Long-term safety of pegloticase in chronic gout refractory to conventional treatment

Abstract

Objective: To evaluate the long-term safety (up to 3 years) of treatment with pegloticase in patients with refractory chronic gout.

Methods: This open-label extension (OLE) study was conducted at 46 sites in the USA, Canada and Mexico. Patients completing either of two replicate randomised placebo-controlled 6-month trials received pegloticase 8 mg every 2 weeks (biweekly) or every 4 weeks (monthly). Safety was evaluated as the primary outcome, with special interest in gout flares and infusion-related reactions (IRs). Secondary outcomes included urate-lowering and clinical efficacy.

Results: Patients (n=149) received a mean±SD of 28±18 pegloticase infusions and were followed for a mean of 25±11 months. Gout flares and IRs were the most frequently reported adverse events; these were least common in patients with a sustained urate-lowering response to treatment and those receiving biweekly treatment. In 10 of the 11 patients with a serious IR, the event occurred when uric acid exceeded 6 mg/dl. Plasma and serum uric acid levels remained <6 mg/dl in most randomised controlled trial (RCT)-defined pegloticase responders throughout the OLE study and were accompanied by sustained and progressive improvements in tophus resolution and flare incidence.

Conclusions: The safety profile of long-term pegloticase treatment was consistent with that observed during 6 months of RCT treatment; no new safety signals were identified. Improvements in clinical status, in the form of flare and tophus reduction initiated during RCT pegloticase treatment in patients maintaining goal range urate-lowering responses were sustained or advanced during up to 2.5 years of additional treatment.

Keywords: Gout; Rheumatoid Arthritis; Treatment.

Figure 1

Study design schematic for the open-label extension study. AE, adverse event; IR, infusion-related reaction; OLE, open-label extension; PUA, plasma uric acid; RCT, randomised controlled trial; SUA, serum uric acid.

Figure 2

Disposition for all patients entering the open-label extension (OLE) study. ITT, intention-to-treat; RCT, randomised controlled trial.

Figure 3

Percentage of patients with serum uric acid (SUA) <6 mg/dl by study week, uric acid responder status in the randomised controlled trial (RCT) and pegloticase dose regimen. (A) All patients who entered the open-label extension (OLE) study after receiving pegloticase during the RCTs. Subgroups were defined by SUA response during the RCTs. (B) All patients who entered the OLE study after receiving placebo during the RCT and therefore had their first exposure to pegloticase in the OLE study. Subgroups are defined by the pegloticase dose administered at OLE entry.

Figure 4

Proportions of patients who received (A) biweekly pegloticase or (B) monthly pegloticase throughout the randomised controlled trial (RCT) and open-label extension periods and reported gout flares (per 3-month interval).