Wednesday, 11 Dec 2019

You are here

Treat-to-Target Strategy Cuts Mortality in Gout Patients

More intense treatment of gout with a treat-to-target strategy can reduce patients' risk for death, a Spanish researcher told a press conference Monday at the American College of Rheumatology annual meeting here.

"Failure to reach a target serum uric acid (sUA) level of 6 mg/dL is an independent predictor of mortality in gout patients. Control of gout with achievement of sUA target less than 6 mg/dL should be considered in order to improve patient survival," said Fernando Perez-Ruiz, MD, PhD, a rheumatologist at Hospital Universitario Cruces in Baracaldo, Spain.

In 2014, a group of European researchers found a series of variables were linked in gout patients to higher mortality risk, including serum urate levels at baseline and during therapy, flares, and comorbidities.

Perez-Ruiz said of the first study of 700 patients, "Severity of gout was associated with increased risk of mortality, but we could not find a signal for serum urate while on treatment."

He said a prospective, follow-up cohort study was conducted in 1,193 patients treated at a gout clinic from 1992 to 2017. Eighty-five percent of these patients had gout confirmed with either microscope or ultrasound scan. They had at least one follow-up visit.

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 6 mg/dL versus more than 6 mg/dL.

Perez-Ruiz said lowering serum uric acid levels to a target of less than 6 mg/dL reduced mortality risk in individuals with gout.

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 6 or more mg/dL despite treatment.

A total of 158 deaths occurred among participants in the study, for rates of 13% overall and 32.7 per 1,000 patient-years.

Mortality was significantly higher for patients whose serum uric acid level was over 6 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 level of 6 mg/dL or higher was associated with higher mortality risk, with a hazard ratio of 2.39.

The approach to managing hyperuricemia in gout often is based on treating flares unless severe gout develops, noted Perez-Ruiz. But he added the new research supports a treat-to-target intervention to reach therapeutic serum urate levels.

"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," he said. "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."

Perez-Ruiz said rheumatologists ought not take a position of "two flares a year, that's not bad."

He said treatment ought to take a treat-to-target approach similar to reducing high cholesterol levels to avoid myocardial infarctions.

Shraddha Jatwani, MD, press conference moderator and an adult rheumatologist at St. Vincent Hospital in Evansville, Indiana, said the findings from the Spanish study should motivate community rheumatologists to persuade non-compliant patients to take their medications to help reduce mortality. She said many gout patients don't see the need for taking daily medications when their gout pain lets up.

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

Rheumatologists' Comments

As happens all too often, causation and association have been confused: the headline of this article and the quote by the author imply causation, suggesting that lowering uric acid will improve longevity. But a study of this type cannot make such a conclusion. These are associated observations (which might or might not be causally linked). Similarly, it is potentially misleading to tell patients they'll live longer by improving compliance with urate-lowering therapy (as well-meaning as that might be).

More Like This

Pegradicase+ImmTOR SEL-212 Shows Promising Results In Active Gout

Therapies targeting sUA accumulation or improving its excretion are widely used for treatment of symptoms and prevention of progression of gout for decades. Despite our best effort, there is still a significant amount of patients who remain symptomatic and/or experiences progressive joint damage and disability. Regardless of the cause, either its lack of compliance or poor tolerability, more effective treatments are needed.

PANLAR Ultrasound Study Group: Recommendations On Imaging Modalities In Gout

Gout is a systemic inflammatory disease with high potential for joint damage due to erosive changes and MSU deposits resulting in disability and chronic pain. Prompt diagnosis and effective treatment are key to better long term outcomes and decreased disability.

T2T Lowers Mortality in Gout

A Spanish prospective cohort of active, uncontrolled gout patients were followed and showed that failure to reach a target serum uric acid (sUA) level of 6 mg/dl (0.36 mmol/L) or less was associated with a 2-3 fold increase in mortality.

Novel Inhibition of MSU Crystal Inflammation

Researchers from Washington State University have shown that inhibition of tumor growth factor-β (TGF-β)-activated kinase 1 (TAK1) can effectively downregulate inflammatory mediators and suppress inflammation caused by gout.

Monosodium urate (MSU) crystals directly activate the inflammasome to produce a plethora of pro-inflammatory cytokines, including interleukin-1β (IL-1β). 

Patients Prefer Nurse Led Care for their Gout

Despite the well known, well publicized treat-to-target (T2T) goal of a serum uric acid (SUA) level < 6 mg/dl, this goal is seldom achieved (< 40%) in clinical practice and patient adherence has been unacceptably low. A recent study shows that nurse-led care led to better outcomes in gout including patient acceptability, long-term adherence, and less flares.