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 Due to hepatotoxicity reports, it was withdrawn from the European market by the manufacturer, however many authors have questioned the product's withdrawal due to a lack of clinical evidence in order to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.

Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Data from South American registries BIOBADABRASIL and BIOBADASAR.

OBJECTIVE: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries. METHODS: We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs. RESULTS: Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016. CONCLUSION: While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.