Options to Treat Gout and Increase Medication Adherence

San Francisco—According to an article in Arthritis & Rheumatism [2008;58(1):26-35], as many as 3 million people in the United States self-reported having gout in 2008. Another study, published online in Arthritis & Rheumatism on July 28, 2011, found an additional 43.3 million adults (21% of the population) have hyperuricemia, a pregout condition.

Allopurinol is typically used to treat gout, but patients are not always adherent to the medication, leading to an increased frequency of flare-ups and higher utilization of healthcare services and increased costs. Although investigational therapies seem promising, speakers at the AMCP meeting said managed care professionals must take gout seriously and closely monitor patients to ensure they are taking the medications.

They spoke at a satellite symposium titled Today’s Gout: Treatment Concerns for the Managed Care Pharmacist.

Glenn E. Farr, MD, professor of clinical pharmacy at the University of Tennessee’s College of Pharmacy in Knoxville, Tennessee, defined gout as a rheumatic disease caused by the overproduction or underexcretion of uric acid. It is commonly found in the large joint of the big toe, but it can affect other joints such as the instep, Achilles tendon, heel, ankle, knee, wrist, finger joints, and elbow.

Gout is the most common inflammatory arthritis in men, and its incidence is increasing among postmenopausal women. It is found mostly in older adults, particularly in those >65 years of age. Dr. Farr cited many reasons for the rising prevalence, including the aging of society and lifestyle factors such as obesity, hypertension, alcohol consumption, diuretic use, and diet of meat and seafood.

Dr. Farr said 60% of people with gout suffer from another episode within a year and 78% have another attack within 2 years of their first attack. He added that gout accounts for >2.2 million ambulatory care visits each year.

Gout and Hyperuricemia

Dana A. Brown, PharmD, assistant dean for academics and associate professor at Palm Beach University in West Palm Beach, Florida, followed with an overview of hyperuricemia.

Dr. Brown defined hyperuricemia as a state of abnormally high serum uric acid levels (>7 mg/dL in men and >6 mg/dL in women). She mentioned patients with gout most likely have hyperuricemia, although patients with hyperuricemia do not necessarily have gout.

Hyperuricemia and gout are commonly associated with chronic conditions such as cardiovascular disease, hypertension, chronic kidney disease, metabolic syndrome, and diabetes, according to Dr. Brown. She discussed a randomized trial following 12,866 men for a mean of 6.5 years that found 10.5% of patients with gout had acute myocardial infarction (MI) compared with 8.4% of patients without gout (P=.018). The authors also concluded that hyperuricemia was an independent risk factor for acute MI (P<.001).

Patients with metabolic syndrome typically have hyperuricemia, with higher levels of hyperuricemia associated with a higher prevalence of metabolic syndrome. For instance, 40.8% of people with a uric acid level between 6.0 and 6.9 mg/dL have metabolic syndrome, while 70.7% of people with a uric acid level ≥10 mg/dL have metabolic syndrome. Dr. Brown also cited data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey that found 62.8% of patients with gout had metabolic syndrome compared with 25.4% of patients who did not have gout.

Dr. Brown said that hyperuricemia consistently predicts the development of hypertension, particularly in adolescents and younger adults. She discussed a meta-analysis from 2011 that found that hyperuricemia was associated with an increased risk for hypertension (risk ratio [RR], 1.41; 95% confidence interval [CI], 1.23-1.58). The same study, which examined 18 prospective cohort studies involving 55,607 patients, found that a 1-mg/dL increase in uric acid was associated with an increased risk for hypertension (RR, 1.13; 95% CI, 1.06-1.20). Dr. Brown added that there is an association between hypertension and a higher risk of a first gout flare-up.

Studies have also shown a relationship between hyperuricemia and chronic kidney disease and albuminuria. One trial of patients with type 1 diabetes found that every 1 mg/dL in uric acid level was associated with an 80% increased risk of developing micro- or macroalbuminuria over 6 years (P=.005).

Dr. Brown said patients have benefitted from taking allopurinol, particularly in reducing chronic kidney disease progression and lowering blood pressure. A randomized, double-blind, placebo-controlled trial found treatment with allopurinol for 4 weeks was associated with a significant decrease in systolic blood pressure (P=.009) and diastolic blood pressure (P=.05).

Gout and Adherence

Diana I. Brixner, RPh, PhD, professor in the University of Utah’s College of Pharmacy in Salt Lake City, Utah, said elevated serum uric acid levels are associated with increased frequency of flare-ups as well as higher utilization and costs. Treatment options include allopurinol, probenecid, febuxostat, and pegloticase.

However, Dr. Brixner cited a study that mentioned among chronic conditions, gout had the worst rate of drug adherence. Reported adherence rates were between 26% and 74%, with the study finding 56% of patients with gout were nonpersistent to their medications within 1 year and 25% were nonpersistent after filling 1 prescription.

According to Dr. Brixner, patients stop taking gout medications for several reasons, chief among them being financial considerations and clinical concerns such as flare-ups or side effects. Risk factors for nonadherence are younger age, fewer comorbidities, fewer number of visits for gout care, and no diagnosis of tophaceous gout.

Dr. Brixner recommended that to increase adherence, physicians and pharmacists should spend more time with patients and educate them about gout’s etiology, the need for chronic therapy, and what to expect when starting therapy.

With an annual burden of new cases of acute gout estimated at $27 billion, managed care professionals have a major incentive to increase adherence. Employees with gout have a mean annual cost of $6870 compared with $3705 for patients without gout. They also miss an average of 3 to 5 days of work per year because of acute gouty arthritis attacks.

“The consequences of chronic gout can be quite significant,” Dr. Brixner said.

Despite having plenty of options to treat gout, Dr. Brixner said there is a need for high-quality cost-effectiveness analyses to compare the medications. She said studies showed febuxostat was more effective than allopurinol, but it was also more expensive. Previous cost-effectiveness trials had limitations that should be addressed, according to Dr. Brixner, including measuring adherence in addition to costs.

Other options may exist in the future, as the FDA may approve investigational agents such as pegadricase, lesinurad, tranilast, and BCX4208.