FRI0224 Management to reducing liver function impairment when initiating febuxostat for gout based on the prediction nomogram
Authors: J. Yu
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Febuxostat is now used widely as urate-lowering therapy in gout, The most common adverse effects of which is liver function impairment (LFI). However, it is still not known in what conditions will the LFI happen. <h3>Objectives</h3> To identify the potential factors associated with LFI and establish an effective prediction nomogram, and also to determine whether febuxostat with stepwise dose increase useful in reducing LFI in patients with high risk calculated basing the nomogram. <h3>Methods</h3> Part A: A retrospective study was performed among patients with gout. Nomogram was established based on logistic regression. The internal validation was performed via the area under the receiver operating characteristic (ROC) curve (AUC). Part B: In the follow-up prospective study, patients were divided into high-risk (&gt;30%) group (stepwise dose increase of febuxostat from 10 to 40 mg/day) and low-risk (≤30%) group (fixed-dose febuxostat 40 mg/day) calculated basing the nomogram. Incidence rate of LFI were analysed. <h3>Results</h3> Part A: 306 subjects were recruited. LFI happened in 38 subjects after initiating fixed-dose febuxostat 40 mg/day. The logistic regression multivariate analysis indicated that age, use of alcohol, chronic renal insufficiency (CRI), medication use of statin and fatty liver were significantly associated with LFI. The AUC was 0.8424 (95% CI: 0.765–0.920). Part B: 108 subjects were recruited. LFI happened in 3/46 in high-risk group and 4/62 in low-risk group. The incidence rate of LFI after management basing prediction nomogram (7/108, 6.48%) was lower than previous study (38/306, 12.42%), with statistically difference (P&lt;0.05). The nomogram allows the user to obtain the probability of liver function impairment risk when initiating febuxostat. As an example, locate the patient's age and draw a line straight upward to the "Points" axis to determine the score associated with that age. Repeat the process for each variable, and sum the scores achieved for each covariate, and locate this sum on the "Total Points" axis. Draw a line straight down to determine the likelihood of liver function impairment. CRI – chronic renal insufficiency. Internal validation using the receiver operating characteristic (ROC) curve. The area under the ROC curve was 0.8424, 95% confidence interval (95% CI: 0.765–0.920). <h3>Conclusions</h3> Predictors including age, use of alcohol, CRI, medication use of statin, and fatty liver, were combined to construct a nomogram. And the current nomogram might help to distinguish gouty patients with high-risk LFI when initiating febuxostat and avoid unnecessary adverse events. Stepwise dose increase of febuxostat in patients with high-risk calculated basing the nomogram effectively reduced incidence rate of LFI. <h3>References</h3> [1] Tausche AK, Reuss-Borst M, Koch U. Urate lowering therapy with febuxostat in daily practice-a multicentre, open-label, prospective observational study. Int J Rheumatol2014;123105. [2] Becker MA, Schumacher HR, Espinoza LR, et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: The CONFIRMS trial. Arthritis Res Ther2010;12:R63. [3] Becker MA, Schumacher HR, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med2005;353:2450–61. [4] Yamanaka H, Tamaki S, Ide Y, et al. Stepwise dose increase of febuxostat is comparable with colchicine prophylaxis for the prevention of gout flares during the initial phase of urate-lowering therapy: Results from FORTUNE-1, a prospective, multicentre randomised study. Ann Rheum Dis. 2018Feb;77(2):270–6. <h3>Disclosure of Interest</h3> J. Yu Grant/research support from: This project was supported by a grant from the Health and Family Planning Commission of Shenzhen Municipality (201601037) and a grant from the Traditional Chinese Medicine Bureau of Guangdong Province (20161228).