Erenumab safety and efficacy in migraine: a systematic review and meta-analysis of randomized clinical trials

Abstract Background: Erenumab is a new medicine approved lately in the US for the preventive treatment of migraine in adults. We aimed to conduct a meta-analysis to evaluate the efficacy and safety of erenumab in patients with migraine. Methods: The electronic database composed of PubMed, Embase and Cochrane library was independently retrieved by two reviewers. Only randomized controlled trials (RCTs) that compared between placebo and erenumab were included in this analysis. mean differences (MDs) and Pooled risk ratios (RRs) as well as their corresponding 95% confidence intervals (CIs) were calculated for continuous and dichotomous data, respectively. Results: Total five RCTs representing 2928 patients were included. Pooled analysis showed significant reductions of the 50% reduction(RR 1.55; 95%CI,1.35 to 1.77; P < 0.00001; I²=49%). In addition, the mean monthly migraine days (MMMDs) from baseline in the erenumab group compared with placebo (MD -1.32, 95%CI, -1.73 to -0.91; P < 0.00001; I²=100%) and migraine-specific medication days (MSMDs) from baseline (MD -1.41; 95%CI, -1.80 to -1.02; P＜0.00001; I²=100%) were significantly increased for the erenumab group compared with placebo. Furthermore, there was significant reduction of MSMDs from baseline in 140mg erenumab group compared to 70mg (MD=0.55; 95%CI:0.54 to 0.66; Z =10.95; P<0.00001; I²=90% ). Finally, there were no significant differences between erenumab group and placebo of any adverse events and serious adverse events. Conclusion: Among patients with migraine, both 70mg and 140mg erenumab are associated with reduction of MMMDs, MSMDs from baseline and increased rate of 50% reduction without increased risk of any adverse events and serious adverse events.

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Different Doses of Erenumab for Preventive Treatment of Episodic Migraine: A Systematic Review and Network Meta-Analysis

10.21203/rs.3.rs-87163/v1 ◽

2020 ◽

Author(s):

Yanbo Yang ◽

Mingjia Chen ◽

Zilan Wang ◽

Yue Sun ◽

Fan Jiang ◽

...

Keyword(s):

Randomized Clinical Trials ◽

Response Rate ◽

Meta Analysis ◽

Preventive Treatment ◽

Episodic Migraine ◽

Cochrane Library ◽

Migraine Treatment ◽

Increased Risk ◽

Significant Difference ◽

Safety Outcomes

Abstract Background Erenumab is a novel monoclonal calcitonin gene–related peptide receptor antibody that is used for the preventive treatment of migraine.Objectives To evaluate overall safety and efficacy and dose-response relationship of erenumab in patients with episodic migraine and patients with prior migraine treatment failures.Methods We searched randomized clinical trials on PUBMED, EMBASE database, and Cochrane Library database. A pair-wise meta-analysis and Bayesian network analysis were performed.Results For efficacy outcomes, the network meta-analysis suggests that compared with erenumab 70 mg, participants received erenumab 140 mg reported significantly decreased MSMD and increased 50% response rate, and erenumab was most likely to be ranked first for MMD, MSMD and 50% response rate. For safety outcomes, the network meta-analysis has found no significant difference between the 70 mg group and the 140 mg group measured by AE and SAE. For patients with ≥2 treatment failures, 140mg erenumab group, patients with ≥2 treatment failures reported significantly reduced MMD and MSMD, increased 50%, and 75% response rate, compared with placebo. For safety outcomes, no significant difference was found between 140 mg erenumab group and the placebo group.Conclusion Erenumab was effective in patients with episodic migraine. 140 mg erenumab was associated with better efficacy outcomes without increased risk for developing adverse events compared with 70 mg erenumab, and 140 mg erenumab was effective in patients with prior migraine treatment failures.Registration number: CRD42020198985

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Role of Statins in the Primary Prevention of Atherosclerotic Cardiovascular Disease and Mortality in the Population with Mean Cholesterol in the Near-Optimal to Borderline High Range: A Systematic Review and Meta-Analysis

10.1101/2020.10.02.20205849 ◽

2020 ◽

Author(s):

Bishnu M. Singh ◽

Hari K. Lamichhane ◽

Sanjay S. Srivatsa ◽

Prabhat Adhikari ◽

Bikash J. Kshetri ◽

...

Keyword(s):

Cardiovascular Disease ◽

Adverse Events ◽

Statin Therapy ◽

Meta Analysis ◽

Density Lipoprotein ◽

Cochrane Library ◽

Atherosclerotic Cardiovascular Disease ◽

Serious Adverse Events ◽

Increased Risk ◽

High Range

AbstractObjectiveThe objective of this meta-analysis was to analyze the benefits and harms of treating the population with statins in those having mean low-density lipoprotein cholesterol (LDL-C) in the near-optimal (100 to 129 mg/dl) to borderline high (130 to 159 mg/dl) range and free of cardiovascular disease (CVD). Methods: We searched PubMed, PubMed Central, Cochrane Library, and Google Scholar databases for randomized controlled trials (RCTs) published between 1994 and July 2020. We included RCTs with greater than 90% of participants free of CVD. Two reviewers independently screened the articles using the Covidence software, assessed the methodological quality using the risk of bias 2 tool, and analyzed the data using the RevMan 5.4 software. Results: Eleven trials were included. Statin therapy was associated with a decreased risk of myocardial infarction (RR=0.56, 95% CI: 0.47 to 0.67), major cerebrovascular events (RR=0.78, 95% CI: 0.63 to 0.96), major coronary events (RR=0.67, 95% CI: 0.57 to 0.80), composite cardiovascular outcome (RR=0.71, 95% CI: 0.62 to 0.82), revascularizations (RR=0.65, 95% CI: 0.57 to 0.74), angina (RR=0.76, 95% CI: 0.63 to 0.92) and hospitalization for cardiovascular causes (RR=0.74, 95% CI: 0.64 to 0.86). There was no benefit associated with statin therapy for cardiovascular mortality and coronary heart disease mortality. All-cause mortality benefit with statin therapy was seen in the population with diabetes and increased risk of CVD. Statin therapy was associated with no significant increased risk of myalgia, creatine kinase elevation, rhabdomyolysis, myopathy, incidence of any cancer, incidence of diabetes, withdrawal of the drug due to adverse events, serious adverse events, fatal cancer, and liver enzyme abnormalities. Conclusion: Statin therapy was associated with a reduced risk of cardiovascular disease and procedures without increased risk of harm in populations with mean LDL-C near-optimal to the borderline high range without prior atherosclerotic cardiovascular disease.

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The safety of MSC therapy over the past 15 years: a meta-analysis

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02609-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yang Wang ◽

Hanxiao Yi ◽

Yancheng Song

Keyword(s):

Adverse Events ◽

Randomized Clinical Trials ◽

Web Of Science ◽

Meta Analysis ◽

Pooled Analysis ◽

High Quality ◽

Serious Adverse Events ◽

The Past ◽

Clinical Investigations ◽

Different Populations

Abstract Background Despite increasing clinical investigations emphasizing the safety of mesenchymal stem cell (MSC) therapy in different populations with different diseases, no article has recently reviewed the adverse events in all populations. Aim To evaluate the safety of MSC therapy in all populations receiving MSC therapy and explore the potential heterogeneities influencing the clinical application of MSCs. Methods The PubMed, Embase, Web of Science and Scopus databases were searched from onset until 1 March 2021. Results All adverse events are displayed as odds ratios (ORs) and 95% CIs (confidential intervals). In total, 62 randomized clinical trials were included that enrolled 3546 participants diagnosed with various diseases (approximately 20 types of diseases) treated with intravenous or local implantation versus placebo or no treatment. All studies were of high quality, and neither serious publication bias nor serious adverse events (such as death and infection) were discovered across the included studies. The pooled analysis demonstrated that MSC administration was closely associated with transient fever (OR, 3.65, 95% CI 2.05–6.49, p < 0.01), administration site adverse events (OR, 1.98, 95% CI 1.01–3.87, p = 0.05), constipation (OR, 2.45, 95% CI 1.01–5.97, p = 0.05), fatigue (OR, 2.99, 95% CI 1.06–8.44, p = 0.04) and sleeplessness (OR, 5.90, 95% CI 1.04–33.47, p = 0.05). Interestingly, MSC administration trended towards lowering rather than boosting the incidence rate of arrhythmia (OR, 0.62, 95% CI 0.36–1.07, p = 0.09). Conclusions Conclusively, MSC administration was safe in different populations compared with other placebo modalities.

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Optimal treatment strategy of fremanezumab in migraine prevention: a systematic review with network meta-analysis of randomized clinical trials

Scientific Reports ◽

10.1038/s41598-020-75602-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

I-Hsin Huang ◽

Po-Chien Wu ◽

Ya-Han Lee ◽

Yi-No Kang

Keyword(s):

Adverse Events ◽

Treatment Strategy ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Reduction Rate ◽

High Dose ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Mean Differences

Abstract Identifying the optimal fremanezumab treatment strategy is crucial in treating patients with migraines. The optimal strategy was investigated by assessing the cumulative 50% reduction rate (50%CRR), cumulative 75% reduction rate (75%CRR), reduction in the number of migraine days, treatment-related adverse events, and serious adverse events in patients treated with fremanezumab 225 mg monthly (225 mg), 675 mg monthly (675 mg), 900 mg monthly (900 mg), a single high dose of 675 mg (S675mg), 675 mg at baseline with 225 mg monthly (675/225 mg), and placebo. Biomedical databases were searched for randomized controlled trials on this topic, and data were individually extracted. Risk ratios and mean differences were used to present the pooled results. The surface under the cumulative ranking curve (SUCRA) was used to determine the effects of the medication strategies of fremanezumab. Five trials (n = 3404) were used to form a six-node network meta-analysis. All fremanezumab medication strategies displayed significantly higher cumulative 50% reduction rates than the placebo. The SUCRA revealed that treatment with 675 mg yielded the highest 50%CRR value (mean rank = 2.5). S675 mg was the only treatment with significantly higher 75%CRR reduction rate than placebo, whereas the SUCRA for 225 mg displayed the highest mean rank (2.2). Moreover, 225 mg (mean rank = 2.2) and S675 mg (mean rank = 2.2) presented lower probabilities of serious adverse events. Collectively, S675mg and 225 mg exhibited the optimal balance between efficacy and safety within three months. Long-term efficacy and safety remain unclear, and future studies should further evaluate the long-term outcomes.

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Comparative Effectiveness and Safety of Seven Qi-Tonifying Chinese Medicine Injections for AECOPD Patients: A Systematic Review and Network Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6517515 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Xueyi Deng ◽

Fuqin Kang ◽

Xueyin Chen ◽

Jiaqi Lai ◽

Xuanchen Guan ◽

...

Keyword(s):

Clinical Trials ◽

Chinese Medicine ◽

Adverse Events ◽

Comparative Effectiveness ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Small Sample ◽

Cochrane Library ◽

Chronic Obstructive ◽

Serious Adverse Events

Introduction. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) imposes a large burden on economy and society worldwide. In addition to western medicine, multiple kinds of qi-tonifying Chinese medicine injections have been widely used in China as adjunctive treatments. Previous small-sample clinical trials have proven their efficacy in the treatment of AECOPD. However, data on comparative effectiveness and safety of qi-tonifying injections are limited. We conducted this network meta-analysis to compare the efficacy and safety of 7 commonly used qi-tonifying injections in patients with AECOPD. Methods. Literature search was conducted through electronic databases, including PubMed, the Cochrane Library, EMBASE, CINAHL, AMED, CBM, CNKI, Wanfang database, and VIP database. Randomized clinical trials (RCTs) exploring the efficacy of any of these 7 qi-tonifying injections were included. The primary outcome was lung function (FEV1 and FVC). R 4.0.0 and STATA 12.0 were adopted to perform the network meta-analysis using Bayesian statistics. Results. A total of 36 RCTs involving 2657 participants were included. The results of network meta-analyses indicated that Chuankezhi injection (CKZ) combined with routine treatment (RT) was superior to other qi-tonifying injections combined with RT in terms of FEV1 improvement (MD = 0.63, 95% CI: 0.22, 1.04). For improving FVC, Shengmai injection (SGM) combined with RT showed the greatest therapeutic effect (MD = 0.38, 95% CI: 0.13, 0.61). Moreover, SGM combined with RT revealed the best estimates for response rate (MD = 4.00, 95% CI: 1.34, 13.63). The main adverse events in this study were gastrointestinal reactions and injection site reactions. No serious adverse events were reported. Conclusion. In this network meta-analysis, SGM and CKZ were potential best adjunctive therapies in the treatment of AECOPD.

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Optimal dose of erenumab for preventive treatment of episodic migraine: a systematic review and meta-analysis

Current Neuropharmacology ◽

10.2174/1570159x19666210823104916 ◽

2021 ◽

Vol 19 ◽

Author(s):

Yanbo Yang ◽

Mingjia Chen ◽

Da Wu ◽

Yue Sun ◽

Fan Jiang ◽

...

Keyword(s):

Adverse Events ◽

Response Rate ◽

Meta Analysis ◽

Preventive Treatment ◽

Episodic Migraine ◽

Cochrane Library ◽

Migraine Treatment ◽

Increased Risk ◽

Significant Difference ◽

Safety Outcomes

Background : Erenumab is a novel monoclonal calcitonin gene–related peptide receptor antibody that is used for the preventive treatment of migraine. Objectives : To evaluate overall safety and efficacy and dose-response relationship of erenumab in patients with episodic migraine and patients with prior migraine treatment failures. Methods : We searched randomized clinical trials on PUBMED, EMBASE database, and Cochrane Library database. A pair-wise meta-analysis and Bayesian network analysis were performed. Results : For efficacy outcomes, the network meta-analysis suggests that compared with erenumab 70 mg, participants received erenumab 140 mg reported significantly decreased monthly acute migraine-specific medication days(MSMD) and increased 50% response rate, and erenumab was most likely to be ranked first for monthly migraine days(MMD), MSMD and 50% response rate. For safety outcomes, the network meta-analysis has found no significant difference between the 70 mg group and the 140 mg group measured by adverse events and serious adverse events. For patients with ≥2 treatment failures, 140mg erenumab group, patients with ≥2 treatment failures reported significantly reduced MMD and MSMD, increased 50%, and 75% response rate, compared with placebo. For safety outcomes, no significant difference was found between 140 mg erenumab group and the placebo group. Conclusion : Erenumab was effective in patients with episodic migraine. 140 mg erenumab was associated with better efficacy outcomes without increased risk for developing adverse events compared with 70 mg erenumab, and 140 mg erenumab was effective in patients with prior migraine treatment failures.

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Role of Statins in the Primary Prevention of Atherosclerotic Cardiovascular Disease and Mortality in the Population with Mean Cholesterol in the Near-Optimal to Borderline High Range: A Systematic Review and Meta-Analysis

Advances in Preventive Medicine ◽

10.1155/2020/6617905 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Bishnu M. Singh ◽

Hari K. Lamichhane ◽

Sanjay S. Srivatsa ◽

Prabhat Adhikari ◽

Bikash J. Kshetri ◽

...

Keyword(s):

Cardiovascular Disease ◽

Adverse Events ◽

Statin Therapy ◽

Meta Analysis ◽

Density Lipoprotein ◽

Cochrane Library ◽

Atherosclerotic Cardiovascular Disease ◽

Serious Adverse Events ◽

Increased Risk ◽

High Range

Objective. The objective of this meta-analysis was to analyze the benefits and harms of treating the population with statins in those having mean low-density lipoprotein cholesterol (LDL-C) in the near-optimal (100 to 129 mg/dl) to borderline high (130 to 159 mg/dl) range and free of cardiovascular disease (CVD). Methods. We searched PubMed, PubMed Central, Cochrane Library, and Google Scholar databases for randomized controlled trials (RCTs) published between 1994 and July 2020. We included RCTs with greater than 90% of participants free of CVD. Two reviewers independently screened the articles using the Covidence software, assessed the methodological quality using the risk of bias 2 tool, and analyzed the data using the RevMan 5.4 software. Results. Eleven trials were included. Statin therapy was associated with a decreased risk of myocardial infarction (RR = 0.56, 95% CI: 0.47 to 0.67), major cerebrovascular events (RR = 0.78, 95% CI: 0.63 to 0.96), major coronary events (RR = 0.67, 95% CI: 0.57 to 0.80), composite cardiovascular outcome (RR = 0.71, 95% CI: 0.62 to 0.82), revascularizations (RR = 0.65, 95% CI: 0.57 to 0.74), angina (RR = 0.76, 95% CI: 0.63 to 0.92), and hospitalization for cardiovascular causes (RR = 0.74, 95% CI: 0.64 to 0.86). There was no benefit associated with statin therapy for cardiovascular mortality and coronary heart disease mortality. All-cause mortality benefit with statin therapy was seen in the population with diabetes and increased risk of CVD. Statin therapy was associated with no significant increased risk of myalgia, creatine kinase elevation, rhabdomyolysis, myopathy, incidence of any cancer, incidence of diabetes, withdrawal of the drug due to adverse events, serious adverse events, fatal cancer, and liver enzyme abnormalities. Conclusion. Statin therapy was associated with a reduced risk of cardiovascular disease and procedures without increased risk of harm in populations with mean LDL-C in the near-optimal to the borderline high range and without prior atherosclerotic cardiovascular disease.

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Safety of IL-23/17 Antagonists in Patients with Psoriasis or Other Immune-mediated Inflammatory Diseases: A Systematic Meta-Analysis.

10.21203/rs.3.rs-49001/v1 ◽

2020 ◽

Author(s):

Siying Li ◽

Suhan Zhang ◽

Guishao Tang ◽

Ruifang Wu ◽

Yuwen Su

Keyword(s):

Adverse Events ◽

Randomized Clinical Trials ◽

Inflammatory Diseases ◽

Meta Analysis ◽

Cardiovascular Disorder ◽

Control Group ◽

Placebo Control ◽

Serious Adverse Events ◽

Immune Mediated ◽

Increased Risk

Abstract Background: The IL-23/17 axis plays central role in the pathogenesis of several immune-mediated inflammatory diseases (IMIDs). IL-23/17 antagonists showed significant improvement in the treatment for psoriasis and other IMIDs, including psoriasis(PSO), psoriatic arthritis(PsA), rheumatoid arthritis(RA) and ankylosing spondylitis(AS).Objective: To assess the safety of IL-23/17 antagonists therapy on patients with psoriasis and other IMIDs.Methods: Pooled analysis from thirty-nine placebo-controlled randomized clinical trials (RCTs) of IL-23/17 axis antagonists for IMIDs. Incidences of adverse events (AEs), serious adverse events (SAEs) and AEs of interest were applied to evaluate the safety profile.Result: A Total of 15967 patients were exposed to IL-23/17 axis antagonists. The proportions of patients suffered at least one AE in antagonists group and placebo-control group are 67.5% and 51.1% respectively. Incidence of SAE was increased in patients treated with IL-23/17 axis antagonists compared to patients given placebo (relative risk 2.03; 95% CI, 1.62, 2.56). Incidence of AEs of interest were all increased in patients treated with IL-23/17 axis antagonists compared to patients given placebo.Conclusion: In this analysis, we found increased risk of AEs, SAEs, nervous system disorder, cardiovascular disorder and hypertension among patients with IMIDs treated with IL-23/17 axis antagonists.

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Effect of antihypertensive drugs on cognition and behavioral symptoms of patients with Alzheimer’s disease: A meta-analysis

Current Pharmaceutical Biotechnology ◽

10.2174/1386207323666201211101720 ◽

2020 ◽

Vol 21 ◽

Author(s):

Roja Rahimi ◽

Shekoufeh Nikfar ◽

Masoud Sadeghi ◽

Mohammad Abdollahi ◽

Reza Heidary Moghaddam ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Randomized Clinical Trials ◽

Antihypertensive Drugs ◽

Meta Analysis ◽

Behavioral Symptoms ◽

Cochrane Library ◽

Mean Differences ◽

Global Impression Of Change ◽

State Examination

Background: It has been found that there is a link between hypertension and elevated risk of Alzheimer’s disease (AD). Herein, a meta-analysis based on randomized clinical trials (RCTs) was used to assess the effect of antihypertensive drugs on cognition and behavioral symptoms of AD patients. Method: The three databases – PubMed/Medline, Scopus, and Cochrane Library- were searched up to March 2020. The quality of the studies included in the meta-analysis was evaluated by the Jadad score. Clinical Global Impression of Change (CGIC) included in two studies, Mini-Mental State Examination (MMSE) included in three studies, and Neuropsychiatric Inventory (NPI) in three studies were the main outcomes in this systematic review. Results: Out of 1506 studies retrieved in the databases, 5 RCTs included and analyzed in the meta-analysis. The pooled mean differences of CGIC, MMSE, and NPI in patients with AD receiving antihypertensive drugs compared to placebo was -1.76 with (95% CI = -2.66 to -0.86; P=0.0001), 0.74 (95% CI = 0.20 to 1.28; P= 0.007), and -9.49 (95% CI = -19.76 to 0.79; P = 0.07), respectively. Conclusion: The findings of the present meta-analysis show that antihypertensive drugs may improve cognition and behavioral symptoms of patients with AD. However, more well-designed RCTs with similar drugs are needed to achieve more conclusive results.

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