The ACR’s annual State-of-the-Art Clinical Symposium took place April 13–15 in Chicago. Here are some highlights from the symposium.
Exciting Year for Gout
In “Selected Topics in the Advanced Management of Crystal Disease,” Lloyd B. Klickstein, MD, PhD, a rheumatologist in the translational medicine depatment of Novartis Institutes for Biomedical Research in Cambridge, Mass., provided an update on recent findings in gout and covered management of calcium crystal disease in dialysis patients—something “rheumatologists don’t do all that well,” he says. “They assume the nephrologists handle it, and the nephrologists assume the rheumatologists do it.”
Research is helping us understand the mechanism of crystal-induced arthritis for the first time. A paper published in Nature showed that gout-associated uric acid crystals activate the NALP3 inflammasome, leading to the production of interleukin-1 (IL-1). A second study from University of Massachusetts demonstrated an absolute requirement for IL-1 receptor signaling for gouty inflammation.
“MSU [monosodium urate] crystals trigger IL-1beta release from resident inflammatory cells, and IL-1beta then activates pro-inflammatory pathways in many cell types,” he says. “If all this is correct, then anti–IL-1 therapy should be really effective in crystal-induced disease.”
Dr. Klickstein provided an overview of the status of drugs in late stage clinical trials for gout, including febuxostat and puricase. He also discussed alternative therapeutic options for gout patients, which included a combination treatment using anti-hyperuricaemic agents together with fenofibrate and/or losartan to provide a modest additional benefit in lowering uric acid. Another randomized trial showed that the organic polymer sevelamer (Renagel) lowered uric acid levels by an average of 0.72 mg/dl, compared to 0.15 mg/dl in the control group.
Research is helping us understand the mechanism of crystal-induced arthritis for the first time.
Rasburicase may become a new tool for the treatment of hyperuricemia in refractory gout, according to a series of recent case reports. It is currently approved in the U.S. for tumor lysis syndrome. “It does have significant drawbacks,” says Dr. Klickstein. “It’s a cancer drug, so it’s very expensive. Allergic reactions are very common and can be rather ferocious. And … patients with G6PD deficiency are at risk for acute drug-induced methemoglobinemia.”
For the management of calcium crystal disease in dialysis patients, Dr. Klickstein stresses that a top priority is getting the phosphate (PO4) level under control, with a goal of lowering it below 5.5 mg.
“MSU is to gout what PO4 is to calcium crystal disease in dialysis patients,” he says, offering these management recommendations:
- Before dialysis, measure serum calcium, PO4, and immunoreactive parathyroid hormone;
- Stress the importance of dietary counseling;
- Prescribe PO4 binders, preferably sevelamer;
- Use vitamin D analogs such as paricalcitol instead of calcitriol;
- If the previous steps have no effect, consider a new class of drugs called calcimimetics; and
- If all else fails, use longer dialysis runs.
Eye on Ocular Inflammatory Diseases
James T. Rosenbaum, MD, chair of the arthritis and rheumatologic diseases division at Oregon Health & Science University in Portland, presented cutting-edge information on “Inflammatory Eye Disease.”