Indirect Meta-Analysis of Brexpiprazole Versus Aripiprazole in the Acute Treatment of Schizophrenia

Abstract Background: Brexpiprazole and aripiprazole are atypical antipsychotics that act as partial agonists at the dopamine D2 receptor. No head-to-head trial comparing brexpiprazole and aripiprazole in the treatment of schizophrenia is available. Here, we carry out a systematic review and comparison of the efficacy and safety of brexpiprazole and aripiprazole in schizophrenia treatment.Methods: We employed an indirect meta-analysis to determine effect sizes from randomised placebo-controlled trials with brexpiprazole and aripiprazole in the acute treatment of schizophrenia. We compared responder rates, incidences of adverse events and serious adverse events, the number needed to treat (NNT) for response, number needed to harm (NNH) for adverse events or treatment discontinuation, and likelihood to be helped or harmed (LHH) as efficacy and safety indices of the two drugs. Results: Five studies for each drug were included in the analysis. Similar risk differences vs. placebo were observed for responder rates under brexpiprazole (10.2%, p = 0.0015) and aripiprazole (10.3%, p = 0.0003). Higher incidences of adverse events and serious adverse events were seen under aripiprazole compared with brexpiprazole, however, the risk differences were not statistically significant. The NNT for response was 11 for both substances. For brexpiprazole compared with placebo, we did not find an increase of adverse events (NNH = 27, not significant), however, we found an increased number of adverse events for aripiprazole versus placebo (NNH = 17, p < 0.05). For both drugs, benefits were encountered more often than harms, with an LHH for any adverse event of 2.41 for brexpiprazole and 1.56 for aripiprazole, respectively. Conclusions: The likelihood to be helped rather than harmed was greater with brexpiprazole compared to aripiprazole for the total rate of adverse events (ratio of brexpiprazole LHH/aripiprazole LHH = 1.54).

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Efficacy and safety of colchicine in COVID-19: a meta-analysis of randomised controlled trials

RMD Open ◽

10.1136/rmdopen-2021-001746 ◽

2021 ◽

Vol 7 (3) ◽

pp. e001746

Author(s):

Kedar Gautambhai Mehta ◽

Tejas Patel ◽

Paragkumar D Chavda ◽

Parvati Patel

Keyword(s):

Adverse Events ◽

Supportive Care ◽

Meta Analysis ◽

Ventilatory Support ◽

Length Of Hospital Stay ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Quality Of Evidence ◽

Randomised Controlled

BackgroundColchicine, an anti-inflammatory drug is prescribed nowadays for COVID-19. In this meta-analysis, we evaluated efficacy and safety of colchicine in patients with COVID-19.MethodsWe searched databases for randomised controlled studies evaluating efficacy and/or safety of colchicine as compared with supportive care in patients with COVID-19. The efficacy outcomes were mortality, ventilatory support, intensive care unit (ICU) admission and length of hospital stay. The safety outcomes were adverse events, serious adverse events and diarrhoea. A meta-analytical summary was estimated using random effects model through Mantle-Hanzle method. An I2 test was used to assess heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used to assess quality of evidence for each outcome.ResultsOut of 69 full texts assessed, 6 studies (16148 patients with COVID-19) were included in meta-analysis. Patients receiving colchicine did not show significant reduction in mortality (risk difference, RD −0.00 (95% CI −0.01 to 0.01), I2=15%), ventilatory support (risk ratio, RR 0.67 (95% CI 0.38 to 1.21), I2=47%), ICU admission (RR 0.49 (95% CI 0.19 to 1.25), I2=34%), length of hospital stay (mean difference: −1.17 (95% CI −3.02 to 0.67), I2=77%) and serious adverse events (RD −0.01 (95% CI −0.02 to 0.00), I2=28%) than those who received supportive care only. Patients receiving colchicine had higher rates of adverse events (RR 1.58 (95% CI 1.07 to 2.33), I2=81%) and diarrhoea (RR 1.93 (95% CI 1.62 to 2.29), I2=0%) than supportive care treated patients. The GRADE quality of evidence was moderate for most outcomes.ConclusionThe moderate quality evidence suggests no benefit of addition of colchicine to the standard care regimen in patients with COVID-19.

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Efficacy and safety of pharmacological cachexia interventions: systematic review and network meta-analysis

BMJ Supportive & Palliative Care ◽

10.1136/bmjspcare-2020-002601 ◽

2020 ◽

pp. bmjspcare-2020-002601

Author(s):

Manit Saeteaw ◽

Phitjira Sanguanboonyaphong ◽

Jukapun Yoodee ◽

Kaitlyn Craft ◽

Ratree Sawangjit ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Meta Analysis ◽

Total Body Weight ◽

Megestrol Acetate ◽

High Dose ◽

Efficacy And Safety ◽

Pharmacological Interventions ◽

Serious Adverse Events ◽

Significant Difference

AimsRandomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy and safety are not available. We conducted a systematic review and network meta-analysis (NMA) to evaluate the relative efficacy and safety of pharmacological interventions for cachexia.MethodsPubMed, EmBase, Cochrane, and ClinicalTrials.gov were searched for RCTs until October 2019. Key outcomes were total body weight (TBW) improvement, appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias. NMA was performed to estimate weight gain and APP score increase at 8 weeks, presented as mean difference (MD) or standardised MD with 95% CI.Results80 RCTs (10 579 patients) with 12 treatments were included. Majority is patients with cancer (7220). Compared with placebo, corticosteroids, high-dose megestrol acetate combination (Megace_H_Com) (≥400 mg/day), medroxyprogesterone, high-dose megestrol acetate (Megace_H) (≥400 mg/day), ghrelin mimetic and androgen analogues (Androgen) were significantly associated with MD of TBW of 6.45 (95% CI 2.45 to 10.45), 4.29 (95% CI 2.23 to 6.35), 3.18 (95% CI 0.94 to 5.41), 2.66 (95% CI 1.47 to 3.85), 1.73 (95% CI 0.27 to 3.20) and 1.50 (95% CI 0.56 to 2.44) kg. For appetite improvement, Megace_H_Com, Megace_H and Androgen significantly improved standardised APP score, compared with placebo. There is no significant difference in serious adverse events from all interventions compared with placebo.ConclusionsOur findings suggest that several pharmacological interventions have potential to offer benefits in treatment of cachexia especially Megace_H and short-term use corticosteroids. Nonetheless, high-quality comparative studies to compare safety and efficacy are warranted for better management of cachexia.

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Efficacy and Safety of Hydroxychloroquine for Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10112503 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2503

Author(s):

Adrian V. Hernandez ◽

Mi T. Phan ◽

Jonathon Rocco ◽

Vinay Pasupuleti ◽

Joshuan J. Barboza ◽

...

Keyword(s):

Adverse Events ◽

Meta Analysis ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Non Invasive ◽

Non Invasive Ventilation ◽

Inverse Variance ◽

Secondary Outcomes ◽

Meta Analyses

We systematically reviewed the efficacy and safety of hydroxychloroquine as treatment for hospitalized COVID-19. Randomized controlled trials (RCTs) evaluating hydroxychloroquine as treatment for hospitalized COVID-19 patients were searched until 2nd of December 2020. Primary outcomes were all-cause mortality, need of mechanical ventilation, need of non-invasive ventilation, ICU admission and oxygen support at 14 and 30 days. Secondary outcomes were clinical recovery and worsening, discharge, radiological progression of pneumonia, virologic clearance, serious adverse events (SAE) and adverse events. Inverse variance random effects meta-analyses were performed. Thirteen RCTs (n=18,540) were included. Hydroxychloroquine total doses ranged between 2000 and 12,400 mg; treatment durations were from 5 to 16 days and follow up times between 5 and 30 days. Compared to controls, hydroxychloroquine non-significantly increased mortality at 14 days (RR 1.07, 95%CI 0.92–1.25) or 30 days (RR 1.08, 95%CI 1.00–1.16). Hydroxychloroquine did not affect other primary or secondary outcomes, except SAEs that were significantly higher than the control (RR 1.24, 95%CI 1.05–1.46). Eleven RCTs had high or some concerns of bias. Subgroup analyses were consistent with main analyses. Hydroxychloroquine was not efficacious for treating hospitalized COVID-19 patients and caused more severe adverse events. Hydroxychloroquine should not be recommended as treatment for hospitalized COVID-19 patients.

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Efficacy and safety of biologics in the treatment of moderate to severe psoriasis: a comprehensive meta-analysis of randomized controlled trials

Cadernos de Saúde Pública ◽

10.1590/0102-311x00157013 ◽

2013 ◽

Vol 29 (suppl 1) ◽

pp. s17-s31 ◽

Cited By ~ 3

Author(s):

Cassyano Januário Correr ◽

Inajara Rotta ◽

Thaís de Souza Teles ◽

Rangel Ray Godoy ◽

Bruno Salgado Riveros ◽

...

Keyword(s):

Adverse Events ◽

Meta Analysis ◽

Biological Agents ◽

Severe Psoriasis ◽

Biological Agent ◽

Controlled Trials ◽

Efficacy And Safety ◽

Short Term ◽

Serious Adverse Events

We conducted a systematic review and metaanalysis of randomized placebo-controlled trials in moderate-to-severe psoriasis treated with biological agents, with a follow-up of 10-14 weeks. Overall, 41 studies, with mean Jadad score of 4.4, and 15,586 patients were included. For the efficacy outcomes PASI 50, 75 and 90 our findings are not conclusive to point what biological agent has the greatest response in short term follow-up. There were no statistical differences between placebo and biologics for the occurrence of infections and serious adverse events. Ustekinumab 45mg showed lower withdrawal due to adverse events compared with the placebo. Based on data available up to now, it is not possible to determine which biological agent is the best for PASI 50, 75 or 90 after 10-14 weeks of treatment. At the same follow-up, overall safety seems to be the same for all biological agents and Ustekinumab 45mg the most well tolerated drug. To better understand efficacy and safety, indirect meta-analysis comparing drug-to-drug is required since randomized placebo-controlled trials may not be feasible.

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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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Prevention of Succinylcholine-induced Fasciculation and Myalgia

Anesthesiology ◽

10.1097/00000542-200510000-00027 ◽

2005 ◽

Vol 103 (4) ◽

pp. 877-884 ◽

Cited By ~ 55

Author(s):

Jan-Uwe Schreiber ◽

Christopher Lysakowski ◽

Thomas Fuchs-Buder ◽

Martin R. Tramèr

Keyword(s):

Meta Analysis ◽

Nonsteroidal Antiinflammatory Drugs ◽

Muscle Relaxants ◽

Number Needed To Treat ◽

Antiinflammatory Drugs ◽

Blurred Vision ◽

Serious Adverse Events ◽

Risk Benefit Assessment ◽

Dose Dependent ◽

Number Needed To Harm

Fifty-two randomized trials (5,318 patients) were included in this meta-analysis. In controls, the incidence of fasciculation was 95%, and the incidence of myalgia at 24 h was 50%. Nondepolarizing muscle relaxants, lidocaine, or magnesium prevented fasciculation (number needed to treat, 1.2-2.5). Best prevention of myalgia was with nonsteroidal antiinflammatory drugs (number needed to treat, 2.5) and with rocuronium or lidocaine (number needed to treat, 3). There was a dose-dependent risk of blurred vision, diplopia, voice disorders, and difficulty in breathing and swallowing (number needed to harm, < 3.5) with muscle relaxants. There was evidence of less myalgia with 1.5 mg/kg succinylcholine (compared with 1 mg/kg). Opioids had no impact. Succinylcholine-induced fasciculation may best be prevented with muscle relaxants, lidocaine, or magnesium. Myalgia may best be prevented with muscle relaxants, lidocaine, or nonsteroidal antiinflammatory drugs. The risk of potentially serious adverse events with muscle relaxants is not negligible. Data that allow for a risk-benefit assessment are lacking for other drugs.

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A Meta-Analysis Comparing the Efficacy and Safety of Peramivir with Other Neuraminidase Inhibitors for Influenza Treatment

Medicina ◽

10.3390/medicina56020063 ◽

2020 ◽

Vol 56 (2) ◽

pp. 63

Author(s):

Jui-Yi Chen ◽

Shih-Kai Wei ◽

Chih-Cheng Lai ◽

Teng-Song Weng ◽

Hsin-Hua Wang

Keyword(s):

Adverse Events ◽

Primary Outcome ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Neuraminidase Inhibitors ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Effect Model ◽

The Difference

Background and Objectives: This meta-analysis compared the efficacy and safety of peramivir compared to other neuraminidase inhibitors (NAIs). Materials and Methods: Data from PubMed, Embase, and Cochrane databases and ClinicalTrials.gov were searched until January 2019. Randomized controlled trials (RCTs) and observational studies (OSs) comparing peramivir with other NAIs for treating influenza were included. The Grading of Recommendations, Assessments, Development, and Evaluations (GRADE) system was used to judge the overall certainty of evidence; the result was moderate. The primary outcome was time to alleviation of symptoms. Twelve articles involving 2681 patients were included in this meta-analysis. We used a random-effect model to pool the effect size, which is expressed as the difference in means (MD), risk ratio (RR), and 95% confidence interval (CI). Results: Overall, peramivir was superior to other NAIs (MD = −11.214 hours, 95% CI: −19.119 to −3.310). The incidence of adverse events (RR = 1.023, 95% CI: 0.717 to 1.460) and serious adverse events (RR = 1.068, 95% CI: 0.702 to 1.625) in the peramivir group was similar to those in the oseltamivir group. In addition, peramivir had higher efficacy than each NAI alone. Conclusion: In conclusion, the efficacy of peramivir might be higher than that of other NAIs, and this agent is tolerated as well as other NAIs.

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Efficacy and Safety of Antigen-specific Immunotherapy in the Treatment of Patients with Non-small-cell Lung Cancer: A Systematic Review and Meta-analysis

Current Cancer Drug Targets ◽

10.2174/1568009618666180430124738 ◽

2019 ◽

Vol 19 (3) ◽

pp. 199-209 ◽

Cited By ~ 1

Author(s):

Bing-Di Yan ◽

Xiao-Feng Cong ◽

Sha-Sha Zhao ◽

Meng Ren ◽

Zi-Ling Liu ◽

...

Keyword(s):

Lung Cancer ◽

Systematic Review ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Specific Immunotherapy ◽

Meta Analysis ◽

Small Cell ◽

Efficacy And Safety ◽

Small Cell Lung

Background and Objective: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). Methods: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. Results: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). Conclusion: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.

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Is it Worth CANVASing for CREDENCE? A Benefit-risk Analysis

Current Diabetes Reviews ◽

10.2174/1573399815666191025094733 ◽

2020 ◽

Vol 16 (5) ◽

pp. 509-514

Author(s):

Binayak Sinha ◽

Samit Ghosal

Keyword(s):

Adverse Events ◽

Fungal Infections ◽

Absolute Risk ◽

Pooled Analysis ◽

Major Adverse Cardiovascular Events ◽

Number Needed To Treat ◽

Pooled Data ◽

The Individual ◽

Fracture Risks ◽

Number Needed To Harm

Background and Aims: A number of significant positive and negative signals emerged from the CANVAS Program and CREDENCE trial with the use of canagliflozin. These signals are confusing. A Likelihood of being Helped of Harmed (LHH) analysis was conducted to determine the risk, benefit ratio associated with canagliflozin use and address the signals as a continuum. Materials &Methods: LHH was calculated from the number needed to treat (NNT) and number needed to harm (NNH) available from the absolute risk reductions reported with the outcomes of interest, in these two trials. Results: In the CANVAS Program, LHH for major adverse cardiovascular events (MACE) points at a significant benefit with canagliflozin use in comparison to amputation (1.65), fractures (1.65) and euglycaemic diabetic ketoacidosis (euDKA) (16.67) risks. Only genital fungal infections were significant more in both sexes (0.21-M and 0.1-F) when LHH was matched against the positive outcomes. In contrast, the hHF benefits were outweighed by amputation (0.95) and fracture risks (0.95). : In CREDENCE trial, the LHH for Primary composite, Renal composite and MACE, all supported the benefits in comparison to any adverse events encountered in the trial. : The LHH from pooled data (CANVAS Program and CREDENCE trial) was in favour of all the benefits (hHF and renal composites) except for MACE matched against amputation (0.66). Conclusion: The outcome benefits were in favour of canagliflozin in comparison to all reported adverse events, when hHF and renal composite were under consideration, in both the individual and pooled LHH analysis. However, the MACE benefits were overwhelmed by amputation risk in the pooled analysis.

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Comparative efficacy and safety of different regimens of ranibizumab for neovascular age-related macular degeneration: a network meta-analysis of randomised controlled trials

BMJ Open ◽

10.1136/bmjopen-2020-040906 ◽

2021 ◽

Vol 11 (2) ◽

pp. e040906

Author(s):

Xinyu Zhao ◽

Lihui Meng ◽

Youxin Chen

Keyword(s):

Adverse Events ◽

Macular Degeneration ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Age Related Macular Degeneration ◽

Controlled Trials ◽

Cochrane Central Register ◽

Efficacy And Safety ◽

Age Related ◽

Randomised Controlled

ObjectiveTo give a comprehensive efficacy and safety ranking of different therapeutic regimens of ranibizumab for neovascular age-related macular degeneration (nAMD).DesignA systematic review and network meta-analysis.MethodsThe PubMed, Embase, Cochrane Central Register of Controlled Trials, and other clinical trial registries were searched up to 1 October 2019 to identify related randomised controlled trials (RCT) of different regimens of ranibizumab for nAMD. The primary efficacy outcome was the changes of best-corrected visual acuity (BCVA) at 1 year, the primary safety outcome was the incidence of severe ocular adverse events. Secondary outcomes such as changes of central retinal thickness (CRT) were evaluated. We estimated the standardised mean difference (SMD), ORs, 95% CIs, the surface under the cumulative ranking curves and the mean ranks for each outcome using network meta-analyses with random effects by Stata 14.0.ResultsWe identified 26 RCTs involving 10 821 patients with nAMD randomly assigned to 21 different therapeutic regimens of ranibizumab or sham treatment. Ranibizumab 0.5 mg (treat and extend, T&E) is most effective in terms of changes of BCVA (letters, SMD=21.41, 95% CI 19.86 to 22.95) and three or more lines of BCVA improvement (OR=2.83, 95% CI 1.27 to 4.38). However, it could not significantly reduce retreatment times compared with monthly injection (SMD=−0.94, 95% CI −2.26 to 0.39). Ranibizumab 0.5 mg (3+pro re nata)+non-steroidal anti-inflammatory drugs (NSAIDs) is most effective in reducing CRT and port delivery system of ranibizumab (100 mg/mL) could reduce the number of retreatment most significantly. All regimes have no more risk of severe ocular complications (including vitreous haemorrhage, rhegmatogenous retinal detachment, endophthalmitis, retinal tear and retinal pigment epithelium tear) or cardiocerebral vascular complications.ConclusionsRanibizumab 0.5 mg (T&E) is most effective in improving the visual outcome. The administration of topical NSAIDs could achieve additional efficacy in CRT reduction and visual improvement. Both interventions had acceptable risks of adverse events.

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