LAS VEGAS – It’s okay to start urate lowering therapy during a gout attack, according to Dr. Brian Mandell, a rheumatology professor at the Cleveland Clinic.
“I was taught that you don’t treat a gout attack with urate lowering therapy” because it could trigger a subsequent mobilization attack. “This has been the paradigm for years,” he said at the annual Perspectives in Rheumatic Diseases held by the Global Academy for Medical Education.
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But a 2012 study casts doubt on that. In the study, 26 men hospitalized for gout attack were randomized to 300 mg allopurinol daily, while 25 were randomized to placebo. All of the patients were on indomethacin and colchicine. Urate levels dropped rapidly to below 6 mg/dL in the allopurinol group, but there were only two flares. Placebo subjects, meanwhile, had three flares (P= 0.60). There was no significant difference in daily pain scores (Am J Med. 2012 Nov;125(11):1126-1134.e7.).
“The bottom line is the groups did essentially the same. If you are using prophylaxis to treat an acute attack, you are probably perfectly fine to use allopurinol; you don’t need to wait,” Dr. Mandell said. “Does this mean you should start everybody in the hospital on full-dose allopurinol? No, but I think this really broadens our thought processes in terms of handling urate lowering therapy.”
It’s also time to rethink allopurinol dose adjustments in patients with chronic kidney disease (CKD). The thought has been that these patients should be on lower doses to prevent metabolite buildup in the kidneys and hypersensitivity reactions, but “if you follow those guidelines, less than 20% of patients will lower their serum urate, so you will be giving the drug for nothing,” Dr. Mandell said.
“It is true that allopurinol hypersensitivity is more common in patients with CKD,” but it happens in a few per thousand people, and hypersensitivity might have nothing to do with allopurinol dose. “There’s no repeated documentation between the levels and reactions, and in a number of small studies there is no evidence that dose adjustment decreases the frequency of hypersensitivity reactions. We have no data to say this is the right route to take,” he said.
In fact, a study that included 45 CKD patients found that increasing allopurinol beyond creatinine clearance-based dosing doesn’t cause problems. “Toxicity was not increased in patients receiving higher doses of allopurinol, including those with renal impairment,” the authors concluded (Arthritis Rheum. 2011 Feb;63(2):412-21.).
Given the rarity of hypersensitivity reactions, it’s not surprising they didn’t occur in the study’s small group of CKD patients, Dr. Mandell said. “If you are really ultra conservative, you are [still] not going to use allopurinol in CKD,” he said.
But Dr. Mandell said he starts patients on 50 mg of allopurinol. “I educate them about allergic reactions and increase the dose every 1-2 weeks until I hit” a serum uric acid below 6 mg/dL, which often takes more than 300 mg per day. “Alternatively, you can start febuxostat, and if I were to do that I would start at 20 mg” – breaking the lowest dose pill of 40 mg in half – “and then titrate up,” he said.
“It just doesn’t make sense,” Dr. Mandell said, that allopurinol hypersensitivity is related to dose. Instead, there seems to be a genetic predisposition for toxicity in, for instance, Asian patients with the HLA-B*5801 genotype, he noted.
Pegloticase is a bit more problematic than allopurinol. It’s highly effective – patients can drop their serum uric acid from 14 to 0.1 mg/dL within hours – but that comes at the cost of a high mobilization flair rate and infusion reactions in about a quarter of patients, Dr. Mandell said.
There’s a partial workaround. Dr. Mandell said he checks the uric acid level before the second infusion. If it’s not below 6 mg/dL after the first infusion, patients have antibodies against pegloticase. “The drug isn’t going to work, and patients are more likely to get an allergic reaction, so stop the drug,” he said.
Dr. Mandell is a consultant for AstraZeneca and Crealta Pharmaceuticals. The Global Academy for Medical Education and this news organization are owned by the same parent company.