VIENNA — A wealth of hard-earned off-label tricks of the trade for serum urate lowering in gout patients who can't take allopurinol may soon fall by the wayside, forgotten in the rush to embrace an anticipated batch of new agents.
A variety of novel hypouricemic drugs intended to earn an indication for gout management are moving through the developmental pipeline. Furthest along is febuxostat, a nonpurine selective inhibitor of xanthine oxidase that has been submitted to the Food and Drug Administration for market approval. Also, looking good in phase II clinical trials for long-term urate lowering to prevent recurrent attacks of gout is a pegylated form of urate oxidase, Dr. Thomas Bardin noted at the annual European Congress of Rheumatology.
Allopurinol is the only readily available approved hypouricemic agent in most countries. It works well in most patients. But it is an old drug with many problems, and large numbers of patients either don't respond adequately, can't tolerate it, or have contraindications to its use. Until febuxostat and other hypouricemic drugs reach the marketplace, physicians who treat large numbers of gout patients will need to continue to reach deep into their bag of tricks in these situations, Dr. Bardin of Lariboisière Hospital, Paris, said at the congress, sponsored by the European League Against Rheumatism.
So what are the alternatives?
▸ Lifestyle modification. Avoidance of purine-rich dietary animal proteins and alcohol—especially beer—is a frequently neglected but effective means of lowering serum urate. So is weight loss.
▸ Probenecid. Having long taken a back seat to allopurinol because of its weaker urate-lowering effect, probenecid is being rediscovered by physicians. It should be started at 250 mg b.i.d., gradually increasing the dose every 2–3 weeks up to a target of 2 g/day.
▸ Losartan. Has a rapid effect, similar to probenecid. Urate lowering is not an ACE inhibitor class effect but is limited to losartan. The drug has the side benefit of reducing urine pH, thereby lessening the risk of uric acid stone formation. An excellent drug in gout patients with comorbid cardiovascular disease or hypertension.
▸ Fenofibrate. Doubles uric acid clearance. Another good choice in patients with cardiovascular disease or with hyperlipidemia. Dr. Bardin often uses it together with allopurinol in patients who don't reach the target serum uric acid level of less than 6 mg/dL with allopurinol alone. Other fibrates don't share fenofibrate's urate-lowering effect.
▸ Switch antirejection drugs in transplant recipients. Azathioprine, 6-mercaptopurine, and cyclosporine are often considered contraindications to allopurinol therapy because of harmful drug interactions. Dr. Bardin has persuaded transplant physicians to substitute mycophenolate mofetil with good results in gout patients he wants on allopurinol.
▸ Desensitization therapy. An option that can enable patients with cutaneous reactions to successfully go back on allopurinol. But it's a difficult, complicated, and bothersome procedure. “In the literature, you'll find a few cases of hypersensitivity syndrome occurring during desensitization. The patient needs to understand the risks, and that the drug should be stopped immediately in the event of skin rash,” Dr. Bardin said.