Gout is a common form of arthritis that is due to the excessive accumulation of uric acid (UA) in the body. This eventually leads to deposits of UA in multiple areas including the joints and kidneys.
This over accumulation of UA is due to abnormal metabolism of purines, a common building block of many foods. In patients with gout, the conversion of purines to UA outpaces the body's ability to excrete it.
Gouty arthritis is manifested by acute attacks of extremely painful debilitating attacks of joint swelling and inflammation.
Over time if gout is not treated the attacks become more frequent and can lead to crippling and disability.
Drugs used to treat gout are divided into two groups. Those that are aimed at treating the acute attack and those aimed at lowering serum UA.
Among the drugs that are used for the acute attack are colchicine, non-steroidal anti-inflammatory drugs, and steroids. Drugs that are used to lower serum UA are probenecid, allopurinol, and febuxostat (Uloric).
A more recent addition to the treatment arsenal is a drug called pegloticase (Krystexxa).
Pegloticase was approved by the FDA for the treatment of chronic gout unresponsive to conventional therapy. Unlike other gout drugs, it is given intravenously. In clinical trials, it was noted that antibodies to pegloticase were common in patients receiving pegloticase, and that high levels of antibodies were associated with loss of response and increased risk of infusion reactions and anaphylactic shock.
One clue to this problem is the measurement of serum UA levels before infusion. When elevated, they indicate reduced efficacy of the drug and the potential for infusion reactions.
Measurement of serum UA levels before each infusion is recommended. Treatment should be discontinued in patients with a pre-treatment serum UA of more than 6 mg/dL.
Pegloticase was used as a single agent in clinical trials. However, pegloticase has been used in clinical practice with other UA lowering therapies, such as allopurinol and febuxostat.
While serious side effects haven't occurred, there is concern that use of combination therapies could mask UA elevation due to loss of efficacy from antibodies to pegloticase. This would potentially hide those patients at higher risk for infusion reactions. It's recommended that other UA lowering drugs should not be used in combination with pegloticase.
Other cautions with pegloticase are it should not be used in patients with congestive heart failure nor in patients with G6PD deficiency. This is a metabolic problem that could lead to severe reactions. Patients receiving pegloticase should be premedicated with antihistamines and steroids.
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