The prevalence of gout is skyrocketing worldwide, and while drugs in the pipeline hold promise for improving the efficacy and safety of treatment, experts warn that “gout remains suboptimally managed.”
“For a really well-understood disease, gout is remarkably undertreated,” said Robert A. Terkeltaub, MD, professor of medicine emeritus at the University of California, San Diego. “This is amazing and depressing because allopurinol has been around for about 60 years or so.”
Randomized, controlled trials show that 80%-90% of patients with gout can be effectively treated to target with existing gout therapies. “Over a year or two, gout flares improve and patients do well,” Dr. Terkeltaub said.
By lowering excessive levels of serum urate, current therapies slow the formation of monosodium urate crystals that precipitate within joints and soft tissues, inducing a highly inflammatory local response with superimposed systemic inflammation. These therapies reduce the frequency of excruciatingly painful gout flares.
“Many patients with gout are not taking urate-lowering therapy at all,” Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, and head of crystal-induced arthritis diseases at Brigham and Women’s Hospital, also in Boston, said in an interview.
“Unfortunately, a common problem in gout is treatment inertia,” said Tuhina Neogi, MD, PhD, chief of rheumatology at Boston Medical Center.
On a global scale, only one-third of patients with gout are started on urate-lowering therapy, and more than 50% abandon treatment after 1 year. As a result, the effectiveness of urate-lowering therapies in reality is well below 50%, Dr. Terkeltaub said.
“I think gout has been taken less seriously than it should be for quite some time,” he explained in an interview. Gout’s impact on health and well-being is no trivial matter. A recent study showed that a diagnosis of gout was associated with an increased risk of anxiety and depression, and there is new evidence suggesting that gout flares are associated with an increased risk of cardiovascular events, including fatal myocardial infarction and stroke.
“We need drugs that are not just effective but also safe, and we need to incorporate real-world data into our assessment of treatment effectiveness, especially in the presence of comorbidities,” Dr. Terkeltaub said.
The prevalence of what used to be thought of as the “disease of kings” has increased 100% over the last 30 years, outstripping world population growth and life expectancy. In the United States, an estimated 5% of adults, or 12 million, have gout. Globally, the number affected exceeds 50 million.
The patient demographics associated with gout have also expanded. Once seen primarily in fleshy, middle-aged men of privilege, gout affects more women, more adults at either end of the age spectrum, and more people in Third World countries than ever before.
Management
In the United States, the optimal management of gout remains the subject of debate, with differences in expert opinion reflected in evidence-based clinical guidelines. “We know that the perception of gout is different between primary care physicians, patients, and rheumatologists,” Dr. Terkeltaub said.
The 2017 American College of Physicians guidelines for the management of gout recommend a treat-to-symptom approach to urate-lowering therapy. However, the 2020 American College of Rheumatology guidelines reinforce a standard treat-to-target strategy to a serum urate target of < 6.0 mg/dL.
In their report, the ACR guidelines’ authors stated that the use of urate-lowering therapy for gout has not increased in the last decade. Research shows that adherence to treatment for gout continues to be the lowest among seven common chronic medical conditions, including hypertension and seizure disorders, they said.
Some physicians don’t recommend urate-lowering medication to their patients with gout, and others don’t up-titrate it sufficiently to meet the recommended serum urate target, said Dr. Tedeschi. The latter “can require increasing the dose of allopurinol well beyond the 300 mg that often seems the landing point for many patients with gout,” she pointed out.
In fact, it can take up to 800 mg a day of allopurinol – less in patients with moderate to severe kidney disease – to reduce the symptom burden in gout. And it can take a year or longer of drug testing and titration to reach the optimal serum urate target. Paradoxically, gout flares usually get worse during this time.
“We need to reduce the time it takes to get the patient to the serum urate target, and simplify regimens with once-a-day dosing,” Dr. Terkeltaub said. “We also need greater precision so that we can get a home run, hitting the serum urate target the first or second visit, with minimal dose titration.”
Clinician education is important, but education alone is not enough, Dr. Neogi emphasized. “Just as clinicians treat-to-target in other conditions such as hypertension and diabetes, or titrate warfarin to maintain a certain level of anticoagulation, gout must be monitored and treatments adjusted accordingly,” she said.
Practice changes, such as partnering with nursing or pharmacy, may help facilitate in-clinic dose titration, “much like a warfarin clinic,” Dr. Neogi suggested.
That’s exactly what Dr. Terkeltaub has done. Overwhelmed by the number of gout consults, Dr. Terkeltaub and his team set up a pharmacist-managed, rheumatology-supervised clinic to care for gout patients remotely. The model has been very successful, he said. Nurses and clinical pharmacists educate the patients and manage their lab testing and prescriptions, all according to ACR guidelines.
The treatment of gout has become more complex, with a greater risk of drug complications and interactions, particularly in older patients with comorbid diabetes, chronic kidney disease, and heart disease. Many of the patients he sees are already on “10, 15, or 20 other medications,” Dr. Terkeltaub noted.
The steps involved in the titration of urate-lowering therapy also complicate the treatment of gout, making it impractical for many patients and impossible for others whose access to primary care is limited to one or two visits a year. The process of drug titration, with steadily increasing doses, can make patients anxious about the possibility of being overmedicated. Taking a drug every day, even when joints feel “normal,” can also increase the risk of nonadherence.
“In our conversations with patients with gout, it’s extremely important that we counsel them about the need to take urate-lowering therapy on an ongoing basis to reduce the risk of a gout flare,” said Dr. Tedeschi. “Patients need to have prescription refills available and know to contact the doctor before they run out, so that the chances of having a gout flare are reduced.”