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

Huai Leng Pisaniello; Mark C. Fisher; Hamish Farquhar; Ana Beatriz Vargas-Santos; Catherine L. Hill; Lisa K. Stamp; Angelo L. Gaffo


Arthritis Res Ther. 2021;23(130) 

In This Article


This literature review was conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Literature Search Strategy

A literature search in PubMed, The Cochrane Library, and EMBASE was conducted from 1 January 1959 to 27 June 2017. A subsequent search from 28 June 2017 to 31 January 2018 was updated to capture any additional studies published during the review process. We included all available gout flare prophylaxis and therapy use in clinical trials and real-world practice, which were colchicine, NSAIDs, glucocorticoids, and interleukin-1 (IL-1) inhibitors such as anakinra, canakinumab, and rilonacept.

In detail, literature search combining gout with either gout flare prophylaxis/therapy and CKD was performed separately to the literature search combining either gout flare prophylaxis/therapy and renal replacement therapy (i.e. haemodialysis and peritoneal dialysis). These two literature searches were subsequently merged prior to the screening phase. This search strategy was applied to all gout flare prophylaxis/therapy, except for glucocorticoids. The initial search attempt in crossing the glucocorticoid-related search terms with renal-related terms led to an excessive number of irrelevant search results. Therefore, for glucocorticoid-related literature search, the search term was only crossed against gout terms, and not with any renal-related terms. The search strategies for each database were outlined in Supplementary Table 1.

Eligibility Criteria and Study Selection

We included studies which fulfil the following criteria: people diagnosed with gout, with CKD ≥ stage 3 (i.e. eGFR or creatinine clearance (CrCl) of < 60 mL/min/1.73 m2), and with exposure to the gout flare prophylaxis/therapy of interest. Only studies published in English were included. Studies in the form of case reports or case series as well as abstracts from the ACR and the European League Against Rheumatism (EULAR) were included for screening.

We excluded studies if the primary study population had a diagnosis other than gout, studies with inadequate or absence of information on the renal function (i.e. absence of CKD stage or eGFR/CrCl measure) and/or on the study drug of interest, and studies that included people with normal renal function or experiencing acute renal failure. In addition, studies published in the form of letters, editorials, opinions, review articles, and studies with animal-, basic science- or laboratory-based focus were excluded.

Study title and abstract screening for eligible studies was independently performed by two reviewers (HLP and CLH for colchicine and IL-1 inhibitors; MCF and AG for NSAIDs and glucocorticoids). Full-text screening for eligible studies for data extraction was independently performed by two reviewers in similar arrangement. Any discrepancy identified during the screening phase was discussed to reach consensus.

Data Extraction

Relevant data for eligible studies were extracted independently by two reviewers (HLP and CLH for colchicine and IL-1 inhibitors; MCF and AG for NSAIDs and glucocorticoids). The extracted data included the primary author, year of study, trial name (where applicable), study design, and sample size. The extracted outcome data included the efficacy of the drug of interest (defined as the clinical resolution of gout flare or absence of gout flare during concomitant ULT use) and/or the safety profile of the drug of interest (defined as adverse events observed in the presence of active use of gout flare prophylaxis/therapy). Where applicable, we extracted studies reporting these outcome data as stratified by renal function. Discrepancies among the reviewers during this data extraction phase were minimal and were resolved by discussion.


The eligible studies were analysed in terms of their overall study characteristics, sample size, drug indication (i.e. either as gout flare prophylaxis or as gout flare treatment), and dosages, and the efficacy and safety outcomes for the study drug of interest and the corresponding renal function stratification, where applicable. We were not able to summarise these studies quantitatively due to the heterogeneity nature of the studies included.