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Seminars in Arthritis and Rheumatism Apr 2018In the management of chronic gout, a large proportion of patients need long-term management with urate lowering therapy (ULT). This study reviews medication adherence to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
In the management of chronic gout, a large proportion of patients need long-term management with urate lowering therapy (ULT). This study reviews medication adherence to ULT and summarizes factors associated with adherence.
METHODS
We performed a systematic literature search for studies on adherence to ULT among gout patients in PubMed, Embase, CINAHL, and PsycINFO. We conducted meta-analysis, with a random effect model, for the studies reporting the proportion of patients considered adherent to at least 80% of prescribed medication or time taken. We explored potential sources of heterogeneity, including geographic area and measure of adherence. Narrative summaries were made for data on adherence assessed/defined by Medication Event Monitoring System (MEMS)/pill-count or patient-reported, occurrence of a gap in therapy ≥30 days (non-persistence), and factors associated with adherence.
RESULTS
Of the 24 studies, 16 assessed adherence using prescription/claims data, two by the MEMS or pill count, and six by patient-reported data. The pooled proportion of adherent patients (n = 13) was 46% (95% CI: 41-51); 45% across studies conducted in the USA (n = 8) and 48% in other countries (n = 5). Adherence assessed by MEMS/pill count and patient-reported was much higher than by studies using prescription/claims data. Non-persistence (n = 6) ranged from 54% to 87%. Factors associated with adherence were investigated in 18 studies. Strong evidence for a positive association with older age, more comorbidities, and the presence of diabetes or hypertension was found.
CONCLUSION
Medication adherence to ULT among gout patients was poor. Better insight into reasons and consequences or poor adherence is needed.
Topics: Allopurinol; Gout; Gout Suppressants; Humans; Medication Adherence
PubMed: 29198878
DOI: 10.1016/j.semarthrit.2017.09.007 -
Cureus Oct 2022Tumor lysis syndrome (TLS) in patients with solid tumors is a rare and potentially fatal condition associated with anti-cancer treatment. Its outcome depends on... (Review)
Review
Tumor lysis syndrome (TLS) in patients with solid tumors is a rare and potentially fatal condition associated with anti-cancer treatment. Its outcome depends on awareness, identification of high-risk patients, and implementation of appropriate preventive measures. A systematic review was conducted according to PRISMA guidelines of case reports describing the occurrence of TLS in patients with solid tumors, primarily to identify potentially unrecognized or unusual clinical findings and outcomes. We searched the PubMed, EMBASE, and Cochrane databases and conference abstracts and performed manual searches for case reports and case series published in English and describing patients who developed TLS. A total of 124 studies (118 case reports and six case series) describing the findings for 132 patients were included. The most common cancers were hepatocellular carcinoma (17%, n = 22), lung cancer (13%, n = 17), and melanoma (10%, n = 13). The most common risk factor was metastatic disease (75%, n = 100). TLS was induced by chemotherapy in 48% (n = 64) of the patients. Clinical manifestations of TLS developed within three days of anti-cancer treatment in 37% of the patients (n = 49), while 52% (n = 68) received the full dose of anti-cancer treatment. Gastrointestinal symptoms occurred in 33% of the patients (n = 44), hyperuricemia in 95% (n = 125), and elevated creatinine level occurred in 85% of the patients (n = 112), While 58% (n = 77) of the patients received intravenous fluids, only 49% received allopurinol, and 24% (n = 32) received rasburicase. A total of 101 patients (77%) were treated in the ward, and 54% (n = 71) died. The mortality rate associated with TLS in patients with solid tumors remains high. Adequate management requires awareness, early recognition, and identification of patients at high risk. Interdisciplinary team management is essential to reduce mortality.
PubMed: 36439565
DOI: 10.7759/cureus.30652 -
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 -
European Review For Medical and... Mar 2016In patients with gout, serum uric acid (sUA) concentrations should be lowered at least below the target of 6 mg/dL (even below 5 mg/dL in patients with severe gout). To... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
In patients with gout, serum uric acid (sUA) concentrations should be lowered at least below the target of 6 mg/dL (even below 5 mg/dL in patients with severe gout). To achieve this goal, urate lowering medications (ULMs) should be considered. Currently-used ULMs include xanthine-oxidase inhibitors such as allopurinol, febuxostat, as well as available uricosuric agents. However, evidence comparing these agents remains scant. We have conducted a systematic review and meta-analysis to retrieve evidence on the clinical trials on the above-mentioned drugs in the treatment of gout.
MATERIALS AND METHODS
The following efficacy outcomes were considered in the meta-analysis: (1) % of patients meeting the therapeutic target for sUA level (<6 mg/dl) and (2) percentage reduction in sUA concentration at the end of the study compared with baseline values. An explorative analysis on safety was also conducted.
RESULTS
In total, 16 papers concerned febuxostat, 15 allopurinol, 4 benzbromarone and none involved probenecid. Overall, 70.7% of patients reached the target of sUA with febuxostat therapy; the reduction in sUA was 45.3%. Corresponding figures with allopurinol were 44.4% and 33.8%, respectively. The number of patients on benzbromarone (N=129) was too low to retrieve definitive findings. The advantage for febuxostat over allopurinol was evident also in patients with renal dysfunction. Safety analysis favored febuxostat over allopurinol (OR 0.85; 95% CI: 0.75-0.97).
CONCLUSIONS
On the basis of the reported data, febuxostat can play a major role in the treatment of hyperuricaemia and gout. Febuxostat is a suitable pharmacological option for first line treatment of gout, given its established efficacy and safety, documented in a high number of clinical studies and in daily practice.
Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Treatment Outcome; Uric Acid
PubMed: 27010159
DOI: No ID Found -
The Journal of Rheumatology. Supplement Sep 2014To systematically review the available literature on the management of tophi in gout. This article is based on the Cochrane Review Interventions for Tophi in Gout... (Review)
Review
OBJECTIVE
To systematically review the available literature on the management of tophi in gout. This article is based on the Cochrane Review Interventions for Tophi in Gout published in the Cochrane Database of Systematic Reviews.
METHODS
Medline, Embase, and The Cochrane Library were searched using a strategy developed with an experienced librarian. We also searched American College of Rheumatology and European League Against Rheumatism conference abstracts from 2010-2011. Included articles were reviewed in detail and a risk of bias (using the Cochrane tool) and quality assessment were performed.
RESULTS
In total, 3206 references were recovered. Of these, 72 articles were selected based on our inclusion criteria. This included 1 report of 2 randomized controlled trials, 2 nonrandomized studies, and 69 case series and reports. The study with 2 randomized controlled trials looked at pegloticase. This showed improvement in tophi with treatment. One observational prospective trial looked at allopurinol and benzbromarone individually and in combination. It noted that achieving lower serum urate levels was associated with a faster reduction of tophi. An open-label extension trial noted that longterm maintenance of serum uric acid < 6.0 mg/dl with febuxostat led to a reduction in tophi. The case series and reports looked at surgical, pharmacological, and other interventions, as well as combination therapies. All surgical interventions reported improvement in pain and/or function. No report had objective measures of outcome.
CONCLUSION
Treatment with urate-lowering therapy such as allopurinol, benzbromarone, allopurinol + benzbromarone in combination, febuxostat, or pegloticase can lead to reduction in tophi. There is some evidence that achieving a lower serum urate level leads to a faster rate of tophi reduction.
Topics: Gout; Gout Suppressants; Humans
PubMed: 25180130
DOI: 10.3899/jrheum.140464 -
Journal of Clinical Medicine Apr 2022Objective: Current guidelines for gout recommend a treat-to-target approach with serum uric acid (SUA). However, there is little evidence for the dose-dependent effects... (Review)
Review
Objective: Current guidelines for gout recommend a treat-to-target approach with serum uric acid (SUA). However, there is little evidence for the dose-dependent effects of urate-lowering therapy (ULT). Herein, we analyzed the reported SUA-lowering effect and SUA target achievement differences for various doses of xanthine oxidase inhibitors. Methods: Approved ULT drugs were selected from the FDA Drug Database. We included prospective randomized controlled trials of ULT drugs from ClinicalTrials.gov, articles published in the journal “Drugs”, and Embase, a literature database. A meta-analysis was performed to determine the ability of different ULT drugs and doses to lower and maintain a target SUA < 6 mg/dL. Results: We identified 35 trials including 8172 patients with a baseline SUA of 8.92 mg/dL. The allopurinol, febuxostat, and topiroxostat showed dose-proportional SUA-lowering responses. Compared with allopurinol 300 mg daily, febuxostat 80 mg daily and 120 mg daily more effectively maintained SUA < 6 mg/dL. Conclusion: Allopurinol, febuxostat, and topiroxostat showed dose-proportional ability to lower and achieve a target SUA < 6 mg/dL. Significance and Innovations. We showed dose-dependent SUA lowering effects of allopurinol, febuxostat, and topiroxostat. Febuxostat is effective at ULT compared to allopurinol and could be potentially offered as an alternative agent when patients (1) have CKD, (2) have the human leukocyte antigen HLA-B*5801 allele, and (3) become refractory to allopurinol. Gradual allopurinol dose increase with a lower starting dose is needed in CKD.
PubMed: 35566594
DOI: 10.3390/jcm11092468 -
Clinical Rheumatology Mar 2022Several previous studies have suggested that uric acid-lowering therapy (ULT) can slow the progression of chronic kidney disease (CKD). Although crucial for CKD... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several previous studies have suggested that uric acid-lowering therapy (ULT) can slow the progression of chronic kidney disease (CKD). Although crucial for CKD patients, few studies have evaluated the effects of different ULT medications on kidney function. This systematic review summarizes evidence from randomized controlled trials (RCTs) regarding the effects of ULT on kidney function.
METHOD
We performed a systematic search of PubMed, MEDLINE, Embase, Scopus, and the Cochrane Library up to September 2021 to identify RCTs in CKD patients comparing the effects of ULT on kidney function with other ULT medications or placebo. A network meta-analysis was performed to compare each ULT indirectly. The primary outcome was a change in estimated glomerular filtration rate (eGFR) from baseline.
RESULTS
Ten studies were selected with a total of 1480 patients. Topiroxostat significantly improved eGFR and reduced the urinary albumin/creatinine ratio compared to placebo (mean difference (MD) and 95% confidence interval [95% CI]: 1.49 [0.08; 2.90], P = 0.038 and 25.65% [13.25; 38.04], P < 0.001, respectively). Although febuxostat did not show a positive effect overall, it significantly improved renal function (i.e., eGFR) in a subgroup of CKD patients with hyperuricemia (MD [95% CI]: 0.85 [0.02; 1.67], P = 0.045). Allopurinol and pegloticase did not show beneficial effects.
CONCLUSIONS
Topiroxostat and febuxostat may have better renoprotective effects in CKD patients than other ULT medications. Further large-scale, long-term studies are required to determine whether these effects will lead, ultimately, to reductions in dialysis induction and major adverse cardiovascular events. Key Points • This study is the first network meta-analysis comparing the nephroprotective effects of ULT in CKD patients. • Topiroxostat and febuxostat showed better renoprotective effects in CKD patients than other ULT medications. • Heterogeneity was low in this study, suggesting consistency of results.
Topics: Febuxostat; Gout Suppressants; Humans; Hyperuricemia; Kidney; Network Meta-Analysis; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome; Uric Acid
PubMed: 34642880
DOI: 10.1007/s10067-021-05956-5 -
Annals of Palliative Medicine Oct 2021To evaluate the major cardiovascular (CV) events of febuxostat compared to allopurinol for the treatment of gout or asymptomatic hyperuricemia. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the major cardiovascular (CV) events of febuxostat compared to allopurinol for the treatment of gout or asymptomatic hyperuricemia.
METHODS
Relevant studies published until August 15, 2020 were identified by a systematic search of the PubMed and Wiley Online Library databases. Any controlled clinical trial, randomised controlled trial (RCT), retrospective cohort study or open label trial (OLT) comparing febuxostat in patients with gout or hyperuricemia with allopurinol. The quality of all identified studies was assessed based on Cochrane Collaboration's risk of bias tool. Odds ratios (OR) were calculated with random effects and reported with corresponding 95% confidence intervals (CI).
RESULTS
Eighteen studies were ultimately included in the analysis, among them 6 articles mentioned serum uric acid (sUA) level before and after treatment, 14 articles mentioned major cardiovascular events, 5 articles mentioned cardiovascular death, 6 articles mentioned skin reactions, 6 articles mentioned musculoskeletal and connective tissue signs and symptoms, 4 articles mentioned joint-related signs and symptoms, 6 articles mentioned upper respiratory infection, 5 articles mentioned gastrointestinal reaction and 7 articles mentioned all-cause mortality. The febuxostat group showed significantly lower sUA levels than allopurinol group (MD =-0.83, 95% CI: -1.22 to -0.44, P<0.0001, I2=98%). There was no markedly difference between the febuxostat and allopurinol (OR 1.01, 95% CI: 0.83 to 1.23, P=0.84, I2=95%) in the major cardiovascular events. The occurrence of skin reactions of febuxostat was significantly fewer than allopurinol (OR 0.55, 95% CI: 0.42 to 0.73, P<0.0001, I2=49%). Regarding to occurrence of CV death, musculoskeletal and connective tissue signs and symptoms, febuxostat group was higher than allopurinol group. However, among patients with gout or hyperuricemia, treatment with febuxostat resulted in other adverse reactions, including all-causes mortality similar to those associated with allopurinol.
DISCUSSION
The limitation of the study was the included studies show high heterogeneity in regard to their design. There was no difference in the incidence of major cardiovascular events between febuxostat and allopurinol, and febuxostat was better in lowering uric acid and has less adverse skin reactions than allopurinol, but the risk of CV death of febuxostat was higher than allopurinol.
Topics: Allopurinol; Cardiovascular Diseases; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Treatment Outcome; Uric Acid
PubMed: 34498481
DOI: 10.21037/apm-21-1564 -
World Journal of Gastroenterology Apr 2018To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations. (Meta-Analysis)
Meta-Analysis Review
AIM
To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations.
METHODS
A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31, 2017. The inclusion criteria were comparative, randomized controlled trials (RCTs) for deceased donor liver (DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin (UW) solution or histidine-tryptophan-ketoglutarate (HTK), Celsior (CS) and Institut Georges Lopez (IGL-1) solutions. Fifteen RCTs (1830 livers) were included; the primary outcomes were primary non-function (PNF) and one-year post-transplant graft survival (OGS-1).
RESULTS
All trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1 (RR = 0.02, 95%CI: 0.01-0.03, = 0.356). Comparing OGS-1 also failed to reveal any difference between UW, HTK, CS and IGL-1 (RR = 0.80, 95%CI: 0.80-0.80, = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and CS were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, CS, HTK and IGL-1 solutions were associated with nearly equivalent outcomes.
CONCLUSION
Alternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted.
Topics: Adenosine; Allopurinol; Disaccharides; Electrolytes; Glucose; Glutamates; Glutathione; Graft Survival; Histidine; Humans; Insulin; Liver Transplantation; Mannitol; Odds Ratio; Organ Preservation; Organ Preservation Solutions; Potassium Chloride; Primary Graft Dysfunction; Procaine; Raffinose; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Treatment Outcome
PubMed: 29713134
DOI: 10.3748/wjg.v24.i16.1812 -
BMC Nephrology Apr 2015Hyperuricemia may contribute to renal injury. We do not know whether use of treatments that lower urate reduce the progression of chronic kidney disease (CKD) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hyperuricemia may contribute to renal injury. We do not know whether use of treatments that lower urate reduce the progression of chronic kidney disease (CKD) and cardiovascular disease. We performed a systematic review and meta-analysis of randomized controlled trials to assess the benefits and risks of treatments that lower urate in patients with stages 3-5 CKD.
METHODS
We searched MEDLINE, EMBASE, CENTRAL, Web of Science and trial registers for randomized controlled trials (RCTs) without language restriction. Two authors independently screened articles, assessed risk of bias and extracted data. Data obtained included serum uric acid, serum creatinine or other estimates of glomerular filtration rate, incidence of end-stage renal disease (ESRD), systolic and diastolic blood pressure, proteinuria, cardiovascular disease and adverse events.
RESULTS
From the 5497 citations screened, 19 RCTs enrolling 992 participants met our inclusion criteria. Given significant heterogeneity in duration of follow-up and study comparators, only trials greater than 3 months comparing allopurinol and inactive control were meta-analyzed using random effects models. Pooled estimate for eGFR was in favour of allopurinol with a mean difference (MD) of 3.2 ml/min/1.73 m(2), 95% CI 0.16-6.2 ml/min/1.73 m(2), p = 0.039 and this was consistent with results for serum creatinine. Statistically significant reductions in serum uric acid, systolic and diastolic blood pressure were found, favouring allopurinol. There were insufficient data on adverse events, incidence of ESRD and cardiovascular disease for analysis.
CONCLUSIONS
Adequately powered RCTs are needed to establish whether treatments that lower urate have beneficial renal and cardiovascular effects.
Topics: Cardiovascular Diseases; Creatinine; Disease Progression; Glomerular Filtration Rate; Gout Suppressants; Humans; Hyperuricemia; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Treatment Outcome; Uric Acid; Uricosuric Agents
PubMed: 25928556
DOI: 10.1186/s12882-015-0047-z