Urate-Lowering Therapy Could Also Lower Blood Pressure in Gout Patients

Richard Johnson, MD
Credit: University of Colorado Anschutz

New research presented at the American Society of Nephrology Kidney Week 2023 suggests use of pegloticase plus methotrexate (Krystexxa) in the management of uncontrolled gout could also confer blood pressure benefit.

Results of the study demonstrate patients randomized to pegloticase plus methotrexate experienced greater and more sustained reductions in systolic blood pressure than their counterparts who received pegloticase plus placebo in the pivotal MIRROR trial.¹

"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 in the Division of Renal Diseases and Hypertension at the University of Colorado Denver - Anschutz Medical Campus.² "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."

The basis for the US Food and Drug administration’s approval of the supplemental Biologics License Application for pegloticase injection for coadministration with methotrexate in July 2022, the MIRROR trial was 12-month, randomized, double-blind, placebo-controlled phase 4 trial comparing pegloticase plus methotrexate against pegloticase plus placebo in patients with uncontrolled gout.³

With a study population of 152 individuals, the trial randomized participants in a 2:1 ratio, with 100 receiving pegloticase plus methotrexate and 52 receiving pegloticase plus placebo. The primary endpoint of the trial was the proportion of serum uric acid (sUA) responders, which investigators defined as an sUA less than 6 mg/dL for at least 80% of the time during weeks 20-24.^1,3

Results indicated use of pegloticase plus methotrexate was associated with a greater than 30 percentage-point increase in response rate during weeks 20-24, with 71% of those receiving pegloticase plus methotrexate achieving the primary endpoint compared to just 39% of the pegloticase plus placebo group (P < .0001).^1,3

At Kidney Week 2023, Johnson presented data from an analysis examining the effects of treatment on blood pressure control among patients included in the study. As per trial protocol, blood pressure was measured before methotrexate and pegloticase exposure and every 2 weeks thereafter.¹

Results of the analysis suggested the mean decrease in systolic blood pressure during treatment was greater at week 24 with pegloticase plus methotrexate than with pegloticase plus placebo (-6±16 vs. -1±18 mmHg). Results also suggested this reduction was more likely to be sustained throughout the 52-week treatment period in patients receiving pegloticase plus methotrexate than with pegloticase plus placebo.¹

Investigators performed subgroups analyses examining the effects on blood pressure based on baseline eGFR. In these analyses, investigators found those with a baseline eGFR of 60 or greater (Systolic: 133±13mmHg; Diastolic: 83±9mmHg; N=98) and less than 60 (Systolic: 130±15mmHg; Diastolic: 80±7mmHg)experienced similar blood pressure changes from baseline early in treatment, but by week 24 this apparent change was more pronounced in 60 or greater group, with investigators pointing out this trend was sustained through week 52.¹

"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 of nephrology at Amgen.² "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."

References:

1. Marder BA, Johnson RJ, Choi H, Obermeyer KL, LaMoreaux B, Lipsky PE. Blood Pressure Changes with Intensive Urate Lowering in Uncontrolled Gout Patients with and Without CKD. Paper Presented at: American Society of Nephrology Kidney Week 2023. November 1-5, 2023.
2. Amgen presents new data that show blood pressure decreases for adults treated with KRYSTEXXA® (pegloticase). Amgen. November 2, 2023. Accessed November 2, 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.
3. FDA approves KRYSTEXXA® (pegloticase) injection co-administered with methotrexate, expanding the labeling to help more people with uncontrolled gout achieve a complete response to therapy. Business Wire. July 8, 2022. Accessed November 2, 2023. https://www.businesswire.com/news/home/20220708005097/en/FDA-Approves-KRYSTEXXA%C2%AE-pegloticase-Injection-Co-Administered-With-Methotrexate-Expanding-the-Labeling-to-Help-More-People-with-Uncontrolled-Gout-Achieve-a-Complete-Response-to-Therapy.