A Review of the Use of Secukinumab for Psoriatic Arthritis.
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ABSTRACT:
SUBMITTER: Patel NU
PROVIDER: S-EPMC5696288 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
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A Review of the Use of Secukinumab for Psoriatic Arthritis.
Patel Nupur U NU Vera Nora C NC Shealy Emily Rose ER Wetzel Margaret M Feldman Steven R SR
Rheumatology and therapy 20170828 2
Psoriatic arthritis (PsA) is a chronic, seronegative spondyloarthropathy associated with psoriasis (PsO). Treatment options range from non-pharmacologic measures to NSAIDS, DMARDs, and biologics, depending on patient presentation. Secukinumab (Cosentyx©) is a new biologic treatment option that was approved for use in treating adult patients with PsA in October 2016. Our paper explores the clinical trial evidence available for secukinumab to examine its safety and efficacy as a therapeutic agent ...[more]
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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: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: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
Project description:Psoriasis is a chronic inflammatory skin disease affecting about 1-3% of the general population. Moderate-to-severe psoriasis is commonly associated with various comorbidities, including psoriatic arthritis (PsA) and cardio-metabolic disorders such as obesity, hypertension, diabetes, and metabolic syndrome. There is increasing recognition that systemic inflammation accompanies severe skin disease. Abnormal innate and adaptive immune responses in the skin are involved in pathogenesis. The cytokine interleukin (IL)-17A is produced by T helper 17 (Th17) cells, neutrophils, mast cells, and T cytotoxic 17 cells. IL-17 plays a key role in host defense against extracellular bacteria and fungi. IL-17A acts on keratinocytes to increase expression of chemokines involved in recruiting myeloid dendritic cells, Th17 cells, and neutrophils to the lesion site. IL-17A also induces the production of antimicrobial peptides and pro-inflammatory cytokines that, in turn, may amplify and sustain immune responses in the skin. Blocking IL-17A improved psoriasis-like pathology in experimental models, and reduction in IL-17 signaling is part of the mechanism of action of tumor necrosis factor-α blockers. Three agents neutralizing IL-17 (i.e., secukinumab and ixekizumab) or antagonizing its receptor (i.e., brodalumab) are currently being tested for efficacy and safety in the treatment of plaque psoriasis and PsA. Secukinumab is a fully human IgG1 monoclonal antibody that selectively binds and neutralizes IL-17A whose efficacy in the therapy of chronic plaque psoriasis has been demonstrated in different phase II clinical trial. No new safety signals have emerged so far.
| S-EPMC4065277 | biostudies-literature
Project description:To assess the comparative effectiveness and safety of novel biologic therapies in psoriatic arthritis (PsA) and to establish the position of the non-anti-tumor necrosis factor ? (TNF-?) biologic drugs in the treatment regimen of the disease. A systematic review and network meta-analysis (NMA) was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) requirements. Two investigators identified the studies, abstracted data, and assessed the risk of bias independently. The NMA was conducted for efficacy [American College of Rheumatology (ACR) criteria, ACR20 and ACR50; psoriasis area and severity index (PASI), PASI75] and safety outcomes [any adverse events (AEs) and serious adverse events (SAEs)]; treatments were ranked using the P score for each outcome. The PROSPERO registration number was 42017072200. MEDLINE/PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from the inception of each database to July 10, 2017. Randomized controlled trials (RCTs) for abatacept, apremilast, secukinumab or ustekinumab in adults with moderate and severe PsA were included. The overall PsA population and anti-TNF-?-naive, anti-TNF-?-failure, or anti-TNF-?-experienced subpopulations were considered. We identified eight eligible RCTs and included them in the systematic review and NMA. Significant differences in ACR20 response rate were revealed between secukinumab 150 mg and apremilast 20 mg [relative risk; RR?=?2.55 (CI-confidence interval; 1.24, 5.23)] and between secukinumab 300 mg and apremilast 20 or 30 mg [RR?=?3.57 CI (1.48, 8.64) and RR?=?2.84 CI (1.18, 6.86), respectively]. Any AEs occurred more often in apremilast 20 and 30 mg compared with placebo [RR?=?0.58 CI (0.45, 0.74) and RR?=?0.58 CI (0.45, 0.75), respectively] but also compared with secukinumab 150 mg [RR?=?0.54 CI (0.35, 0.81) and RR?=?0.45 CI (0.35, 0.82), respectively]. No significant differences were revealed for SAEs among biologics and between biologics and placebo. In the overall population, as well as in the anti-TNF-?-naive subpopulation, secukinumab at a dose of 300 and 150 mg was ranked the highest for the ACR20 endpoint, while in the anti-TNF-?-experienced subpopulation, secukinumab 300 mg and apremilast 30 mg revealed the highest rank. Secukinumab 75 mg was the safest drug in terms of any AEs, but for SEAs the safest was ustekinumab 90 mg. Our study revealed no significant differences among non-anti-TNF-? biologics in the treatment of PsA in the comparisons performed with regards to the highest efficacy and safety. Both in the overall population and in the analyzed subpopulations, secukinumab 300 mg was ranked the highest for the ACR20 response rate. Secukinumab 300 mg was the safest drug in terms of any AEs, and ustekinumab 90 mg presented the lowest overall risk of SAEs. Head-to-head trials and evaluation of comparative efficacy and safety between non-TNF-? biologics are warranted to inform clinical decision making with a relevant treatment paradigm.
| S-EPMC5773655 | biostudies-literature
Project description:Background: Real world evidence data regarding secukinumab (SEC) use in biologic-experienced patients with psoriatic arthritis (PsA) are scarce. Objectives: To assess the real life survival, safety and efficacy of SEC in biologic-experienced patients with PsA. Methods: All biologic-experienced PsA patients treated with SEC in 2 University Rheumatology Units were included (3/2016-12/2018). Patients' and disease characteristics were recorded at baseline and during SEC therapy. Results: 75 patients were included; 76% were females with a mean age of 53.9 years, median disease duration of 6.7 years and median SEC treatment duration of 11.1 months. At baseline, 97% had peripheral arthritis, 42% axial involvement, 22% enthesitis, and 12% dactylitis. Regarding previous biologic exposure, 48 (64%) had been exposed to anti-tumor necrosis factor (TNF) agents only, 5 (7%) to the interleukin (IL)-12/23 inhibitor (Ustekinumab-UST) only while 22 (29%) both to anti-TNFs and UST. Fifty-three percent received SEC in combination with non-biologics and 35% with glucocorticoids, respectively. During follow-up, statistically significant improvement in different disease activity indices were noted (DAS28-CRP, DAPSA, BASDAI). SEC survival rate at the end of follow-up was 64% (48/75), without difference between patients exposed to anti-TNFs only (67%) vs. anti-TNFs and UST (68%) as well as to 1 vs. ?2 anti-TNFs. The rate of serious adverse events and serious infections during follow-up was 4.8 and 1.2/100 patient-years, respectively. Discussion: In real life, in biologic-experienced patients with PsA, SEC displayed a high retention rate, regardless of the type, and number of previous biologics (anti-TNFs ± anti-IL12/23), without significant side effects.
| S-EPMC7317305 | biostudies-literature
Project description:ObjectiveThe aim was to determine the cost effectiveness of secukinumab, a fully human interleukin-17A inhibitor, for adults in the UK with active psoriatic arthritis (PsA) who are tumour necrosis factor inhibitor (TNFi) naïve and without concomitant moderate-to-severe psoriasis, and who have responded inadequately to conventional systemic disease-modifying anti-rheumatic drugs (csDMARDs).Perspective and settingThe study took the perspective and setting of the UK National Health Service (NHS).MethodsThe model structure was a 3-month decision tree leading into a Markov model. Separate analyses based on the number of prior csDMARDs (one and two or more) were conducted, with secukinumab 150 mg compared to standard of care (SoC) and TNFis, respectively, for each subpopulation. Clinical parameters, including response at 3 months, were from the FUTURE 2 trial and a network meta-analysis. Outcomes included total costs and quality-adjusted life years (QALYs) over the 40-year time horizon (3.5% annual discount for both outcomes; cost year 2017), and incremental cost effectiveness ratios (ICERs).ResultsThe ICER for secukinumab 150 mg versus SoC was £28,748 per QALY gained (one prior csDMARD). Secukinumab 150 mg dominated golimumab, certolizumab pegol and etanercept, and had an ICER of £5680 per QALY gained versus adalimumab and > £1 million saved per QALY foregone versus infliximab (two or more prior csDMARDs). Valuing one QALY at between £20,000 and £30,000, the probability of secukinumab having the highest net monetary benefit was 48.9% (one prior csDMARD) and 88.9% (two or more prior csDMARDs). Parameters related to Health Assessment Questionnaire scores were most influential.ConclusionsSecukinumab 150 mg at list price appears to represent a cost-effective use of NHS resources for adults with PsA who have responded inadequately to one or two or more prior csDMARDs.
| S-EPMC5999172 | biostudies-literature
Project description:BackgroundUsing a machine learning approach, the study investigated if specific baseline characteristics could predict which psoriatic arthritis (PsA) patients may gain additional benefit from a starting dose of secukinumab 300 mg over 150 mg. We also report results from individual patient efficacy meta-analysis (IPEM) in 2049 PsA patients from the FUTURE 2 to 5 studies to evaluate the efficacy of secukinumab 300 mg, 150 mg with and without loading regimen versus placebo at week 16 on achievement of several clinically relevant difficult-to-achieve (higher hurdle) endpoints.MethodsMachine learning employed Bayesian elastic net to analyze baseline data of 2148 PsA patients investigating 275 predictors. For IPEM, results were presented as difference in response rates versus placebo at week 16.ResultsMachine learning showed secukinumab 300 mg has additional benefits in patients who are anti-tumor necrosis factor-naive, treated with 1 prior anti-tumor necrosis factor agent, not receiving methotrexate, with enthesitis at baseline, and with shorter PsA disease duration. For IPEM, at week 16, all secukinumab doses had greater treatment effect (%) versus placebo for higher hurdle endpoints in the overall population and in all subgroups; 300-mg dose had greater treatment effect than 150 mg for all endpoints in overall population and most subgroups.ConclusionsMachine learning identified predictors for additional benefit of secukinumab 300 mg compared with 150 mg dose. Individual patient efficacy meta-analysis showed that secukinumab 300 mg provided greater improvements compared with 150 mg in higher hurdle efficacy endpoints in patients with active PsA in the overall population and most subgroups with various levels of baseline disease activity and psoriasis.
| S-EPMC8389345 | biostudies-literature
Project description:ImportanceApproximately one-quarter of the global population have latent tuberculosis infection (LTBI), and tuberculosis (TB) is accountable for more than 1.5 million deaths annually. Methotrexate, cyclosporine, and tumor necrosis factor inhibitors may be associated with increased risk of TB and LTBI reactivation, although data are limited on the risks of TB with use of newer biologics.ObjectiveTo assess the association of secukinumab with reporting of active TB development, TB reactivation, and LTBI activation as an adverse event (AE) in patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis.Design, setting, and participantsThis pooled cohort study pooled data from 28 clinical trials of secukinumab used in psoriasis (17 phase 3 or 3b and 2 phase 4 trials), psoriatic arthritis (5 phase 3 trials), and ankylosing spondylitis (4 phase 3 trials). A search of the Novartis Secukinumab Compound Pool Database was conducted for the 28 trials. All trial participants who had received at least 1 approved subcutaneous dose of secukinumab (150 mg or 300 mg) were included. Before randomization in these trials, patients underwent screening for TB. Patients with active TB were excluded, and patients with LTBI were treated according to local guidelines. Data were analyzed from the start of treatment in the individual studies through December 25, 2018.Main outcomes and measuresReporting of active TB or LTBI as an AE over a 5-year period using exposure-adjusted incidence rates (EAIR; incidence rates per 100 patient-years).ResultsA total of 12 319 patients were included, of whom 8819 patients had psoriasis (71.6%; 5930 men [67.2%]; mean [SD] age, of 44.9 [13.5] years), 2523 had psoriatic arthritis (20.5%; 1323 women [52.4%]; mean [SD] age, 48.8 [12.1] years), and 977 had ankylosing spondylitis (7.3%; 658 men [67.3%]; mean [SD] age, 42.3 [11.9] years). In the total population, 684 patients (5.6%) had tested positive for LTBI at screening. Over 5 years, LTBI as an AE during secukinumab treatment was reported in 13 patients (0.1% of 12 319). Of these 13 patients, 6 had a prior positive LTBI test result, and 7 were newly diagnosed as having LTBI. Four of the 7 patients had psoriasis (EAIR, 0.03; 95% CI, 0.01-0.07), 1 had psoriatic arthritis (EAIR, 0.02; 95% CI, 0.00-0.11), and 2 had ankylosing spondylitis (EAIR, 0.08; 95% CI, 0.01-0.28). No cases of active TB were reported.Conclusions and relevanceThis study found that LTBI reported as an AE after secukinumab treatment was uncommon and appeared to support the use of secukinumab in chronic systemic inflammatory conditions.
| S-EPMC7527940 | biostudies-literature
Project description:BackgroundPsoriatic Arthritis (PsA) is a multifactorial disease, and predicting remission is challenging. Machine learning (ML) is a promising tool for building multi-parametric models to predict clinical outcomes. We aimed at developing a ML algorithm to predict the probability of remission in PsA patients on treatment with Secukinumab (SEC).MethodsPsA patients undergoing SEC treatment between September 2017 and September 2020 were retrospectively analyzed. At baseline and 12-month follow-up, we retrieved demographic and clinical characteristics, including Body Mass Index (BMI), disease phenotypes, Disease Activity in PsA (DAPSA), Leeds Enthesitis Index (LEI) and presence/absence of comorbidities, including fibromyalgia and metabolic syndrome. Two random feature elimination wrappers, based on an eXtreme Gradient Boosting (XGBoost) and Logistic Regression (LR), were trained and validated with 10-fold cross-validation for predicting 12-month DAPSA remission with an attribute core set with the least number of predictors. The performance of each algorithm was assessed in terms of accuracy, precision, recall and area under receiver operating characteristic curve (AUROC).ResultsOne-hundred-nineteen patients were selected. At 12 months, 20 out of 119 patients (25.21%) achieved DAPSA remission. Accuracy and AUROC of XGBoost was of 0.97 ± 0.06 and 0.97 ± 0.07, overtaking LR (accuracy 0.73 ± 0.09, AUROC 0.78 ± 0.14). Baseline DAPSA, fibromyalgia and axial disease were the most important attributes for the algorithm and were negatively associated with 12-month DAPSA remission.ConclusionsA ML approach may identify SEC good responders. Patients with a high disease burden and axial disease with comorbid fibromyalgia seem challenging to treat.
| S-EPMC9271870 | biostudies-literature