2-Stage Plan for Managing Gout May Keep Joints Clean

Original Medscape Article

Janis C. Kelly
Author


December 26, 2011 — Maintaining serum urate levels at less than 6 mg/dL is necessary for clearing tophi and dissolving monosodium urate monohydrate crystals in gout, but once it has been achieved, keeping serum urate just below the threshold for saturation (6.0 - 6.9 mg/dL) is likely to be enough to prevent gout recurrence, according to data reported in the December issue of Arthritis & Rheumatism.
Fernando Perez-Ruiz, MD, PhD, from Hospital Universitario Cruces in Vizcaya, Spain, and colleagues analyzed recurrence and serum urate data in a prospective cohort of 211 patients with gout. For patients who did not have tophi at baseline, urate-lowering therapy was withdrawn after 5 years. For those with tophi at baseline, urate-lowering therapy was withdrawn 5 years after the resolution of the last tophus.
Serum urate levels were measured at least twice during the first year, after withdrawal of urate-lowering therapy, and then at least yearly. Recurrence was defined as a clinical event suggesting gout flare, and was confirmed by a finding of monosodium urate monohydrate crystals.
The analysis included 211 patients, 52 of whom had tophi at baseline. Mean duration of urate-lowering treatment was 66 months, and mean follow-up after withdrawal of urate-lowering therapy was 33.1 months.
Estimated median time to recurrence was 47 months after the end of therapy, and the cumulative recurrence rate was 6.6% at 1 year, 11.4% at 2 years, 20.4% at 3 years, and 29.4% at 4 years. The authors report, "None of the patients who had average serum levels of <7 mg/dl after urate-lowering therapy withdrawal developed a crystal-proven recurrence of gout."
Dr. Perez-Ruiz told Medscape Medical News, "You may need full doses for the first stage (low serum urate target), and lower doses for lifelong maintenance therapy."
A post hoc analysis found that weight loss and use of drugs such as losartan or fenofibrate were associated with maintaining serum urate levels below 7 mg/dL during follow-up after urate-lowering therapy withdrawal, and that use of diuretics was associated with failure to keep serum urate levels below 7 mg/dL.
According to Dr. Perez-Ruiz, this suggests that once crystals are cleared, lower doses of urate-lowering drugs will be sufficient for preventing recurrence. The "therapeutic target" for clearing crystals remains 5 years of serum urate less than 6 mg/dL, but once this has been achieved, the "preventive target" should be 6.00 to 6.99 mg/dL. This approach is being validated in ongoing studies.
Gout expert Eliseo Pascual, MD, who reviewed the article for Medscape Medical News, said, "The point of Dr. Fernando Perez-Ruiz's study is that (1) the rate of crystal dissolution is faster when lower serum urate levels are reached, according to his own work showing faster reduction of tophi size in patients in whom lower serum uric acid were reached, and (2) the real problem in gout patients is that urate crystal formation occurs in some tissues due to local conditions."
He continued, "So, if after fully dissolving the urate crystals by lowering serum uric acid to low levels, serum urate levels are allowed to rise above normal...urate crystals will form again, quite likely on the same tissues, and a new gout flare will occur. To avoid [recurrence]...serum uric acid should be kept within normal values, even if they are high-normal." Dr. Pascual heads the rheumatology section at Universidad Miguel Hernández in Alicante, Spain.
Dr. Perez-Ruiz describes this strategy as the "clean dish" approach: "[T]he initial effort to clean the disease (serum urate therapeutic target) would depend on how dirty it is (urate deposition burden), and, once it is clean, light daily wiping may be enough (serum preventive target) from then on to avoid dust (new urate crystal) accumulation and keep it clean (no recurrence)."
Dr. Perez-Ruiz has received consulting fees and/or speaking fees from Menarini, Ardea, and Novartis. Dr. Pascual has disclosed no relevant financial relationships.
Arthritis Rheum. 2011:63:4002-4006. Abstract