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Comparative Efficacy and Safety of Therapies in IgA Nephropathy: A Network Meta-analysis of Randomized Controlled Trials.

ABSTRACT: The present study aims to compare the relative efficacy and safety of different interventions for IgA nephropathy (IgAN) with proteinuria more than 1 g/d by using network meta-analysis. We searched PubMed, Embase, and the Cochrane Library for studies compared the rate of clinical remission and/or end-stage renal disease (ESRD) and/or serious adverse events in IgAN patients with proteinuria (>1 g/d). The surface under the cumulative ranking area (SUCRA) was calculated to rank the interventions. A total of 21 randomized controlled trials with 1822 participants were included for the comparisons of 7 interventions. The rank of the most effective treatments to induce clinical remission was renin-angiotensin system inhibitors (RASi) plus urokinase, steroid plus tonsillectomy, and RASi plus steroid with a SUCRA of 0.912, 0.710, and 0.583, respectively. As for the prevention of ESRD or doubling of serum creatinine, RASi plus steroid (SUCRA 0.012) was the most effective, followed by RASi (SUCRA 0.282) and steroid (SUCRA 0.494), leaving mycophenolate mofetil as the least effective (SUCRA 0.644). There was no statistical difference among all interventions in the occurrence of serious adverse events. The current network meta-analysis demonstrated for the first time that RASi plus steroid is probably the best therapeutic choice, not only for reducing proteinuria but also for maintaining long-term renal protection.

SUBMITTER: Yang P

PROVIDER: S-EPMC6035132 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Comparative Efficacy and Safety of Therapies in IgA Nephropathy: A Network Meta-analysis of Randomized Controlled Trials.

Yang Pingping P Zou Honghong H Xiao Bufan B Xu Gaosi G

Kidney international reports 20180316 4

The present study aims to compare the relative efficacy and safety of different interventions for IgA nephropathy (IgAN) with proteinuria more than 1 g/d by using network meta-analysis. We searched PubMed, Embase, and the Cochrane Library for studies compared the rate of clinical remission and/or end-stage renal disease (ESRD) and/or serious adverse events in IgAN patients with proteinuria (>1 g/d). The surface under the cumulative ranking area (SUCRA) was calculated to rank the interventions. A ...[more]

PMID: 29989013

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Project description:Background: The efficacy and safety of immunosuppressive monotherapy agents were evaluated for immunoglobulin A nephropathy (IgAN) using a network meta-analysis approach. Methods: Randomized controlled trials (RCTs) published prior to October 1, 2019, using immunosuppressive agents for treating IgAN, were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science databases. Relative risks (RRs) or standard mean differences with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes were clinical remission, end-stage renal disease (ESRD), and serious adverse events (SAEs). The secondary outcomes were urinary protein excretion and serum creatinine. Results: Twenty-five RCTs with 2,005 participants were deemed eligible. Six medications were evaluated: corticosteroids, mycophenolate mofetil (MMF), tacrolimus (TAC), cyclosporine, leflunomide, and hydroxychloroquine (HCQ). Steroids (RR 1.50, 95% CI 1.17-1.93), MMF (RR 2.05, 95% CI 1.15-3.65), TAC (RR 3.67, 95% CI 1.06-12.63), and HCQ (RR 3.25, 95% CI 1.05-10.09) significantly improved clinical remission rates compared to supportive care alone. Only steroids reduced the risk of ESRD (RR 0.35, 95% CI 0.12-0.98); however, there were significantly more SAEs than in the control group (RR 2.90, 95% CI 1.37-6.13). No significantly different effects in serum creatinine levels were found among the therapies. MMF showed no significant improvement in remission when excluding studies with a follow-up of fewer than 2 years in the sensitivity analysis (RR 1.41, 95% CI 0.40-4.92). The effect of TAC in the decrease of proteinuria was reversed after discontinuing medication for 3 months; the long-term effects of HCQ could not be evaluated due to the short follow-up duration. Conclusion: Corticosteroids might induce remission and increase renal survival in IgAN; however, adverse reactions should be taken into consideration. MMF, TAC, and HCQ might improve the remission of proteinuria when treating IgAN, but showed no superiority compared to steroids, and the long-term effects require further study.

Project description:Background and objectivesElevated BP is an important risk factor for cardiovascular disease, with a prevalence of over 80% in patients undergoing maintenance dialysis. We assessed the comparative BP-lowering efficacy and the safety of BP-lowering drugs in patients undergoing maintenance dialysis.Design, settings, participants, & measurementsWe performed a frequentist random effects network meta-analysis of randomized, controlled trials evaluating BP-lowering agents in adult patients undergoing maintenance dialysis. Electronic databases (CENTRAL, MEDLINE, and Embase) were systematically searched (up to August 2018) for relevant trials. The main outcome was systolic BP reduction.ResultsForty trials (4283 participants) met our inclusion criteria. Angiotensin-converting enzyme inhibitors, β-blockers, calcium-channel blockers, and aldosterone antagonists lowered systolic BP to a greater extent than placebo, with effect sizes ranging from -10.8 mm Hg (95% confidence interval, -14.8 to -6.7 mm Hg) for the aldosterone antagonists to -4.3 mm Hg (95% confidence interval, -7.2 to -1.5 mm Hg) for angiotensin-converting enzyme inhibitors. Aldosterone antagonists and β-blockers were superior to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium-channel blockers, and renin inhibitors at lowering systolic BP. Compared with angiotensin-converting enzyme inhibitors, aldosterone antagonists and β-blockers lowered systolic BP by 6.4 mm Hg (95% confidence interval, -11.4 to -1.4 mm Hg) and 4.4 mm Hg (95% confidence interval, -7.4 to -1.3 mm Hg), respectively. Systolic BP reduction was not different with angiotensin receptor blockers, α-blockers, and calcium-channel blockers compared with angiotensin-converting enzyme inhibitors. Renin inhibitors were less effective. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists incurred risks of drug discontinuation due to adverse events and hypotension.ConclusionsBP-lowering agents significantly reduced systolic BP in patients undergoing maintenance dialysis. β-Blockers and aldosterone antagonists may confer larger reductions, although treatment with aldosterone antagonists may be limited by adverse events.

Project description:BackgroundMany of these therapies have been compared against placebos, but have not been directly compared against each other. To evaluate the efficacy and safety of several commonly used drugs for AIS directly or indirectly.MethodsA systematic literature review was performed to identify randomized controlled trials (RCTs) published prior to April 2013 for AIS therapies. The primary outcome measures were the National Institutes of Health Stroke Scale (NIHSS) scores and the clinical effective rate. A fixed-effects meta-analysis and meta-regression are performed; lastly, performed a mixed treatment comparison was performed through the Bayesian methods.ResultsOutcome of efficacy of therapies for acute ischemic stroke are as followed: All of the therapies mentioned above yielded results a more effective result than placebo, Sodium ozagrel (RR 3.86, 95%CI 3.18-4.61); Sodium ozagrel + edaravone (RR 9.60, 95%CI 7.04-13.06); Edaravone (RR 4.07, 95%CI 3.30-5.01); Edaravone + Kininogenase (RR 15.33, 95%CI 10.03-23.05). The significant difference in efficacy between edaravone monotherapy and Sodium ozagrel + edaravone was evident (RR 0.43, 95%CI 0.08-0.61) and was also significant between efficacy of edaravone + Kininogenase and Sodium ozagrel (RR 4.00, 95%CI 2.47-6.24). The differences between the risk and benefit were not significant when comparing Sodium ozagrel and edaravone or edaravone + Kininogenase and Sodium ozagrel + Edaravone for AIS. Outcome of the defect of neurological function: Placebo served a significant difference in treating the defects of neurological function compared with Sodium ozagrel (WMD = -3.11, 95%CI -4.43 to -1.79), Sodium ozagrel + edaravone (WMD = -6.25, 95%CI -7.96 to -4.54) and Edaravone + Kininogenase (WMD = -3.47, 95%CI -5.73 to -1.21).ConclusionsIt provides that the efficacy of edaravone monotherapy in treatment was not more effective than Sodium ozagrel + edaravone.The efficacy of edaravone + Kininogenase monotherapy in treatment was more effective than Sodium ozagrel. Edaravone + Kininogenase and Sodium ozagrel + Edaravone appeared the most effective treatments. And Sodium ozagrel, Sodium ozagrel + edaravone, Edaravone + Kininogenase can improve the nerve dysfunction.

Project description:Context: Several interventions are available for the management of hypoxic ischemic encephalopathy (HIE), but no studies have compared their relative efficacy in a single analysis. This study aims to compare and determine the effectiveness of available interventions for HIE using direct and indirect data. Methods: Large randomized trials were identified from PubMed, EMBASE, CINAHL Plus, AMED, and Cochrane Library of Clinical Trials database from inception until June 30, 2018. Two independent reviewers extracted study data and performed quality assessment. Direct and network meta-analysis of randomized controlled trials was performed to obtained pooled results comparing the effectiveness of different therapies used in HIE on mortality, neurodevelopmental delay at 18 months, as well as adverse events. Their probability of having the highest efficacy and safety was estimated and ranked. The certainty of evidence for the primary outcomes of mortality and mortality or neurodevelopmental delay at 18 months was evaluated using GRADE criteria. Results: Fifteen studies comparing five interventions were included in the network meta-analysis. Whole body cooling [Odds ratio: 0.62 (95% credible interval: 0.46-0.83); 8 trials, high certainty of evidence] was the most effective treatment in reducing the risk of mortality, followed by selective head cooling (0.73; 0.48-1.11; 2 trials, moderate certainty of evidence) and use of magnesium sulfate (0.79; 0.20-3.06; 2 trials, low certainty of evidence). Whole body hypothermia (0.48; 0.33-0.71; 5 trials), selective head hypothermia (0.54; 0.32-0.89; 2 trials), and erythropoietin (0.36; 0.19-0.66; 2 trials) were more effective for reducing the risk of mortality and neurodevelopmental delay at 18 months (moderate to high certainty). Among neonates treated for HIE, the use of erythropoietin (0.36; 0.18-0.74, 2 trials) and whole body hypothermia (0.61; 0.45-0.83; 7 trials) were associated with lower rates of cerebral palsy. Similarly, there were lower rates of seizures among neonates treated with erythropoietin (0.35; 0.13-0.94; 1 trial) and whole body hypothermia (0.64; 0.46-0.87, 7 trials). Conclusion: The findings support current guidelines using therapeutic hypothermia in neonates with HIE. However, more trials are needed to determine the role of adjuvant therapy to hypothermia in reducing the risk of mortality and/or neurodevelopmental delay.

Dataset Information

Comparative Efficacy and Safety of Therapies in IgA Nephropathy: A Network Meta-analysis of Randomized Controlled Trials.

Publications

Comparative Efficacy and Safety of Therapies in IgA Nephropathy: A Network Meta-analysis of Randomized Controlled Trials.

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