Objective:To explore the correlation between erythropoiesis-stimulating agents (ESAs) and seizures.Methods:Drug target Mendelian randomization (MR) and multivariate MR analysis were employed to evaluate the causal correlation between ESAs and seizures as well as status epilepticus. The data were sourced from published genome-wide association studies (GWAS) in the UK Biobank and Finland FinnGen databases. The instrumental variables were ESA-related single-nucleotide polymorphisms (SNPs) with F>10, the exposure factor was ESAs treatment, and outcome measures were seizures and status epilepticus. The methods of inverse variance weighted (IVW), weighted median estimator (WME) and MR-Egger regression were applied in the drug-target MR analysis, and the methods of IVW, MR-Egger regression and MR-LASSO were applied in the multivariate MR analysis. Adverse event reports from January 2004 to June 2024 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were collected. The signals of ESA-related seizures and status epilepticus were detected by reporting odds ratio (ROR) method and proportional reporting ratio (PRR) method. Results:A total of 15 SNPs were included in the MR analysis. Drug-target MR analysis showed that ESAs were significantly associated with the risk of seizures [IVW odds ratio ( OR)=1.575, 95% confidence interval ( CI): 1.055-2.353, P=0.026], but not associated with the risk of status epilepticus ( OR=1.818, 95 %CI: 0.403-8.207, P=0.437). Multivariate MR analysis showed that the above significant association was not found after correcting the risk factors of seizures such as stroke, pulmonary embolism, brain tumor, and dementia ( OR=0.359, 95 %CI: -0.014- 0.732, P=0.059). No risk signals of seizures and status epilepticus caused by 3 ESAs (recombinant human erythropoietin, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta) were detected in FAERS database. Conclusion:ESAs may not lead to an increase in risk of seizures.

Objective:To explore the correlation between erythropoiesis-stimulating agents (ESAs) and seizures.Methods:Drug target Mendelian randomization (MR) and multivariate MR analysis were employed to evaluate the causal correlation between ESAs and seizures as well as status epilepticus. The data were sourced from published genome-wide association studies (GWAS) in the UK Biobank and Finland FinnGen databases. The instrumental variables were ESA-related single-nucleotide polymorphisms (SNPs) with F>10, the exposure factor was ESAs treatment, and outcome measures were seizures and status epilepticus. The methods of inverse variance weighted (IVW), weighted median estimator (WME) and MR-Egger regression were applied in the drug-target MR analysis, and the methods of IVW, MR-Egger regression and MR-LASSO were applied in the multivariate MR analysis. Adverse event reports from January 2004 to June 2024 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were collected. The signals of ESA-related seizures and status epilepticus were detected by reporting odds ratio (ROR) method and proportional reporting ratio (PRR) method. Results:A total of 15 SNPs were included in the MR analysis. Drug-target MR analysis showed that ESAs were significantly associated with the risk of seizures [IVW odds ratio ( OR)=1.575, 95% confidence interval ( CI): 1.055-2.353, P=0.026], but not associated with the risk of status epilepticus ( OR=1.818, 95 %CI: 0.403-8.207, P=0.437). Multivariate MR analysis showed that the above significant association was not found after correcting the risk factors of seizures such as stroke, pulmonary embolism, brain tumor, and dementia ( OR=0.359, 95 %CI: -0.014- 0.732, P=0.059). No risk signals of seizures and status epilepticus caused by 3 ESAs (recombinant human erythropoietin, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta) were detected in FAERS database. Conclusion:ESAs may not lead to an increase in risk of seizures.

OBJECTIVE To systematically evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists(GLP-1RA) in the renal protection of type 2 diabetes(T2DM) patients, and provide evidence for clinic. METHODS Computer retrieval of PubMed, Embase, The Cochrane Library, Clinical Trials.gov, CNKI, WanFang Data and VIP databases, and manual retrieval of the included references. Randomized controlled trials(RCTs) for T2DM using GLP-1RA alone or GLP-1RA in combination with other conventional agents(experimental group) versus conventional treatment without GLP-1RA or placebo(control group). The search period spanned from the establishment of the database to January 30, 2022. Meta-analysis of the included data was performed using RevMan 5.4 statistical software. RESULTS A total of 7 studies were included, including 7 985 cases in experimental group and 6 633 cases in control group. Meta-analysis showed that the experimental group significantly reduced the incidence of renal complex endpoint events[Z=2.17, P=0.03, RR=0.79, 95%CI(0.64, 0.98)], urinary albumin creatinine ratio[Z=11.66, P<0.00001, MD=–23.74, 95%CI(–27.73, –19.74)], incidence of new macroalbuminuria[Z=5.79, P<0.000 01, MD=0.76, 95%CI(0.69, 0.83)], hemoglobin A1c[Z=12.76, P<0.000 01, MD=–0.94, 95%CI(–1.09, –0.80)] and estimated glomerular filtration rate[P=0.0007, Z=3.39, MD=–7.37, 95%CI(–11.63, –3.10)], the differences were statistically significant. One study showed that the experimental group could significantly reduce 24-hour urinary albumin excretion rate. However, there was no significant difference in the incidence of acute renal failure between the two groups[Z=0.63, P=0.53, MD=1.13, 95%CI(0.78, 1.63)]. In terms of safety, except the incidence of hypoglycemia, the incidence of adverse reactions in the experimental group was higher than that in the control group, including diarrhea, nausea, vomiting and loss of appetite, with statistically significant differences. CONCLUSION Existing research evidence shows that the common adverse reactions of GLP-1RA are gastrointestinal reactions and can be tolerated. Compared with placebo or conventional treatment without GLP-1RA, GLP-1RA may have a protective effect on the kidney of T2DM patients, and this conclusion needs to be further verified by RCTs.

Objective:To mine the risk signals of thromboembolism and hepatotoxicity related to thrombopoietin receptor agonists (TPO-RAs) and provide references for safe use of these drugs in clinic.Methods:Adverse event (AE) reports on eltrombopag, romiplostim, and avatrombopag from October 2009 to September 2023 were collected by searching US FDA Adverse Event Reporting System database. AEs were classified and standardized according to the systematic organ class (SOC) and preferred terms (PT) of Medical Dictionary for Regulatory Activities version 25.0. The AE risk signals of thromboembolism and hepatotoxicity related to the 3 TPO-RAs were mined using reporting odds ratio (ROR) method. An AE with reports ≥3 and the lower limit of the 95% confidence interval of ROR >1 was defined as a risk signal. Results:The number of AE reports with eltrombopag, romiplostim and avatrombopag as the primary suspect drugs were 25 215, 18 762, and 1 204, respectively. Fifty-two, 51, and 9 PTs of thromboembolic events (TEEs) related to eltrombopag, romiplostim and avatrombopag were mined, respectively. The top 5 PTs in the signal strength of eltrombopag were renal embolism, portal vein thrombosis, splenic thrombosis, splenic vein thrombosis and hepatic artery thrombosis. The top 5 PTs in the signal strength of romiplostim were embolism arterial, cerebral vascular occlusion, vertebral artery occlusion, portal vein thrombosis, and thrombosis mesenteric vessel. The top 5 PTs in the signal strength of avatrombopag were renal vein thrombosis, portal vein thrombosis, cerebral venous sinus thrombosis, embolism, and deep vein thrombosis. In addition, 25, 14 and 4 PTs of hepatotoxicity related to eltrombopag, romiplostim, and avatrombopag were mined, respectively. The top 5 PTs in the signal strength of eltrombopag were portal vein dilatation, portal vein thrombosis, hepatic artery thrombosis, indirect bilirubin increase, and chronic hepatic failure. The top 5 PTs in the signal strength of romiplostim were portal vein thrombosis, chronic hepatic failure, alcoholic liver disease, hepatic haematoma, and hepatic cirrhosis. The PTs in the signal strength of avatrombopag were portal vein thrombosis, liver function test abnormality, hepatic function abnormality, and hepatic enzyme increase. A total of 24 PTs not recorded in drug labels of the 3 TPO-RAs were mined. The top 5 PTs in the signal strength were portal vein dilatation, chronic hepatic failure, liver function test abnormality, alcoholic liver disease, and ocular icterus.Conclusions:TEEs and hepatotoxicity are common adverse reactions of the 3 TPO-RAs. The coagulation function and liver function of patients should be monitored before and after application of TPO-RAs. It should be alert for the adverse reactions not recorded in the drug labels.

Objective:To mine the risk signals of thromboembolism and hepatotoxicity related to thrombopoietin receptor agonists (TPO-RAs) and provide references for safe use of these drugs in clinic.Methods:Adverse event (AE) reports on eltrombopag, romiplostim, and avatrombopag from October 2009 to September 2023 were collected by searching US FDA Adverse Event Reporting System database. AEs were classified and standardized according to the systematic organ class (SOC) and preferred terms (PT) of Medical Dictionary for Regulatory Activities version 25.0. The AE risk signals of thromboembolism and hepatotoxicity related to the 3 TPO-RAs were mined using reporting odds ratio (ROR) method. An AE with reports ≥3 and the lower limit of the 95% confidence interval of ROR >1 was defined as a risk signal. Results:The number of AE reports with eltrombopag, romiplostim and avatrombopag as the primary suspect drugs were 25 215, 18 762, and 1 204, respectively. Fifty-two, 51, and 9 PTs of thromboembolic events (TEEs) related to eltrombopag, romiplostim and avatrombopag were mined, respectively. The top 5 PTs in the signal strength of eltrombopag were renal embolism, portal vein thrombosis, splenic thrombosis, splenic vein thrombosis and hepatic artery thrombosis. The top 5 PTs in the signal strength of romiplostim were embolism arterial, cerebral vascular occlusion, vertebral artery occlusion, portal vein thrombosis, and thrombosis mesenteric vessel. The top 5 PTs in the signal strength of avatrombopag were renal vein thrombosis, portal vein thrombosis, cerebral venous sinus thrombosis, embolism, and deep vein thrombosis. In addition, 25, 14 and 4 PTs of hepatotoxicity related to eltrombopag, romiplostim, and avatrombopag were mined, respectively. The top 5 PTs in the signal strength of eltrombopag were portal vein dilatation, portal vein thrombosis, hepatic artery thrombosis, indirect bilirubin increase, and chronic hepatic failure. The top 5 PTs in the signal strength of romiplostim were portal vein thrombosis, chronic hepatic failure, alcoholic liver disease, hepatic haematoma, and hepatic cirrhosis. The PTs in the signal strength of avatrombopag were portal vein thrombosis, liver function test abnormality, hepatic function abnormality, and hepatic enzyme increase. A total of 24 PTs not recorded in drug labels of the 3 TPO-RAs were mined. The top 5 PTs in the signal strength were portal vein dilatation, chronic hepatic failure, liver function test abnormality, alcoholic liver disease, and ocular icterus.Conclusions:TEEs and hepatotoxicity are common adverse reactions of the 3 TPO-RAs. The coagulation function and liver function of patients should be monitored before and after application of TPO-RAs. It should be alert for the adverse reactions not recorded in the drug labels.

Objective:To systematically evaluate the efficacy and safety of reslizumab targeting interleukin 5 in adjuvant therapy for patients with refractory asthma.Methods:The PubMed, Embase, Cochrane Library, Clinicaltrials.gov, CNKI, VIP, and Wanfang databases were searched (up to June 2022). Randomized controlled trials (RCTs) of reslizumab in adjuvant therapy of refractory asthma were collected. On the basis of conventional treatment for asthma, patients in the trial group was given additional reslizumab while the control group was given placebo. Primary outcome measures included the acute asthma attacks incidence, the changes of forced expiratory volume in the first second (FEV 1), asthma control questionnaire (ACQ) score, asthma quality of life questionnaire (AQLQ) score, and blood eosinophil count before and after adjuvant therapy, and incidence of adverse events. RevMan 5.3 software was used for meta-analysis. The effect sizes of counting data were odds ratio ( OR) and its 95% confidence interval ( CI), while the effect sizes of measurement data were mean difference ( MD) and its 95 %CI. Results:A total of 7 RCTs and 2 506 patients were entered in the analysis, including 1 456 in the trial group and 1 050 in the control group. The meta-analysis showed that, compared to the control group, the acute asthma attacks incidence was lower in patients of the trial group during adjuvant therapy[18.1%(263/1 456) vs. 31.3%(329/1 050), OR=0.50, 95 %CI: 0.41-0.62, P<0.001]; FEV1 and AQLQ score after treatment were higher ( MD=0.13 L, 95 %CI: 0.08-0.17 L, P<0.001; MD=0.18, 95 %CI: 0.04-0.33, P=0.01); the ACQ score and blood eosinophil count were higher ( MD=-0.19, 95 %CI: -0.28--0.10, P<0.001; MD=-0.45×10 9/L, 95 %CI:-0.48×10 9/L--0.42×10 9/L, P<0.001). There were no statistically significant difference in the incidences of overall adverse events, serious adverse events, allergic reactions, and pneumonia compared to those in the control group [63.7% (928/1 456) vs. 71.4% (750/1 050), OR=0.76, 95 %CI: 0.55-1.06, P=0.10; 6.4% (93/1 456) vs. 8.2% (86/1 050), OR=0.91, 95 %CI: 0.66-1.24, P=0.55; 0.4% (5/1 403) vs. 0.1% (1/997), OR=1.66, 95 %CI: 0.41-6.65, P=0.47; 0.6% (9/1 456) vs. 1.0% (10/1 050), OR=0.81, 95 %CI: 0.35-1.87, P=0.63]. Conclusion:Reslizuma has a good efficacy and safety profile in adjuvant treatment for patients with refractory asthma.

Objective:To systematically evaluate the efficacy and safety of reslizumab targeting interleukin 5 in adjuvant therapy for patients with refractory asthma.Methods:The PubMed, Embase, Cochrane Library, Clinicaltrials.gov, CNKI, VIP, and Wanfang databases were searched (up to June 2022). Randomized controlled trials (RCTs) of reslizumab in adjuvant therapy of refractory asthma were collected. On the basis of conventional treatment for asthma, patients in the trial group was given additional reslizumab while the control group was given placebo. Primary outcome measures included the acute asthma attacks incidence, the changes of forced expiratory volume in the first second (FEV 1), asthma control questionnaire (ACQ) score, asthma quality of life questionnaire (AQLQ) score, and blood eosinophil count before and after adjuvant therapy, and incidence of adverse events. RevMan 5.3 software was used for meta-analysis. The effect sizes of counting data were odds ratio ( OR) and its 95% confidence interval ( CI), while the effect sizes of measurement data were mean difference ( MD) and its 95 %CI. Results:A total of 7 RCTs and 2 506 patients were entered in the analysis, including 1 456 in the trial group and 1 050 in the control group. The meta-analysis showed that, compared to the control group, the acute asthma attacks incidence was lower in patients of the trial group during adjuvant therapy[18.1%(263/1 456) vs. 31.3%(329/1 050), OR=0.50, 95 %CI: 0.41-0.62, P<0.001]; FEV1 and AQLQ score after treatment were higher ( MD=0.13 L, 95 %CI: 0.08-0.17 L, P<0.001; MD=0.18, 95 %CI: 0.04-0.33, P=0.01); the ACQ score and blood eosinophil count were higher ( MD=-0.19, 95 %CI: -0.28--0.10, P<0.001; MD=-0.45×10 9/L, 95 %CI:-0.48×10 9/L--0.42×10 9/L, P<0.001). There were no statistically significant difference in the incidences of overall adverse events, serious adverse events, allergic reactions, and pneumonia compared to those in the control group [63.7% (928/1 456) vs. 71.4% (750/1 050), OR=0.76, 95 %CI: 0.55-1.06, P=0.10; 6.4% (93/1 456) vs. 8.2% (86/1 050), OR=0.91, 95 %CI: 0.66-1.24, P=0.55; 0.4% (5/1 403) vs. 0.1% (1/997), OR=1.66, 95 %CI: 0.41-6.65, P=0.47; 0.6% (9/1 456) vs. 1.0% (10/1 050), OR=0.81, 95 %CI: 0.35-1.87, P=0.63]. Conclusion:Reslizuma has a good efficacy and safety profile in adjuvant treatment for patients with refractory asthma.

Objective To perform a network meta-analysis (NMA) for the efficacy of 11 drugs in preventing chronic peripheral neuropathy induced by platinum and taxane (PTIPN). Methods PubMed, Cochrane library, Embase, CNKI, WanFang database and VIP database were searched up to February 2021 for relevant randomized controlled trials (RCTs) addressing the drugs to prevent PTIPN. After extracting relevant data, Stata 14.0 and ADDIS 1.16.6 softwares were used for statistical analysis. Results A total of 70 studies involving 6201 patients were included. The results of network Meta-analysis showed that amifostine, ganglioside, Huangqi Guizhi Wuwu decoction (HQGZT), vitamin E, calcium and magnesium infusion and omega-3 fatty acids were superior to placebo or blank groups in reducing the incidence of overall or severe PTIPN. The rank probability plot and the SUCRA calculation results suggested that amifostine, HQGZT and omega-3 fatty acids were in first order. The differences between the 11 drugs and placebo or blank groups were not statistically significant, except for amifostine which was reported to aggravate the adverse reactions of nausea and vomiting and hypotension in patients. Conclusion HQGZT, Ganglioside, Vitamin E, omega-3 fatty acids, calcium and magnesium infusion and glutathione can reduce the occurrence of PTIPN, and HQGZT has the highest efficiency.

Objective To explore the potential adverse reactions of acalabrutinib by mining and analyzing the pharmacovigilance signal of acalabrutinib, to provide a reference for clinically safe and rational drug use. Methods Data related to acalabrutinib in the FAERS database were searched, and pharmacovigilance signals were obtained using the disproportionality measurement. Results A total of 3, 155 reports of adverse events with acalabrutinib as the primary suspected drug were extracted, and 73 warning signals were detected involving 15 system organ classifications, 36 of which were not included in the drug instructions of acalabrutinib. The strong signals of acalabrutinib were mainly concentrated in various inflammatory and bleeding, anemia, contusion, atrial fibrillation, and so on. The largest number of system organ classification signals were focused on the blood and lymphatic system disorders, investigations, infections, and so on. In addition, the drug may cause tachycardia, brittle nails, and other warning signs. Through further analysis of gender-related adverse events, there were a total of 49 high-risk signals with gender differences found. Herein, male patients should pay attention to adverse reactions in bleeding, heart, urinary system, hypertension, and so on; meanwhile, female patients should be alert to adverse reactions in liver function, skin inflammation, and so on. Conclusion A total of 36 drug warning signs that are not mentioned in the instructions for acalabrutinib are mined using FAERS, and blood, infection, and cardiac toxicity require special attention. Thus, these signals should be detected promptly for effective prevention in clinical medication to reduce the risk of medication use for patients.