Duration of Krystexxa (Pegloticase) Availability for Gout Treatment
Krystexxa (pegloticase) has been available for the treatment of gout since September 2010 when it was approved by the FDA for patients with chronic treatment-refractory gout. 1
Background and Development
Pegloticase is a pegylated uricase enzyme that works by converting uric acid to allantoin, a more soluble compound that is easily excreted by the kidneys. It was specifically developed to address the needs of patients with severe gout who have failed conventional urate-lowering therapies.
The development timeline includes:
- Clinical trials were conducted between June 2006 and October 2007 2
- Phase II studies were completed around 2008 3
- FDA approval was granted in September 2010 1
Clinical Indications
Pegloticase is indicated for a specific subset of gout patients:
- Those with chronic tophaceous gout
- Patients who have failed or cannot tolerate conventional urate-lowering therapies
- Individuals with severe debilitating gout and poor quality of life 4
Position in Treatment Guidelines
Both major rheumatology societies position pegloticase as a later-line therapy:
European League Against Rheumatism (EULAR) Guidelines (2017):
- Recommends pegloticase only for patients with crystal-proven severe debilitating chronic tophaceous gout
- For use when serum urate target cannot be reached with any other available drug at maximal dosage (including combinations) 4
American College of Rheumatology (ACR) Guidelines:
- In 2012 guidelines: Recommended only for patients with severe gout disease burden refractory to or intolerant of appropriately dosed oral urate-lowering therapy 4
- In 2020 guidelines: Strongly recommended for patients who have failed XOI treatment and uricosurics and continue to have frequent gout flares (≥2 flares/year) OR have nonresolving subcutaneous tophi 4
- Strongly recommended against for patients with infrequent gout flares (<2 flares/year) and no tophi, even if they haven't reached serum urate targets 4
Efficacy and Administration
- Pegloticase is administered as an intravenous infusion every 2 weeks at a dose of 8 mg
- Clinical trials demonstrated that 42% of patients achieved the primary endpoint of maintaining serum uric acid levels below 6 mg/dL 2
- It can rapidly reduce plasma urate levels within 6 hours of administration 3
- Particularly effective for tophaceous gout, with 45% of patients showing complete resolution of one or more tophi versus 8% in placebo groups 4
Safety Considerations
Important safety issues to be aware of:
- Infusion reactions occur in approximately 25% of patients 4
- Development of anti-pegloticase antibodies can reduce efficacy in some patients 3
- Gout flares are common during initial treatment (reported in 88% of patients in some studies) 3
- Caution is advised in patients with cardiovascular disease due to reports of heart failure exacerbation and myocardial infarction in clinical trials 1
Duration of Therapy
There is no consensus on the optimal duration of pegloticase therapy. The EULAR task force suggested considering a switch to oral urate-lowering therapy once all tophi have disappeared 4. This approach may help reduce the long-term costs and risks associated with continued infusion therapy.
In summary, Krystexxa has been available for approximately 13 years since its FDA approval in 2010, representing an important but specialized treatment option for patients with severe refractory gout.