By: SHERRY BOSCHERT
The first guidelines on the management of gout from the American College of Rheumatology recommend new ways of using old drugs and changes in prophylaxis strategies, among other things.
The two-part guidelines, published online, should help speed up effective treatment of gout and get physicians to treat patients to a target urate level of less than 6 mg/dL in order to improve symptoms, Dr. John D. FitzGerald said in an interview.
“There has been a fair amount of recent movement on gout medications” including new alternatives to allopurinol and colchicine and new data on how to use those traditional drugs in safer ways, said Dr. FitzGerald, acting chief of the rheumatology division at the University of California, Los Angeles. “It’s a fair number of changes for medications that people had been using for decades.”
The documents update previous guidelines from medical organizations in Europe, the Netherlands, and Japan. Part 1 of the American College of Rheumatology (ACR) guidelines covers nonpharmacologic and pharmacologic approaches to managing hyperuricemia (Arthritis Care Res. 2012;64:1431-46). Part 2 addresses prophylaxis and treatment for acute gouty arthritis (Arthritis Care Res. 2012;64:1447-61).
Dr. FitzGerald and two other coleaders of the project, Dr. Dinesh Khanna of the University of Michigan, Ann Arbor and Dr. Robert Terkeltaub of the University of California, San Diego, reviewed the medical literature on gout from the 1950s to the present and drew up nine clinical case scenarios commonly seen in practice. A task force panel comprising seven rheumatologists, two primary care physicians, a nephrologist, and a patient representative used the scenarios to create consensus recommendations.
Among the recommendations, for example, on the use of allopurinol is to start at a low dose of 100 mg/day (instead of the common practice of starting with 300 mg/day), or even lower for patients with chronic kidney disease, and then gradually titrate upward every 2-5 weeks. That recommendation supports previous statements from the Food and Drug Administration and the European League Against Rheumatism.
Also, allopurinol therapy should be actively managed and patients followed to make sure the uric acid target is achieved. “You can’t just give a prescription and say your job is done,” though some recent studies suggest that many physicians do just that, Dr. FitzGerald said. “The corollary would be if someone gave blood pressure medication and then didn’t follow the patient’s blood pressure. That wouldn’t be seen as good medicine.”
Maintenance doses of allopurinol to prevent acute gout attacks can exceed 300 mg even in patients with chronic kidney disease provided there is adequate patient education and monitoring.
A new recommendation drops the starting dose of oral colchicine for acute gout attacks to a loading dose of 1.2 mg, followed by 0.6 mg an hour later, and then starting prophylaxis 12 hours later at dosing of 0.6 mg once or twice daily.
“We used to give up to eight tablets a day," Dr. FitzGerald said. “That is dropped down to three to four tablets at the start of an attacks, because of findings that more colchicine didn’t really help outcomes” and that smaller doses are safer. The authors called this recommendation from ACR “a paradigm shift” that’s in accordance with Food and Drug Administration-approved label language.
Other highlights of the new ACR recommendations include sections on screening for HLA-B*5801 in patients at high risk of severe adverse reaction to allopurinol, combination therapy when target urate levels are not achieved, medication options including new drugs, and more.
Although the reports are titled “Guidelines,” the text makes clear that they are expert recommendations and that clinicians are expected to take active roles in choosing the best management strategies for their particular patients. The authors were “very concerned” that the guidelines not be used by third-party payers to restrict access to medications or to promote one drug over another if there isn’t clear evidence to support it, Dr. FitzGerald said.
The methodology of the project precluded evaluations of costs and cost effectiveness, instead focusing on efficacy. So, for example, the guidelines say that allopurinol and febuxostat can be used equivalently in some circumstances, but clinicians need to consider all other aspects of these options including cost, patient preference, and more.
The ACR plans to update the guidelines as new data become available. The task force panel did create specific indications for use of imaging studies because results should be available in the next few years from studies on the use of high-resolution ultrasound and dual-energy CT for patients with gout.
In the United States, gout affects an estimated 4% of adults – more than 8 million people.
“I’m most excited and hopeful about trying to get this out to internal medicine and family practice doctors,” Dr. FitzGerald said. “They see more gout than rheumatologists.”
In an interview, Dr. Christopher M. Burns explained that “writing guidelines on gout is a difficult task. I think they made a very good effort to cover as many treatment issues as they could.
“Most patients with gout in the United States are cared for by primary care physicians. The guidelines will be helpful to both primary practitioners and rheumatologists, but the subtleties may be lost on the general practitioner, whereas the rheumatologist would pick these up right away. The devil is often in the details when it comes to treating gout. If physicians use the guidelines employing a cookbook approach, they might run into some problems, said Dr. Burns, a rheumatologist at the Geisel School of Medicine at Dartmouth, Hanover, N.H.
For instance, the guidelines cover the use of colchicine as a first-line agent for an acute attack: “It’s a good choice, but even the randomized controlled trials that have been published on this, especially using the low-dose approach, show that a significant proportion of patients will not respond to this regimen. The guidelines recommend a dosage higher than what has been advised previously for the low-dose colchicine approach. This may actually be a better method, so I hope this will allow primary practitioners to be able identify more people using this approach. But there are definitely going to be people who do not respond to the colchicine,” he said.
“Another example of where the guidelines may mislead primary care physicians is the recommendation on when to start urate-lowering therapy (ULT). Their indications for starting pharmacologic ULT include an established diagnosis of gouty arthritis and at least two attacks per year. My colleagues and I think that may exclude too many people. Theoretically, you could have a patient with one attack per year who is having gout-related joint damage and, with these criteria, wouldn’t qualify for ULT. A rheumatologist would pick that up right away, but general practitioners who adhere to these guidelines might end up undertreating some patients.
“Also, they recommend using adrenocorticotropic hormone (ACTH) for people who cannot take oral medications. Not only is ACTH is extremely expensive, but the Food and Drug Administration has taken gout off the list of indications for ACTH, so I doubt it would be readily available in a real clinical situation,” according to Dr. Burns.
“When the recommendations discuss using prednisone as a prophylactic against gout attacks, they suggest using 10 mg or less. I think that the authors are trying for the best of both worlds and ending up not having either. We generally try to avoid using steroids long term, so the authors suggest using low-dose prednisone; the problem is that 10 mg would probably be ineffective. There are data suggesting that gout prophylaxis requires higher doses, maybe as much as 20 mg/day. You could try 10 mg but I anticipate that it is not going to work very well.
“In their defense, were the authors to go into the subtleties and side effects, what to do with a patient with liver or coronary disease, or issues of cost effectiveness, the guidelines would have become an unmanageable length. But the devil is in the details.
“That said, it’s a major effort here. It’s good work. They tried to answer a lot of questions,” said Dr. Burns.
Dr. FitzGerald reported having no financial conflict of interest. Some members of the task force reported financial associations with multiple pharmaceutical companies but, by design, a majority of task force members had no perceived potential conflicts of interest. Dr. Burns reported having no conflict.
Sherry Boschert is with the San Francisco bureau of IMNG Medical News.
The pain and joint inflammation from uric acid buildup has been known for centuries as a demon, as in this 1799 painting "Podagra: The Gout" by James Gillray.
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