Comparative risk of gout flares when initiating or escalating various urate-lowering therapy: a systematic review with network meta-analysis.

OBJECTIVE: Systematically examine: comparative flare risk post initiation or escalation of different urate-lowering therapies (ULTs); comparative flare risk with and without concomitant flare prophylaxis; adverse event rates associated with flare prophylaxis; and optimal duration of flare prophylaxis.

METHODS: We searched Medline, Embase, Web of Science, Cochrane database and clinical trial registries from inception to November 2021 for trials investigating adults with gout initiating or escalating ULT. We performed random-effects network meta-analyses and calculated risk ratios (RR) between treatments. Bias was assessed using the Revised Cochrane risk-of-bias tool.

RESULTS: We identified 3775 records, of which 29 publications (27 trials) were included. When compared to placebo+prophylaxis, the RR of flares ranged from 1·08 [95% confidence interval (95% CI) 0·87-1·33] for febuxostat 40mg+prophylaxis to 2·65 [95% CI 1·58-4·45] for febuxostat 80mg+lesinurad 400mg+prophylaxis. Compared to ULT alone, the RR of flares was lower for ULT+rilonacept 160mg (RR=0·35 [95% CI 0·25-0·50]), ULT+rilonacept 80mg (RR=0·43 [95% CI 0·31-0·60]) and ULT+colchicine (RR=0·50 [95% CI 0·35-0·72]). There was limited evidence for other flare prophylaxis, and on prophylaxis harms and optimal duration. Primarily due to missing outcome data and bias in the selection of reported results, 71·4% and 63·4% of studies were assessed as high risk of bias for flares and adverse events respectively.

CONCLUSION: The relative risk of flares when introducing ULT varies depending on ULT drug and dosing strategy. There was limited data on ULT escalation. Flare prophylaxis with colchicine and rilonacept reduces flare incidence. More research is required on the harms and optimal duration of prophylaxis.