1.05, 2.10); p = 0.026]; effective sample size [ESS] = 177). Differences in 52-week efficacy outcomes between bimekizumab and secukinumab 300 mg dose escalation were non-significant (ESS = 120). Bimekizumab versus ixekizumab 80 mg comparisons (COAST-V only; ESS = 84) also suggested that differences were non-significant for most key efficacy outcomes. Other ixekizumab comparisons (COAST-V/-W; ESS = 45) suggested bimekizumab may have higher comparative efficacy for many of the same efficacy outcomes, however ixekizumab analyses were limited by poor population overlap, likely due to the greater proportion of patients with previous TNFi exposure.ConclusionsPatients treated with bimekizumab may have a higher likelihood of achieving improved longer-term efficacy versus secukinumab 150 mg, suggesting bimekizumab may be a favorable therapeutic option for r-axSpA. Differences in efficacy outcomes with bimekizumab versus ixekizumab 80 mg were mostly non-significant, depending on the populations considered.

Dataset Information

Secukinumab provides sustained low rates of radiographic progression in psoriatic arthritis: 52-week results from a phase 3 study, FUTURE 5.

Publications

Secukinumab provides sustained low rates of radiographic progression in psoriatic arthritis: 52-week results from a phase 3 study, FUTURE 5.

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