Only Half of Patients Starting ULT After Pegloticase Discontinuation Achieved Target SU

Results of a retrospective analysis showed only half of patients with gout who discontinued treatment with pegloticase and initiated another urate lowering therapy (ULT) were able to achieve target serum urate (SU), according to research published in Arthritis Research & Therapy.¹ Investigators believe close follow-up could help to optimize the outcomes of treatment post-pegloticase.

Although gout is commonly treated with ULT, some patients are unable to tolerate oral ULTs. In these cases, pegloticase, a US Food and Drug Administration (FDA)-approved recombinant pegylated uricase, is often prescribed to treat this patient population. However, discontinuation of this treatment is commonly necessary in cases in which loss of treatment efficacy is observed or in patients who develop anti-drug antibodies (ADAs).²

“The optimal gout treatment after pegloticase discontinuation has not yet been established, and little is known about long-term SU management following discontinuation,” wrote a team of investigators led by Emily E Holladay, MPH, Program Manager II in the Division of Clinical Immunology & Rheumatology at the University of Alabama at Birmingham. “Additionally, more information is needed on how or if pegloticase influences renal function and systemic inflammation. Renal impairment is common in gout patients, and gout increases the risk of chronic kidney disease (CKD). This association is further complicated as CKD can limit the use of both oral ULTs and gout flare treatments.”

To better understand optimal treatment practices in patients with gout who discontinued pegloticase, investigators performed a retrospective analysis using data from the Rheumatology Informatics System for Effectiveness (RISE) registry between January 2016 and June 2022. Discontinuation was defined as a gap of ≥ 12 weeks post infusion. ULT use, inflammatory biomarkers, renal function, and SU were evaluated after pegloticase discontinuation.

Outcomes were assessed starting 2 weeks after the last dose and the team identified new ULT therapies. Changes in laboratory tests, such as SU, C-reactive protein (CRP), estimated glomerular filtration rate (eGFR), and erythrocyte sedimentation rate (ESR), were compared during treatment and after discontinuation.

A total of 375 patients with gout discontinuing pegloticase were included in the analysis. The mean age of patients was 60.3 years, most (82.9%) were male, 62.7% were White, and 76.8% had tophi.

Post-discontinuation, median laboratory changes were SU: +2.4 mg/dL (0.0 — 6.3); CRP: -0.8 mg/L (-12.8 — 0.0); eGFR: -1.9 mL/min (− 8.7 — 3.7); and ESR: -4.0 mm/hr (-13.0 — 0.0).

The most common therapy following pegloticase was an oral ULT (86.0%), while 4.5% of patients restarted treatment with pegloticase and 9.5% of patients did not report receiving any ULT. Among the oral ULTs documented, 62.7% received allopurinol and 34.1% received febuxostat.

The median time to starting or restarting ULT treatment was 92.0 days (55.0 — 173.0).

After being prescribed another ULT for ≥ 30 days, only 51.0% of patients were able to achieve SU < 6 mg/dL. Those who restarted treatment with pegloticase were able to obtain a median SU of 0.9 mg/dL and 58.3% of these patients reported SU levels of < 6 mg/dL.

Investigators mentioned the strengths of the study included the large sample size using real-world data to determine patient outcomes post-pegloticase. However, the study was limited by a significant portion of missing laboratory information. Additionally, SU measurement timing following discontinuation varied among the cohort, which may have impacted the interpretation of the full response to oral ULTs. Further, results may not be generalizable to patients treated in academic and subspecialty clinics as RISE data is mainly collected from community rheumatology practices. Lastly, the reasons for treatment discontinuation were not accounted for.

“Given that pegloticase is most-often used in patients refractory to oral ULT, this finding is important,” investigators concluded. “This study offers some of the first insight on post-pegloticase gout management, but further study is needed to determine optimal treatment regimens and the possible use of pegloticase re-treatment.”

References

1. ^{Holladay EE, Mudano AS, Xie F, et al. Urate-lowering therapy, serum urate, inflammatory biomarkers, and renal function in patients with gout following pegloticase discontinuation. Arthritis Res Ther. 2024;26(1):86. Published 2024 Apr 12. doi:10.1186/s13075-024-03318-5}
2. ^{Guttmann A, Krasnokutsky S, Pillinger MH, Berhanu A. Pegloticase in gout treatment - safety issues, latest evidence and clinical considerations. Ther Adv Drug Saf. 2017;8(12):379–88.}