3.
Pharmacodynamics: Urate oxidase enzyme, absent in humans and some higher primates, converts uric acid to allantoin. This product is highly soluble and can be easily eliminated by the kidney. Pegloticase has been shown to maintain low urate levels for up to 21 days after a single dose at doses of 4–12 mg, allowing for IV dosing every 2 weeks. Pegloticase should not be used for asymptomatic hyperuricemia.
4. Adverse Effects: Gout flare can occur during treatment with pegloticase, especially during the first 3–6 months of treatment, requiring prophylaxis with NSAIDs or colchicine. Large numbers of patients show immune responses to pegloticase. The presence of antipegloticase antibodies is associated with shortened circulating half-life, loss of response leading to a rise in plasma urate levels, and a higher rate of infusion reactions and anaphylaxis. Anaphylaxis occurs in more than 6–15% of patients receiving pegloticase. Monitoring of plasma uric acid level, with rising level as an indicator of antibody production, allows for safer administration and monitoring of efficacy. In addition, other oral urate-lowering agents should be avoided in order not to mask the loss of pegloticase efficacy. Nephrolithiasis, arthralgia, muscle spasm, headache, anemia, and nausea may occur. Other less frequent side effects noted include upper respiratory tract infection, peripheral edema, urinary tract infection, and diarrhea. There is some concern for hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency because of the formation of hydrogen peroxide by uricase; therefore, pegloticase should be avoided in these patients.
Corticosteroids are sometimes used in the treatment of severe symptomatic gout, by intra-articular, systemic, or subcutaneous routes, depending on the degree of pain and inflammation.
The most commonly used oral corticosteroid is prednisone. The recommended oral dose is 30–50 mg/d for 1–2 days, tapered over 7–10 days. Intra-articular injection of 10 mg (small joints), 30 mg (wrist, ankle, elbow), and 40 mg (knee) of triamcinolone acetonide can be given if the patient is unable to take oral medications.
Drugs targeting the IL-1 pathway, such as anakinra, canakinumab, and rilonacept, are used for the treatment of gout. Although the data are limited, these agents may provide a promising treatment option for acute gout in patients with contraindications to, or who are refractory to, traditional therapies like NSAIDs or colchicine. A recent study suggests that canakinumab, a fully human antiIL-1β monoclonal antibody, can provide rapid and sustained pain relief at a dose of 150 mg subcutaneously. These medications are also being evaluated as therapies for prevention of gout flares while initiating urate-lowering therapy.