Pegloticase is a prescription medicine used to treat chronic gout in adults when other treatments have not worked well enough or cannot be used. It lowers uric acid, the substance that forms painful crystals in the joints. Given through a vein, usually every two weeks, pegloticase can help reduce gout attacks and shrink deposits of uric acid crystals called tophi. It requires careful monitoring because serious reactions can occur.
How Does Pegloticase Work for Gout?
Pegloticase is an enzyme-based medicine that helps the body break down uric acid. Uric acid forms naturally when the body processes substances called purines. When uric acid levels remain too high, crystals can collect in joints and other tissues, leading to gout attacks and, over time, persistent inflammation or joint damage.
Unlike medicines such as allopurinol, which reduce the body's production of uric acid, pegloticase converts uric acid into a different substance called allantoin. The kidneys can then remove allantoin from the body through urine. This process can lower blood uric acid levels substantially and help the body gradually clear existing crystal deposits.
According to the American College of Rheumatology (ACR), pegloticase is intended for people with severe, chronic gout whose disease remains active despite other treatments. It is not usually the first medicine prescribed for gout.
When Is Pegloticase Used for Gout?
Pegloticase is generally considered when standard uric acid-lowering treatments have failed to control the disease adequately. The decision depends on ongoing gout activity, previous treatment results, the presence of tophi, and the person's overall health.
According to the American College of Rheumatology's gout management guideline, pegloticase is strongly recommended over continuing the existing uric acid-lowering regimen in appropriate patients who have not reached their uric acid target despite other treatments and who continue to experience frequent gout attacks or have tophi that do not resolve.
Situations in which a specialist may consider pegloticase include:
- Frequent gout attacks: Repeated flares continue despite appropriate treatment with other uric acid-lowering medicines.
- Persistent tophi: Deposits of uric acid crystals under the skin remain or fail to improve with standard treatment.
- Inadequate response to other medicines: Treatments such as allopurinol, febuxostat, or uricosuric medicines have not achieved the desired uric acid level despite appropriate use.
- Difficulty using standard treatments: Other medicines may be unsuitable because of contraindications, intolerance, or other clinical considerations.
Pegloticase is not generally recommended simply because someone has an elevated uric acid level. For people whose gout is well controlled, or who have infrequent attacks and no tophi, the potential benefits may not justify its risks and treatment burden.
Who Can Receive Pegloticase?
Pegloticase is approved in the United States for adults with chronic gout that has not responded adequately to conventional treatment or for whom other treatments are not appropriate. A rheumatologist or another clinician experienced in managing difficult-to-treat gout can assess whether it is suitable.
Before treatment, the healthcare team reviews previous gout medicines, current medications, medical history, and relevant blood tests. One particularly important assessment is testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency, an inherited condition that can make pegloticase dangerous.
Pegloticase can cause the breakdown of red blood cells and a condition called methemoglobinemia in people with G6PD deficiency. These complications can be serious. People with this deficiency must not receive the medicine.
How Is Pegloticase Given?
Pegloticase is administered as an intravenous infusion, meaning the medicine enters a vein through a needle or intravenous line. Treatment takes place in a healthcare facility where staff can monitor the patient and respond promptly to an allergic or infusion-related reaction.
According to MedlinePlus, pegloticase is usually administered once every two weeks, and the infusion takes at least two hours. The healthcare team may give medicines beforehand to reduce the risk of infusion reactions and will observe the patient during and after treatment.
Before each infusion, the healthcare team checks the blood uric acid level. If this level rises during treatment, it may indicate that pegloticase is no longer working adequately and that the risk of an infusion reaction has increased. The prescribing clinician may need to stop treatment based on these results and the patient's clinical circumstances.
Is Methotrexate Used With Pegloticase?
Yes. Methotrexate is commonly used alongside pegloticase when it is appropriate for the patient. It can reduce the body's immune response against pegloticase, helping the medicine remain effective and lowering the risk of infusion reactions. Folic acid is also given with methotrexate as directed by the prescribing clinician.
The current US prescribing information recommends pegloticase with methotrexate for most eligible patients unless methotrexate is contraindicated or not clinically appropriate. In those circumstances, the clinician may consider pegloticase alone after evaluating the potential benefits and risks.
Methotrexate requires its own safety assessment and monitoring. Patients should discuss liver disease, kidney problems, blood disorders, infections, pregnancy, and other medicines with their healthcare team before starting combination treatment.
How Effective Is Pegloticase?
Pegloticase can lower uric acid levels rapidly and substantially in people with difficult-to-treat gout. When the treatment works, sustained low uric acid levels allow crystal deposits to dissolve over time. This can help reduce tophi and improve gout control.
However, not everyone responds to pegloticase, and some people develop antibodies that reduce its effectiveness. Regular uric acid testing helps the clinician identify when the medicine is no longer providing adequate benefit. The treatment plan may then need to change.
Gout attacks can also become more frequent during the first few months of treatment, even when pegloticase is lowering uric acid. Preventive medicines, such as colchicine or a nonsteroidal anti-inflammatory drug (NSAID), may be prescribed when appropriate to reduce this risk. Pegloticase is intended to control chronic gout over time; it is not a rescue medicine for an acute attack.
What Are the Side Effects of Pegloticase?
Pegloticase can cause common side effects as well as uncommon but potentially life-threatening complications. The healthcare team discusses these risks before treatment and monitors patients throughout therapy.
Common Side Effects
Some people receiving pegloticase may experience:
- Nausea or vomiting
- Constipation
- Fatigue
- Joint pain
- Bruising
- Sore throat
- Gout flares, particularly early in treatment
Not everyone experiences these effects. Patients should tell their healthcare team about symptoms that persist, worsen, or interfere with daily activities.
Serious Risks to Know About
The most important safety concerns include:
- Severe allergic reactions: Anaphylaxis can cause difficulty breathing or swallowing, swelling of the face or throat, hives, dizziness, or fainting.
- Infusion reactions: Reactions may occur during or after an infusion and can involve chest discomfort, flushing, shortness of breath, or changes in blood pressure.
- Blood complications in G6PD deficiency: Red blood cell breakdown and methemoglobinemia can reduce the blood's ability to carry oxygen.
- Reduced treatment effectiveness: Rising uric acid levels can signal that the medicine is no longer working adequately and may increase the risk of an infusion reaction.
The official US prescribing information for Krystexxa includes boxed warnings for anaphylaxis, infusion reactions, and complications associated with G6PD deficiency. Infusions must be given in a setting equipped to manage serious reactions.
Difficulty breathing, swelling of the tongue or throat, or fainting during or after an infusion requires immediate emergency assessment. Patients should alert healthcare staff immediately if any concerning symptoms develop.
What Monitoring Is Needed During Treatment?
Monitoring is an essential part of pegloticase treatment. It helps the healthcare team assess whether the medicine is working and identify risks before another infusion is given.
Monitoring may include:
- Blood uric acid testing: Levels are checked before each infusion to assess the response and help guide decisions about continuing treatment.
- G6PD testing: Screening is performed before treatment to identify people at risk of serious blood complications.
- Observation around infusions: Staff monitor for allergic and infusion-related reactions and provide premedication when indicated.
- Medication and health reviews: The clinician assesses other medicines, possible side effects, and whether methotrexate or other accompanying treatments remain appropriate.
Patients should attend scheduled appointments and blood tests, even when they feel better. They should not change or discontinue their treatment plan without discussing it with their prescribing clinician.
Pegloticase Compared With Other Gout Medicines
Pegloticase differs from commonly prescribed oral gout medicines in its mechanism, route of administration, and intended use.
- Allopurinol: Reduces uric acid production and is a common first-line long-term treatment.
- Febuxostat: Also reduces uric acid production and may be used when clinically appropriate.
- Uricosuric medicines: Help the kidneys remove more uric acid.
- Pegloticase: Breaks down uric acid directly and is reserved for selected adults whose chronic gout remains inadequately controlled with other approaches.
Because pegloticase requires intravenous infusions and carries a risk of serious reactions, it is generally reserved for patients who are likely to gain meaningful benefit from this more intensive treatment. The best option depends on the person's gout activity, previous response to medicines, other medical conditions, and treatment preferences.
What Should You Discuss With Your Doctor Before Starting Pegloticase?
Before starting treatment, discuss any history of G6PD deficiency, heart problems, allergies, infections, liver or kidney disease, pregnancy or plans for pregnancy, and all prescription medicines, over-the-counter products, and supplements you take. These details can affect whether pegloticase, methotrexate, or other accompanying medicines are suitable.
It is also helpful to understand the expected infusion schedule, the need for blood tests, how gout flares will be prevented or managed, and which symptoms require urgent attention. Your clinician can explain how treatment success will be assessed and what alternatives may be available if pegloticase does not work well enough.