Asymptomatic hyperuricemia, why do you recommend lowering uric acid?

Whether asymptomatic hyperuricemia requires uric acid-lowering therapy (ULT) has been controversial
.

European and American guidelines do not recommend treatment, while Asian countries such as China and Japan recommend treatment
.

The "Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout in China (2019)" pointed out that asymptomatic hyperuricemia patients with blood uric acid level ≥540 µmol/L or blood uric acid level ≥480 µmol/L and comorbidities such as hypertension should receive ULT
.

So, what are the benefits of lowering uric acid levels for asymptomatic hyperuricemia patients? On June 22, the Japanese scholar Ruriko Koto equals the journal Ann Rheum Dis.
(Impact Factor 16.
102) published a real-world retrospective cohort study to explore the "influence of asymptomatic hyperuricemia control of uric acid levels on gout attacks.
" The results It is shown that in asymptomatic hyperuricemia patients, controlling the blood uric acid level ≤ 6.
0 mg/dL (357 µmol/L) may delay the first attack of gout, reduce the number of gout attacks, and reduce the risk of gout attacks
.

Study Design The study was based on the data from the JMDC database from April 2012 to June 2019, and included subjects with at least one blood uric acid level (sUA) ≥8.
0 mg/dL during the physical examination from April 2013 to April 2016 (N=19261)
.

The study mainly includes two phases: Phase 1 (the subject's sUA is ≥8.
0 mg/dL for the first time, followed by 1 year): Record ULT, gout attacks, sUA changes and other information; Phase 2 (Phase 1 to the end of the study): Record The time of the first attack of gout and the number of attacks (Figure 1)
.

Figure 1 Study design: Gout subjects refer to authors who experienced gout in the first phase; subjects with asymptomatic hyperuricemia refer to subjects other than "gout subjects"; neither of these two types of population include those who have experienced gout.
ULT, subjects whose sUA decreased from ≥8mg/dL to <8.
0mg/dL
.

With reference to the goal of gout ULT, stratified analysis was performed with sUA≤6.
0mg/dL
.

Multivariate analysis was used to evaluate the relationship between gout attacks and sUA control
.

The results of the study were mainly male subjects (98.
3%), the average sUA±standard deviation was 8.
47±0.
53 mg/dL, and most subjects (71.
6%) had no comorbidities
.

The researchers divided the subjects into 7 subgroups based on the data from Phase 1
.

No treatment group (n=10480), that is, without ULT, sUA decreased from ≥8mg/dL to <8.
0mg/dL, and the number was the largest
.

Other subgroups include the subgroup with ULT and sUA≤6.
0mg/dL (n=337), the subgroup with ULT and sUA>6.
0mg/dL (n=884), and the subgroup without ULT and sUA≥8.
0mg/dL.
Group (n=7049) and so on
.

Blood uric acid level ≤6.
0mg/dL can significantly delay the first onset of gout in asymptomatic hyperuricemia patients.
Among asymptomatic hyperuricemia subjects, those with ULT and sUA≤6.
0mg/dL have the first onset of gout The time of the latest gout was significantly better than the subjects who received ULT and sUA>6.
0mg/dL and those who did not have ULT and sUA≥8.
0mg/dL, and the time to the first onset of gout in these two groups was equivalent (Picture 2)
.

Figure 2 In the second phase, the first time blood uric acid level of gout in each subgroup of subjects is ≤6.
0 mg/dL, which may reduce the gout attack rate in asymptomatic hyperuricemia patients.
Among asymptomatic hyperuricemia and gout subjects, Subjects with ULT and sUA≤6.
0mg/dL had the lowest gout attack rate, which was 0.
033 (95%CI: 0.
023-0.
043)/person-year (Figure 3)
.

Figure 3 Compared with ≥8mg/dL, the incidence of gout in each subgroup in the second phase, 5.
0<blood uric acid level≤6.
0mg/dL, can significantly reduce the risk of gout attack by 55%.
The COX regression model is used to analyze gout for the first time The time of onset showed that in subjects with asymptomatic hyperuricemia, compared with subjects with sUA≥8mg/dL, subjects with treated blood uric acid of 5.
0<sUA≤6.
0mg/dL had a greater risk of gout attacks Reduced by 55% (HR=0.
45, 95%CI: 0.
27-0.
76, p=0.
002)
.

Research conclusions This real-world retrospective cohort study shows that in asymptomatic hyperuricemia patients, uric acid-lowering therapy to control sUA≤6.
0mg/dL (357µmol/L) has benefits such as delaying the first attack of gout and reducing the attack of gout.

.

Based on research data, the authors found that gout subjects whose sUA dropped to ≤5.
0 mg/dL had a higher risk of gout attacks
.

Therefore, it is inferred that the rapid reduction of sUA in the early stage of uric acid lowering treatment may cause gout attacks
.

Finally, the author emphasizes that by controlling the blood uric acid level of asymptomatic hyperuricemia patients, it is possible to reduce or even eliminate gout attacks and bring long-term benefits to patients
.

In short, patients with asymptomatic hyperuricemia should be considered for treatment, especially those with higher blood uric acid levels
.

In terms of its treatment, the guidelines suggest that allopurinol or benzbromarone can be used as the first-line medication for lowering uric acid in patients with asymptomatic hyperuricemia
.

References: 1.
Koto R, Nakajima A, Horiuchi H,et al.
Serum uric acid control for prevention of gout flare in patients with asymptomatic hyperuricaemia: a retrospective cohort study of health insurance claims and medical check-up data in Japan.
Ann Rheum Dis[J].
2021 Jun 22:annrheumdis-2021-220439.
2.
Chinese Medical Association Endocrinology Branch.
Guidelines for the diagnosis and treatment of hyperuricemia and gout in China (2019)[J].
Chinese Journal of Endocrinology and Metabolism, 2020, 36( 1):1-13.
doi:10.
3760/cma.
j.
issn.
1000-6699.
2020.
01.
001.