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1.
Med Sci Monit ; 30: e944314, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38865287

RESUMEN

BACKGROUND Hyperuricemia, which is common in chronic kidney disease and diabetes mellitus patients, raises health concerns. Febuxostat, a first-line urate-lowering agent, prompts cardiovascular risk questions, especially in high-risk patients. This study compared the effects of febuxostat and allopurinol on cardiovascular risk in diabetes mellitus and chronic kidney disease patients. MATERIAL AND METHODS This retrospective observational cohort study, conducted using Taiwan's National Health Insurance Research Database, focused on patients diagnosed with chronic kidney disease and diabetes between January 2012 and December 2017. The study population was divided into 2 groups: allopurinol users (n=12 901) and febuxostat users (n=2997). We performed 1: 1 propensity score matching, resulting in subgroups of 2997 patients each. The primary outcomes were assessed using a competing risk model, estimating hazard ratios (HR) for long-term outcomes, including the risks of all-cause hospitalization, hospitalization for heart failure, and hospitalization for cardiovascular interventions. RESULTS Febuxostat users, compared to allopurinol users, had higher all-cause hospitalization (HR: 1.33; 95% confidence interval [CI]: 1.25 to 1.42; P<.001), hospitalization for heart failure (HR: 1.62; 95% CI: 1.43 to 1.83; P<.001), and hospitalization for cardiovascular interventions (HR: 1.51; 95% CI: 1.32 to 1.74; P<.001). Moreover, the adverse effects of febuxostat on cardiac health were consistent across most subgroups. CONCLUSIONS Use of febuxostat in patients with diabetes mellitus and chronic kidney disease is associated with higher cardiovascular risks compared to allopurinol. Prudent evaluation is essential when recommending febuxostat for this at-risk group.


Asunto(s)
Alopurinol , Enfermedades Cardiovasculares , Febuxostat , Supresores de la Gota , Hiperuricemia , Insuficiencia Renal Crónica , Humanos , Febuxostat/uso terapéutico , Febuxostat/efectos adversos , Alopurinol/uso terapéutico , Alopurinol/efectos adversos , Masculino , Femenino , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Taiwán/epidemiología , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/complicaciones , Supresores de la Gota/uso terapéutico , Supresores de la Gota/efectos adversos , Diabetes Mellitus/tratamiento farmacológico , Factores de Riesgo , Adulto , Hospitalización
2.
Int J Rheum Dis ; 27(5): e15165, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38769820

RESUMEN

OBJECTIVE: To compare the clinical efficacy of febuxostat combined with a low-purine diet versus allopurinol combined with a low-purine diet in the treatment of gout. METHODS: In this prospective controlled trial, 98 gout patients admitted to our hospital from February 2021 to December 2022 were enrolled as study subjects. Patients were randomly assigned to the study group (febuxostat combined with a low-purine diet) and the control group (allopurinol combined with a low-purine diet), with 49 patients in each group. The therapeutic effect was evaluated based on joint function and serum uric acid levels after treatment, and classified into three levels: markedly effective, effective, and ineffective. The levels of inflammatory factors, including tumor necrosis factor-a (TNF-a), cytokine interleukin-1beta (IL-1ß), and interleukin (IL)-18 (IL-18), were collected. The Numeric Rating Scale (NRS) was used to assess the degree of pain in patients. Clinical indicators before and 6 months after treatment were compared between the two groups. RESULTS: There was no statistically significant difference in age and gender between the two groups. After 6 months of treatment, the effective rate in the study group (48 cases, 97.96%) was higher than that in the control group (42 cases, 85.71%), with a statistically significant difference (p = .027). At the same time, the study group had significantly lower levels of serum uric acid (162.39 µmol/L ± 17.23 µmol/L vs. S198.32 µmol/L ± 18.34 µmol/L, p < .001), creatinine (87.39 mmol/L ± 9.76 mmol/L vs. 92.18 mmol/L ± 9.27 mmol/L, p = .014), total cholesterol (3.65 mmol/L ± 0.65 mmol/L vs. 4.76 mmol/L ± 0.73 mmol/L, p < .001), and triglycerides (1.76 mmol/L ± 0.32 mmol/L vs. 2.28 mmol/L ± 0.41 mmol/L, p < .001) compared to the control group, with statistically significant differences (p < .05). After treatment, the levels of inflammatory factors and degree of pain in the study group were significantly lower than those in the control group (all p < .05). During the treatment process, the incidence of adverse reactions in the study group (2 cases, 4.08%) was lower than that in the control group (9 cases, 18.37%), with a statistically significant difference (p = .025). CONCLUSION: Febuxostat combined with a low-purine diet can reduce inflammatory factors and alleviate the degree of pain in gout patients, significantly improving their clinical symptoms.


Asunto(s)
Alopurinol , Febuxostat , Supresores de la Gota , Gota , Ácido Úrico , Humanos , Febuxostat/uso terapéutico , Febuxostat/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Alopurinol/uso terapéutico , Gota/tratamiento farmacológico , Gota/sangre , Gota/diagnóstico , Supresores de la Gota/uso terapéutico , Supresores de la Gota/efectos adversos , Estudios Prospectivos , Resultado del Tratamiento , Ácido Úrico/sangre , Anciano , Purinas/uso terapéutico , Biomarcadores/sangre , Terapia Combinada , Factores de Tiempo , Adulto , Mediadores de Inflamación/sangre
3.
Int J Rheum Dis ; 27(5): e15162, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38720421

RESUMEN

BACKGROUND: Recent findings suggest a link between gout and the development of dementia. Early treatment with colchicine is recommended as a first-line therapy for gout flares. Animal studies demonstrate that colchicine could induce cognitive impairment. This cohort study aimed to investigate the association between colchicine use and the risk of developing dementia. METHODS: In this nationwide cohort study, we performed comparative analysis on 6147 patients ≥40 years, with gout and colchicine new users against 6147 controls to assess subsequent dementia risk. The colchicine group and the control group (urate lowering therapy group) were matched on the bases of age, sex, index year, and comorbidities. All participants were followed for up to 14 years for a diagnosis of dementia considering medical records were retrospectively checked over this period. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Sensitivity analyses were performed to validate our findings. RESULTS: The adjusted hazard ratio (aHR) of dementia for colchicine users was 1.45 (95% CI = 1.05, 1.99) relative to comparison group after adjusting for sex, age, and comorbidities. Sensitivity analysis aiming to minimize underdiagnosed occult dementia at the time of index year yielded consistent positive association. In higher accumulative dose colchicine group (cumulative defined daily dose [cDDD] >30), the aHR of dementia risk for colchicine users was 1.42 (95% CI = 1.03, 1.97) compared with nonusers. For those duration of colchicine use >30 days, the aHR was 1.53 (95% CI = 1.01-2.32) compared to the nonuser group. CONCLUSIONS: A significant risk of dementia was observed in this study in patients with gout using colchicine at higher cDDD and for a longer period. Further research is needed to elucidate the relationship between colchicine, gout, and dementia.


Asunto(s)
Colchicina , Demencia , Supresores de la Gota , Gota , Humanos , Colchicina/efectos adversos , Colchicina/uso terapéutico , Gota/epidemiología , Gota/tratamiento farmacológico , Demencia/epidemiología , Demencia/inducido químicamente , Demencia/diagnóstico , Femenino , Masculino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Supresores de la Gota/efectos adversos , Factores de Riesgo , Medición de Riesgo , Factores de Tiempo , Taiwán/epidemiología , Adulto , Anciano de 80 o más Años , Bases de Datos Factuales
4.
Rheumatol Int ; 44(7): 1245-1253, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38538820

RESUMEN

OBJECTIVE: The objective of this study was to analyze and compare the effects of different urate-lowering agents on testicular functions in men with gout in a clinical setting. METHODS: In this prospective cohort study (Clinical Trial Registration Number: NCT04213534), a total of 49 male patients aged 18-45 years with gout were enrolled. They were divided into three groups and received treatment with either allopurinol, febuxostat or benzbromarone for a duration of 3 months. Semen parameters, reproductive hormones and biochemical assessments were evaluated at baseline, month 1, and month 3. RESULTS: Overall, 40 individuals (81.6%) completed the follow-up visits. In allopurinol group, there were no significant differences in semen parameters from baseline to month 3. Most of sperm parameters in febuxostat group did not show notable changes, except for a decrease in sperm motility at month 3(33.6%, [22.9-54.3] vs 48.4%, [27.4-67.6], p = 0.033). However, the total motile sperm count did not differ significantly after febuxostat treatment. Surprisingly, administration of benzbromarone resulted in improved sperm concentration (37.19 M/mL, [29.6-69.92] vs 58.5 M/mL, [49.8-116.6], p = 0.001). There were no significant changes observed in sperm DNA integrity and reproductive hormones in the three groups from baseline to month 3. The incidence of adverse events did not differ significantly among the three groups as well. CONCLUSION: This study is the first to demonstrate that urate-lowering agents, allopurinol and febuxostat, do not have clinically relevant negative effects on sperm quality and reproductive hormones in men with gout, and benzbromarone presents improving sperm concentration. Results provide important preliminary guidance for the development of reproductive health management guidelines for patients RCID with gout.


Asunto(s)
Alopurinol , Benzbromarona , Febuxostat , Supresores de la Gota , Gota , Espermatozoides , Humanos , Masculino , Gota/tratamiento farmacológico , Gota/sangre , Adulto , Estudios Prospectivos , Supresores de la Gota/uso terapéutico , Supresores de la Gota/efectos adversos , Persona de Mediana Edad , Febuxostat/uso terapéutico , Febuxostat/farmacología , Benzbromarona/uso terapéutico , Adulto Joven , Alopurinol/uso terapéutico , Espermatozoides/efectos de los fármacos , Motilidad Espermática/efectos de los fármacos , Análisis de Semen , Adolescente , Recuento de Espermatozoides , Ácido Úrico/sangre
5.
Arterioscler Thromb Vasc Biol ; 44(5): 1031-1041, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38511324

RESUMEN

Colchicine-an anti-inflammatory alkaloid-has assumed an important role in the management of cardiovascular inflammation ≈3500 years after its first medicinal use in ancient Egypt. Primarily used in high doses for the treatment of acute gout flares during the 20th century, research in the early 21st century demonstrated that low-dose colchicine effectively treats acute gout attacks, lowers the risk of recurrent pericarditis, and can add to secondary prevention of major adverse cardiovascular events. As the first Food and Drug Administration-approved targeted anti-inflammatory cardiovascular therapy, colchicine currently has a unique role in the management of atherosclerotic cardiovascular disease. The safe use of colchicine requires careful monitoring for drug-drug interactions, changes in kidney and liver function, and counseling regarding gastrointestinal upset. Future research should elucidate the mechanisms of anti-inflammatory effects of colchicine relevant to atherosclerosis, the potential role of colchicine in primary prevention, in other cardiometabolic conditions, colchicine's safety in cardiovascular patients, and opportunities for individualizing colchicine therapy using clinical and molecular diagnostics.


Asunto(s)
Enfermedades Cardiovasculares , Colchicina , Humanos , Antiinflamatorios/uso terapéutico , Antiinflamatorios/efectos adversos , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Colchicina/uso terapéutico , Colchicina/efectos adversos , Interacciones Farmacológicas , Supresores de la Gota/uso terapéutico , Supresores de la Gota/efectos adversos , Resultado del Tratamiento
6.
BMJ ; 384: q514, 2024 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-38458626

RESUMEN

The studyRoddy E, Bajpai R, Forrester H, et al. Safety of colchicine and NSAID prophylaxis when initiating urate-lowering therapy for gout: propensity score-matched cohort studies in the UK Clinical Practice Research Datalink. Ann Rheum Dis 2023;82:1618-25.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/how-common-are-side-effects-of-treatment-to-prevent-gout-flares-when-starting-allopurinol/.


Asunto(s)
Gota , Humanos , Gota/tratamiento farmacológico , Alopurinol/efectos adversos , Supresores de la Gota/efectos adversos , Ácido Úrico , Brote de los Síntomas
7.
J Rheumatol ; 51(6): 556-562, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38490676

RESUMEN

Allopurinol is the most widely used urate-lowering medication worldwide. However, allopurinol failure is frequently observed in clinical practice. In this review, we provide a framework for assessing allopurinol failure, which includes failure of allopurinol to control serum urate concentrations, failure of allopurinol to control clinical symptoms, and failure of allopurinol due to an adverse drug reaction. Understanding the causes of allopurinol failure underpins the approach required to turn failure into success in gout management.


Asunto(s)
Alopurinol , Supresores de la Gota , Gota , Insuficiencia del Tratamiento , Alopurinol/uso terapéutico , Alopurinol/efectos adversos , Humanos , Gota/tratamiento farmacológico , Gota/sangre , Supresores de la Gota/uso terapéutico , Supresores de la Gota/efectos adversos , Ácido Úrico/sangre
8.
Clin Transl Sci ; 17(3): e13757, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38488426

RESUMEN

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.


Asunto(s)
Enfermedades Cardiovasculares , Gota , Hiperuricemia , Humanos , Alopurinol/efectos adversos , Febuxostat/efectos adversos , Hiperuricemia/complicaciones , Hiperuricemia/tratamiento farmacológico , Supresores de la Gota/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/epidemiología , Gota/tratamiento farmacológico , Resultado del Tratamiento
9.
Clin Rheumatol ; 43(5): 1745-1754, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38492092

RESUMEN

OBJECTIVE: Urate-lowering therapy (ULT) is widely recognized as the primary treatment for hyperuricemia and gout. Xanthine oxidase inhibitors (XOI), particularly febuxostat, have gained popularity as a frontline approach. However, the divergent efficacy and safety between febuxostat and the traditional ULT drug, benzbromarone, remain poorly understood. This knowledge gap necessitates a comprehensive analysis and evidence update to guide drug selection for physicians and patients. METHOD: We conducted a systematic analysis by extracting relevant clinical studies from four medical literature databases. Forest plots, funnel plots, sensitivity analysis, Egger's test, and subgroup analysis were utilized to compare relevant indicators. RESULTS: The advantages and disadvantages of the two drugs were evaluated based on various indicators such as serum uric acid (SUA), triglyceride (TG), urinary uric acid (UUA), white blood cell count (WBC), total cholesterol (TC), blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine (SC). Benzbromarone demonstrated better efficacy in rapidly reducing SUA levels and inhibiting inflammation for hyperuricemia and gout patients. Febuxostat was slightly less effective in lowering SUA, but there was no significant difference in its impact on liver and kidney function after long-term use. CONCLUSION: This study highlights the superiority of benzbromarone in rapidly reducing SUA and inhibiting inflammation. Febuxostat shows comparable effects on liver and kidney function after long-term use. These findings provide valuable insights for clinicians and patients in drug selection. Key Points • Benzbromarone stands out as a highly effective treatment for hyperuricemia and gout, offering rapid reduction of serum uric acid levels and potent anti-inflammatory effects. • When it comes to long-term use, febuxostat demonstrates comparable effects on liver and kidney function. This provides reassurance for patients who require extended treatment duration. • Moreover, our study goes beyond previous research by presenting a more comprehensive and detailed analysis.


Asunto(s)
Gota , Hiperuricemia , Humanos , Febuxostat/uso terapéutico , Hiperuricemia/tratamiento farmacológico , Benzbromarona/uso terapéutico , Ácido Úrico , Supresores de la Gota/efectos adversos , Gota/tratamiento farmacológico , Resultado del Tratamiento , Inflamación/tratamiento farmacológico , Alopurinol/uso terapéutico
10.
Arthritis Care Res (Hoboken) ; 76(6): 871-881, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38303574

RESUMEN

OBJECTIVE: We systematically examined comparative gout flare risk after initiation or escalation of different urate-lowering therapies (ULTs), comparative flare risk with and without concomitant flare prophylaxis, adverse event rates associated with flare prophylaxis, and optimal duration of flare prophylaxis. METHODS: We searched the Medline, Embase, Web of Science, and Cochrane databases and clinical trial registries from inception to November 2021 for trials investigating adults with gout initiating or escalating ULT. We performed random effects network meta-analyses and calculated risk ratios (RRs) between treatments. Bias was assessed using the revised Cochrane risk-of-bias tool. RESULTS: We identified 3,775 records, of which 29 publications (27 trials) were included. When compared to placebo plus prophylaxis, the RR of flares ranged from 1.08 (95% confidence interval [CI] 0.87-1.33) for febuxostat 40 mg plus prophylaxis to RR 2.65 [95% CI 1.58-4.45] for febuxostat 80 mg plus lesinurad 400 mg plus prophylaxis. Compared to ULT alone, the RR of flares was lower for ULT plus rilonacept 160 mg (RR 0.35 [95% CI 0.25-0.50]), ULT plus rilonacept 80 mg (RR 0.43 [95% CI 0.31-0.60]) and ULT plus colchicine (RR 0.50 [95% CI 0.35-0.72]). There was limited evidence for other flare prophylaxis and on prophylaxis harms and optimal duration. Primarily because of missing outcome data and bias in the selection of reported results, 71.4% and 63.4% of studies were assessed as high risk of bias for flares and adverse events, respectively. CONCLUSION: The RR of flares when introducing ULT varies depending on ULT drug and dosing strategies. There were limited data on ULT escalation. Flare prophylaxis with colchicine and rilonacept reduces flare incidence. More research is required on the harms and optimal duration of prophylaxis.


Asunto(s)
Supresores de la Gota , Gota , Metaanálisis en Red , Brote de los Síntomas , Ácido Úrico , Humanos , Gota/tratamiento farmacológico , Gota/sangre , Supresores de la Gota/uso terapéutico , Supresores de la Gota/efectos adversos , Supresores de la Gota/administración & dosificación , Ácido Úrico/sangre , Medición de Riesgo , Colchicina/uso terapéutico , Colchicina/efectos adversos , Colchicina/administración & dosificación , Febuxostat/uso terapéutico , Febuxostat/administración & dosificación , Febuxostat/efectos adversos , Resultado del Tratamiento , Factores de Riesgo , Quimioterapia Combinada , Proteínas Recombinantes de Fusión
11.
Clin Pharmacol Ther ; 115(6): 1358-1364, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38389505

RESUMEN

A recent meta-analysis found no benefit of uric acid-lowering therapy including febuxostat on death, cardiovascular events, or renal impairment. However, there may be populations that benefit from febuxostat in reducing mortality and cerebral and cardiovascular events. The aim of the present study was to examine the clinical benefit of febuxostat in elderly patients stratified by age using Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) data. FREED was a randomized study involving patients aged 65 years or older with hyperuricemia and risk factors for cerebral, cardiovascular, or renal diseases. A total of 1,070 patients were included in this post hoc analysis, divided into 2 age groups: 65-74 years and ≥ 75 years. Patients were randomized into febuxostat and non-febuxostat groups, with uric acid levels monitored for 36 months. The primary composite end point included cerebral, cardiovascular, and renal events. In patients aged between 65 and 74 years, febuxostat significantly reduced the risk of future cerebral and cardiorenovascular events. However, no effects of febuxostat were found in the older population aged ≥ 75 years. Heterogeneity in potential interactions between the age and febuxostat treatment was particularly observed in non-fatal cerebral and cardiovascular events and all-cause death. Patients aged ≥ 75 years exhibited more pre-existing factors associated with cerebral and cardiorenovascular events than those aged 65-74 years. The effectiveness of febuxostat varies by age group, with potential benefits for patients aged 65-74 years. The effects of febuxostat are complex and it is important to consider patient characteristics in its clinical use.


Asunto(s)
Enfermedades Cardiovasculares , Febuxostat , Supresores de la Gota , Hiperuricemia , Ácido Úrico , Humanos , Febuxostat/uso terapéutico , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/sangre , Anciano , Masculino , Femenino , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/mortalidad , Supresores de la Gota/uso terapéutico , Supresores de la Gota/efectos adversos , Ácido Úrico/sangre , Factores de Edad , Anciano de 80 o más Años , Trastornos Cerebrovasculares/prevención & control , Factores de Riesgo , Resultado del Tratamiento
14.
Rheumatology (Oxford) ; 63(4): 1058-1067, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-37449908

RESUMEN

OBJECTIVES: Serum urate (SU) lowering with PEGylated uricases in gout can reduce flares and tophi. However, treatment-emergent anti-drug antibodies adversely affect safety and efficacy and the currently approved PEGylated uricase pegloticase requires twice-monthly infusions. Investigational SEL-212 therapy aims to promote uricase-specific tolerance via monthly sequential infusions of a proprietary rapamycin-containing nanoparticle (ImmTOR) and pegadricase. METHODS: COMPARE was a randomized, phase 2, open-label trial of SEL-212 vs pegloticase in adults with refractory gout. SEL-212 [ImmTOR (0.15 mg/kg) and pegadricase (0.2 mg/kg)] was infused monthly or pegloticase (8 mg) twice monthly for 6 months. The primary endpoint was the proportion of participants with SU <6 mg/dl for ≥80% of the time during 3 and 6 months. Secondary outcomes were mean SU, gout flares, number of tender and/or swollen joints and safety. RESULTS: During months 3 and 6 combined, numerically more participants achieved and maintained a SU <6 mg/dl for ≥80% of the time with SEL-212 vs pegloticase (53.0% vs 46.0%, P = 0.181). The percentage reductions in SU levels were statistically greater during months 3 and 6 with SEL-212 vs pegloticase (-73.79% and -47.96%, P = 0.0161). Reductions in gout flare incidence and number of tender and/or swollen joints were comparable between treatments. There were numerical differences between the most common treatment-related adverse events of interest with SEL-212 and pegloticase: gout flares (60.2% vs 50.6%), infections (25.3% vs 18.4%) and infusion-related reactions (15.7% vs 11.5%), respectively. Stomatitis (and related terms) was experienced by eight participants (9.6%) with SEL-212 and none with pegloticase. Stomatitis, a known event for rapamycin, was associated with ImmTOR only. CONCLUSIONS: SEL-212 efficacy and tolerability were comparable to pegloticase in refractory gout. This was associated with a substantial reduction in treatment burden with SEL-212 due to decreased infusion frequency vs pegloticase. CLINICAL TRIAL REGISTRATION: NCT03905512.


Asunto(s)
Gota , Estomatitis , Adulto , Humanos , Urato Oxidasa/uso terapéutico , Urato Oxidasa/efectos adversos , Supresores de la Gota/efectos adversos , Ácido Úrico , Resultado del Tratamiento , Brote de los Síntomas , Polietilenglicoles/efectos adversos , Uricosúricos/uso terapéutico , Estomatitis/inducido químicamente , Estomatitis/tratamiento farmacológico
15.
Int J Rheum Dis ; 27(1): e14986, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38014453

RESUMEN

BACKGROUND: Studies have demonstrated the association of hyperuricemia with hypertension, metabolic syndrome, cardiovascular disease, and chronic renal disease. Although Western medicine presents promising effects for treating hyperuricemia and gout, identifying a safe and effective alternative to traditional Chinese medicine (TCM) for treating hyperuricemia is essential. OBJECTIVE: To evaluate the efficacy and safety of TCM formulas, "Wu-Ling San" and "Yin Chen Wu-Ling San," in patients with hyperuricemia. METHODS: A randomized, double-blinded, placebo-controlled clinical trial in adults with hyperuricemia was conducted. Sixty patients with serum urate level higher than 8 mg/dL were enrolled in the study. Patients were then randomized into three arms: "Wu-Ling San," "Yin Chen Wu-Ling San," and placebo for 4 weeks. Efficacy and safety were evaluated at weeks 2, 4, and 8. Primary and secondary endpoints were set to evaluate the serum urate concentration and related indicators at weeks 2, 4, and 8. RESULTS: No significant differences were observed among the three arms in terms of the serum urate level (<6 mg/dL) at week 4. The serum urate level was lower in the "Yin Chen Wi-Ling" arm at week 8 (8.1 mg/dL vs. 9.1 mg/dL, p = .034). The serum urate levels were significantly different in both the "Wu-Ling San" and "Yin Chen Wu-Ling San" arms from those at the baseline (p < .05). CONCLUSIONS: Two TCM formulas were found to be relatively safe for the short-term treatment of the patients with hyperuricemia. No statistically significant difference was observed in reaching the target-serum urate level <6 mg/dL.


Asunto(s)
Gota , Hiperuricemia , Adulto , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/tratamiento farmacológico , Ácido Úrico , Medicina Tradicional China , Gota/diagnóstico , Gota/tratamiento farmacológico , Supresores de la Gota/efectos adversos , Resultado del Tratamiento
16.
Rheumatology (Oxford) ; 63(4): 936-944, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38019947

RESUMEN

Colchicine has an important role in managing various conditions, including gout, familial Mediterranean fever, amyloidosis, Behçet's syndrome, recurrent pericarditis and calcium pyrophosphate deposition disease. The adverse effect profile of colchicine is well understood. However, due to its narrow therapeutic index, colchicine has been associated with overdose and fatalities. When ingested in toxic amounts, the mainstay of management is supportive care. Strategies to minimize the risk of colchicine poisoning can focus on three broad causes: unauthorized access, intentional overdose and inappropriate dosing. Culturally safe and appropriate education about storage and appropriate use of colchicine is essential to minimize the risk of overdose.


Asunto(s)
Amiloidosis , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Fiebre Mediterránea Familiar , Gota , Humanos , Colchicina/efectos adversos , Fiebre Mediterránea Familiar/tratamiento farmacológico , Supresores de la Gota/efectos adversos , Gota/tratamiento farmacológico , Gota/inducido químicamente , Amiloidosis/tratamiento farmacológico
18.
J Clin Rheumatol ; 30(2): e46-e53, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38115182

RESUMEN

INTRODUCTION: To this date, a causal relationship between febuxostat and cardiovascular disease remains controversial as comparison between trials can be challenging and may lead to misleading conclusions, especially when facing heterogeneous cardiovascular outcomes. We aimed to compare the cardiovascular outcomes in the most pertinent trials of febuxostat compared with controls. METHODS: We searched electronic databases using a PICOS-style approach search strategy of randomized controlled trials (RCTs) on cardiovascular outcomes of febuxostat in patients with gout or hyperuricemia. We conducted a quality and risk of bias assessment of the included clinical trials. The definition of major adverse cardiovascular event as well as all reported cardiovascular outcomes were retrieved from every involved trial. RESULTS: Of the 1173 records identified from all sources, 20 RCTs were included in the analysis. The mean duration of follow-up was 69.7 ± 81.5 weeks, and febuxostat dose ranged from 10 to 240 mg with 80 mg being the most commonly used dosage. Overall, the quality of evidence deriving from all RCTs showed concerns in most studies (65%). Major adverse cardiovascular event was defined in 7 of the 20 RCTs (35%), and cardiovascular outcome reporting was very heterogeneous. Overall, the data of cardiovascular safety of febuxostat were reassuring. CONCLUSIONS: Our systematic review showed high level of concerns in quality assessment domains as well heterogeneous cardiovascular outcomes across included studies. Cardiovascular outcomes in the majority of White males with gout treated with febuxostat were reassuring when compared with allopurinol. Further studies are needed to draw conclusions in patients with severe cardiovascular disease.


Asunto(s)
Enfermedades Cardiovasculares , Gota , Hiperuricemia , Masculino , Humanos , Febuxostat/efectos adversos , Hiperuricemia/tratamiento farmacológico , Supresores de la Gota/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Gota/tratamiento farmacológico , Alopurinol , Resultado del Tratamiento
19.
BMC Pharmacol Toxicol ; 24(1): 79, 2023 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-38098046

RESUMEN

BACKGROUND: The prevalence of hyperuricemia has increased steadily with the continuous improvement of living standards. Some studies have reported the clinical effectiveness and safety of different doses of febuxostat in comparison with allopurinol in hyperuricemia treatment, but the sample sizes of the studies have been small, and the results have been inconsistent. We designed this meta-analysis to evaluate the effectiveness and safety of different doses of febuxostat compared with allopurinol in the treatment of hyperuricemia. METHODS: The Cochrane Library, Embase, PubMed, Web of Science and ClinicalTrials.gov databases were searched to identify randomized controlled trials (RCTs) comparing the use of febuxostat and allopurinol for the treatment of hyperuricemia. The effectiveness and safety of different doses of febuxostat and allopurinol in treating hyperuricemia were assessed using meta-analysis. RESULTS: A total of 11 randomized controlled trials were included in the meta-analysis. The results of the meta-analysis showed that the percentage of patients achieving serum uric acid levels of 6.0 mg/dL or less was higher among patients taking febuxostat (80 mg/d) than among patients taking allopurinol (200-300 mg/d) [RR = 1.79, 95% CI (1.55, 2.08), P < 0.00001]. However, there was no statistically significant difference in the percentage of patients achieving serum uric acid levels of 6.0 mg/dL or less between febuxostat (40 mg/d) and allopurinol (200-300 mg/d) [RR = 1.10, 95% CI (0.93, 1.31), P = 0.25]. There was also no statistically significant difference in the incidence of gout between the febuxostat (40 mg/d) and allopurinol (200-300 mg/d) [RR = 0.97, 95% CI (0.64, 1.49), P = 0.91] or between the febuxostat (80 mg/d) and allopurinol (200-300 mg/d) [RR = 1.13, 95% CI (0.81, 1.58), P = 0.48].No significant difference in the incidence of major adverse reactions as observed between the febuxostat (40 mg/d) and allopurinol (200-300 mg/d) [RR = 1.16; 95% CI (0.43, 3.16), P = 0.77] or between the febuxostat (80 mg/d) and allopurinol (200-300 mg/d) [RR = 1.06; 95% CI (0.79, 1.42), P = 0.70]. The incidence of adverse cardiovascular events did not differ significantly between the febuxostat (40 mg/d) and allopurinol (200-300 mg/d) [RR = 1.30; 95% CI (0.57, 2.95), P = 0.53] or between the febuxostat (80 mg/d) and allopurinol (200-300 mg/d) [RR = 1.79; 95% CI (0.74, 4.32), P = 0.20]. CONCLUSIONS: Febuxostat (80 mg/d) was associated with a higher percentage of patients achieving serum uric acid levels of 6.0 mg/dL or less than allopurinol (200-300 mg/d), however, febuxostat (80 mg/d) did not exhibit better efficacy in reducing the incidence of gout. More attention should be devoted to the adverse reactions caused by an increase in febuxostat doses.


Asunto(s)
Gota , Hiperuricemia , Humanos , Febuxostat/efectos adversos , Alopurinol/efectos adversos , Hiperuricemia/tratamiento farmacológico , Supresores de la Gota/efectos adversos , Ácido Úrico , Tiazoles/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Gota/tratamiento farmacológico , Gota/complicaciones , Resultado del Tratamiento
20.
RMD Open ; 9(4)2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37973536

RESUMEN

OBJECTIVES: Gout, as the most prevalent form of inflammatory arthritis, necessitates the use of animal models to investigate the molecular mechanisms involved in its development. Therefore, our objective was to develop a novel chronic mouse model of gout that more closely mimics the progression of gout in humans. METHODS: A novel chronic mouse model of gout was established by a simple method, which does not require high technical proficiency, predominantly involves daily intraperitoneal injections of potassium oxonate for approximately 4 months, combined with a high fat-diet and injections of acetic acid into the hind paws to facilitate the formation of monosodium urate (MSU). Arthritis scores and paw oedema were assessed, behavioural tests were conducted, and histopathological and imaging evaluations of the arthritic paw joints were performed. RESULTS: After 4 months of induction, mice in the model group exhibited noticeable increases in arthritis severity, joint and cartilage damage, as well as bone erosion. Gomori's methenamine silver stain revealed the presence of MSU crystal deposition or tophi in the paw joints or ankle joints of up to 37.9% of the model mice (11 out of 29 mice). Moreover, treatment with benzbromarone effectively prevented the further development of gout or tophi formation in model mice. CONCLUSIONS: Our model more accurately replicates the pathological features of gouty arthritis compared with gout induced by MSU crystal injections. Therefore, it is particularly suitable for further investigations into the pathogenesis of gout and also serves as a valuable platform for screening potential antigout agents.


Asunto(s)
Artritis Gotosa , Gota , Humanos , Ratones , Animales , Artritis Gotosa/inducido químicamente , Artritis Gotosa/tratamiento farmacológico , Artritis Gotosa/patología , Gota/tratamiento farmacológico , Ácido Úrico , Supresores de la Gota/efectos adversos , Modelos Animales de Enfermedad
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