Gout and Hyperuricemia
Conventional Treatment of Gout
Treatments for acute gout attacks typically manage pain and inflammation, and include NSAIDS, corticosteroids, and colchicine. While treatments for acute gout are typically short term, there are risks of significant gastrointestinal side effects for NSAIDs and colchicine in some individuals. Moreover, though colchicine is approved by the Food and Drug Administration (FDA) to treat acute gout flares, it has a low therapeutic index, meaning the dose required to exert a beneficial effect is near that which is potentially toxic. Aspiration of affected joints to relieve pressure, and injection of long-acting steroids are commonly used treatments in practice, although they have not been investigated in controlled trials.49
After the initial attack has subsided, patients are usually encouraged to adopt lifestyle changes that may reduce hyperuricemia and gout risk (such as lower purine diets, weight loss, or exercise). Many will be placed on longer-term uric acid-reduction therapy. Recall that uric acid levels are controlled by the rate of uric acid production and the rate of uric acid excretion; current therapies address either of these two aspects.
Xanthine oxidase inhibitors reduce the activity of xanthine oxidase, the final step in uric acid synthesis. This has the effect of lowering uric acid production. Allopurinol (Zyloprim) has a long history of usage as a xanthine oxidase inhibitor; recently febuxostat (Uloric) has been approved for treatment of hyperuricemia in the United States. Febuxostat exhibits greater uric acid-lowering effects than allopurinol, although the incidence of gout flares is similar between the two drugs.50
Uricosuric drugs increase the excretion of uric acid from the kidneys, primarily by reducing the absorption of uric acid from the kidneys back into the blood. Probenecid (Benemid) and sulfinpyrazone (Anturane) are two examples. These drugs tend to increase urinary uric acid levels, which can cause kidney stones.
The tophi of chronic gout, if severe enough to cause joint dysfunction or deformity, can also be treated by surgical removal.51,52
Innovative New Drugs for the Management of Chronic Gout
As mentioned earlier in this protocol, in most mammals uric acid is converted into the more soluble compound allantoin by an enzyme called uricase. This conversion allows for the urinary excretion of allantoin, thereby reducing uric acid blood levels. However, humans are unable to facilitate this conversion due to an evolutionary loss of the uricase enzyme.
Recently, scientists have recreated the mammalian uricase enzyme in the laboratory and generated injectable medications that deliver the recombinant enzyme it into the blood. Once in the blood stream, the recombinant uricase enzyme breaks down uric acid into allantoin, which is then easily excreted through the human kidneys.
By injecting this enzyme otherwise not present in higher primates, the rate of uric acid excretion can be expedited.
Two such medications are available—rasburicase (Elitek), and a chemically modified version of this same drug, called pegloticase (Krystexxa). Pegloticase is FDA approved to lower uric acid levels in patients with chronic gout.53
In two concurrent randomized, double-blind, placebo-controlled trials, pegloticase, administered at a dose of 8 mg either every two weeks or every four weeks, efficiently lowered uric acid levels.54 The participants in these studies consisted of patients with chronic gout, which had not been relieved by allopurinol, and blood uric acid levels above 8.0 mg/dL at baseline. Reduction of uric acid levels to <= 6.0 mg/dL was the primary endpoint, and was achieved in 38% of patients receiving biweekly injections, and in 49% of those receiving monthly injections.
However, pegloticase may cause some side effects. In the studies mentioned previously, between a quarter and a half of subjects experienced an injection site reaction, of which 6.5% were considered to be anaphylaxis. This means that physicians may opt to administer corticosteroids before pegloticase in order to suppress the immune system in hopes of avoiding an inflammatory response. The long-term effects of corticosteroids in combination with pegloticase have not been studied as of yet, so the side effects in gout patients remain unknown.55
Many physicians may not be aware of the availability of pegloticase for lowering uric acid levels in gout patients due to its recent FDA approval. Individuals with chronic gout that has not improved after the use of conventional gout medications should consider asking their healthcare professional if pegloticase is right for them.