It was once seen as the disease of kings, afflicting only the lazy and gluttonous. These days, however, gout is everywhere — and a bitter battle has broken out among physicians about how best to treat it.
A form of arthritis, gout is characterized by unsightly bulges under the skin and incredible pain in the joints. Typically seen in older men, the disease now increasingly afflicts women and younger adults, often accompanied by obesity, diabetes, and high blood pressure.
“It used to be the disease of kings, but now it’s really the disease of the people,” said Dr. Robert Terkeltaub, a professor of medicine at the University of California, San Diego.
There are several medicines to combat gout, which is caused by a buildup of uric acid in the blood, and more are on the way.
But the American College of Physicians, the nation’s largest specialty medical association, this month put out new guidelines that call for less aggressive pharmaceutical treatment. That’s angered many gout specialists, who in recent years have created two new professional groups — both backed by drug companies — one to bolster gout research and the other to promote long-term use of medication to lower uric acid.
In an era when many long-standing medical guidelines — such as how often to get a mammogram or how aggressively to target blood pressure — are being vigorously scrutinized, the terse disagreement highlights recurring tensions over just what constitutes scientific evidence.
It’s true, as the ACP says, that there’s a lack of gold-standard evidence — in the form of randomized, controlled clinical trials — to prove that patients with gout should be put on a long-term drug regimen to lower their uric acid to any specific level.
“Strong data just doesn’t exist,” said Dr. Robert McLean, a rheumatologist with Northeast Medical Group in New Haven, Conn., and associate clinical professor at the Yale School of Medicine. “It may be the right thing to do in many clinical situations, but we don’t have data to say that with certainty, so we can’t endorse it.”
But rheumatologists argue that the expensive clinical trials that the ACP wants to see are unlikely to be conducted on already approved drugs and that it makes no sense to wait until a patient suffers from a painful flare-up before treating him or her.
They say their own experience in the clinic and numerous observational studies — which don’t control for the placebo effect — show that lowering uric acid prevents the recurring, painful flares that bedevil 70 percent of gout patients and may also prevent permanent bone and joint damage. They recommend reducing uric acid to levels of 6 mg/dL or lower as a matter of course.
“Would you manage hypertension without looking at blood pressure?” Terkeltaub asked.
“I would say rheumatologists around the world are upset about the guidelines,” said Dr. N. Lawrence Edwards, a longtime gout researcher and vice chair of graduate medical education at the University of Florida College of Medicine who also consults for pharmaceutical companies.
The debate is also airing another key question that resonates across the medical community: Does drug company money sway treatment decisions?
Terkeltaub, a staunch advocate for medication, has received about $35,000 in consulting fees from drug companies that make gout medications in recent years, according to the Open Payments database that tracks such payments. Many of the rheumatologists who have called for treating gout with drugs have also received money from pharmaceutical companies. Edwards, for instance, received about $27,000 in 2015.
Terkeltaub dismissed concerns about a conflict of interest, saying it was unlikely that commercial bias could have tainted three different rheumatology groups that in recent years all came up with similar guidelines for pharmaceutical intervention to treat gout. Others argue that banishing all physicians with ties to drug companies from the debate would mean losing the input of people like Terkeltaub and Edwards, who are considered leaders in the field.
But studies have shown that doctors who receive compensation (even in the form of inexpensive lunches) from pharma companies are more likely to prescribe brand-name drugs than their peers. The Institute of Medicine urges professional physicians’ groups to limit such conflicts of interest on any panel that writes up treatment guidelines. Most groups do not do that.
The American College of Physicians, which published the guidelines that urged less pharmaceutical intervention, does maintain a strict policy: Committee members cannot have any pharma ties. McLean, for instance, used to serve as a paid speaker for Takeda (TAK) Pharmaceuticals’s gout drug Uloric; he dropped that job to join the ACP committee that was working on treatment guidelines.
Gout is a booming market and many drug companies are rushing to get a piece of it — and to win over physicians. As many as 10 novel compounds to lower uric acid levels are in various stages of testing. A recent report estimated the global market for gout drugs will grow 17 percent in coming years, with AstraZeneca (AZN), Horizon Pharma, and Takeda as leading vendors.
The debate frustrates Dr. Tuhina Neogi, a rheumatologist, epidemiologist, and professor of medicine at Boston University. She understands the virtues of high-quality evidence, yet said it’s myopic to ignore decades of wisdom that specialists have gained from treating actual patients.
“As an epidemiologist I would love to have clinical trial data for every important clinical question,” Neogi said. “But in the absence of that, we still need to advise our colleagues. We can’t leave physicians blind.”
Neogi, who has no financial conflicts with makers of gout drugs, said she’ll teach her students about the ACP guidelines. But in the clinic? She plans to keep urging patients to take medication to lower uric acid levels.
Caught in the middle of the fight: the estimated 8 to 10 million Americans with gout.
“There’s still a lot of shame attached to it. People make fun of you,” said Spiro Koulouris, a 41-year-old Montreal native who was diagnosed with gout in his 20s and now runs the blog GoutandYou.com.
Koulouris took the medication colchicine to treat his attacks — and suffered severe diarrhea as a side effect. He also drastically changed his diet — giving up the steaks, burgers, fries, and Jack Daniels and Cokes he so loved. His weight dropped from 245 to 180.
He’s now on low doses of medication, now with few side effects, eats a plant-based diet that includes very little sugar or alcohol, and gets his blood checked every six months. His gout is completely under control.
But he still remembers how painful it was when the disease flared. “I couldn’t put any pressure on my big toe whatsoever,” he said. “I couldn’t even put a bed sheet on it.”