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Therapeutics and Clinical Risk... 2023This study aims to systematically review the hepatic safety of febuxostat and allopurinol in adult gout patients. (Review)
Review
PURPOSE
This study aims to systematically review the hepatic safety of febuxostat and allopurinol in adult gout patients.
METHODS
We searched for information using the following databases: PubMed, Cochrane Library, and Scopus. The inclusion criteria were to review all randomized controlled trials (RCT) that compared allopurinol and febuxostat for adult gout patients that had an assessment of liver function outcomes. Non-English studies on case reports, case series, reviews, and abstracts only were excluded. We extracted information from the studies to answer the research question, ie, study design, publication year, population, sample size, patient characterization, duration, Jadad score, and liver function outcomes.
RESULTS
We screened 512 publications from the databases and identified 11 studies that met the inclusion criteria. Ten out of 11 included studies were double-blind RCTs. In the majority of the included studies, no statistically significant differences were observed in terms of hepatic safety data between febuxostat and allopurinol. However, in studies where allopurinol titration was used, it posed a challenge to maintain blinding. Notably, consistent adverse events related to liver function findings were observed across all reviewed RCTs. These abnormal liver function test results sometimes led to study withdrawal based on the investigators' assessment. Nevertheless, the investigators classified most liver function test elevations as mild to moderate in severity.
CONCLUSION
Our analysis concluded that adult gout patients enrolled in the included RCTs exhibited similar hepatic safety profiles for both febuxostat and allopurinol treatment. Liver function abnormalities were identified in all RCTs included in this systematic review. Consequently, it is important for the product labeling information of both allopurinol and febuxostat to present and describe the current safety data to guide healthcare practitioners when prescribing these medications to patients. Pharmacovigilance and post-marketing pharmacoepidemiology data are essential in establishing the comprehensive safety profile.
PubMed: 37744559
DOI: 10.2147/TCRM.S424598 -
Journal of Cardiovascular Development... Sep 2023The effects of allopurinol in patients with cardiovascular disease are not well defined; therefore, the latest evidence is summarized in this study. (Review)
Review
BACKGROUND
The effects of allopurinol in patients with cardiovascular disease are not well defined; therefore, the latest evidence is summarized in this study.
METHODS
PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) of allopurinol in patients with cardiovascular disease published up to 11 February 2023. The primary outcome was cardiovascular death.
RESULTS
We combined the results of 21 RCTs that included 22,806 patients. Compared to placebo/usual care, allopurinol treatment was not associated with a significant reduction in cardiovascular death (RR 0.60; 95% CI 0.33-1.11) or all-cause death (RR 0.90; 95% CI 0.72-1.12). However, evidence from earlier trials and studies with small sample sizes indicated that allopurinol might confer a protective effect in decreasing cardiovascular death (RR 0.34; 95% CI 0.15-0.76) across patients undergoing coronary artery bypass grafting (CABG) or having acute coronary syndrome (ACS). In comparisons between allopurinol and febuxostat, we observed no difference in cardiovascular death (RR 0.92; 95% CI 0.69-1.24) or all-cause death (RR 1.02; 95% CI 0.75-1.38).
CONCLUSION
Allopurinol could not reduce cardiovascular (CV) death or major adverse CV outcomes significantly in patients with existing cardiovascular diseases. Given the limitations of the original studies, the potential advantages of allopurinol observed in patients undergoing CABG or presenting with ACS necessitate further confirmation through subsequent RCTs. In the comparisons between allopurinol and febuxostat, our analysis failed to uncover any marked superiority of allopurinol in reducing the risk of adverse cardiovascular incidents.
PubMed: 37754808
DOI: 10.3390/jcdd10090379 -
Clinical and Translational Science Mar 2024The cardiovascular (CV) safety of febuxostat compared to allopurinol for the treatment of hyperuricemia among Asian patients is uncertain. In this study, we conducted a... (Meta-Analysis)
Meta-Analysis
The cardiovascular (CV) safety of febuxostat compared to allopurinol for the treatment of hyperuricemia among Asian patients is uncertain. In this study, we conducted a systematic review and meta-analysis to compare the CV safety profiles of febuxostat with allopurinol in Asian patients with hyperuricemia. A total of 13 studies were included. On the basis of the pooled results of cohort studies, febuxostat users were at a significantly higher risk for acute coronary syndrome (ACS; hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 1.03-1.09, p < 0.01), atrial fibrillation (HR: 1.19, 95% CI: 1.05-1.35, p < 0.01) than allopurinol users, whereas no significant difference between febuxostat and allopurinol existed for urgent coronary revascularization (HR: 1.07, 95% CI: 0.98-1.16, p = 0.13), and stroke (HR: 0.96, 95% CI: 0.91-1.01, p = 0.13). Nevertheless, that difference in results of acute decompensated heart failure (ADHF; HR: 0.73, 95% CI: 0.35-1.53, p = 0.40) and all-cause death (HR = 0.86, 95% CI: 0.49-1.51, p = 0.60) was not significant based on randomized controlled trials. In the Chinese subgroup, febuxostat could increase the risk of ADHF (HR: 1.22, 95% CI: 1.01-1.48, p < 0.05), CV death (HR: 1.25, 95% CI: 1.03-1.50, p < 0.05), and all-cause mortality (HR: 1.07, 95% CI: 1.01-1.14, p < 0.05) compared to allopurinol. In conclusion, the use of febuxostat, compared with allopurinol among Asian patients, was associated with a significantly increased risk of adverse CV events.
Topics: Humans; Allopurinol; Febuxostat; Hyperuricemia; Gout Suppressants; Cardiovascular Diseases; Gout; Treatment Outcome
PubMed: 38488426
DOI: 10.1111/cts.13757 -
Seminars in Arthritis and Rheumatism Apr 2024There is uncertainty about the optimal time to start urate-lowering therapy (ULT) in the setting of a gout flare. The aim was to perform a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is uncertainty about the optimal time to start urate-lowering therapy (ULT) in the setting of a gout flare. The aim was to perform a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the effects of ULT initiation during a gout flare.
METHODS
This systematic review was conducted in accordance with PRISMA methodology. MEDLINE, EMBASE and The Cochrane Library were searched for studies published between database inception to 1 March 2023. RCTs published in English that examined ULT initiation during a gout flare in adults ≥18 years were included. The quality of included studies was assessed using the revised Cochrane Risk of Bias tool 2.0. Data were extracted for the following outcomes: patient-rated pain score, duration of gout flare, recurrent gout flares, time to achieve target serum urate, adherence to ULT, patient satisfaction with treatment and adverse events. Meta-analyses were performed using Review Manager v5.4. This study is registered on PROSPERO, number CRD42023404680.
RESULTS
A total of 972 studies were identified and of these, six RCTs met the criteria for inclusion in the analysis. Three studies were assessed as having high risk of bias, one study as having some concerns, and two studies as having low risk of bias. In total, there were 445 pooled participants; 226 participants randomised to early initiation of ULT and 219 to placebo or delayed initiation of ULT. Allopurinol was used in three studies, febuxostat in two studies and probenecid in one study. Few participants (n = 62, 13.9 %) had tophaceous gout. Participants with renal impairment were excluded from most studies. There were no differences in patient-rated pain scores at baseline, days 3-4, days 7-8, day 10 or days 14-15 (p ≥ 0.42). Additionally, there was no significant difference in time to resolution of gout flare (standardised mean difference 0.77 days; 95 % CI -0.26 to 1.79; p = 0.14) or the risk of recurrent gout flare in the subsequent 28 to 30 days (RR 1.06; 95 % CI 0.59 to 1.92; p = 0.84). Adverse events were similar between groups. The included studies did not report time to achieve target serum urate, long-term adherence to ULT, or patient satisfaction with treatment.
CONCLUSION
There appears to be no evidence for harm or for benefit to initiating ULT during a gout flare. These findings have limited applicability to patients with tophaceous gout, or those with renal impairment.
Topics: Adult; Humans; Uric Acid; Gout Suppressants; Gout; Allopurinol; Pain; Randomized Controlled Trials as Topic
PubMed: 38215627
DOI: 10.1016/j.semarthrit.2024.152367 -
Frontiers in Pharmacology 2024Accumulating evidence suggests that hyperuricemia is a pathological factor in the development and progression of chronic kidney disease. However, the potential benefit...
Accumulating evidence suggests that hyperuricemia is a pathological factor in the development and progression of chronic kidney disease. However, the potential benefit afforded by the control of uric acid (UA) is controversial. Individual studies show discrepant results, and most existing meta-analysis, especially those including the larger number of studies, lack a placebo or control group as they aim to compare efficacy between drugs. On these grounds, we performed a me-ta-analysis restricted to studies including the action of any anti-gout therapies referenced to a control or placebo arm. This approach allows for a clearer association between UA reduction and renal effect. Of the twenty-nine papers included, most used allopurinol and febuxostat and, therefore, solid conclusions could only be obtained for these drugs. Both were very effective in reducing UA, but only allopurinol was able to significantly improve glomerular filtration rate (GFR), although not in a dose-dependent manner. These results raised doubts as to whether it is the hypouricemic effect of anti-gout drugs, or a pleiotropic effect, what provides protection of kidney function. Accordingly, in a correlation study that we next performed between UA reduction and GFR improvement, no association was found, which suggests that additional mechanisms may be involved. Of note, most trials show large inter-individual response variability, probably because they included patients with heterogeneous phenotypes and pathological characteristics, including different stages of CKD and comorbidities. This highlights the need to sub classify the effect of UA-lowering therapies according to the pathological scenario, in order to identify those CKD patients that may benefit most from them. CRD42022306646 https://www.crd.york.ac.uk/prospero/.
PubMed: 38601468
DOI: 10.3389/fphar.2024.1373258 -
Cureus Feb 2024The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs)... (Review)
Review
The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs) are antibodies that target cytotoxic thymus (T) lymphocyte antigen-4 (CTLA-4) and its receptor. They function by stimulating T-cell activity against malignancies. Immune-related adverse events (irAEs) are a distinct class of inflammatory side effects that are specific to a given organ. Antineoplastic medications can impact any part of the kidney, leading to the development of proteinuria, hypertension, electrolyte abnormalities, glomerulonephritis, and both acute and chronic interstitial nephritis. We reviewed the scientific literature regarding kidney problems that can arise from chemotherapy and immunotherapy for neoplasms, such as various cancers, melanoma, non-small cell lung cancer, and colorectal cancer. We discussed the pathophysiology, associated risk factors, management, and safety measures for patients experiencing acute renal injury after a new immunotherapy medication treatment. Antineoplastic drugs have the potential to damage the renal tubules, glomeruli, parenchyma, and blood vessels, among other kidney tissues. This can result in a broad spectrum of complications, spanning from a rise in serum creatinine levels without symptoms to the development of acute kidney injury (AKI). The research examined a range of risk factors associated with acute kidney injury (AKI). These factors encompassed age, gender, preexisting medical conditions (such as diabetes, hypertension, and chronic kidney disease), and the medications that patients were taking at the beginning of the study, which included non-steroidal anti-inflammatory drugs, renin-angiotensin system inhibitors, allopurinol, diuretics, corticosteroids, and proton pump inhibitors. The data suggests that patients who were receiving baseline treatment with proton pump inhibitors (PPIs) or corticosteroids had a higher risk of mortality. This study serves as an illustration of the effective management of acute kidney injury and proteinuria linked to novel immunotherapy drugs like pembrolizumab. The approach involved the use of corticosteroids tailored to the patient's condition. Furthermore, it references the recommendations outlined in the Common Terminology Criteria for Adverse Events (CTCAE). Prompt recognition and effective management of these side effects are essential to optimizing outcomes for patients undergoing immunotherapy. Our results were refined and focused by utilizing Medical Subject Headings (MeSH) keywords in our search strategy. The MeSH keywords used were "renal side effects" OR "immunotherapy" OR "cancer treatment." The studies reviewed encompassed a total of 48,529 participants among the 21 studies examined.
PubMed: 38516472
DOI: 10.7759/cureus.54487 -
Journal of Rheumatic Diseases Apr 2024While urate-lowering therapy (ULT) is linked to increased cardioprotective benefits on primary prevention of cardiovascular events such myocardial infarction or heart...
OBJECTIVE
While urate-lowering therapy (ULT) is linked to increased cardioprotective benefits on primary prevention of cardiovascular events such myocardial infarction or heart failure, little is known regarding their effects on arrhythmia risk. The purpose of this study was to investigate the relationship between incident arrhythmias and ULT.
METHODS
We searched MEDLINE and Embase from inception to May 2023. Included studies were randomized controlled trials and cohort studies that compared the risk of cardiac arrhythmias among ULT users with non-ULT users.
RESULTS
A total of 12,420 patients from five studies were analyzed, comprising 7,359 subjects in the ULT group and 5,061 subjects in the non-ULT group. Our results showed that ULT users had significant reductions in the risk of arrhythmias (pooled relative risk [RR] 0.82, 95% confidence interval [CI] 0.74~0.92, p<0.001, I2=0.0%) compared to non-ULT users. Subgroup analysis did not show that ULT users had a significant reduced risk of atrial fibrillation (pooled RR 0.76, 95% CI 0.54~1.05, p=0.096 with I2=15.4%) compared to non-ULT users.
CONCLUSION
ULT is associated with lower risk of overall arrhythmias. Further studies are warranted to confirm our findings.
PubMed: 38559794
DOI: 10.4078/jrd.2023.0059 -
Cardiology Journal May 2024Xanthine oxidase inhibitors, including allopurinol and febuxostat, are the first-line treatment of hyperuricemia. This meta-analysis investigated the association between...
Xanthine oxidase inhibitors, including allopurinol and febuxostat, are the first-line treatment of hyperuricemia. This meta-analysis investigated the association between urate-lowering therapy and all-cause mortality in different chronic diseases to match its users and non-users in a real-world setting. Overall, 11 studies were included, which reported adjusted hazard ratios for all-cause mortality over at least 12 months. Meta-analysis of all included studies showed no effect of the therapy on all-cause mortality. However, subgroup analyses showed its beneficial effect in patients with chronic kidney disease (14% risk reduction) and hyperuricemia (14% risk reduction), but not in patients with heart failure (28% risk increase). Urate-lowering therapy reduces all-cause mortality among patients with hyperuricemia and chronic kidney disease, but it seems to increase mortality in patients with heart failure and should be avoided in this subgroup.
PubMed: 38771265
DOI: 10.5603/cj.97807