Efficacy and Treatment-Related Adverse Events of Romidepsin in PTCL Clinical Studies: A Systematic Review and Meta-Analysis.
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SUBMITTER: Du J
PROVIDER: S-EPMC8602095 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveOverview on risks of acupuncture-related adverse events (AEs).DesignSystematic review and meta-analyses of prospective studies.Data sourcesPubMed, Scopus and Embase from inception date to 15 September 2019.Eligibility criteria for selecting studiesProspective studies assessing AEs caused by needle acupuncture in humans as primary outcome published in English or German.Data extraction and synthesisTwo independent researchers selected articles, extracted the data and assessed study quality. Overall risks and risks for different AE categories were obtained from random effects meta-analyses.Main outcomesOverall risk of minor AEs and serious adverse events (SAEs) per patients and per treatments.ResultsA total of 7679 publications were identified. Twenty-two articles reporting on 21 studies were included. Meta-analyses suggest at least one AE occurring in 9.31% (95% CI 5.10% to 14.62%, 11 studies) of patients undergoing an acupuncture series and in 7.57% (95% CI 1.43% to 17.95%, 5 studies) of treatments. Summary risk estimates for SAEs were 1.01 (95% CI 0.23 to 2.33, 11 studies) per 10 000 patients and 7.98 (95% CI 1.39 to 20.00, 14 studies) per one million treatments, for AEs requiring treatment 1.14 (95% CI 0.00 to 7.37, 8 studies) per 1000 patients. Heterogeneity was substantial (I2 >80%). On average, 9.4 AEs occurred in 100 treatments. Half of the AEs were bleeding, pain or flare at the needle site that are argued to represent intended acupuncture reaction. AE definitions and assessments varied largely.ConclusionAcupuncture can be considered among the safer treatments in medicine. SAEs are rare, and the most common minor AEs are very mild. AEs requiring medical management are uncommon but necessitate medical competence to assure patient safety. Clinical and methodological heterogeneity call for standardised AE assessments tools, clear criteria for differentiating acupuncture-related AEs from therapeutically desired reactions, and identification of patient-related risk factors for AEs.Prospero registration numberCRD42020151930.
| S-EPMC8422480 | biostudies-literature
Project description:Background: Although clinical practice guidelines for the management of Immune Checkpoint Inhibitor (ICI)-related adverse events have recently been published, precise and nuanced toxicity data for combination ICI therapy are lacking. Therefore, herein we have conducted a systematic review and meta-analysis of published clinical trials on combination ICI to synthesize the treatment-related adverse event (TRAE) profile of combination ICI therapy. Methods: PUBMED, EMBASE, and the Cochrane Database/EBM were searched for eligible studies. Clinical trials evaluating combination immune checkpoint inhibitor therapy in advanced unresectable cancer were included in the analysis based on prespecified criteria. Risk of bias across studies was evaluated using Begg's funnel plot and Egger's regression test. The summary outcomes were pooled risk ratios (RR) and the logit-transformed proportion for incidence data. Results: A total of 18 studies comprising 2,767 patients across 10 cancer types were included in the final analysis. Combination ICI was associated with a slightly higher risk of all-grade adverse events (RR 1.07 [95% CI 1.03-1.11]) and markedly greater risk of grade 3 or higher adverse events (RR 2.21 [95% CI 1.57-3.10]) compared to monotherapy ICI. Subgroup analyses showed significant differences in risk of grade 3 or higher adverse events between treatment types (PD-1 + CTLA-4 and PD-L1 + CTLA-4), among cancer types, and among dosing regimens (N1I3, N3I1, and D20T1). The incidence of all-grade adverse events was 0.905 [95% CI 0.842-0.945], and the ratio of grade 3 or higher events to all-grade adverse events was 0.396 [95% CI 0.315-0.483]. The most common all-grade TRAEs were diarrhea/colitis, fatigue/asthenia, nausea/vomiting, rash, and pruritis. Conclusion: Combination ICI therapy has a significantly different treatment-related adverse event profile compared to monotherapy.
| S-EPMC7090167 | biostudies-literature
Project description:Lymphangioleiomyomatosis (LAM) is a rare lung disease and the mammalian target of the rapamycin (mTOR) inhibitors has been used as an effective therapy. Here we conducted a systematic review and meta-analysis with the aims to quantify the efficacy and safety of mTOR inhibitors in LAM patients.The following databases were searched for clinical trials regarding LAM patients treated with mTOR inhibitors until December 2017: Pubmed, Embase, Cochrane Library and OVID medicine. Random effect models were used for the quantitative analysis.Nine eligible studies were included in our systematic review, 7 of which were used for the meta-analysis. In LAM patients, mTOR inhibitors improved forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) significantly, with the weighted mean difference (WMD) 0.15 L (95%CI: 0.08 to 0.22, P?<?0.01, I2 =?0%) and 0.22 L (95%: 0.11 to 0.32, P?<?0.01, I2 =?0%) respectively. There was no significant change in neither the diffusing capacity for carbon monoxide (WMD: 0.51 ml/mm Hg/min, 95%CI: -0.48 to 1.49, P?=?0.31, I2 =?0%) nor 6-min walking distance (WMD: 5.29 m, 95%CI: -18.01 to 28.59, P?=?0.66, I2 =?1%). The weighted partial response rate was 0.68 (95%CI: 0.53 to 0.84, P <?0.01, I2 =?72%) for renal angiomylipoma. The cumulative incidence rates of common safety events were 50, 40, 23, 20 and 19% for oral mucositis, hyperlipidemia, headache, bone marrow suppression, and diarrhea, respectively. And most events were low grade and tolerant.In LAM patients, there are improvements of FEV1 and FVC after the application of mTOR inhibitors and over a half achieved the shrinkage of renal angiomyolipoma.PROSPERO registration number: CRD42018085470. Registered 22 January 2018.
| S-EPMC6092843 | biostudies-other
Project description:BackgroundThe wide use of antibody-drug conjugates (ADCs) is transforming the cancer-treatment landscape. Understanding the treatment-related adverse events (AEs) of ADCs is crucial for their clinical application. We conducted a meta-analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies.MethodsWe searched the PubMed, Embase, and Cochrane Library databases for articles published from January 2001 to October 2022. The overall profile and incidence of all-grade and grade ≥ 3 treatment-related AEs were the primary outcomes of the analysis.ResultsA total of 138 trials involving 15,473 patients were included in this study. The overall incidence of any-grade treatment-related AEs was 100.0% (95% confidence interval [CI]: 99.9%-100.0%; I 2 = 89%) and the incidence of grade ≥ 3 treatment-related AEs was 6.2% (95% CI: 3.0%-12.4%; I² = 99%).ConclusionsThis study provides a comprehensive overview of AEs related to ADCs used for cancer treatment. ADC use resulted in a high incidence of any-grade AEs but a low incidence of grade ≥ 3 AEs. The AE profiles and incidence differed according to cancer type, ADC type, and ADC components.
| S-EPMC10686142 | biostudies-literature
Project description:to evaluate the risk of treatment-related adverse events of different severity and different system with PD-1 or PD-L1 inhibitors. randomized controlled trials (RCTs) that using PD-1/PD-L1 for cancer treatment were searched in the PubMed, Embase, Cochrane Library, and Web of Science from 1 January 2019 to 31 May 2021. Adverse events data were extracted from clinical trials website or original article by two authors separately. Meta-analysis was used to determine risk ratio (RR) and 95% confidence interval (95% CI) of adverse events in PD-1/PD-L1 inhibitors groups compared to that of control groups. Subgroup analyses were also performed. a total of 5,807 studies were initially identified and after exclusion, 41 studies were included in meta-analysis. All the trials were international multicenter, randomized, phase II/III clinical trials, with the median follow-up of 27.5 months on average. Analysis of all grade adverse events showed that PD-1/PD-L1 inhibitors treatment significantly increased the risk of immune-related adverse events, including pruritus (RR: 2.34, 95% CI: 1.85-2.96), rash (RR: 1.53, 95% CI: 1.25-1.87), ALT elevation (RR 1.54, 95% CI 1.23-1.92), AST elevation (AST: RR 1.49, 95% CI 1.20-1.85), hepatitis (RR: 3.54, 95% CI: 1.96-6.38) and hypothyroid (RR: 5.29, 95% CI: 4.00-6.99) compared with that of control group. Besides that, PD-1/PD-L1 inhibitors were associated with higher risk of adverse events related to respiratory system including cough (RR: 1.33, 95% CI: 1.21-1.48), dyspnea (RR:1.23, 95% CI: 1.12-1.35) and chest pain (RR: 1.26, 95% CI: 1.07-1.47) compared with that of control groups in our meta-analysis and the dyspnea was taken high risk both in all grade and grade 3 or higher (RR: 1.55, 95% CI: 1.13-2.12). The risk of arthralgia was increased with PD-1/PD-L1 inhibitors (RR: 1.27, 95% CI: 1.10-1.47). Although the risk of myalgia was similar with PD-1/PD-L1 inhibitors and control groups, under subgroup analysis, PD-1/PD-L1 inhibitors decreased the risk of myalgia (RR: 0.56, 95% CI: 0.45-0.70) compared with that of chemotherapy. our results provide clear evidence that the risk of treatment-related adverse events in PD-1 or PD-L1 varies widely in different system. In particular, when using PD-1/PD-L1 inhibitors for oncology treatment, besides the common immune-related adverse events like pruritus, rash, hepatitis, and hypothyroid, the respiratory disorders and musculoskeletal disorders, such as cough, dyspnea, arthralgia, and myalgia, should also be taken into consideration.
| S-EPMC8618590 | biostudies-literature
Project description:ObjectiveTo examine the association between antihypertensive treatment and specific adverse events.DesignSystematic review and meta-analysis.Eligibility criteriaRandomised controlled trials of adults receiving antihypertensives compared with placebo or no treatment, more antihypertensive drugs compared with fewer antihypertensive drugs, or higher blood pressure targets compared with lower targets. To avoid small early phase trials, studies were required to have at least 650 patient years of follow-up.Information sourcesSearches were conducted in Embase, Medline, CENTRAL, and the Science Citation Index databases from inception until 14 April 2020.Main outcome measuresThe primary outcome was falls during trial follow-up. Secondary outcomes were acute kidney injury, fractures, gout, hyperkalaemia, hypokalaemia, hypotension, and syncope. Additional outcomes related to death and major cardiovascular events were extracted. Risk of bias was assessed using the Cochrane risk of bias tool, and random effects meta-analysis was used to pool rate ratios, odds ratios, and hazard ratios across studies, allowing for between study heterogeneity (?2).ResultsOf 15?023 articles screened for inclusion, 58 randomised controlled trials were identified, including 280?638 participants followed up for a median of 3 (interquartile range 2-4) years. Most of the trials (n=40, 69%) had a low risk of bias. Among seven trials reporting data for falls, no evidence was found of an association with antihypertensive treatment (summary risk ratio 1.05, 95% confidence interval 0.89 to 1.24, ?2=0.009). Antihypertensives were associated with an increased risk of acute kidney injury (1.18, 95% confidence interval 1.01 to 1.39, ?2=0.037, n=15), hyperkalaemia (1.89, 1.56 to 2.30, ?2=0.122, n=26), hypotension (1.97, 1.67 to 2.32, ?2=0.132, n=35), and syncope (1.28, 1.03 to 1.59, ?2=0.050, n=16). The heterogeneity between studies assessing acute kidney injury and hyperkalaemia events was reduced when focusing on drugs that affect the renin angiotensin-aldosterone system. Results were robust to sensitivity analyses focusing on adverse events leading to withdrawal from each trial. Antihypertensive treatment was associated with a reduced risk of all cause mortality, cardiovascular death, and stroke, but not of myocardial infarction.ConclusionsThis meta-analysis found no evidence to suggest that antihypertensive treatment is associated with falls but found evidence of an association with mild (hyperkalaemia, hypotension) and severe adverse events (acute kidney injury, syncope). These data could be used to inform shared decision making between doctors and patients about initiation and continuation of antihypertensive treatment, especially in patients at high risk of harm because of previous adverse events or poor renal function.RegistrationPROSPERO CRD42018116860.
| S-EPMC7873715 | biostudies-literature
Project description:Background and aimsWhile endoscopic retrograde cholangiopancreatography (ERCP) is a valuable diagnostic and therapeutic tool in primary sclerosing cholangitis (PSC), there is conflicting data on associated adverse events. The aims of this systematic review and meta-analysis are to (1) compare ERCP-related adverse events in patients with and without PSC and (2) determine risk factors for ERCP-related adverse events in PSC.MethodsEmbase, PubMed, and CENTRAL were searched between January 1, 2000, and May 12, 2021. Eligible studies included adults with PSC undergoing ERCP and reported at least one ERCP-related adverse event (cholangitis, pancreatitis, bleeding, and perforation) or an associated risk factor. The risk of bias was assessed with the Newcastle-Ottawa scale and Cochrane Risk of Bias 2. Raw event rates were used to calculate odds ratios (ORs) and then pooled using random-effects models.ResultsTwenty studies met eligibility criteria, of which four were included in a meta-analysis comparing post-ERCP adverse events in patients with PSC (n = 715) to those without PSC (n = 9979). We found a significant threefold increase in the 30-day odds of cholangitis in PSC compared to those without (OR 3.263, 95% CI 1.076-9.896; p=0.037). However, there were no significant differences in post-ERCP pancreatitis (PEP), bleeding, or perforation. Due to limitations in primary data, only risk factors contributing to PEP could be analyzed. Accidental passage of the guidewire into the pancreatic duct (OR 7.444, 95% CI 3.328-16.651; p < 0.001; I 2 = 65.0%) and biliary sphincterotomy (OR 4.802, 95% CI 1.916-12.033; p=0.001; I 2 = 73.1%) were associated with higher odds of PEP in a second meta-analysis including five studies.ConclusionsIn the context of limited comparative data and heterogeneity, PSC patients undergoing ERCP have higher odds of cholangitis despite the majority receiving antibiotics. Additionally, accidental wire passage and biliary sphincterotomy increased the odds of PEP. Future studies on ERCP-related risks and preventive strategies are needed.
| S-EPMC9334029 | biostudies-literature
Project description:ObjectivesTo perform a systematic review and meta-analysis of interferon and endocrine side effects, including their incidence, evaluation, and management.MethodsPubMed was searched through March 7th, 2021, by 2 authors independently (LH Wang and H Zhao). Early phase I/II, phase III experimental trials, prospective and retrospective observational studies were included. Stata 16.0 (StataCorp LLC, 16.0) was the main statistical software for meta-analysis. The weighted incidence and risk ratio were estimated for primary thyroid disease and diabetes mellitus.ResultsA total of 108 studies involving 46265 patients were included. Hypothyroidism was the most common thyroid disorder, followed by hyperthyroidism. IFN α+RBV treated patients experienced hypothyroidism in 7.8% (95%CI, 5.9-9.9), which was higher than IFN α (5.2%; 95%CI, 3.7-6.8) and IFN β (7.0%; 95%CI, 0.06-23.92). IFN α+RBV treated patients experienced hyperthyroidism in 5.0% (95%CI, 3.6-6.5), which was higher than IFN α (3.5%; 95%CI, 2.5-4.8) and IFN β (3.4%; 95%CI, 0.9-7.5). The summary estimated incidence of painless thyroiditis was 5.8% (95%CI, 2.8-9.8) for IFN α, and 3.5% (95%CI,1.9-5.5) for IFN α+RBV. The summary estimated incidence of diabetes was 1.4% (95%CI, 0.3-3.1) for IFN, 0.55% (95%CI, 0.05-1.57) for IFN α, 3.3% (95%CI,1.1-6.6) for IFN α+RBV.ConclusionsOur meta-analysis shows a high incidence of endocrine adverse events provoked by IFN, further reinforced by combined RBV treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022334131.
| S-EPMC9388759 | biostudies-literature
Project description:ImportanceProgrammed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related adverse events of these drugs is critical for clinical practice.ObjectiveTo evaluate the incidences of treatment-related adverse events of PD-1 and PD-L1 inhibitors and the differences between different drugs and cancer types.Data sourcesPubMed, Web of Science, Embase, and Scopus were searched from October 1, 2017, through December 15, 2018.Study selectionPublished clinical trials on single-agent PD-1 and PD-L1 inhibitors with tabulated data on treatment-related adverse events were included.Data extraction and synthesisTrial name, phase, cancer type, PD-1 and PD-L1 inhibitor used, dose escalation, dosing schedule, number of patients, number of all adverse events, and criteria for adverse event reporting data were extracted from each included study, and bayesian multilevel regression models were applied for data analysis.Main outcomes and measuresIncidences of treatment-related adverse events and differences between different drugs and cancer types.ResultsThis systematic review and meta-analysis included 125 clinical trials involving 20 128 patients; 12 277 (66.0%) of 18 610 patients from 106 studies developed at least 1 adverse event of any grade (severity), and 2627 (14.0%) of 18 715 patients from 110 studies developed at least 1 adverse event of grade 3 or higher severity. The most common all-grade adverse events were fatigue (18.26%; 95% CI, 16.49%-20.11%), pruritus (10.61%; 95% CI, 9.46%-11.83%), and diarrhea (9.47%; 95% CI, 8.43%-10.58%). The most common grade 3 or higher adverse events were fatigue (0.89%; 95% CI, 0.69%-1.14%), anemia (0.78%; 95% CI, 0.59%-1.02%), and aspartate aminotransferase increase (0.75%; 95% CI, 0.56%-0.99%). Hypothyroidism (6.07%; 95% CI, 5.35%-6.85%) and hyperthyroidism (2.82%; 95% CI, 2.40%-3.29%) were the most frequent all-grade endocrine immune-related adverse events. Nivolumab was associated with higher mean incidences of all-grade adverse events compared with pembrolizumab (odds ratio [OR], 1.28; 95% CI, 0.97-1.79) and grade 3 or higher adverse events (OR, 1.30; 95% CI, 0.89-2.00). PD-1 inhibitors were associated with a higher mean incidence of grade 3 or higher adverse events compared with PD-L1 inhibitors (OR, 1.58; 95% CI, 1.00-2.54).Conclusions and relevanceDifferent PD-1 and PD-L1 inhibitors appear to have varying treatment-related adverse events; a comprehensive summary of the incidences of treatment-related adverse events in clinical trials provides an important guide for clinicians.
| S-EPMC6487913 | biostudies-literature
Project description:BackgroundDespite a historical association with poor tolerability, a comprehensive review on safety of antileishmanial chemotherapies is lacking. We carried out an update of a previous systematic review of all published clinical trials in visceral leishmaniasis (VL) from 1980 to 2019 to document any reported serious adverse events (SAEs).MethodsFor this updated systematic review, we searched the following databases from 1st Jan 2016 through 2nd of May 2019: PUBMED, Embase, Scopus, Web of Science, Cochrane, clinicaltrials.gov, WHO ICTRP, and the Global Index Medicus. We included randomised and non-randomised interventional studies aimed at assessing therapeutic efficacy and extracted the number of SAEs reported within the first 30 days of treatment initiation. The incidence rate of death (IRD) from individual treatment arms were combined in a meta-analysis using random effects Poisson regression.ResultsWe identified 157 published studies enrolling 35,376 patients in 347 treatment arms. Pentavalent antimony was administered in 74 (21.3%), multiple-dose liposomal amphotericin B (L-AmB) in 52 (15.0%), amphotericin b deoxycholate in 51 (14.7%), miltefosine in 33 (9.5%), amphotericin b fat/lipid/colloid/cholesterol in 31 (8.9%), and single-dose L-AmB in 17 (4.9%) arms. There was a total of 804 SAEs reported of which 793 (including 428 deaths) were extracted at study arm level (11 SAEs were reported at study level only). During the first 30 days, there were 285 (66.6%) deaths with the overall IRD estimated at 0.068 [95% confidence interval (CI): 0.041-0.114; I2 = 81.4%; 95% prediction interval (PI): 0.001-2.779] per 1,000 person-days at risk; the rate was 0.628 [95% CI: 0.368-1.021; I2 = 82.5%] in Eastern Africa, and 0.041 [95% CI: 0.021-0.081; I2 = 68.1%] in the Indian Subcontinent. In 21 study arms which clearly indicated allowing the inclusion of patients with HIV co-infections the IRD was 0.575 [95% CI: 0.244-1.355; I2 = 91.9%] compared to 0.043 [95% CI: 0.020-0.090; I2 = 62.5%] in 160 arms which excluded HIV co-infections.ConclusionMortality within the first 30 days of VL treatment initiation was a rarely reported event in clinical trials with an overall estimated rate of 0.068 deaths per 1,000 person-days at risk, though it varied across regions and patient populations. These estimates may serve as a benchmark for future trials against which mortality data from prospective and pharmacovigilance studies can be compared. The methodological limitations exposed by our review support the need to assemble individual patient data (IPD) to conduct robust IPD meta-analyses and generate stronger evidence from existing trials to support treatment guidelines and guide future research.
| S-EPMC8031744 | biostudies-literature