Long-term Safety of Pegloticase in Chronic Gout Refractory to Conventional Treatment

Overview

Journal Ann Rheum Dis

Specialty Rheumatology

Date 2012 Nov 13

PMID 23144450

Citations 38

Authors

Michael A Becker

Herbert S B Baraf

Robert A Yood

Aileen Dillon

Janitzia Vazquez-Mellado

Faith D Ottery

Dinesh Khanna

John S Sundy

Affiliations

Soon will be listed here.

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.

Citing Articles

Rasburicase Plus Methotrexate Combination Therapy in a Case of Tophaceous, Difficult-to-Treat Gout.

Pino-Zambrano M, Cardoso Penafiel P, Calvo-Aranda E Cureus. 2025; 16(12):e76265.

PMID: 39845222 PMC: 11753581. DOI: 10.7759/cureus.76265.

Patient Experience with Chronic Refractory Gout and Its Impact on Health-Related Quality of Life: Literature Review and Qualitative Analysis.

Strand V, Pillinger M, Oladapo A, Yousefian C, Brooks D, Kragh N Rheumatol Ther. 2024; 11(5):1271-1290.

PMID: 39098965 PMC: 11422411. DOI: 10.1007/s40744-024-00697-8.

Engineered microorganisms: A new direction in kidney stone prevention and treatment.

Wan W, Wu W, Amier Y, Li X, Yang J, Huang Y Synth Syst Biotechnol. 2024; 9(2):294-303.

PMID: 38510204 PMC: 10950756. DOI: 10.1016/j.synbio.2024.02.005.

Arthroscopic surgery for ankle gouty arthritis: a retrospective analysis of clinical outcomes at six month follow-up based on a novel classification system.

Zhang B, Li Y, Yang X, Gong X, Sun N, Lai L Int Orthop. 2023; 48(4):1031-1037.

PMID: 38099959 PMC: 10933192. DOI: 10.1007/s00264-023-06057-5.

The Role of Uric Acid in Human Health: Insights from the Gene.

Roman Y J Pers Med. 2023; 13(9).

PMID: 37763176 PMC: 10532990. DOI: 10.3390/jpm13091409.

References

Doghramji P, Edwards N, McTigue J . Managing gout in the primary care setting: what you and your patients need to know. Am J Med. 2010; 123(8):S2. DOI: 10.1016/j.amjmed.2010.06.005. View

Shoji A, Yamanaka H, Kamatani N . A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis with antihyperuricemic therapy. Arthritis Rheum. 2004; 51(3):321-5. DOI: 10.1002/art.20405. View

Day R, Williams K . Open-label extension studies: do they provide meaningful information on the safety of new drugs?. Drug Saf. 2007; 30(2):93-105. DOI: 10.2165/00002018-200730020-00001. View

Schlesinger N, Yasothan U, Kirkpatrick P . Pegloticase. Nat Rev Drug Discov. 2011; 10(1):17-8. DOI: 10.1038/nrd3349. View

Perez-Ruiz F, Liote F . Lowering serum uric acid levels: what is the optimal target for improving clinical outcomes in gout?. Arthritis Rheum. 2007; 57(7):1324-8. DOI: 10.1002/art.23007. View

Edwards N . Treatment-failure gout: a moving target. Arthritis Rheum. 2008; 58(9):2587-90. DOI: 10.1002/art.23803. View

Zhu Y, Pandya B, Choi H . Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011; 63(10):3136-41. DOI: 10.1002/art.30520. View

Sundy J, Baraf H, Yood R, Edwards N, Gutierrez-Urena S, Treadwell E . Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA. 2011; 306(7):711-20. DOI: 10.1001/jama.2011.1169. View

Sherman M, Saifer M, Perez-Ruiz F . PEG-uricase in the management of treatment-resistant gout and hyperuricemia. Adv Drug Deliv Rev. 2007; 60(1):59-68. DOI: 10.1016/j.addr.2007.06.011. View

10.

Zhang W, Doherty M, Bardin T, Pascual E, Barskova V, Conaghan P . EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006; 65(10):1312-24. PMC: 1798308. DOI: 10.1136/ard.2006.055269. View

11.

Hamburger M, Baraf H, Adamson 3rd T, Basile J, Bass L, Cole B . 2011 Recommendations for the diagnosis and management of gout and hyperuricemia. Postgrad Med. 2011; 123(6 Suppl 1):3-36. DOI: 10.3810/pgm.2011.11.2511. View

12.

Perez-Ruiz F, Calabozo M, Pijoan J, Herrero-Beites A, Ruibal A . Effect of urate-lowering therapy on the velocity of size reduction of tophi in chronic gout. Arthritis Rheum. 2002; 47(4):356-60. DOI: 10.1002/art.10511. View

13.

Brook R, Forsythe A, Smeeding J, Edwards N . Chronic gout: epidemiology, disease progression, treatment and disease burden. Curr Med Res Opin. 2010; 26(12):2813-21. DOI: 10.1185/03007995.2010.533647. View

14.

Jordan K, Cameron J, Snaith M, Zhang W, Doherty M, Seckl J . British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of gout. Rheumatology (Oxford). 2007; 46(8):1372-4. DOI: 10.1093/rheumatology/kem056a. View

15.

Becker M, Schumacher H, MacDonald P, Lloyd E, Lademacher C . Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout. J Rheumatol. 2009; 36(6):1273-82. DOI: 10.3899/jrheum.080814. View

16.

Pascual E, Sivera F . Time required for disappearance of urate crystals from synovial fluid after successful hypouricaemic treatment relates to the duration of gout. Ann Rheum Dis. 2007; 66(8):1056-8. PMC: 1954685. DOI: 10.1136/ard.2006.060368. View

17.

Li-Yu J, Clayburne G, Sieck M, Beutler A, Rull M, Eisner E . Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout?. J Rheumatol. 2001; 28(3):577-80. View

18.

Richette P, Bardin T . Gout. Lancet. 2009; 375(9711):318-28. DOI: 10.1016/S0140-6736(09)60883-7. View