Efficacy and safety of low-dose combination urate-lowering agent therapy versus standard-dose monotherapy in patients with hyperuricemia and/or gout: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Treatment to lower uric acid levels is usually administered using monotherapy. However, this may be insufficiently effective for all patients. We hypothesized that a low-dose combination of drugs with different mechanisms of action might be more effective than standard-dose monotherapy. To test this theory, we conducted a systematic review and meta-analysis. METHOD: We searched MEDLINE and the Cochrane Library to identify randomized controlled trials that compared combination therapy involving low-dose urate-lowering drugs with standard-dose monotherapy. The primary outcome was serum uric acid levels at the end of treatment, and the data were analyzed using a random-effects model. Adverse events were assessed qualitatively. RESULTS: This review included four trials involving 342 participants. Statistically significant reductions in serum uric acid levels were observed with low-dose combination therapy compared to monotherapy (mean difference: -0.47 mg/dL; 95% confidence interval: -0.68 to -0.26). No statistically significant heterogeneity was observed (I² = 0.0%). No serious adverse events were reported in either group. CONCLUSIONS: The results suggest that low-dose combination therapy with urate production inhibitors and urate excretion promoters may be more effective at lowering serum uric acid levels compared with standard-dose monotherapy. However, as the assessment of adverse events was qualitative and the certainty of the safety evidence was extremely low, it remains unclear whether there are differences in the safety profiles between treatment strategies. Further randomized controlled trials are needed to confirm these findings.