Krystexxa, known by its generic name pegloticase, is a prescription intravenous medication used to treat adults with chronic gout. It is intended for cases where the condition is considered refractory, meaning it has not responded to standard treatments.
How Krystexxa Works and Who It Is For
Krystexxa introduces a recombinant enzyme, a lab-created version of uricase, into the body. This enzyme actively targets and breaks down uric acid, the substance that crystallizes in joints and tissues to cause gout. It converts uric acid into a harmless chemical called allantoin, which is water-soluble and easily flushed from the body through urine.
This treatment is not a first-line defense but is reserved for adults with chronic refractory gout. These patients have persistently high uric acid levels and may suffer from tophi, which are visible, often painful, deposits of uric acid crystals under the skin. Krystexxa is considered when conventional drugs like allopurinol or febuxostat have failed to manage these severe symptoms.
Efficacy and Patient-Reported Outcomes
Clinical data indicates Krystexxa can produce a rapid and substantial decrease in serum uric acid levels. A primary benefit is the gradual dissolution of painful tophi. As these uric acid crystal deposits shrink, patients often report improved joint function and a decrease in the chronic pain that characterizes severe gout.
Over several months, the reduction in the body’s uric acid burden can lead to a lower frequency of gout flares. While flares can occur initially, the long-term trend is toward fewer and less intense episodes. Patients frequently report an improvement in their quality of life, citing the ability to regain mobility, wear normal footwear again, and return to activities previously limited by pain.
The goal of treatment is to maintain a low uric acid level (below 6 mg/dL) for a sustained period. This consistent reduction allows the body to dissolve existing crystal deposits, leading to the tangible improvements patients experience.
Common Side Effects and Infusion Reactions
Krystexxa carries a risk of infusion reactions, which can occur during or shortly after administration. Reactions can be mild, but some patients may have a serious allergic response, including anaphylaxis, which often manifests within two hours. Due to this risk, the medication must be given in a healthcare setting equipped to manage these events immediately.
An increase in gout flares is common, particularly in the first few months of treatment. This paradoxical effect occurs as dissolving uric acid crystals mobilize from tissues into the bloodstream before being eliminated, which can trigger an inflammatory response from the immune system.
Other reported side effects include nausea, bruising at the infusion site, and chest pain. A rising uric acid level can signal a loss of response to the drug and an increased risk for infusion reactions. Therefore, regular monitoring of uric acid before each infusion is part of the treatment protocol.
Mitigating Risks with Immunomodulation
A challenge with Krystexxa is the body’s potential to develop anti-drug antibodies against it. This immune response can reduce the drug’s effectiveness over time and is linked to a higher risk of infusion reactions. These antibodies can neutralize the drug, causing uric acid levels to rise and signaling that the treatment is failing.
To address this immune response, Krystexxa is often prescribed with an immunomodulator, such as methotrexate. Taking a medication like methotrexate helps suppress the immune system’s tendency to attack the Krystexxa enzyme. This co-therapy approach increases the number of patients who maintain a positive response to the treatment long-term.
By preventing the formation of anti-drug antibodies, immunomodulation preserves the drug’s uric-acid-lowering effects and reduces the likelihood of severe infusion reactions. This strategy has become a standard of care to improve both the safety and the durable efficacy of the treatment, allowing more patients to benefit from the therapy for a longer duration.