Researchers writing in Nature Scientific Reports rank febuxostat as the most effective urate-lowering drug for reaching serum uric acid targets for gout patients with the least amount of adverse events.
The article, a systematic review and network meta-analysis, by Yaogang Wang of Tianjin Medical University in China where the prevalence of gout has increased in rent years. The analysis compares the effectiveness and safety of different pharmaceutical treatments for hyperuricemia.
Gout occurs as a result of hyperuricemia, which occurs either from the overproduction of uric acid (10%) or the under-excretion of urate (90%), which leads to the development of monosodium urate crystals in and around the joints. Generally, the higher the serum urate acid (sUA) levels, the higher the risk of gout and associated comorbidities.
In 2012, the American College of Rheumatology (ACR) recommended that gout patients strive to achieve a sUA level of < 6 mg/dl and that gout patient with tophi aim for < 5 mg/dl.
Researchers reviewed 15 randomized controlled trials (involving 7,246 patients through January 2016) that compared the effects of different urate-lowering drugs: allopurinol, benzbromarone, febuxostat, pegloticase and probenecid to reduce urate acid levels in the blood. They considered drug efficacy and safety, whether serum uric acid (sUA) targets were met and whether there were any adverse events.
Each of the drugs proved to be effective as compared to placebos, but febuxostat had the best efficacy and safety compared to the other drugs and at 120 mg QD, febuxostat was more effective at achieving urate-lowering targets (OR: 0.17, 95% CI: 0.12–0.24) and safer (OR: 0.72, 95% CI: 0.56–0.91) than allopurinol.
The findings appear in the Sept. 8 issue of Nature Scientific Reports.
Benzbromarone and probenecid were found to have moderate therapeutic effects, but they were associated with more side effects. Pegloticase and similar new uricase drugs need more research in order to fully assess effects and outcomes.
Allopurinol, febuxostat and in particular Xanthine oxidase inhibitors (XOIs) are recommended as first-line drugs in many countries. However, allopurinol has been reported to be associated with severe cutaneous adverse reactions, the authors reported.
Pegloticase, a recombinant polyethylene glycol conjugate of uricase (PEG-uricase), has been approved for the treatment of refractory chronic gout in the U.S. and European Union.
The authors noted that this is the first-known network meta-analysis that compares the efficacy and safety of different urate lowering therapies for gout. However, the authors note the limited number of trials included in the analysis.
Li S, Yang H, Guo Y, et al. “Comparative efficacy and safety of urate-lowering therapy for the treatment of hyperuricemia: a systematic review and network meta-analysis,” Nature Scientific Repoprts. www.nature.com/scientificreports 6:33082 DOI: 10.1038/srep33082