Real - rheumatoid arthritis in real life -study cohort: a sociodemographic profile of rheumatoid arthritis in Brazil

Abstract Background: In Brazil, socioeconomic differences in the incidence of rheumatoid arthritis (RA) have been demonstrated, which are important in the formulation of hypotheses regarding the association between environmental factors, lifestyle and the risk of disease development. This study examines how the socioeconomic condition of the patient with RA in Brazil, assessed according to social class, educational level, employment situation and use of caregivers, affects the times between the beginning of symptoms and diagnosis and the beginning of the use of disease-modifying antirheumatic drugs, as well as the presence of erosive disease and functional status. Methods: This work is part of a multicentric study called REAL - Rheumatoid Arthritis in Real Life in Brazil, which is a prospective observational cohort study. Results: As described in the REAL study, we included a total of 1115 patients. It was noted that patients with an educational classification of up to second grade incomplete presented with erosion percentages above those with a higher grade complete. Patients with caregivers presented a higher percentage of erosion than patients without caregivers. We verified that patients from economic classes above B2 presented fewer occurrences of erosion than those from classes C2, D-E. We also analyzed the average time differences from the beginning of symptoms and diagnosis and the beginning of treatment, according to academic level, erosion and economic classification. Patients with first grade complete showed an HAQ-DI averages higher than those with second grade complete. The patients who had employment showed lower HAQ-DI averages than patients who were not employed. The patients with erosion showed an HAQ-DI value higher than those without erosion. Patients with caregivers showed an HAQ-DI average higher than that of without caregivers. Conclusion: This study showed that the therapeutic window of RA is not being reached, and therefore we should have a policy to expand and ensure access to public health for all patients, especially those with lower levels of education and income. Trial registration: This study was approved by the National Commission of Ethics in Research.(AU)

Benzbromarone in the treatment of gout.

BACKGROUND: Benzbromarone is a uricosuric drug that has been used in the treatment of gout over the last 30 years. Due to its potent inhibition of the dominant apical (luminal) urate exchanger in the human proximal tubule URAT1, it reduces the urate reabsorption, diminishing serum urate levels and therefore preventing gout flares. Through several clinical trials, Benzbromarone has been proved effective and safe, inclusive in patients with chronic kidney disease and as combination therapy with allopurinol. Due to hepatotoxicity reports, it was withdrawn from the European market by the manufacturer, however many authors have questioned the product's withdrawal due to a lack of clinical evidence in order to support its hepatotoxicity. Benzbromarone is still available in several European countries, New Zealand, Brazil and several other countries. Despite the product's marketing over more than 20 years after the first hepatotoxicity reports, we have found only five reports in our literature search, and no prospective or retrospective study correlating hepatotoxicity with benzbromarone use. SHORT CONCLUSION: Benzbromarone is a safe and effective molecule for the treatment of gout. However, due to in vitro and in vivo data related to hepatotoxicity, it is prudent to prescribe it with some caution, especially for patients with an already known liver condition.

Cause-Specific Mortality in Gout: Novel Findings of Elevated Risk of Non-Cardiovascular-Related Deaths.

OBJECTIVE: To examine cause-specific mortality beyond cardiovascular diseases (CVDs) in patients with gout compared to the general population. METHODS: We included all residents of Skåne (Sweden) age ≥18 years in the year 2002. Using the Skåne Healthcare Register, we identified subjects with a new diagnosis of gout (2003-2013) and matched each person with gout with 10 comparators free of gout, by age and sex. We used information on the underlying cause of death from the Swedish Cause of Death Register (through December 31, 2014) to estimate hazard ratios (HRs, with 95% confidence intervals [95% CIs]) of mortality for specific causes of death in a multi-state Cox model, with adjustment for potential confounders. RESULTS: Among 832,258 persons, 19,497 had a new diagnosis of gout (32% women) and were matched with 194,947 comparators. Subjects with gout had higher prevalence of chronic kidney disease, metabolic disease, and CVD. Gout was associated with 17% increased hazard of all-cause mortality overall (HR 1.17 [95% CI 1.14-1.21]), 23% in women (HR 1.23 [95% CI 1.17-1.30]), and 15% in men (HR 1.15 [95% CI 1.10-1.19]). In terms of cause-specific mortality, the strongest associations were seen in the relationship of gout to the risk of death due to renal disease (HR 1.78 [95% CI 1.34-2.35]), diseases of the digestive system (HR 1.56 [95% 1.34-1.83]), CVD (HR 1.27 [95% CI 1.22-1.33]), infections (HR 1.20 [95% CI 1.06-1.35]), and dementia (HR 0.83 [95% CI 0.72-0.97]). CONCLUSION: Several non-CV causes of mortality are increased in persons with gout, emphasizing the need for improved management of comorbidities.

Benzbromarone in the treatment of gout

Abstract Background Benzbromarone is a uricosuric drug that has been used in the treatment of gout over the last 30 years. Due to its potent inhibition of the dominant apical (luminal) urate exchanger in the human proximal tubule URAT1, it reduces the urate reabsorption, diminishing serum urate levels and therefore preventing gout flares. Main body of the abstract Through several clinical trials, Benzbromarone has been proved effective and safe, inclusive in patients with chronic kidney disease and as combination therapy with allopurinol. Due to hepatotoxicity reports, it was withdrawn from the European market by the manufacturer, however many authors have questioned the product's withdrawal due to a lack of clinical evidence in order to support its hepatotoxicity. Benzbromarone is still available in several European countries, New Zealand, Brazil and several other countries. Despite the product's marketing over more than 20 years after the first hepatotoxicity reports, we have found only five reports in our literature search, and no prospective or retrospective study correlating hepatotoxicity with benzbromarone use. Short conclusion Benzbromarone is a safe and effective molecule for the treatment of gout. However, due to in vitro and in vivo data related to hepatotoxicity, it is prudent to prescribe it with some caution, especially for patients with an already known liver condition.

Association of Chronic Kidney Disease With Allopurinol Use in Gout Treatment.

Importance: Clinicians are often cautious about use of allopurinol in patients with gout when renal function declines. Objective: To assess the association of allopurinol use in gout with the risk of developing chronic kidney disease stage 3 or higher. Design, Setting, and Participants: A time-stratified propensity score-matched, population-based, prospective cohort study of individuals with newly diagnosed gout who initiated allopurinol (≥300 mg/d) compared with those who did not initiate allopurinol, using the Health Improvement Network (THIN), a United Kingdom general practitioner electronic health records database, was carried out. The data were analyzed using Cox proportional hazards regression. Among adults aged 18 to 89 years with newly diagnosed gout, we propensity score matched 4760 initiators of allopurinol (≥300 mg/d) to the same number of noninitiators of allopurinol, excluding those with chronic kidney disease stage 3 or higher or urate-lowering therapy use before their gout diagnosis. Exposures: Allopurinol initiation at a dose of 300 mg or more per day. Main Outcomes and Measures: Development of chronic kidney disease stage 3 or higher. Results: Of the 4760 allopurinol initiators (3975 men, 785 women) and same number of noninitiators (3971 men, 789 women), 579 and 623, respectively, developed chronic kidney disease stage 3 or higher, with a mean follow-up time of 5 and 4 years, mean age of 57 years, and mean body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 for both groups. Use of allopurinol of at least 300 mg/d was associated with lower risk of developing chronic kidney disease stage 3 or higher compared with nonusers, with a hazard ratio (HR) of 0.87 (95% CI, 0.77-0.97). Allopurinol initiation at less than 300 mg/d was not associated with renal function decline (HR, 1.00; 95% CI, 0.91-1.09). Conclusions and Relevance: In this large cohort, allopurinol initiation of at least 300 mg/d was associated with a lower risk of renal function deterioration. Because allopurinol does not appear to be associated with renal function decline, clinicians should consider evaluating other potential causes when patients with gout experience renal function decline.

Management of Gout and Hyperuricemia in CKD.

Hyperuricemia and gout, the clinical manifestation of monosodium urate crystal deposition, are common in patients with chronic kidney disease (CKD). Although the presence of CKD poses additional challenges in gout management, effective urate lowering is possible for most patients with CKD. Initial doses of urate-lowering therapy are lower than in the non-CKD population, whereas incremental dose escalation is guided by regular monitoring of serum urate levels to reach the target level of <6mg/dL (or <5mg/dL for patients with tophi). Management of gout flares with presently available agents can be more challenging due to potential nephrotoxicity and/or contraindications in the setting of other common comorbid conditions. At present, asymptomatic hyperuricemia is not an indication for urate-lowering therapy, though emerging data may support a potential renoprotective effect.

Adherence to the 2012 American College of Rheumatology (ACR) Guidelines for Management of Gout: A Survey of Brazilian Rheumatologists.

OBJECTIVE: To describe the current pharmacological approach to gout treatment reported by rheumatologists in Brazil. METHODS: We performed a cross-sectional survey study using an online questionnaire e-mailed to 395 rheumatologists, randomly selected, from among the members of the Brazilian Society of Rheumatology. RESULTS: Three hundred and nine rheumatologists (78.2%) responded to the survey. For acute gout attacks, combination therapy (NSAIDs or steroid + colchicine) was often used, even in monoarticular involvement, and colchicine was commonly started as monotherapy after 36 hours or more from onset of attack. During an acute attack, urate-lowering therapy (ULT) was withdrawn by approximately a third of rheumatologists. Anti-inflammatory prophylaxis (98% colchicine) was initiated when ULT was started in most cases (92.4%), but its duration was varied. Most (70%) respondents considered the target serum uric acid level to be less than 6 mg/dl. Approximately 50% of rheumatologists reported starting allopurinol at doses of 100 mg daily or less and 42% reported the initial dose to be 300 mg daily in patients with normal renal function. ULT was maintained indefinitely in 76% of gout patients with tophi whereas in gout patients without tophi its use was kept indefinitely in 39.6%. CONCLUSION: This is the first study evaluating gout treatment in a representative, random sample of Brazilian rheumatologists describing common treatment practices among these specialists. We identified several gaps in reported gout management, mainly concerning the use of colchicine and ULT and the duration of anti-inflammatory prophylaxis and ULT. Since rheumatologists are considered as opinion leaders in this disease, a program for improving quality of care for gout patients should focus on increasing their knowledge in this common disease.

Study for Updated Gout Classification Criteria: Identification of Features to Classify Gout.

OBJECTIVE: To determine which clinical, laboratory, and imaging features most accurately distinguished gout from non-gout. METHODS: We performed a cross-sectional study of consecutive rheumatology clinic patients with ≥1 swollen joint or subcutaneous tophus. Gout was defined by synovial fluid or tophus aspirate microscopy by certified examiners in all patients. The sample was randomly divided into a model development (two-thirds) and test sample (one-third). Univariate and multivariate association between clinical features and monosodium urate-defined gout was determined using logistic regression modeling. Shrinkage of regression weights was performed to prevent overfitting of the final model. Latent class analysis was conducted to identify patterns of joint involvement. RESULTS: In total, 983 patients were included. Gout was present in 509 (52%). In the development sample (n = 653), the following features were selected for the final model: joint erythema (multivariate odds ratio [OR] 2.13), difficulty walking (multivariate OR 7.34), time to maximal pain <24 hours (multivariate OR 1.32), resolution by 2 weeks (multivariate OR 3.58), tophus (multivariate OR 7.29), first metatarsophalangeal (MTP1) joint ever involved (multivariate OR 2.30), location of currently tender joints in other foot/ankle (multivariate OR 2.28) or MTP1 joint (multivariate OR 2.82), serum urate level >6 mg/dl (0.36 mmoles/liter; multivariate OR 3.35), ultrasound double contour sign (multivariate OR 7.23), and radiograph erosion or cyst (multivariate OR 2.49). The final model performed adequately in the test set, with no evidence of misfit, high discrimination, and predictive ability. MTP1 joint involvement was the most common joint pattern (39.4%) in gout cases. CONCLUSION: Ten key discriminating features have been identified for further evaluation for new gout classification criteria. Ultrasound findings and degree of uricemia add discriminating value, and will significantly contribute to more accurate classification criteria.