Efficacy and safety of urate-lowering therapy in people with kidney impairment: a GCAN-initiated literature review.

OBJECTIVES: The aim was to evaluate the efficacy, defined as achieving target serum urate <6.0 mg/dl, and safety of urate-lowering therapies (ULTs) for people with gout and chronic kidney disease (CKD) stages 3-5. METHODS: PubMed, The Cochrane Library and EMBASE were searched from 1 January 1959 to 31 January 2018 for studies that enrolled people with gout, who had an estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) of <60 ml/min and exposure to allopurinol, febuxostat, probenecid, benzbromarone, lesinurad or pegloticase. All study designs other than case reports were included, except for people on dialysis, for whom we did include case reports. RESULTS: There were 36 reports with an analysis of efficacy and/or safety based upon renal function: allopurinol (n = 12), febuxostat (n = 10), probenecid (n = 3), benzbromarone (n = 5), lesinurad (n = 5) and pegloticase (n = 1). There were 108 reports that involved people with gout and renal impairment but did not contain any analysis on efficacy and/or safety based upon renal function: allopurinol (n = 84), febuxostat (n = 14), benzbromarone (n = 1), lesinurad (n = 3) and pegloticase (n = 6). Most studies excluded people with more severe degrees of renal impairment (eGFR or CrCl of <30 ml/min). For allopurinol, in particular, there was significant variability in the dose of drug used and the efficacy in terms of urate lowering, across all levels of renal impairment. CONCLUSION: There is a lack of evidence regarding the efficacy and/or safety of currently used ULTs according to different levels of renal function. Future studies should include patients with CKD and should report study outcomes stratified by renal function.

Management of gout in chronic kidney disease: a G-CAN Consensus Statement on the research priorities.

Gout and chronic kidney disease (CKD) frequently coexist, but quality evidence to guide gout management in people with CKD is lacking. Use of urate-lowering therapy (ULT) in the context of advanced CKD varies greatly, and professional bodies have issued conflicting recommendations regarding the treatment of gout in people with concomitant CKD. As a result, confusion exists among medical professionals about the appropriate management of people with gout and CKD. This Consensus Statement from the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) discusses the evidence and/or lack thereof for the management of gout in people with CKD and identifies key areas for research to address the challenges faced in the management of gout and CKD. These discussions, which address areas for research both in general as well as related to specific medications used to treat gout flares or as ULT, are supported by separately published G-CAN systematic literature reviews. This Consensus Statement is not intended as a guideline for the management of gout in CKD; rather, it analyses the available literature on the safety and efficacy of drugs used in gout management to identify important gaps in knowledge and associated areas for research.

Flare Rate Thresholds for Patient Assessment of Disease Activity States in Gout.

OBJECTIVE: To determine the relationship between gout flare rate and self-categorization into remission, low disease activity (LDA), and patient acceptable symptom state (PASS). METHODS: Patients with gout self-categorized as remission, LDA, and PASS, and reported number of flares over the preceding 6 and 12 months. Multinomial logistic regression was used to determine the association between being in each disease state (LDA and PASS were combined) and flare count, and self-reported current flare. A distribution-based approach and extended Youden index identified possible flare count thresholds for each state. RESULTS: Investigators from 17 countries recruited 512 participants. Remission was associated with a median recalled flare count of zero over both 6 and 12 months. Each recalled flare reduced the likelihood of self-perceived remission compared with being in higher disease activity than LDA/PASS, by 52% for 6 months and 23% for 12 months, and the likelihood of self-perceived LDA/PASS by 15% and 5% for 6 and 12 months, respectively. A threshold of 0 flares in preceding 6 and 12 months was associated with correct classification of self-perceived remission in 58% and 56% of cases, respectively. CONCLUSION: Flares are significantly associated with perceptions of disease activity in gout, and no flares over the prior 6 or 12 months is necessary for most people to self-categorize as being in remission. However, recalled flare counts alone do not correctly classify all patients into self-categorized disease activity states, suggesting that other factors may also contribute to self-perceived gout disease activity.