Pegloticase (Krystexxa; Amgen) is approved to treat chronic gout in adults who fail to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors.
Pegloticase (Krystexxa; Amgen) was found to lower blood pressure in adults with chronic gout that is refractory to oral urate-lowering treatment, both with and without chronic kidney disease (CKD), according to clinical data from the MIRROR trial presented at the American Society of Nephrology Kidney Week meeting.1 Pegloticase is approved to treat chronic gout in adults who fail to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated.
"As we seek to address the overall burden of uncontrolled gout, especially in those with coexisting chronic kidney disease, it is critical to further understand the benefits of treatment," said Brad Marder, MD, medical director, nephrology at Amgen.1 "Recognizing the high prevalence of hypertension among these patients, we're excited to present data that offers new insight into the potential role of urate reduction with Krystexxa with methotrexate in regulating blood pressure."
Pegloticase is a recombinant uricase that shows its effect by catalyzing the oxidation of uric acid to allantoin, resulting in lower serum uric acid. Allantoin, a purine metabolite that is inert and water soluble, is primarily eliminated by renal excretion. The pharmacokinetics of the drug are not affected by age, sex, weight, or creatinine clearance.2 It is the first and only biologic medication that is FDA-approved to treat individuals with uncontrolled gout.
Gout, a chronic, progressive inflammatory form of arthritis, is caused by elevated urate levels that cause small, needle-like crystals to develop in the body. Those with uncontrolled gout have persistently high levels of uric acid as well as ongoing symptoms of gout regardless of whether they take oral urate-lowering therapies. The chronic, systemic disease may have significant clinical consequences if it is not addressed.
The FDA approved expanded labeling in 2022 that includes co-administration of pegloticase with methotrexate.
MIRROR was a controlled trial that randomly assigned 152 adults 2:1 to receive pegloticase plus methotrexate (n=100) or pegloticase with placebo (n=52) for 52 weeks. Both patient cohorts had similar blood pressure before treatment was initiated.
The reduction in systolic blood pressure during treatment was found to be greater at week 24 of treatment and was more sustained over 52 weeks of treatment among those administered pegloticase with methotrexate compared with patients administered pegloticase with placebo.
Patients without pre-treatment CKD experienced a more pronounced drop in blood pressure after 24 weeks of treatment compared to patients with pre-treatment CKD, as the differences persisted through week 52 of treatment.
"Given the myriad of comorbidities uncontrolled gout patients live with, it is critical that clinicians understand the systemic connections and potential benefits of urate reduction," said Richard J. Johnson, MD, professor, Division of Renal Diseases and Hypertension, University of Colorado Denver - Anschutz Medical Campus, in a press release. "These new data add to prior studies and further support the potential role that both Krystexxa urate-lowering and methotrexate administration played in the blood pressure changes observed."
1. Amgen Presents New Data That Show Blood Pressure Decreases For Adults Treated With Krystexxa® (Pegloticase). Amgen. News release. November 6, 2023. https://www.amgen.com/newsroom/press-releases/2023/11/amgen-presents-new-data-that-show-blood-pressure-decreases-for-adults-treated-with-krystexxa-pegloticase
2. Krystexxa complete prescribing information. www.krystexxa.com/pdfs/KRYSTEXXA_Prescribing_Information.pdf. Accessed November 2023.