Elevated serum CA72-4 predicts gout flares during urate lowering therapy initiation: a prospective cohort study

Abstract

Objective: Gout flares during urate-lowering therapy (ULT) initiation are common, but predictors of these flares are poorly understood. The aim of this study was to determine whether serum CA72-4 is an independent predictor for gout flares during ULT initiation.

Methods: A prospective cohort study was conducted between March 2021 and January 2022. Men with gout, at least one gout flare in the past year, and at least three serum CA72-4 measurements in the previous six months were enrolled. Participants were grouped according to their highest recorded serum CA72-4 levels (above or within the normal range). All participants took oral febuxostat 20 mg daily without flare prophylaxis therapy, and attended face-to-face visits every four weeks until 24 weeks. The incidence of gout flare was compared between the two groups. Backward stepwise logistic regression analyses were used to identify risk factors associated with flares. Receiver operating characteristic curve analysis was used to evaluate prediction efficacy.

Results: A total of 193 completed the study (79 with high CA72-4; 114 with normal CA72-4). The cumulative incidence of at least one gout flare was 48.1% (62.1% in the high CA72-4 group, 38.4% in the normal CA72-4 group, P = 0.001), and recurrent (≥2) flares was 33.0% (47.1% in the high CA72-4 group, 23.2% in the normal CA72-4, P < 0.001). High CA72-4, disease duration, intra-articular tophus size, glucose, high-density lipoprotein-cholesterol and ESR were independent risk factors for gout flares. Serum CA72-4 alone predicted recurrent flares with an area under the curve of 0.63 (95% CI = 0.54, 0.71), and 0.78 (95% CI = 0.71, 0.85) when combined with other independent variables.

Conclusion: High serum CA72-4 predicts the risk of gout flares during ULT initiation.

Trial registration: ChiCTR; https://www.chictr.org.cn/; ChiCTR2100043573.

Keywords: CA72-4; gout flare; prediction.

Figure 1.

Flow chart

Figure 2.

Gout flares in the high and normal CA72-4 group over the 24-week study period. (A) Kaplan Meier analysis of the accumulated flare-free survival curves. (B) Kaplan Meier analysis of the accumulated recurrent (≥2) flares-free survival curves. (C) The proportion of patients with flares. (D) The proportion of patients with recurrent (≥2) flares. *means comparisons between the two groups P < 0.05; **means comparisons between the two groups P < 0.01

Figure 3.

Other clinical and laboratory variables in the high and normal CA72-4 group over the 24-week study period. (A) Serum CA72-4. (B) Serum urate. (C) C-reactive protein. (D) Erythrocyte sedimentation rate. (E) Size of intra-articular tophus. Data are expressed as median (IQR), except serum urate as mean (s.d.). *means comparisons between the two groups P <0.05; **means comparisons between the two groups P < 0.01; ***means comparisons between the two groups P < 0.001

Figure 4.

ROC curves for recurrent gout flares. All variables including CA72-4 >6.9U/mL, disease duration, intra-articular tophus size, glucose, high-density lipoprotein cholesterol and ESR. AUC: area under the curve; ROC: receiver operating characteristic.