Pegloticase Does Not Increase Risk of CV/TE Events in People With Gout

Pegloticase (Krystexxa; Amgen) was not found to put patients with gout at a higher risk of thromboembolic (TE) and cardiovascular (CV) events, according to a new post-hoc analysis of multiple trials assessing the therapy.1

“In these trials, the proportion of patients experiencing gout flares increased during the first month of pegloticase therapy but rapidly and progressively declined to nearly 0% over 12 months of therapy. Although CV safety signals were not identified in pegloticase clinical trials, the demonstrated relationship between gout flares and CV/TE events has raised the important question of whether or not pegloticase treatment increases these events in uncontrolled gout patients,” first author Orrin M. Troum, MD, Division of Rheumatology, University of Southern California Keck School of Medicine and Providence Saint John’s Health Center, and colleagues wrote.1

Troum and colleagues conducted a post hoc analysis of pooled data from 4 trials examining treatment-emergent gout flare and CV/TE events in patients with uncontrolled gout, including 2 phase 3 trials (NCT00325195), the MIRROR open-label trial (NCT03635957), and the MIRROR randomized controlled trial (NCT03994731). Participants in these studies received pegloticase (8 mg) every 2 (all trials) or 4 weeks (phase 3 trials). This analysis included data from the first 24 weeks of therapy. Some MIRROR patients received methotrexate (15 mg/week) as co-therapy. Investigators considered the high-risk window for CV/TE events as 120 days following flare onset based on prior studies.

The investigators found that 5/328 (1.5%) patients experienced at least 1 CV/TE event during pegloticase treatment, including 3/244 (1.2%) patients who received on-label (biweekly) dosing (35.4 events/1000 person-years). All events occurred within the high-risk, 120-day gout flare exposure window.1

“In conclusion, treatment with pegloticase did not increase the frequency of CV/TE events and the overall incidence of CV/TE events reported in this post hoc analysis was similar to that in the general gout population. Further, all identified CV/TE events occurred within 120 days after gout flare onset, a window of higher risk determined by a prior study. Given that gout flare occurrence is lower in patients who maintain SU levels <6 mg/dL, ULT use in a treat-to-target SU approach is not only an important component of gout management, but could play a role in maintaining long-term health in patients with gout,” Troum and colleagues concluded.1

Troum previously presented findings from the phase 4 AGILE study investigating shortened, 1-hour infusion times of pegloticase in combination with methotrexate at November 2024’s American College of Rheumatology (ACR) Convergence. The data demonstrated that shortened infusions of pegloticase was well-tolerated with preserved efficacy in patients with uncontrolled gout, demonstrating a promising option for reducing treatment burden.2

“Pegloticase is currently approved to be given over a 2-hour period and this often has an impact… on [patients’] daily lives, if this is an every 2 week therapy for at least 6 to 12 months,” Troum told HCPLive® during the meeting.

REFERENCES

1. Troum OM, Duong M, Obermeyer K, Padnick-Silver L, LaMoreaux B. Treatment-Emergent Major Adverse Cardiovascular and Thromboembolic Events were Infrequent During Clinical Trials of Pegloticase. Rheumatology. Published online January 10, 2025. keaf017. doi: 10.1093/rheumatology/keaf017

2. Troum O, Botson J, Fang F, et al. Safety, Tolerability and Efficacy of Pegloticase Administered with a Shorter Infusion Duration in Subjects with Uncontrolled Gout Receiving Methotrexate: Primary Findings of the AGILE Open-label Trial. Presented at: Presented at: ACR Convergence 2024; November 14-19; Washington, DC. Abstract 2012.