CHICAGO — Physicians treating gout and other crystal deposition diseases should consider both new medications and new uses for already available drugs, Dr. Lloyd Klickstein said at a meeting sponsored by the American College of Rheumatology.
“Some of the most exciting news in 2006 was the new understanding of the role of IL-1 in crystal-induced arthritis,” Dr. Klickstein said.
Basic science research indicates that interleukin (IL)-1R is needed to signal gouty inflammation. An open-label study of 10 patients showed that treatment with anakinra, a recombinant interleukin-1RA inhibitor, effectively lessened the symptoms of acute gout.
Other new drugs for gout are also in clinical trials. The U.S. Food and Drug Administration is currently reviewing febuxostat, an oral drug that noncompetitively inhibits xanthine oxidase production.
“It is very unlikely to have any of the problems associated with allopurinol,” said Dr. Klickstein, of the Novartis Institutes for Biomedical Research in Cambridge, Mass. Approval of the drug seemed imminent early in 2006, but the agency seems stalled in its decision.
Researchers recently completed phase III trials assessing the safety and efficacy of puricase, a pegylated recombinant porcine uricase that is given subcutaneously.
For patients who have not responded to conventional therapy, clinicians may also consider using drugs currently available for other conditions. Fibric acid derivatives, such as losartan, can lower uric acid, and some patients may have improved symptoms with this drug, said Dr. Klickstein.
“These little changes can really make a difference,” he said. Sevelamer, a phosphate binder, also binds uric acid. Dr. Klickstein pointed out that this treatment is not used as often as it could be. Sevelamer is “an option we don't think about very often in rheumatology,” he said.
Rarely patients may need treatment with rasburicase, an aspergillus-derived enzyme used in tumor lysis syndrome. Although it can be effective in lowering uric acid, it can lead to allergic reactions and should not be used in patients with known glucose-6-phosphate dehydrogenase deficiency.
In addition to gout patients who do not respond well to traditional therapy, dialysis patients with musculoskeletal complaints also may benefit from treatment that does not rely on conventional therapy. Lowering phosphorus may be the key to treating musculoskeletal complaints, which affect half of the 0.12% of the U.S. population on dialysis.
Clinicians should start by measuring calcium phosphate and encourage a low-phosphate diet. But phosphates are present in many foods, so encouraging a low-phosphate diet may lead to minimal results. “This is always worth talking about, but it's not always successful,” said Dr. Klickstein.
Another approach is to try lanthanum or another phosphate binder. This drug requires gastric acid to work properly, so patients cannot take proton pump inhibitors concurrently. Patients who fail treatment with phosphate binders may respond better to calcimimetics. Cinacalcet, the only drug in its class currently available, treats the secondary hyperparathyroidism of renal disease by lowering phosphate.
Ultimately, patients with end-stage renal disease who do not respond to drug therapy may require nocturnal dialysis for the treatment of crystal arthropathies. Clinicians should not be put off by the complexity of arranging for this treatment if it leads to an improvement in symptoms. “Management can make a huge difference in people's lives so they can live without pain,” he said.