January 18, 2012
On December 7, 2011, Savient, the manufacturer of Pegloticase (Krystexxa), circulated a Dear Healthcare Provider Letter advising against concomitant use of pegloticase and other urate-lowering therapies. This Hotline addresses this concern and is intended to update the previous ACR Hotline on pegloticase published on November 1, 2010.
Pegloticase has been approved by the FDA for the treatment of chronic gout refractory to conventional therapy. In the clinical trials leading to approval, it was noted that antibodies to pegloticase were common in treated patients, and that high titer antibody was associated with loss of response and increased risk of infusion reactions and anaphylaxis. While pegloticase antibody assays are not commercially available, elevations in pre-infusion plasma urate levels (e.g. > 6 mg/dL) are believed to serve as a marker, reflecting decreased efficacy due to increased clearance of drug and potentially identifying patients at higher risk for infusion reactions. Measurement of serum urate levels prior to each infusion is currently recommended in the product labeling, along with a recommendation to consider discontinuing treatment in patients with a pre-treatment serum urate level > 6 mg/dL and to definitely discontinue treatment if this occurs more than once.
Pegloticase was used as monotherapy in clinical trials. However, post-marketing surveillance conducted by Savient has noted that pegloticase is being used in clinical practice with concomitant urate lowering therapies, including allopurinol and febuxostat (Uloric). While serious adverse outcomes have not been reported with this regimen, there is concern that use of these concomitant therapies might mask uric acid elevations attributable to loss of efficacy due to antibodies to pegloticase, thereby impairing identification of patients at higher risk for infusion reactions. In their letter, Savient suggested that additional urate lowering therapy should be discontinued prior to initiating therapy with pegloticase and that these agents should not be started in patients being treated with pegloticase.
The Bottom Line:
- Patients with gout who respond to and can tolerate conventional urate lowering therapies such as allopurinol or febuxostat should be treated with these drugs before considering pegloticase.
- Urate lowering therapies should be discontinued prior to the use of pegloticase and should not be initiated during a course of pegloticase therapy.
- Pegloticase should be used with caution in patients with CHF.
- Patients with G6PD deficiency should not receive pegloticase.
- Pre-medication with an antihistamine and a corticosteroid prior to dosing should be used to help reduce the risk of infusion-related reactions.
- Measurement of a routine serum urate level several days prior to each infusion may be helpful in identifying patients who have lost a therapeutic response to pegloticase and may be at increased risk of infusion reactions and anaphylaxis. Consider discontinuing treatment in patients with a pre-treatment serum urate level > 6 mg/dL; definitely discontinue if this occurs more than once.
- Clinicians administering pegloticase should have the capabilities and experience to manage infusion reactions and anaphylaxis.
Hotline Editors: Arthur Kavanaugh, MD, and Eric Ruderman, MD
Disclosures: Dr. Ruderman: Nothing to disclose. Dr. Kavanaugh: clinical investigator on pegloticase trials.
In addition to review by the editors, this Hotline has been reviewed by all members of the ACR Executive Committee, Communications and Marketing Committee and Drug Safety Committee.
The ACR Hotline is provided by the ACR Communications and Marketing Committee as a service to members. This Hotline reflects the views of the editors and does not represent a position statement of the American College of Rheumatology.