P5367Indirect comparison of the safety and efficacy of alirocumab and evolocumab: from a comprehensive meta-analysis of 30 randomized controlled trials

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Guedeney ◽  
S Sorrentino ◽  
G Giustino ◽  
C Chapelle ◽  
B Claessen ◽  
...  
Keyword(s):  
Injection Site ◽  
Meta Analysis ◽  
Injection Site Reaction ◽  
Fixed Effect Model ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Site Reaction ◽  
Eligibility Criteria ◽  
Safety And Efficacy ◽  
Increased Risk

Abstract Background Alirocumab and evolocumab, two proprotein convertase subtilisin–kexin type 9 inhibitors, have both been associated with improved outcomes in patients with atherosclerotic cardiovascular disease in addition to standard lipid-lowering therapies. However, their comparative safety and efficacy profiles are unknown. Purpose To compare the safety and efficacy of alirocumab versus evolocumab. Methods We conducted a systematic review and network meta-analysis of placebo-controlled randomized trials available up to November 2018 evaluating the safety and efficacy of alirocumab and evolocumab. We estimated risk ratio and 95% confidence intervals using fixed effect model in a frequentist pairwise and network metanalytic approach. The primary safety endpoints were any adverse events leading to treatment-discontinuation, injection site reaction, systemic allergic reaction, neurocognitive events, ophthalmologic events and new-onset of diabetes mellitus (DM) or worsening of pre-existing DM. The primary efficacy endpoints were all-cause and cardiovascular (CV) death, myocardial infarction (MI) and stroke. This study was registered in PROSPERO (CRD42018090768). Results A total of 30 trials, enrolling 59,026 patients were included in this analysis, of whom 13,607 received alirocumab and 17,931 received evolocumab. Mean weighted follow-up time was 2.5 years, with an exposure time of 144,907 patients-years. Eligibility criteria varied significantly across trials evaluating alirocumab and evolocumab. There were no significant differences between alirocumab and evolocumab in terms of safety endpoints, except for injection site reaction with a 27% increased risk of injection site reaction with alirocumab compared to evolocumab (Figure). Compared with evolocumab, alirocumab was associated with a reduction of all-cause death but not CV death. There were no significant differences in MI or stroke between alirocumab and evolocumab. Conclusion Alirocumab and evolocumab share a similar safety profile. No significant differences were observed across the efficacy endpoints, except for all-cause death, which may be related to heterogeneity of the studied populations between the two drugs.

Indirect comparison of the efficacy and safety of alirocumab and evolocumab: a systematic review and network meta-analysis

2020 ◽  
Author(s):  
Paul Guedeney ◽  
Sabato Sorrentino ◽  
Gennaro Giustino ◽  
Celine Chapelle ◽  
Silvy Laporte ◽  
...  
Keyword(s):  
Systematic Review ◽  
Injection Site ◽  
Meta Analysis ◽  
Injection Site Reaction ◽  
Indirect Comparison ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Efficacy And Safety ◽  
Site Reaction ◽  
Increased Risk

Abstract Aims Although alirocumab and evolocumab have both been associated with improved outcomes in patients with dyslipidaemia or established atherosclerotic cardiovascular disease, data on their respective performances are scarce. This study aimed at providing an indirect comparison of the efficacy and safety of alirocumab vs. evolocumab. Methods and results We conducted a systematic review and network meta-analysis of randomized trials comparing alirocumab or evolocumab to placebo with consistent background lipid-lowering therapy up to November 2018. We estimated the relative risk (RR) and the 95% confidence intervals (CIs) using fixed-effect model in a frequentist pairwise and network meta-analytic approach. A total of 30 trials, enrolling 59 026 patients were included. Eligibility criteria varied significantly across trials evaluating alirocumab and evolocumab. Compared with evolocumab, alirocumab was associated with a significant reduction in all-cause death (RR 0.80, 95% CI 0.66–0.97) but not in cardiovascular death (RR 0.83, 95% CI 0.65–1.05). This study did not find any significant differences in myocardial infarction (RR 1.15, 95% CI 0.99–1.34), stroke (RR 0.96, 95% CI 0.71–1.28), or coronary revascularization (RR 1.13, 95% CI 0.99–1.29) between the two agents. Alirocumab was associated with a 27% increased risk of injection site reaction compared to evolocumab; however, no significant differences were found in terms of treatment discontinuations, systemic allergic reaction, neurocognitive events, ophthalmologic events, or new-onset of or worsening of pre-existing diabetes. Conclusion Alirocumab and evolocumab share a similar safety profile except for injection site reaction. No significant differences were observed across the efficacy endpoints, except for all-cause death, which may be related to the heterogeneity of the studied populations treated with the two drugs.

scholarly journals Cardiovascular and safety events of PCSK9 inhibitors in statin-treated patients with cardiovascular risk: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 23 ◽  
pp. 422-436
Author(s):  
Zinan ZHAO ◽  
Xin HU ◽  
Yatong ZHANG ◽  
Deping LIU
Keyword(s):  
Myocardial Infarction ◽  
Ischemic Stroke ◽  
Cardiovascular Risk ◽  
Injection Site ◽  
Randomized Clinical Trials ◽  
Adverse Drug Events ◽  
Meta Analysis ◽  
Injection Site Reaction ◽  
Nonfatal Myocardial Infarction ◽  
Site Reaction

Objectives: To evaluate whether proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is associated with cardiovascular and safety events in statin-treated patients with cardiovascular risk. Methods: Electronic databases (Pubmed, Cochrane, MEDLINE, EMBASE, ClinicalTrials.gov) were searched through March 31, 2020. Included randomized clinical trials (RCTs) compared PCSK9i use with no PCSK9i in statin treated patients. Two investigators abstracted data and appraised risks of bias. A meta-analysis was performed to calculate risk ratios (RRs) and 95% CIs using fix-effects models. Adjudicated cardiovascular events (CVE) and adverse drug events (ADE) were defined as the primary outcome. Secondary outcomes were cardiovascular (CV) death, all-cause death, nonfatal myocardial infarction, ischemic stroke, serious ADE and injection-site reaction. Results: A total of 10 RCTs 50 053 participants were included. PCSK9i use was associated with signigicant reductions in the CVE (RR, 0.87 [95%CI, 0.83-0.91]; NNT, 54; P<0.00001; I2=0%, heterogeneity P=0.86), nonfatal myocardial infarction (RR, 0.86 [95% CI, 0.78-0.96]; NNT, 95; P=0.005; I2=0%, heterogeneity P=0.88), and ischemic stroke (RR, 0.75 [95%CI 0.64-0.87]; NNT, 244; P=0.00; I2=0%, heterogeneity P=0.82) compared with no PCSK9i in statin-treated patients with CV risk. No significant associations were found between PCSK9i use and no PCSK9i in ADE and serious ADE. PCSK9i use was associated with signigicant increasing in injection-site reaction (RR, 1.55 [95%CI 1.38-1.75]; NNT, 101; P<0.00001; I2=0%, heterogeneity P=0.44). Conclusions: Among statin-treated patients with CV risk, the use of PCSK9i was associated with improving CV outcomes. The use of PCSK9i was well tolerated, but had significantly injection-site reactions.

A phase 1b study of personalized neoantigen vaccine plus pembrolizumab in adults with advanced cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2615-2615
Author(s):  
Aaron Miller ◽  
Zeynep Kosaloglu-Yalcin ◽  
Luise Westernberg ◽  
Leslie Montero ◽  
Milad Bahmanof ◽  
...  
Keyword(s):  
T Cell ◽  
Injection Site ◽  
Cell Function ◽  
Injection Site Reaction ◽  
Therapeutic Vaccine ◽  
T Cell Responses ◽  
Patient Specific ◽  
Clinical Activity ◽  
Site Reaction ◽  
Cell Responses

2615 Background: Neoantigens (NeoAg) are key targets for personalized immunotherapy but efficient methods for their systematic identification and therapeutic targeting remain elusive. We developed a methodology to reliably identify and verify somatic alteration-derived neoantigens based on natural T cell responses against them which formed the basis of an individualized therapeutic vaccine strategy. Methods: This is a phase Ib study to assess the immunogenicity, safety and early clinical activity of personalized synthetic long peptides (PSLP) cancer vaccines in combination with pembrolizumab for patients with treatment refractory metastatic solid tumors or PSLP vaccine alone as an adjuvant treatment with patients with no evidence of disease (NED) that incorporates patient-specific NeoAg identified by an HLA-agnostic, functional T-cell assay (see table). Results: At the time of data cutoff, a total of 5 patients had been treated on ARM-A, 5 patients on ARM-C and 2 patients on ARM-D. AES possibly attributed to personalized vaccine (PSLP), or pembrolizumab, or both include: Grade 1: Arthralgia (1); Diarrhea (1); Fever (4); Fatigue (7); Generalized muscle weakness (1); Headache (2); Nausea (1); Confusion (1); Injection site reaction (5); Rash maculo-papular (3); Flu like symptoms (5); Myalgia (1); and Grade 2: Diarrhea (1); Fatigue (1); Hyperhidrosis (1); Hypothyroidism (1); Injection site reaction (1); Proteinuria (1); Renal and Urinary – other (1); and Grade 3: Colitis (1). For the 9 patients with at least 1 radiographic assessment at the time of analysis 6 had a best response of stable disease (SD) and 3 had progressive disease (PD). Immune monitoring of peripheral blood specimens consistently demonstrated that NeoAg-specific T cell responses were enhanced following administration of PSLP vaccine. On-treatment biopsies demonstrated immune-editing with the variant allele frequency of targeted mutations decreasing following administration of the PSLP vaccine. Conclusions: Taken together, these data meet the trial primary endpoint by demonstrating PSLP vaccines targeting NeoAg identified using the HLA-agnostic pipeline augment effector T cell function against these targets. Clinical trial information: NCT02287428. [Table: see text]

Correlation between methylene tetrahydrofolate reductase (MTHFR) gene rs1801133 C>T polymorphisms and risk of osteoporosis

Pteridines ◽  
2021 ◽  
Vol 32 (1) ◽  
pp. 117-125
Author(s):  
Xiao Chen ◽  
Weiran Zhang ◽  
Jingmin Huang
Keyword(s):  
Clinical Studies ◽  
Meta Analysis ◽  
Recessive Gene ◽  
Fixed Effect Model ◽  
Gene Model ◽  
Methylene Tetrahydrofolate Reductase ◽  
Effect Model ◽  
Increased Risk ◽  
Regression Test ◽  
Methylene Tetrahydrofolate

Abstract Objective To evaluate the correlation between methylene tetrahydrofolate reductase (MTHFR) gene rs1801133 C>T polymorphisms and risk of osteoporosis. Methods We searched the clinical studies related to MTHFR gene rs1801133 C>T polymorphisms and risk of osteoporosis in the electronic databases of PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM) and included the suitable publications in the present meta-analysis according to the inclusion and exclusion criteria. The data of included studies were extracted and pooled by a random or fixed-effect model. The odds ratio (OR) and 95% confidence interval (95% CI) were applied to demonstrate the correlation between MTHFR gene rs1801133 C>T polymorphisms and the risk of osteoporosis. Publication bias was assessed by Begg’s funnel plot and Egger’s line regression test. Results Seven case–control clinical studies were included and a data combination was made. The data was pooled by the fixed effect model because of no obvious statistical heterogeneity. The pooled results indicated that people with the T allele had increased risk of developing osteoporosis under the homologous gene model (TT vs CC) (OR = 2.36, 95% CI: 1.81–3.08, p < 0.05), dominant gene model (TT + CT) vs CC (OR = 1.47, 95% CI: 1.21–1.77, p < 0.05) and recessive gene model TT vs (CC + CT) (OR = 2.16, 95% CI: 1.71–2.74, p < 0.05). Egger’s line regression test indicated no significant publication bias for the present meta-analysis in the above homologous, dominant, and recessive gene models. Conclusion The MTHFR gene rs1801133 C>T polymorphisms are associated with osteoporosis and subjects with the T allele have an increased risk of developing osteoporosis.

Is shift-work associated with increased risk of rectal cancer? A meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15600-e15600
Author(s):  
Chenyu Sun ◽  
Ce Cheng ◽  
Kelly Kozma ◽  
Gopika Chandra ◽  
Na Hyun Kim ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Risk ◽  
Shift Work ◽  
Meta Analysis ◽  
Night Shift ◽  
Fixed Effect Model ◽  
Night Shift Work ◽  
Increased Risk ◽  
Rotating Shift Work ◽  
Trim And Fill

e15600 Background: Globally, more than 1.8 million people were diagnosed of colorectal cancer (CRC) in 2018, with over 30% of CRC in the rectum. Shift-work, involving circadian disruption, sleep deprivation and lifestyle changes, was designated as a probable cause of cancer by The International Agency for Research on Cancer. Previous studies investigating the impact of permanent night-shift work and rotating shift-work on rectal cancer risk showed controversial results. Thus, this meta-analysis was conducted. Methods: A comprehensive literature search on PubMed was conducted to identify all relevant studies published prior to January 2021 according to the established inclusion criteria. The quality assessment was performed by the Newcastle-Ottawa Scale (NOS). The pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated to estimate the association between the shift-work and rectal cancer risk. Based on heterogeneity significance, random-effect or fixed-effect model was used. Subgroup analyses were conducted to explore the night-shift and rotating-shift, respectively. Sensitivity analysis and publication bias detection were performed, and trim and fill analysis was also conducted. All statistical analyses were performed using RevMan software (version 5.3; Cochrane library) and STATA 15.0 statistical software (Stata Corp., College Station, TX), and all P values were two-tailed, the test level was 0.05. Results: Thirty-seven articles were obtained from database searching. Three articles involving 1,063 rectal cancer cases were included. All studies were considered moderate to high quality. All included studies investigated on the association between shift-work and rectal cancer risk. A statistically significant association between shift-work and increased rectal cancer risk was found (OR 1.53, 95%CI: 1.31, 1.79, P< 0.00001, I 2 = 35%). In subgroup analyses, night-shift work was associated with a non-statistically significant increased risk of rectal cancer (OR 1.25, 95%CI: 0.47, 3.32, P = 0.66, I 2 = 93%). In contrast, Rotating-shift was associated with a statistically significant increased rectal cancer risk (OR 1.35, 95%CI: 1.10, 1.65, P = 0.004, I 2 = 6%). Sensitivity analysis confirmed the stability of the result. Funnel plot, Egger's test (t = 1.69, P = 0.341), and Begg's test (z = 1.04, P = 0.296) found no publication bias of analysis. Trim and fill analysis on fixed-effect model showed the pooled OR kept stable after adding two “missing” studies (OR 1.403, 95%CI: 1.224, 1.609, P <0.05). Conclusions: The current meta-analysis demonstrates that shift-work is associated with increased rectal cancer risk. However, no association between night-shift work and rectal cancer risk was found. In contrast, association between rotating-shift work and increased rectal cancer risk was found. More original studies on this topic are needed to further explore shift-work impacts on rectal cancer risk.

scholarly journals A prospective study comparing injectable interferon beta-1a (Rebif 22-44), (Avonex 30) and 1b (Betaseron 250) injection site reaction in multiple sclerosis patients

10.19082/7574 ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 7574-7579
Author(s):  
Foziah Jabbar Alshamrani ◽  
Hind Alnajashi ◽  
Fahad Alkhamis ◽  
Ibrahim Alghanimi ◽  
Abdulla Alsulaiman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Prospective Study ◽  
Injection Site ◽  
Interferon Beta ◽  
Injection Site Reaction ◽  
Site Reaction ◽  
Multiple Sclerosis Patients ◽  
A Prospective Study

Abstract 181: A Systematic Review of Interventions to Increase tPA Administration

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Mollie McDermott ◽  
Lesli E Skolarus ◽  
James F Burke
Keyword(s):  
Systematic Review ◽  
Public Education ◽  
Small Sample Size ◽  
Case Reports ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Fixed Effect Model ◽  
Small Sample ◽  
Eligibility Criteria ◽  
Design Elements

Introduction: Rates of tPA administration remain low nationally and globally despite its demonstrated efficacy. We performed a systematic review and meta-analysis of interventions to increase the rate of tPA administration. Methods: We searched PubMed and EMBASE to identify all studies (excluding case reports) published between 1995 and January 8, 2015 documenting interventions to increase the utilization of tPA. We screened each study with pre-specified inclusion and exclusion criteria. Design elements and study data were extracted from eligible studies. The principal summary measure was the percentage change in rate of tPA administration. Fixed and random effects meta-analytic models were built to summarize the effect of intervention compared to control as well as intervention subtypes. Results: Our search yielded 1457 results of which 25 met eligibility criteria. We identified 13 pre-post studies and 11 randomized or quasi-experimental studies. Included studies utilized EMS (n=14), telemedicine (n=6), and public education (n=5). Intervention settings included urban (n=13), rural (n=4), and combined (n=4). In a fixed effect model, tPA administration was significantly higher in the intervention arm across all studies that limited enrollment to ischemic stroke patients (n=14) with a risk ratio (RR) of 1.71. Interventions involving EMS were associated with an increased rate of tPA administration with a RR of 1.51, (95% CI: 1.43-1.59, p<0.0001); promoting public education RR = 2.62, (95% CI: 1.54-4.43, p<0.01); and utilizing telemedicine RR = 2.97, (95% CI: 2.61-3.39, p<0.0001). Conclusions: Interventions to increase tPA use appear to have considerable efficacy. Comparative inferences between intervention types are limited by small sample size and intervention heterogeneity.

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