Initiation of urate-lowering therapy (ULT) during intercritical periods of gout results in improved arterial endothelial function and reduced systemic inflammation, according to study results published in Arthritis Care & Research. Researchers observed that intercritical ULT was associated with significant improvements in brachial artery function and significant reductions in certain inflammatory biomarkers in patients with gout.
The prospective, observational study included patients with gout who were initiating ULT at ambulatory care centers in New York City, New York. Eligible patients were aged ≥18 years and were between flares at the time of enrollment. All patients met the American College of Rheumatology (ACR) guidelines for initiating ULT.
Participants received colchicine 0.6 mg twice daily for 6 weeks, after which treatment with a xanthine oxidase inhibitor (XOI; allopurinol 100 mg or febuxostat 40 mg daily) was initiated. Treatment with XOI was titrated until patients reached ACR-defined target serum urate levels (≤6.0 mg/dL). Once patients achieved the target serum urate concentration, treatment was maintained for 4 additional weeks, followed by a reassessment of serum urate concentration. At each study visit, brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) were used to assess endothelium-dependent and -independent arterial responsiveness, respectively. Researchers also assessed markers of systemic inflammation, including erythrocyte sedimentation rate (ESR) and concentrations of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-1β, IL-6, and myeloperoxidase. The primary outcome was the difference in FMD between baseline and 4 weeks after achieving target serum urate concentration. Secondary outcomes included the changes in NMD and inflammatory markers between baseline and follow-up.
The study cohort included 38 patients with gout, all of whom were men. Mean age at enrollment was 58.6±13.1 years; 39.4% were White, 47.4% were African American, and 13.2% were Asian. A majority of patients (84.2%) received allopurinol as their XOI, with 5.2% receiving febuxostat. Treatment with colchicine-only for 6 weeks did not significantly change mean serum urate concentration (9.69±1.50 mg/dL); however, after completing colchicine plus XOI treatment, all patients achieved their prespecified target serum urate concentration (mean value, 5.08±0.66 mg/dL). Median time from initiating ULT to achieving serum urate target was 21 weeks (range, 13-28 weeks). Four weeks after achieving target serum urate concentration, significant improvements from baseline were observed in FMD (58% increase; P =.03). Significant improvements were also observed for hsCRP, ESR, IL-1β, and IL-6 (30%, 27%, 19.5%, and 18.8% decrease, respectively; all P ≤.03). However, NMD and myeloperoxidase concentration did not significantly change over the study period. A moderate inverse association was observed between hsCRP concentration and FMD responsiveness (r=-0.41; P =.01), suggesting that inflammatory and endothelial function may be closely linked in patients with gout.
In subgroup analyses, patients without vs with established cardiovascular risk factors and comorbidities had greater improvements in FMD responsiveness. Specifically, patients without vs with hypertension or hyperlipidemia had better FMD outcomes.
Overall, these data support the efficacy of ACR guideline-concordant treatment for improving endothelial-dependent arterial function and systemic inflammation in patients with gout, particularly those without cardiovascular comorbidities.
Study limitations included the small cohort size, lack of a control population, and cohort homogeneity (all men).
Researchers concluded that further study was necessary to clarify the effects of gout treatment on arterial function and systemic inflammation, particularly among patients with cardiovascular comorbidities.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Toprover M, Shah B, Oh C, et al. Initiating guideline-concordant gout treatment improves arterial endothelial function and reduces intercritical inflammation: a prospective observational study [published online July 11, 2020]. Arthritis Res Ther. doi:10.1186/s13075-020-02260-6