Efficacy and safety of gout flare prophylaxis and therapy use in people with chronic kidney disease: a Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN)-initiated literature review

Abstract

Gout flare prophylaxis and therapy use in people with underlying chronic kidney disease (CKD) is challenging, given limited treatment options and risk of worsening renal function with inappropriate treatment dosing. This literature review aimed to describe the current literature on the efficacy and safety of gout flare prophylaxis and therapy use in people with CKD stages 3–5. A literature search via PubMed, the Cochrane Library, and EMBASE was performed from 1 January 1959 to 31 January 2018. Inclusion criteria were studies with people with gout and renal impairment (i.e. estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) < 60 ml/min/1.73 m2), and with exposure to colchicine, interleukin-1 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids. All study designs were included. A total of 33 studies with efficacy and/or safety analysis stratified by renal function were reviewed—colchicine (n = 20), anakinra (n = 7), canakinumab (n = 1), NSAIDs (n = 3), and glucocorticoids (n = 2). A total of 58 studies reported these primary outcomes without renal function stratification—colchicine (n = 29), anakinra (n = 10), canakinumab (n = 6), rilonacept (n = 2), NSAIDs (n = 1), and glucocorticoids (n = 10). Most clinical trials excluded study participants with severe CKD (i.e. eGFR or CrCl of < 30 mL/min/1.73 m2). Information on the efficacy and safety outcomes of gout flare prophylaxis and therapy use stratified by renal function is lacking. Clinical trial results cannot be extrapolated for those with advanced CKD. Where possible, current and future gout flare studies should include patients with CKD and with study outcomes reported based on renal function and using standardised gout flare definition.

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

“…G-CAN therefore endorsed systematic reviews of the evidence for the use of medications to manage gout flares as well as ULTs. These reviews 33 , 34 form the basis for this Consensus Statement and provide the evidence to support key areas for research in each section. People with gout were not directly involved in this Consensus Statement.…”

“…The systematic literature review of ULTs 33 was led by L.K.S. in conjunction with the fellows H.F. and A.B.V.-S., and the systematic literature review of therapies for gout flares and prophylaxis 34 was led by A.L.G. and C.L.H.…”

“…Two reviewers independently screened the full texts to identify eligible studies for data extraction; any discrepancy identified during the screening phase was discussed by the two reviewers to reach consensus. Detailed methods and results of the literature reviews have been previously reported 33 , 34 .…”

“…For example, serum urate was reported differently in these studies, as percentage reduction in serum urate, percentage of participants who achieved a target serum urate concentration, absolute reduction in serum urate and mean serum urate concentration at study end 25 , 44 . Likewise, gout flare was also inconsistently reported 25 , 26 , 34 . Such variability in study outcome reporting precludes meta-analysis, owing to difficulty comparing different studies.…”

“…NSAIDs are generally contra-indicated in people with CKD, and the published literature in gout generally aimed to show the potential for renal-related adverse effects in people with CKD 34 . Although NSAIDs have well-established adverse effects, there has been some suggestion that these drugs could be used in those with end-stage renal disease for short periods of time 45 .…”