Krystexxa (Pegloticase): A Powerful Option for Severe, Treatment-Resistant Gout
For most people, gout — a painful form of arthritis caused by uric acid buildup — can be controlled with diet changes and medications like allopurinol or febuxostat. However, for some individuals, these treatments aren’t enough.
When gout becomes chronic, severe, or unresponsive to standard therapy, patients can face ongoing pain, joint damage, and large uric acid deposits known as tophi.
That’s where Krystexxa® (pegloticase) comes in. Approved by the U.S. Food and Drug Administration (FDA) in 2010, Krystexxa is the first and only intravenous biologic medication specifically designed to lower uric acid in adults with chronic gout refractory (resistant) to conventional therapy.
What Is Krystexxa?
Krystexxa (pegloticase) is a prescription biologic drug used to treat chronic gout in adults who have not responded to or cannot tolerate standard uric acid–lowering treatments.
It is administered by intravenous (IV) infusion and works differently from traditional gout medications. Instead of reducing uric acid production or improving its excretion, Krystexxa breaks down uric acid directly into a harmless substance that the body can easily remove.
Understanding Gout and Uric Acid
Gout occurs when there is too much uric acid (hyperuricemia) in the blood. Over time, this excess uric acid forms sharp crystals that deposit in joints, tendons, and surrounding tissues, causing painful inflammation.
Symptoms of chronic gout may include:
- Intense joint pain (often in the big toe, ankles, knees, or elbows)
- Redness, swelling, and warmth in affected joints
- Hard uric acid deposits called tophi under the skin
- Limited joint mobility and deformity over time
When oral medications such as allopurinol, febuxostat, or probenecid fail to control uric acid levels, gout can become disabling and significantly affect quality of life.
How Krystexxa Works
Krystexxa contains pegloticase, a recombinant uricase enzyme that converts uric acid into allantoin — a water-soluble compound easily eliminated by the kidneys.
Humans naturally lack uricase, so Krystexxa essentially replaces this missing enzyme function.
Here’s how it helps:
- Breaks down uric acid directly, quickly lowering blood urate levels.
- Dissolves tophi (uric acid deposits) over time.
- Prevents new uric acid buildup, reducing inflammation and joint pain.
Because it acts directly on uric acid, Krystexxa can bring levels to near zero within hours of the first infusion — something oral medications typically cannot achieve in severe cases.
How Krystexxa Is Administered
- Route: Intravenous (IV) infusion
- Schedule: Every two weeks (biweekly)
- Duration: Each infusion takes about 2 hours, followed by observation for side effects.
Krystexxa is given in a healthcare setting (such as an infusion center) under the supervision of a healthcare professional experienced in gout management.
Clinical Evidence and Effectiveness
Krystexxa’s approval was based on two pivotal clinical trials involving adults with chronic gout refractory to conventional therapy.
Key results:
- Within 6 months, 42% of patients receiving Krystexxa achieved and maintained normal uric acid levels, compared with 0% in the placebo group.
- Many patients showed visible reduction or complete resolution of tophi.
- Improvements were also seen in pain, physical function, and overall quality of life.
In real-world studies, combining Krystexxa with immunomodulators such as methotrexate has been shown to improve treatment durability and reduce infusion-related reactions.
Benefits of Krystexxa
For patients with treatment-resistant gout, Krystexxa offers a number of important benefits:
- Rapid and sustained uric acid reduction
- Dissolves tophi, improving joint appearance and mobility
- Decreases gout flares over time
- Improves quality of life for those with chronic, disabling gout
- Effective even when other medications fail
It is often considered a “last-line” or advanced therapy reserved for patients with severe, difficult-to-control gout.
Possible Side Effects
While Krystexxa is highly effective, it can cause side effects that require careful monitoring.
Common side effects include:
- Gout flares (especially during the first few months of treatment)
- Nausea or mild digestive discomfort
- Fatigue
Serious potential risks:
- Infusion reactions or allergic reactions (can occur during or after infusion)
- Anaphylaxis (severe allergic reaction; rare but possible)
- Formation of anti-drug antibodies, which can reduce effectiveness and increase reaction risk
To help minimize these risks, patients usually receive premedication (antihistamines and corticosteroids) before each infusion.
Important note:
Krystexxa can interact with urate-lowering drugs like allopurinol or febuxostat. These medications should be stopped before starting Krystexxa, as they can interfere with how the drug works and make side effects more likely.
Who Can Receive Krystexxa
Krystexxa is approved for:
Adults with chronic gout who have not achieved target uric acid levels with other medications or cannot tolerate standard therapy.
It is not recommended for people with:
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency, as it can cause hemolysis (red blood cell breakdown)
- Uncontrolled heart failure (use with caution)
Before starting Krystexxa, patients are tested for G6PD deficiency, and their doctor reviews their full medical history and medication list.
Monitoring and Follow-Up
During Krystexxa therapy, healthcare providers will regularly:
- Check uric acid levels prior to each infusion (to ensure continued response)
- Monitor for infusion reactions
- Assess tophi and joint health over time
If uric acid levels start rising again, treatment may be discontinued, as this suggests the body is forming antibodies that neutralize the medication.
Practical Considerations
- Duration of treatment: Typically several months to a year, depending on patient response.
- Lifestyle support: Staying hydrated, avoiding alcohol, and limiting purine-rich foods remain important for long-term gout control.
- Combination therapy: In many cases, Krystexxa is used with a low-dose immunosuppressant to improve outcomes.
- Support programs: Manufacturer and patient foundations offer assistance with infusion scheduling and cost management.
The Bottom Line
Krystexxa (pegloticase) is a powerful, disease-modifying treatment option for adults with severe, chronic gout that does not respond to standard therapy. By directly breaking down uric acid, it can rapidly reduce tophi, relieve pain, and improve mobility — giving patients a chance to reclaim comfort and function when other treatments have failed.
While it requires careful monitoring and professional administration, Krystexxa represents hope for those living with advanced gout — turning what was once an untreatable condition into a manageable one.