SNOWMASS, COLO. – The current American College of Rheumatology gout guidelines contain a number of recommendations that may come as a surprise to rheumatologists and primary care physicians alike.
The guidelines state, for example, that urate-lowering therapy should be undertaken routinely in any patient with an established diagnosis of gout who has comorbid chronic kidney disease (CKD) that is stage 2 or worse, meaning an estimated glomerular filtration rate of 89 mL/minute per 1.73 m2 or less.
Dr. Michael H. Pillinger
The rationale is that it’s particularly important to try to prevent acute gout attacks in such patients because their renal dysfunction makes it problematic to use colchicine and NSAIDs to quell attacks. Intriguing studies suggest that lowering serum urate may actually slow progression of CKD, Dr. Michael H. Pillinger said at the Winter Rheumatology symposium sponsored by the American College of Rheumatology.
The guidelines name the other indications for urate lowering in gout patients as the presence of a tophus on clinical examination or an imaging study, a history of two or more gout attacks per year, or a history of kidney stones.
Traditionally, urate-lowering therapy has been initiated during quiescent periods, but the ACR guidelines state that it also can be started during an acute attack if effective anti-inflammatory management has been instituted.
"This goes against what I was taught," observed Dr. Pillinger, a rheumatologist and director of the crystal diseases study group at New York University.
The guidelines (Arthritis Care Res. 2012;64:1431-46 and 1447-61) emphasize the importance of a treat-to-target approach.
"The primary care physicians I talk to still don’t know this. The ACR recommends a minimum serum urate target of less than 6.0 mg/dL, but the guidelines are very clear that if 6 isn’t good enough, you keep going. You go below 5. When I see patients with tophaceous gout, my target is never 6. My target is 5 or 4. That’s what I teach my fellows," explained Dr. Pillinger, who served on an expert panel that advised the guideline-writing task force.
The ACR urate-lowering algorithm begins with either allopurinol or febuxostat (Uloric) as first-line therapy. The guideline committee, which expressly excluded cost as a consideration, offered no guidance as to which xanthine oxidase inhibitor is preferred. Dr. Pillinger noted that febuxostat is a more specific xanthine oxidase inhibitor, is simpler to dose, and is far less likely to cause hypersensitivity reactions than is allopurinol. It is also more effective, although not dramatically more so. And it is considerably more expensive.
Febuxostat is approved by the Food and Drug Administration specifically for use in patients with mild to moderate CKD. Allopurinol is not. However, the gout guidelines endorse the use of allopurinol in that setting.
When allopurinol is the initial drug, the guidelines recommend dosing it in a manner that is different from how most physicians have been using it, the rheumatologist said. The recommended starting dose is lower than has been customary: 100 mg/day, and 50 mg/day in patients with stage 4 or 5 CKD. The drug is to be titrated upward every 2-5 weeks as needed to achieve the target urate level. The maximum dose is 800 mg/day, even in patients with comorbid CKD. Although the guidelines don’t provide guidance as to the size of the stepwise dosing increases, Dr. Pillinger usually boosts the allopurinol dose by 100 mg at a time, or 50 mg in patients with CKD.
"Most patients don’t get to target at 300 mg/day. You’ve got to go higher," he said.
An important innovation in the current guidelines is the recommendation for testing for the HLA-B*5801 allele in patients of Korean, Thai, or Han Chinese ancestry who are being considered for allopurinol therapy. The presence of this allele confers a several hundred–fold increased risk of allopurinol hypersensitivity.
Probenecid is endorsed as the alternative first-line urate-lowering agent, but only if at least one xanthine oxidase inhibitor is contraindicated or not tolerated. No other agents get the nod as first-line therapy.
The guidelines state that if a patient’s serum urate is not at target despite maximum-dose therapy with a first-line xanthine oxidase inhibitor, it is not appropriate to switch to the other xanthine oxidase inhibitor. Instead, it is time to add a uricosuric agent: probenecid, losartan, or fenofibrate. If the urate level still is not at target and the patient is generally well, with few gout attacks, then that’s an acceptable result. However, if the patient has moderate tophaceous gout or chronic gouty arthropathy, it’s appropriate to place the patient on pegloticase (Krystexxa) while discontinuing all other urate-lowering agents.