Full Papers
Post-hoc analysis of pegloticase pivotal trials in chronic refractory gout: relationship between fluctuations in plasma urate levels and acute flares
B.F. Mandell1, T.R. Fields2, N.L. Edwards3, A.E. Yeo4, P.E. Lipsky5
- Department of Rheumatologic and Immunologic Disease, Cleveland Clinic, Cleveland, OH, USA.
- Division of Rheumatology, Hospital for Special Surgery, New York, NY, USA.
- Department of Medicine, Division of Rheumatology, Immunology and Allergy, University of Florida, Gainesville, FL, USA.
- Yeo Analytics, LLC, Jersey City, NJ, USA.
- AMPEL BioSolutions, LLC, Charlottesville, VA, USA. peterlipsky@comcast.net
CER13812
2021 Vol.39, N°5
PI 1085, PF 1092
Full Papers
PMID: 33427618 [PubMed]
Received: 14/07/2020
Accepted : 28/09/2020
In Press: 06/01/2021
Published: 31/08/2021
Abstract
OBJECTIVES:
To determine factors associated with gout flares in subjects treated with pegloticase.
METHODS:
Gout flares from two randomised controlled trials comparing pegloticase (8 mg every 2 weeks [q2] or monthly [q4]) versus placebo were analysed. Responders had persistent urate lowering (<6mg/dL) whereas, non-responders had transient urate lowering during the 6-month RCTs. Gout flares (self-reported) were defined as acute joint pain and swelling requiring treatment. Gout flare prophylaxis (colchicine, 0.6 mg once or twice daily, or a non-steroidal anti-inflammatory drug) was initiated 1 week before the first infusion and continued throughout the study. Plasma urate at the time of flare and the change in urate preceding a flare were analysed.
RESULTS:
Mean flare rates increased with pegloticase versus placebo during the first 3 months followed by marked reductions during months 4–6. The increase in flares with pegloticase during the first 3 months was most evident (p=0.0006) and the decrease during the second 3 months was least marked (p=0.0006) in subjects receiving monthly pegloticase. Fluctuation in urate levels was highest in monthly responders (p=0.002) and was associated with flare occurrence. Multivariate linear regression analysis indicated the only variables significantly associated with flares were treatment group and absolute change in plasma urate before flares.
CONCLUSIONS:
Pegloticase treatment increased flares during the first 3 months of treatment in all groups when plasma urate was significantly lowered and was followed by a decline in months 4-6 in patients maintaining a low plasma urate. Flares associated with pegloticase treatment were associated with decreases and fluctuations in plasma urate levels.
