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Background: We sought to examine the cardiovascular safety of intensive treat-to-target serum urate strategies for gout using Medicare claims data linked to electronic health record laboratory data. Methods: We selected patients with gout who initiated urate-lowering therapy. We emulated a hypothetical trial comparing the rate of major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) among seven different strategies over 24 months. Three aspects were considered in defining increasingly intensive strategies: (1) continuation of uratelowering therapy, (2) serum urate monitoring, and (3) modification of urate-lowering therapy when serum urate >6 mg/dl. We applied the "clone-censor-weight" method to account for baseline and timevarying confounding. Results: We identified 4402 patients with gout who initiated uratelowering therapy (mean age 77; male 60%). During a total of 6611 person-years (PY) of follow-up under usual care, the rate of major cardiovascular events (first and recurrent) was 4.5/100 PY (95% CI = 4.0, 5.1). The rate ratios (RRs) suggested reductions (RR point estimates 0.88-0.84) compared with usual care. All 95% CIs were imprecise, but their upper bounds excluded substantial increase in RRs. RRs were closer to 1.0 for the analysis focusing on the first major adverse cardiovascular event during follow-up and on comparison to the strategy requiring continuation of urate-lowering therapy (but not necessarily titration). Conclusions: Our treatment strategy trial emulation did not find increased risk of major adverse cardiovascular events with intensive urate-lowering strategies. Results may provide reassurance of the cardiovascular safety of intensive treat-to-target serum urate strategies recommended by rheumatology societies. [ABSTRACT FROM AUTHOR]

The definition and management of asymptomatic hyperuricemia has been an area of controversy for many decades. Debate persists regarding the benefit of treating all cases of asymptomatic hyperuricemia and hence, unsurprisingly there are no clear clinical practice guidelines from our country. Ten members consisting of eminent physicians, endocrinologists, nephrologist and a rheumatologist were selected by the Integrated Diabetes & Endocrine Academy (IDEA) for a closed meeting with the aim to come to a consensus. A literature search was performed using PubMed and Cochrane library following which published articles in indexed peer review journals were selected. Each participant voiced their opinion after reviewing the available data and a consensus was reached after three meetings by voting. Recommendations were made on important areas such as definition, investigation and management of asymptomatic hyperuricemia. • There are no clear clinical practice guidelines on management of asymptomatic hyperuricemia from India. • Unnecessary investigation of serum uric acid for all patients with rheumatological symptoms should be discouraged. • Urate lowering therapy are well known for its side effects however, new evidence showing benefit of therapy cannot be ignored. • This consensus statement aims to lay down clear recommendations in the management of asymptomatic hyperuricemia. [ABSTRACT FROM AUTHOR]

Gout is an inflammatory musculoskeletal disorder with a prevalence of 1.6–6.8% in Australia. Gout is characterised by acute attacks of severe joint pain secondary to raised serum concentrations of uric acid and joint deposits of monosodium urate crystals. Recurrent attacks can affect quality of life and lead to irreversible joint damage. The prevalence of gout is increased in older people, and age‐related renal impairment, altered drug distribution and increased prevalence of comorbidities have significant consequences for safe and effective gout pharmacotherapy. For treatment of acute attacks in older people, dose reduction of colchicine may be needed due to renal impairment, and potential drug interactions require consideration. Use of non‐steroidal anti‐inflammatory drugs is limited by peptic ulceration, ischaemic heart disease, hypertension and renal impairment. Short courses of oral glucocorticoids may be preferable. For long‐term urate‐lowering therapy, allopurinol, probenecid and febuxostat are available in Australia. Lower starting doses of allopurinol are recommended in patients with renal impairment, but dose escalation to achieve target urate should follow. Concerns regarding increased cardiovascular risk with febuxostat are relevant to older patients. Despite the availability of effective therapy, gout remains undertreated, with maintenance of urate‐lowering therapy a major challenge. Education of patients and health professionals is essential to improve adherence to therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 metaanalysis: (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. [ABSTRACT FROM AUTHOR]