Treatment-emergent major adverse cardiovascular and thromboembolic events were infrequent during clinical trials of pegloticase.

Abstract

Objectives: Long-term maintenance of serum urate levels <6 mg/dl reduces gout flare frequency. However, urate-lowering therapy (ULT) initiation can induce gout flare. The incidence of thromboembolic (TE) and cardiovascular (CV) events has been shown to increase in the 30 and 120 days following gout flare, respectively; therefore, the question of ULT initiation increasing patient risk for CV/TE events has been raised. Here, we investigate CV/TE event incidence following pegloticase initiation in clinical trials.

Methods: This post hoc analysis of pooled data from four trials examined treatment-emergent gout flare and CV/TE events in patients with uncontrolled gout. Studies included two phase 3 trials (NCT00325195), the MIRROR open-label trial (NCT03635957), and the MIRROR randomized controlled trial (NCT03994731). Per protocol, pegloticase (8 mg) was administered every 2 (all trials) or 4 weeks (phase 3 trials); data from the first 24 weeks of therapy were included in this analysis. Some MIRROR patients received MTX (15 mg/week) as co-therapy. Based on prior studies, the high-risk window for CV/TE events was defined as 120 days following flare onset.

Results: Overall, 5/328 (1.5%) patients experienced ≥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 120-day gout flare exposure window.

Conclusions: CV/TE event incidence during pegloticase treatment was similar to the general gout population (31.7 events/1000 person-years). These findings suggest that pegloticase initiation does not put patients at a higher risk for CV/TE events.