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GOUT PATIENTS WHO FAIL TO REACH OPTIMAL SERUM URATE TARGET HAVE HIGHER DEATH RISK
Newswise — CHICAGO – Failure to reach a serum urate target of 6 mg/dl independently predicts mortality in patients with gout, and a treat-to-target gout control strategy should be considered as a way to improve a patient’s chance of survival, according to new research findings presented this week at the 2018 ACR/ARHP Annual Meeting (Abstract #869).
Gout is a painful form of arthritis, and it occurs more often in men, post-menopausal women and people with kidney disease. Gout happens when excess uric acid, a waste product, collects in the body, and leads to urate crystals depositing in and around the joints. Crystals may settle and form tophi that appear under the skin. Diet and lifestyle modification, as well as medications may help patients lower serum urate levels and manage gout.
Gout is associated with a higher risk of cardiovascular events and death. Research shows that increasing gout severity is associated with risk of death, and is reflected in the number of tophi. In 2014, a group of European researchers published a study analyzing gout patients in Spain and found that several variables contributed to higher mortality risk, including serum urate levels at baseline and during therapy, flares and comorbidities. In their new study, these researchers evaluated whether lowering serum uric acid levels to a target of less than 6 mg/dl would improve mortality risk in individuals with gout.
At the time of their first study, “700 patients were available for an analysis that showed that, among others, severity of gout was associated with increased risk of mortality, but we could not yet find a signal for serum urate while on treatment,” said Fernando Perez Ruiz, MD, PhD, Senior Specialist, Rheumatology Division, Hospital Universitario Cruces in Spain, and the study’s co-author. “That was to assume that once you develop severe gout, treatment has no impact on reducing the risk of mortality. Our results were afterwards replicated by colleagues from New Zealand. Doubling the number of our patients in this study, and with a greater number of patients failing to reach the serum urate target, we have found new signals for not reaching therapeutic target serum urate levels.”
The prospective, follow-up cohort study included 1,193 patients treated at a gout clinic from 1992 to 2017, and 85 percent of these patients had confirmed diagnosis of gout with either microscope or ultrasound. All had at least one follow-up visit. The researchers confirmed mortality from medical records, patients’ families or local death registries. Patients’ serum uric acid levels were monitored during follow-up, and the study used the average serum uric acid level until stabilization as the primary exposure, defined as less than six mg/dl versus more than six mg/dl.
Variables and potential confounders included age, sex, body-mass index (BMI), previous treatment with urate-lowering drugs, the number of joints affected at entry to the study, presence of subcutaneous tophi, radiographic evidence of articular damage, number of gout flares in the year before evaluation, previous cardiovascular disease diagnosis, loop diuretic use, alcohol intake, diabetes, hypertension, hyperlipidemia and renal function impairment. The researchers used the Kaiser Permanente comorbidity model to risk-stratify patients from low to high death risk.
The mean serum uric acid level at baseline was 9.1 mg/dl, and 16.3 percent of patients maintained serum uric acid levels of six or more mg/dl despite treatment. There were a total of 158 deaths among participants in the study, which represents a 13 percent overall mortality rate. There was a loss to follow-up in 286 cases, or 24 percent. Overall crude mortality rate was 32.7 per 1,000 patient-years. This was significantly higher for patients whose serum uric acid level was over six mg/dl(80.9 per 1,000 person-years). After adjusting for age, sex, previous cardiovascular events, and baseline serum uric acid concentration, a serum uric acid levelof six mg/dl or higher was associated with higher mortality risk, or a hazard ratio of 2.39. Failure to reach a target serum urate level of six mg/dl is an independent predictor of mortality in gout patients, the study concluded.
“There are two current approaches for hyperuricemia in gout: treat-to-target interventions to reach therapeutic serum urate levels, or treat to flare unless severe gout develops,” said Dr. Perez Ruiz. “This new analysis shows that although a signal for developing severe gout remains, reaching serum urate therapeutic target is associated with lower mortality risk than being over target. Although we cannot exclude other variables not included in our database, such as control of comorbid conditions, our results encourage making any clinically acceptable effort to reach and maintain serum urate levels on target. Keep in mind that development of severe gout is not a desirable outcome either.”
About the ACR/ARHP Annual Meeting
The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. With more than 450 sessions and thousands of abstracts, if offers a superior combination of basic science, clinical science, tech-med courses, career enhancement education and interactive discussions on improving patient care. For more information about the meeting, visit https://www.rheumatology.org/Annual-Meeting, or join the conversation on Twitter by following the official #ACR18 hashtag.
About the American College of Rheumatology
The American College of Rheumatology is an international medical society representing over 9,400 rheumatologists and rheumatology health professionals with a mission to empower rheumatology professionals to excel in their specialty. In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases. For more information, visit www.rheumatology.org.
Abstract #: 869
Failure to Reach Serum Urate Target Is Associated with Elevated Mortality in Gout
Fernando Perez-Ruiz, BioCruces Health Research Institute, Barakaldo, Spain, Pascal Richette, Lariboisière Hospital, Lariboisière, University of Paris 7, Paris, France, Austin Stack, University Hospital Limerick & Health Research Institute,University of Limerick, Limerick, Ireland, Ravichandra Karra Gurunath, Grünenthal GmbH, Aachen, Germany, MARIA JESUS GARCIA DE YEBENES Y PROUS, Institute for Musculoskeletal Health, Madrid, Spain and Loreto Carmona, Instituto de Salud Musculoesquelética (InMusc), Madrid, Spain
Background/Purpose: Gout is associated with an increased risk of cardiovascular events and death. It has been shown that both overall and risk of death are associated with increasing gout severity, as reflected by the number of tophi. It remains to be proven whether better control of gout through lowering of serum uric acid (sUA) confers a survival advantage. To determine the impact of achieving sUA less than 6 mg/dl (vs greater) on mortality risk among gout patients.
Methods: Analysis of data from a prospective follow-up cohort (1992 to 2017) of patients attending a gout clinic (85% of patients with microscope or ultrasound diagnosis) and with at least one follow-up visit. Mortality was confirmed from medical records, patients’ families, or local death registries if needed. sUA levels were monitored during follow-up and the average sUA until sUA was stable was used as the primary exposure dichotomized as < 6 mg/dl (versus > 6 mg/dl). Descriptive variables and potential confounders included: age, gender, body mass index, previous treatment with urate-lowering drugs (ULDs), number of joints affected at entry, presence of subcutaneous tophi, radiographic evidence of articular damage, number of gout flares in the year preceding evaluation, previous diagnosis of cardiovascular (CV) disease, loop diuretic use, alcohol intake, diabetes, hypertension, hyperlipidemia, and renal function impairment. In addition, the Kaiser Permanente stratification of comorbidity was further used to risk stratify patients from low to high risk of death. Univariate and multivariate Cox proportional hazards models were used to determine mortality risks expressed a hazard ratios (HR) and 95% Confidence Intervals (CI).
Results: The study cohort included 1,193 patients (92% men, mean age 60, 6.8 years disease duration, with an average of 3 to 4 flares in the previous year). Mean follow-up was 48 (median 30, IQR 12-66), with 4,830 patient-year observation. Mean sUA at baseline was 9.1 mg/dl and 16.3% of the patients maintained sUA levels ≥6 mg/dl despite treatment. A total of 158 deaths occurred (13% overall mortality), with loss to follow-up in 286 cases (24%). Overall crude mortality rate was 32.7 per 1,000 patient-years, (95% CI: 28.0-38.2) and was significantly higher for patients with sUA ≥ 6 mg/dl, 80.9 per 1, 000 person years (95% CI 59.4-110.3) compared to patients with sUA <6 mg/dl, 25.7 per 1,000 person-years (95% CI: 21.3-30.9). With adjustment for age, sex, previous CV events, and baseline sUA concentration, a sUA ≥ 6 mg/dl was associated with a HR of 2.39 (1.64 - 3.50).
Conclusion: Failure to reach a target sUA level of 6 mg/dl is an independent predictor of mortality in gout patients. Control of gout with achievement of sUA target <6 mg/dl should be considered in order to improve patient survival.
Disclosures: F. Perez-Ruiz, Amgen Inc., 5, 8, Grünenthal, 5, 8, Menarini, 5, 8, Asociación de Reumatólogos de Cruces, 2 P. Richette, Menarini, 5, Grünenthal, 5 A. Stack, Health Research Board, 2, Midwest Research and Education Foundation, 2, Menarini International Operation Luxemburg, 2, 5, Grünenthal, 5, Astellas, 5 R. Karra Gurunath, Grünenthal, 3 M. J. GARCIA DE YEBENES Y PROUS, None L. Carmona, None
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