High Serum Urate Levels Tied to Poor Outcomes, QOL, Function in Gout

In patients with gout, high serum urate (SU) levels are associated with poor health-related quality of life (HRQOL), pain, and Sheehan disability score (SDS). Recent fluctuations in SU levels were also linked to be the primary driver of poorer health outcomes. These findings were published in Seminars in Arthritis & Rheumatism.

Researchers sought to evaluate the relationship between changes in SU levels and HRQOL among patients with gout. They examined whether, and to what extent, initial changes in SU levels after initiation or change in urate-lowering therapy (ULT) were linked to changes in HRQOL as a key patient-reported outcome (PRO). They hypothesized that initial changes in urate (ie, increase or decrease) would be associated with worse HRQoL (the primary outcome) and other PROs (secondary outcomes).

The study used data from 4 interventional trials:

• Combining Lesinurad With Allopurinol in Inadequate Responders (CLEAR1 and CLEAR2);
• Combination Treatment Study in Subjects With Tophaceous Gout With Lesinurad and Febuxostat (CRYSTAL); and
• Lesinurad Monotherapy in Gout Subjects Intolerant to Xanthine Oxidase Inhibitors (LIGHT).

Data from 1 observational, open-label study (Long-term Allopurinol Safety Study Evaluating Outcomes in Gout [LASSO]) was also used. Participants in LASSO who had also participated in the CLEAR or LIGHT trials were excluded from the study.

The initial 6 months of data from the aforementioned 4 interventional trials and the 1 observational, open-label study on the use of ULT was used. They assessed HRQOL at baseline and then every 3 months; SU levels were measured monthly.

The primary study outcome measures included Short-Form 36 (SF-36) physical component summary (PCS) and mental component summary (MCS), Health Assessment Questionnaire Disability Index (HAQ-DI), SDS, Patient Global Assessment, and pain scores during the previous week. For each of the outcomes, adjustments were made to linear mixed models as appropriate for current SU level; change in urate during the previous month; number of flare-affected days in the prior month; tophi status; baseline body mass index (BMI); sex; ethnicity; and trial/study/treatment combination. Baseline urate was associated with urate concentration for each month (β=0.37; 95% CI, 0.34-0.40) and with absolute urate change (β=0.13; 95% CI, 0.12-0.15).

The mean patient age was 52 years to 54 years (<90% men, >75% European ethnicity). The mean BMI varied from 32 kg/m² to 34 kg/m², and 17% to 25% of patients had gouty tophi, except for those in the CRYSTAL trial, in whom 100% exhibited tophi. The mean number of gout flares in the prior year per the included trials ranged from 5.5 to 6.7. Baseline SU level varied from 5.3 to 9.3 mg/dL; the 6-month SU level ranged from 4.3 to 8.0 mg/dL.

Higher current SU levels were associated with reduced physical and mental HRQoL, as well as with increased SDS and pain, but not with HAQ-DI score. In the initial 6 months of new or escalating use of ULT, the absolute change in SU concentrations in the prior month, evaluated in the same model as current SU levels, also demonstrated significant associations with poorer outcomes:

• SF-36 MCS: β=-0.33, 95% CI, -0.47 to -0.18;
• HAQ-DI: β=0.013, 95% CI, 0.007-0.019;
• SDS: β=0.19, 95% CI, 0.05-0.32;
• PGA: β=0.49, 95% CI, 0.09-0.89; and
• Pain in the past week: β = 0.68, 95% CI, 0.18-1.18.

One exception within these outcomes was SF-36 PCS (β=-0.13, 95% CI, -0.27 to 0.01).

Per multivariable-adjusted analyses, baseline SU levels were significantly associated with all baseline PROs, as well as with 6-month SF-36 PCS, HAQ-DI, SDSS, PGA, and pain scales, but not with SF-36 MCS. Reduction in SU levels was linked to poorer outcomes in all 6 of the measures.

Limitations of the study included the fact that heterogeneity in the patient populations existed because of the requirement of clinical trial recruitment. It is possible that confounding bias was present based on such unmeasured confounders as concomitant medications and comorbidities that were not included in the models.

 “Clinical emphasis on slow rather than fast SU reduction and the routine use of effective, anti-inflammatory medications at ULT initiation/escalation may avoid short-term poor outcomes,” the study authors concluded.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference 

Topless R, Noorbaloochi S, Merriman TR, Singh JA. Change in serum urate level with urate-lowering therapy initiation associates in the immediate term with patient-reported outcomes in people with gout. Semin Arthritis Rheum. 2022;56:152057. doi:10.1016/j.semarthrit.2022.152057