Efficacy of Inclisiran in Patients Having Familial Hypercholesterolemia: Heterozygous Compared to Homozygous Trait, a Systematic Review and Meta-analysis.

OBJECTIVE: To find out whether inclisiran sodium has different efficacy in heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH) patient groups. METHODS: We conducted the systematic review and meta-analysis of ORION clinical trials. PubMed, Embase, and Clinicaltrials.gov databases were searched for the relevant studies. Atheroscalerotic parameters considered for our objective were low-density lipoprotein cholesterol, total cholesterol, proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B, and nonhigh-density lipoprotein cholesterol. Primary outcomes were the percentage difference in atheroscalerotic parameters at follow-up relative to baseline values. Our study examined these primary outcomes to determine whether there is a statistically significant difference between the HeFH and HoFH groups. Risk of bias was assessed by the Cochrane risk of bias tool. Meta-analysis was performed when at least 2 studies reported on the same variable. RESULTS: Four ORION clinical trials provided the data related to the mean difference in the atheroscalerotic parameters at follow-up relative to baseline, of HeFH and HoFH patient populations, after administration of 300 mg inclisiran subcutaneously. We pooled together these mean differences for each group and applied a statistical test to analyze if the values were significantly different between the groups. The results of our study unveiled the significant difference in pooled mean differences in low-density lipoprotein cholesterol (HeFH: -48.62%; HoFH: -9.12%; P < 0.05), total cholesterol (HeFH: -30.31%; HoFH: -11.50%; P < 0.05), apolipoprotein (HeFH: -39.97%; HoFH: -14.68%; P < 0.05), and nonhigh-density lipoprotein (HeFH: -44.51%; HoFH: -12.22%; P < 0.05) between HeFH and HoFH groups. However, the difference in pooled mean difference in PCSK9 values (HeFH: -68.41%; HoFH: -56.25%; P = 0.2) between HeFH and HoFH groups was statistically insignificant. Studies were of high quality. CONCLUSIONS: There was a significant difference in the reductions in atherosclerotic lipid parameters in heterozygous and homozygous populations after the administration of inclisiran except for PCSK9 parameter. Further studies are needed to support this conclusion.

Serious Adverse Events of Inclisiran in Patients With Hypercholesterolemia, a Meta-Analysis of ORION Trials.

BACKGROUND: Several studies have been conducted over the years to find an effective and safe therapeutic agent to treat hypercholesterolemia. Inclisiran is a novel drug being studied for its efficacy and safety in reducing low-density lipoprotein cholesterol levels in patients to reduce the risk of cardiovascular diseases. No previous study was done to review the trials for the serious adverse events of this drug. The primary objective of this research is to investigate the incidence of serious adverse events of this drug. DESIGN: A systematic review and meta-analysis of clinical trials is performed. METHODS: A systematic search of PubMed, Embase, and ClinicalTrials.gov, from their inception till July 3, 2023, was performed for ORION trials, studying the efficacy and safety of inclisiran. The random-effects model was used in the meta-analysis to provide a pooled proportion of serious adverse events. The risk of bias in each study was assessed by the Cochrane Risk of Bias Tool. RESULTS: From 319 studies searched from the databases, only 8 relevant articles remained after a detailed evaluation. These studies, having a total of 4981 patients, were involved in the analysis, with a pooled estimate showing a nonsignificant incidence of serious adverse events. Each adverse event was studied individually, and product issues and endocrine disorders had the highest odds ratio among them. All included studies were classified as moderate quality. CONCLUSION: Following systematic review and meta-analysis, we found no significant differences in any serious adverse events following the administration of inclisiran. However, larger ongoing trials will provide additional data to evaluate the safety profile of this agent.

Efficacy of baricitinib in the treatment of Systemic lupus erythematosus (SLE): A Systemic review and meta-analysis.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. It affects multiple organ systems and is associated with significant morbidity and mortality. The treatment for SLE primarily aims at controlling and remitting the disease. Baricitinib is a kinase inhibitor that selectively inhibits JAK1 and JAK2 enzymes. Recently this drug is being investigated as a potential therapeutic option for SLE. Objective: To analyze the efficacy of baricitinib in treating SLE. Methods: Search of databases identified relevant studies that reported the efficacy of baricitinib. Data of patient characteristics, intervention details, and outcomes was extracted. The data from the studies were pooled using a random-effects model. The odds ratio with their respective 95 % confidence intervals (CI) were calculated to analyze the results. A p value of <0.05 was considered statistically significant. Results: 3 RCTs were included in the analysis. 1849 patients were extracted from the included studies, most of the participants were females with a mean age of 43 years. The studies showed a significant effect of Baricitinib 4 mg in achieving SRI-4 [OR = 1.42 (95 % CI: 1.01, 2.00); p = 0.04]. There was no significant association of Baricitinib 2 mg in achieving SRI-4. Both dosages of the drug did not have any significant association in achieving LLDAS as compared to placebo. Serious adverse side effects were significantly associated with Bar 4 mg as compared to Bar 2 mg. Conclusion: Our meta-analysis suggests that baricitinib might be a potential treatment option for SLE. Further large-scale clinical trials are needed to confirm our findings. Potential side effects should also be considered while the administration of this drug.

Fetal cardiac intervention in hypoplastic left heart syndrome with intact or restrictive atrial septum, systematic review, and meta-analysis.

To investigate outcomes of fetuses with hypoplastic left heart syndrome (HLHS) with an intact or restrictive atrial septum (I/RAS) managed expectantly or with fetal atrial septal intervention (FASI PubMed, Scopus, and Web of Science were searched systematically from inception until April 2023. Outcomes were classified by those who had FASI and those who had expectant management (EM). To estimate the overall proportion of each endpoint, a meta-analysis of proportions was employed using a random-effects model. Heterogeneity was assessed using the I2 value. Thirty-two studies reporting on 746 fetuses with HLHS and I/RAS met our inclusion criteria. Eleven studies (123 fetuses) were in the FASI group and 21 studies (623 fetuses) were in the EM group. Among the 123 FASI cases, 107 (87%) were reported to be technically successful. The mean gestational age (GA) at diagnosis was comparable between the groups (26.2 weeks FASI vs. 24.4 weeks EM group). The mean GA at FASI was 30.4 weeks (95% CI 28.5, 32.5). The mean GA at delivery was also comparable (37.7 weeks FASI vs. 38.1 weeks EM group). Neonatal outcomes, including live birth, neonatal death, and survival to hospital discharge pooled proportions, were also comparable between groups (live birth: 92% (95% CI 64, 99) FASI versus 93% (95% CI 79, 98) in EM, neonatal death: 32% (95% CI 11, 65) FASI versus 30% (95% CI 21, 41) EM, survival to hospital discharge: 37% (95% CI 25, 52) FASI versus 52% (95% CI 42, 61) EM). Age at neonatal death was higher in the FASI group (mean: 17 days FASI vs. 7.2 days EM group). There was a lower rate of postnatal atrial restrictive septum in the FASI group 38% (95% CI 17, 63) compared to the EM group 88% (95% CI 57, 98). Our review shows variations across centers in the selection criteria and techniques used for FASI. Although survival including livebirth, neonatal death, and survival to hospital discharge did not differ between groups, the procedure may translate into a less restrictive septum at birth. Future multicenter studies are needed to better identify the subset of cases that might have improved outcomes, use standardized definitions, unified techniques, utilize core outcome set, and assess long-term benefits.

Long-term outcome of treatments for Graves disease in the children and adolescent population.

BACKGROUND: Several studies were conducted over the years to find a significant association between non-surgical therapies such as Antithyroid Drug (ATD) Therapy and Radio-iodo therapy (RIT) with Graves' disease (GD) remission and relapse. However, these investigations did not have a specific focus on the age category of children and adolescents. Hence, this Research is performed to assess the association of non-surgical therapy (ATD and RIT) with Graves' disease (GD) remission and relapse in the children and adolescent population. DESIGN: A systematic review and meta-analysis of observational studies and clinical trials were carried out. METHODS: A systematic search of PubMed, EMBASE, and SCOPUS from their inception till April 2022 was performed for studies stating an association between ATD therapy and GD remission and relapse in participants 1-17 years old. The random-effects model was used in the meta-analysis to provide a pooled proportion of both primary outcomes. The quality and each study were assessed using the Newcastle Ottawa Scale (NOS). RESULT: From 6195 studies searched from the databases, only 16 relevant articles remained after a detailed evaluation. These studies, having a total of 2557 patients aged 5-17 years, were involved in the analysis with a pooled estimate showing a significant association of ATD therapy with GD remission (Estimate: 0.400, 95% Confidence interval: 0.265-0.535; I^2 = 98.16%) and with GD relapse (Estimate: 0.359, 95% Confidence interval: 0.257-0.461; I^2 = 98.26%). Subgroup analyses were conducted to assess the remission rate of different therapies suggesting that antithyroid drugs play a significant role in the remission of the patients. All included studies were classified as moderate quality. CONCLUSION: Following meta-analysis suggested that the ATD used in the analysis is effective in remitting GD in the children and adolescents population. Nevertheless, long-term RIT therapy and thyroidectomy leads to hypothyroidism. Still, large-sample, and high-quality studies targeting ATDs' use in children and adolescents with long-term surveillance of prognosis are needed.