Data on the Need for Chronic Treatment of Hyperuricemia

Data Regarding Chronic Treatment

The management of gout should include lowering sUA levels with the goal of reducing the risk of recurrent disease and progression. The treatment target for chronic antihyperuricemic therapy is reduction of serum urate concentration to 6.0 mg/dL (0.36 mmol/L)—below the threshold for extracellular fluid precipitation in vitro at 37°C. For some time, the commonly cited level for hyperuricemia was 7.0 mg/dL for men and > 6.0 mg/dL for women. However, it has been suggested that this definition of hyperuricemia results in considerable overlap between the gouty and nongouty populations.

A growing number of studies support this goal for chronic treatment and provide evidence that serum urate levels below 6 mg/dL can improve signs and symptoms of gout over time. The following section presents several studies demonstrating support for a target level of < 6 mg/dL.

Reducing Risk of Attacks

A retrospective analysis of 267 patients by Shoji et al evaluated the relationship between persistent reduction of serum uric acid and the incidence of acute gout attacks. The investigators concluded that the goal of ≤ 6.0 mg/dL is the appropriate aim of antihyperuricemic therapy. The chart below shows the incidence of acute gout attacks among patients with different average serum urate concentrations:

Relationship between average serum urate concentration and the incidence of acute gouty arthritis more than 1 year after each patient’s first visit.

From Shoji A, Yamanaka H, Kamatani N. A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis with antihyperuricemic therapy. Arthritis Rheum. 2004;51:321-325.

Figure copyright © 2004. American College of Rheumatology. Reproduced with permission of John Wiley & Sons, Inc. (Takeda Pharmaceuticals North America Inc. cannot assure the accuracy or timeliness of the information available via this link.)

Tissue Damage and Nephrolithiasis

Comprehensive gout treatment must address deposition of urate crystals in cartilage, bone, and soft tissue as well as the development of kidney stones. These concerns go beyond the issue of reducing the risk of flares. Much evidence highlights the intercritical periods as crucial times of gout progression.

Joint damage associated with inflammation can progress and continue even between attacks. Crystals may be found in an asymptomatic joint during intercritical periods—in fact, they have been found to be present as long as hyperuricemia persisted. It has been suggested that urate crystals and low-grade chronic inflammation occur in joints before acute gout is experienced in those joints.

One study of 60 patients with gout found that:

24% did not experience symptoms in joints that show radiographic changes of gout.
42% showed radiographic changes characteristic of gout without evidence of tophi on examination.

Another study of 101 gout patients (91 analyzed) in Spain examined synovial fluid analysis as a diagnostic tool by comparing patients taking urate-lowering therapy with those who were not. It concluded that:

As a result of hyperuricemia, uric acid crystals can be found in affected joints at any time—not just during flares.
When serum urate levels are reduced to normal, crystals slowly dissolve and finally disappear from the joint (as has been noted in tophi).

Kidney stones are found in up to a quarter of primary gout patients. Both calcium-containing and uric acid stones are more common in patients with gout than in the general population, and the risk for developing kidney stones increases with increasing serum urate levels and increasing amounts of urinary acid excretion.

Resorption of Tophi

A Spanish prospective, observational study of 70 gout patients (63 completed) by Perez-Ruiz et al found that urate-lowering therapy reduced the size of existing tophi and that the velocity of this reduction was related to the serum urate level achieved. Based on their study (and analysis of previously published studies), the authors concluded that “the lower the serum urate level during [urate-lowering therapy], the faster the reduction of tophaceous deposits.”

Conclusions

As we learn more about hyperuricemia in gout, the target for urate-lowering therapy becomes better defined. A serum urate level of < 6 mg/dL may reduce the risk of recurrent gout attacks over time. Urate reduction may also address joint damage that progresses and continues between attacks and more quickly reduce the size of existing tophi.