Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Mar 17;2010(3):CD008335.
doi: 10.1002/14651858.CD008335.pub2.

Pegloticase for chronic gout

Amy Anderson  1 , Jasvinder A Singh
Affiliations

Pegloticase for chronic gout

Amy Anderson et al. Cochrane Database Syst Rev. .

Abstract

Background: Pegloticase is a potential new treatment option for patients with chronic gout intolerant to other urate-lowering therapies.

Objectives: To assess safety (adverse events, death) and efficacy (pain, function, frequency of flares, quality of life, uric acid level, radiographic damage) of pegloticase in various doses or as compared to placebo or other interventions for treatment of hyperuricemia in patients with chronic gout.

Search strategy: We searched six databases: The Cochrane Central Register of Controlled Trials (CENTRAL), via The Cochrane Library, OVID MEDLINE, CINAHL (via EBSCOHost), OVID SPORTdiscus, EMBASE and the Science Citation Index (Web of Science).

Selection criteria: All published randomized controlled trials (RCTs) or controlled clinical trials that compared various doses of pegloticase alone or pegloticase alone or in combination with other urate-lowering or anti-inflammatory medications to placebo alone or placebo in combination with these medications, in patients with gout.

Data collection and analysis: Two review authors (AA, JS) independently extracted data from the included trials, including trial and population characteristics, primary and secondary outcomes. For dichotomous and continuous outcomes, we calculated the risk ratio and mean difference, respectively with 95% confidence interval. Major outcomes were: (a)

Efficacy: frequency of gout flares and change in serum uric acid; and (b) safety: adverse events, serious adverse events, withdrawals and death. Minor/secondary outcomes were pain, patient/physician global assessment, tophus burden, health related quality of life, function and radiographic progression.

Main results: Only one open-label, phase-II RCT (n=41) met the selection criteria that compared various doses of pegloticase without comparison to placebo or another treatment. Patients were randomized to one of the four doses of pegloticase for 12 to 14 weeks - 4mg every 2 weeks, 8mg every 2 weeks, 8mg every 4 weeks and 12mg every 4 weeks. Percent responders (uric acid below 6 mg/dl 80% or more time) in the four dose groups were 56%, 88%, 52% and 62%. Percent time without hyperuricemia (uric acid below 6 mg/dl) was 78%, 92%, 76% and 76% respectively. No between dose differences were noted. Most common adverse events (10% or more patients) included nephrolithiasis, arthralgia, anemia, dyspnea, headache, muscle spasms, nausea and pyrexia. 89% reported one or more gout flares during the study. Pain, patient/physician global, function, quality of life, tophus size/regression and radiographic progression were not reported in this study.

Authors' conclusions: There are no published double-blind, placebo-controlled RCTs of pegloticase. More evidence is needed to assess risks/benefits of pegloticase in patients with chronic gout.

PubMed Disclaimer

Conflict of interest statement

JS ‐ Research grants from Takeda, Savient and AMGEN pharmaceuticals; Consultant/honraria‐ Savient, Abbott and URL pharmaceuticals; Research grants from National Institues of Health, Department of Veterans Affairs, Arthritis Foundation, University of Minnesota, Minnesota Medical Foundation and Cochrane Collaboration.

AA ‐ None

Figures

1
1
Study Selection Flow Chart
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Sundy 2008 {published data only}
    1. Sundy JS, Becker MA, Baraf HSB, Barkhuizen A, Moreland LW, Huang W, et al. Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol‐conjugated uricase) in patients with treatment‐failure gout: Results of a phase II randomized study. Arthritis & Rheumatism 2008;58(9):2882‐91. - PubMed

References to studies excluded from this review

Arora 2009 {published data only}
    1. Arora J, Nandwani S, Bhambi M, Pundir CS. Fabrication of dissolved O2 metric uric acid biosensor using uricase epoxy resin biocomposite membrane. Analytica Chimica Acta 2009;647(2):195‐201. - PubMed
Baker 2009 {published data only}
    1. Baker DE. New drugs approved by the FDA: New dosage forms and indications approved by the FDA ‐ Agents pending FDA approval. New drug or biologics license applications filed by manufacturer: Supplemental applications filed by manufacturer ‐ Significant labeling changes or "dear health care professional" letters related to safety. Hospital Pharmacy 2009;44(4):340‐4.
Baraf 2005 {published data only}
    1. Baraf HS, Kim S, Matsumoto AK, Maroli AN. Resolution of tophi with intravenous peg‐uricase in refractory gout. Conference proceedings. 2005.
Baraf 2006 {published data only}
    1. Baraf HS, Kim S, Matsumoto AK, Maroli AN. Resolution of tophi with intravenous peg‐uricase in treatment failure gout. Conference proceedings. 2006.
Baraf 2008 {published data only}
    1. Baraf HS, Becker MA, EdwardS NL, Gutierrez‐Urena SR, Sundy JS, Treadwell EL, et al. Resolution of gouty tophi after twelve weeks of pegloticase treatment. Conference Proceedings. 2008. - PubMed
Baraf 2008a {published data only}
    1. Baraf HS, Becker MA, EdwardS NL, Gutierrez‐Urena SR, Sundy JS, Treadwell EL, et al. editors. Tophus response to pegloticase (PGL) therapy: Pooled results from GOUT1 and GOUT2, PGL phase 3 randomized, double blind, placebo‐controlled trials. Conference proceedings. 2008.
Becker 2005 {published data only}
    1. Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Eustace D, Palo WA, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. New England Journal of Medicine 2005;353:2450‐61. - PubMed
Becker 2008 {published data only}
    1. Becker MA, Treadwell EL, Baraf HS, Edwards NL, Gutierrez‐Urena SR, Sundy JS, et al. Immunoreactivity and clinical response to pegloticase (PGL): Pooled data from GOUT1 and GOUT2, PGL phase 3 randomized, double blind, placebo‐controlled trials. Conference proceedings. 2008.
Bieber 2004 {published data only}
    1. Bieber JD, Terkeltaub RA, Bieber JD, Terkeltaub RA. Gout: on the brink of novel therapeutic options for an ancient disease. Arthritis & Rheumatism 2004;50(8):2400‐14. - PubMed
Biggers 2008 {published data only}
    1. Biggers K, Scheinfeld N, Biggers K, Scheinfeld N. Pegloticase, a polyethylene glycol conjugate of uricase for the potential intravenous treatment of gout. Current Opinion in Investigational Drugs 2008;9(4):422‐9. - PubMed
Bomalaski 2002 {published data only}
    1. Bomalaski JS, Holtsberg FW, Ensor CM, Clark MA, Bomalaski JS, Holtsberg FW, et al. Uricase formulated with polyethylene glycol (uricase‐PEG 20): biochemical rationale and preclinical studies. Journal of Rheumatology 2002;29(9):1942‐9. - PubMed
Campara 2009 {published data only}
    1. Campara M, Shord SS, Haaf CM. Single‐dose rasburicase for tumour lysis syndrome in adults: weight‐based approach. Journal of Clinical Pharmacy and Therapeutics 2009;34(2):207‐13. - PubMed
Cao 2009 {published data only}
    1. Cao, Y. Meng, X.Liu, J. Enteric coated preparation for controlling hyperuricemia and gout comprises coated capsule of uricase. Patent.
Cleveland 2009 {published data only}
    1. Cleveland BM, Leonard SS, Klandorf H, Blemings KP. Urate oxidase knockdown decreases oxidative stress in a murine hepatic cell line. Conference Proceedings. 2009. - PMC - PubMed
Ea 2009 {published data only}
    1. Ea HK, Bardin T, Jinnah HA, Aral B, Liote F, Ceballos‐Picot I. Severe gouty arthritis and mild neurologic symptoms due to F199C, a newly identified variant of the hypoxanthine guanine phosphoribosyltransferase. Arthritis & Rheumatism 2009;60(7):2201‐4. - PMC - PubMed
Edwards 2008 {published data only}
    1. Edwards NL, Baraf HS, Becker MA, Gutierrez‐Urena SR, Sundy JS, Treadwell EL, et al. Improvement in health‐related quality of life (HRQL) and disability index in treatment failure gout (TFG) after pegloticase (PGL) therapy: pooled results from GOUT1 and GOUT2, phase 3, randomized double blind, placebo (PBO)‐controlled trials. Conference proceedings. 2008.
Fridolin 2009 {published data only}
    1. Fridolin I, Jerotskaja J, Lauri K, Luman, M. Substance's i.e. uric acid, concentration measuring device for treating e.g. hyperuricemia, has data representing module for executing program for data representation, where module has data visualization module. Patent.
Ganson 2006 {published data only}
    1. Ganson NJ, Kelly SJ, Scarlett E, Sundy JS, Hershfield MS, Ganson NJ, et al. Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase. Arthrtiis Research and Therapy 2006;8(1):R12. - PMC - PubMed
George 2009 {published data only}
    1. George V, Grujic D, Khalaf N, McGrath M, Patel R, Shenoy B, Watson E. New uricase composition, useful for treating a disorder associated with elevated uric acid concentration. Patent.
Gruber 2009 {published data only}
    1. Gruber J. Gout: New treatment for an old disease. Journal fur Mineralstoffwechsel 2009;16(3):111‐4.
Joseph‐Ridge 2006 {published data only}
    1. Joseph‐Ridge N, Cazzetta S, MacDonald P. Clinical Trials in Crystal Arthropathy. Rheumatic Disease Clinics of North America 2006;32(2):359‐82. - PubMed
Liu 2009 {published data only}
    1. Liu G, Yang Z, Liu Q, Wu X, Liu M, Lai, Q. New polyethylene glycol urate oxidase compound, useful for preparing drugs for treating and preventing gout, reducing the level of blood uric acid, preventing tumor lysis syndrome and improving kidney functions. Patent.
Louyot 1970 {published data only}
    1. Louyot P, Montet Y, Roland J, Pourel J. [Urate oxidase in the treatment of gout and hyperuricemia]. Revue du Rhumatisme et des Maladies Osteo‐Articulaires 1970;37(12):795‐808. - PubMed
Louyot 1971 {published data only}
    1. Louyot P, Laurent‐Montet Y, Roland J, Pourel G. [Experimentation with urate oxidase]. Journal Belge de Rhumatologie et de Medecine Physique. Belgisch Tijdschrift Voor Reumatologie En Fysische Geneeskunde 1971;26(4):169‐78. - PubMed
Mizon 1971 {published data only}
    1. Mizon JP, Plaquet R, Gentit F, Quiret JC. NEW ORIENTATION OF TREATMENT OF GOUT ‐ CLINICAL AND BIOLOGICAL STUDY ON URATE OXIDASE. Lille Medical 1971;16(9):1332‐. - PubMed
MIzon 1971a {published data only}
    1. Mizon JP, Plaquet R, Gentit F, Quiret JC. [New trend in gout treatment. Clinical and biological study of urate oxidase]. Lille Medical 1971;16(9):1332‐45. - PubMed
Ribeiro 2009 {published data only}
    1. Ribeiro A, Bogas M, Costa J, Costa L, Araujo D. [Rasburicase for tophaceus gout treatment]. Acta Reumatol Port 2009;34(3):551‐4. - PubMed
Riches 2009 {published data only}
    1. Riches PL, Wright AF, Ralston SH. Recent insights into the pathogenesis of hyperuricaemia and gout. Human Molecular Genetics 2009;18(R2):R177‐84. - PubMed
Saketkoo 2009 {published data only}
    1. Saketkoo LA, Robertson HJ, Dyer HR, Virk ZU, Ferreyro HR, Espinoza LR. Axial gouty arthropathy. American Journal of the Medical Sciences 2009;338(2):140‐6. - PubMed
Schumacher 2008 {published data only}
    1. Schumacher HR, Jr, Becker MA, Wortmann RL, MacDonald P, Hunt B, Streit J, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28‐week, phase III, randomized, double‐blind, parallel‐group trial. Arthritis Care & Research 2008;59(11):1540‐8. - PubMed
Sherman 2008 {published data only}
    1. Sherman MR, Saifer MG, Perez‐Ruiz F, Sherman MR, Saifer MGP, Perez‐Ruiz F. PEG‐uricase in the management of treatment‐resistant gout and hyperuricemia. Advanced Drug Delivery Reviews 2008;60(1):59‐68. - PubMed
Smith 2009 {published data only}
    1. Smith RG. The diagnosis and treatment of gout. US Pharmacist 2009;34(5):40‐47.
Sundy 2004 {published data only}
    1. Sundy JS, Ganson N, Kelly SJ, Scarlett EL, Hershfield MS. A Phase I study of pegylated‐uricase (Puricase (R) in subjects with gout. Conference proceedings. 2004.
Sundy 2005 {published data only}
    1. Sundy JS, Becker MA, Baraf HSB, Barkhuizen A, Moreland L, Huang B, et al. A phase 2 study of multiple doses of intravenous polyethylene glycol (PEG)‐uricase in patients with hyperuricemia and refractory gout. Conference proceedings. 2005.
Sundy 2006 {published data only}
    1. Sundy JS, Becker MA, Baraf HSB, Barkhuizen A, Moreland LW, Huang B, et al. A phase 2 study of multiple doses of intravenous polyethylene glycol (PEG)‐uricase in patients with hyperuricemia and treatment failure gout. Conference proceedings. 2006.
Sundy 2007 {published data only}
    1. Sundy JS, Ganson NJ, Kelly SJ, Scarlett EL, Rehrig CD, Huang W, et al. Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinant mammalian urate oxidase in patients with refractory gout. Arthritis and Rheumatism 2007;56(3):1021‐8. - PubMed
Sundy 2007a {published data only}
    1. Sundy JS, Ganson NJ, Kelly SJ, Scarlett EL, Rehrig CD, Huang W, et al. Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinant mammalian urate oxidase in patients with refractory gout [erratum]. Arthritis and Rheumatism 2007;56(4):1370. - PubMed
Sundy 2008a {published data only}
    1. Sundy JS, Baraf HS, Becker MA, Edwards NL, Gutierrez‐Urena SR, Treadwell EL, et al. Efficacy and safety of intravenous (IV) pegloticase (PGL) in subjects with treatment failure gout (TFG): Phase 3 results from GOUT1 and GOUT2. Conference proceedings. 2008.
Sundy 2009 {published data only}
    1. Sundy JS, Becker MS, Huang WY, Waltrip RW, Chandraker AK. Treatment Failure Gout: Efficacy and Safety of Pegloticase in Phase 3 Trials. Conference proceedings. 2009.
Terkeltaub 2009 {published data only}
    1. Terkeltaub R, Zelman D, Scavulli J, Perez‐Ruiz F, Liote F. Gout Study Group: Update on hyperuricemia and gout. Joint Bone Spine 2009;76(4):444‐6. - PubMed
Traynor 2009 {published data only}
    1. Traynor K. New gout treatment approved. American Journal of Health‐System Pharmacy 2009;66(7):606. - PubMed
Wipfler‐Freibmuth 2009 {published data only}
    1. Wipfler‐Freibmuth E, Dejaco C, Duftner C, Gaugg M, Kriessmayr‐Lungkofler M, Schirmer M. Urate oxidase (rasburicase) for treatment of severe acute gout: a case report. Clinical and Experimental Rheumatology 2009;27(4):658‐60. - PubMed
Yue 2006 {published data only}
    1. Yue CS, Marier J, Huang B, Alton M, Maroli A, Wright D, et al. Population pharmacokinetic and pharmacodynamic analysis of PEG‐uricase in subjects with hyperuricemia and refractory gout. Conference proceedings. 2006.
Yue 2008 {published data only}
    1. Yue CS, Huang W, Alton M, Maroli AN, Waltrip RW, Wright D, et al. Population pharmacokinetic and pharmacodynamic analysis of pegloticase in subjects with hyperuricemia and treatment‐failure gout. Journal of Clinical Pharmacology 2008;48(6):708‐18. - PubMed

Additional references

Arromdee 2002
    1. Arromdee E, Michet CJ, Crowson CS, O'Fallon WM, Gabriel SE. Epidemiology of gout: is the incidence rising?. Journal of Rheumatology 2002;29(11):2403‐6. - PubMed
Atkins 2004
    1. Atkins D, Best D, Briss PA, Eccles M, Falck‐Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. BMJ 2004;328(7454):1490. - PMC - PubMed
Atkins 2004a
    1. Atkins D, Eccles M, Flottorp S, Guyatt GH, Henry D, Hill S, et al. Systems for grading the quality of evidence and the strength of recommendations I: critical appraisal of existing approaches The GRADE Working Group. BMC Health Services Research 2004;4(1):38. - PMC - PubMed
Biggers 2008
    1. Biggers K, Scheinfeld N. Pegloticase, a polyethylene glycol conjugate of uricase for the potential intravenous treatment of gout. Current Opinion in Investigational Drugs 2008;9(4):422‐9. - PubMed
Cates 2009
    1. Cates C. Visual Rx NNT Calculator version 3 [Computer program]. Dr Chris Cates' EBM web site. Available from http://www.Nntonline.Net/visualrx/, Accessed 13 February 2009.
Chohan 2009
    1. Chohan S, Becker MA. Update on emerging urate‐lowering therapies. Current Opinion in Rheumatology 2009;21(2):143‐9. - PubMed
Choi 2005
    1. Choi HK, Curhan G. Gout: epidemiology and lifestyle choices. Current Opinion in Rheumatology 2005;17(3):341‐5. - PubMed
Deeks 2008
    1. Deeks J, Higgins J, Altman D. Chapter 9: Analysing data and undertaking meta‐analyses, Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 (updated February 2008). The Cochrane Collaboration. Available from: www.cochrane‐handbook.org. 2008.
Eggebeen 2007
    1. Eggebeen AT. Gout: an update. American Family Physician 2007;76(6):801‐8. - PubMed
Fries 1980
    1. Fries JF, Spitz PW, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis & Rheumatism 1980;23:137‐45. - PubMed
Grainger 2009
    1. Grainger R, Taylor WJ, Dalbeth N, Perez‐Ruiz F, Singh J, Waltrip RW, et al. Progress in measurement instruments in acute and chronic gout studies. Journal of Rheumatology 2009;36(10):2346‐55. - PubMed
Higgins 2008
    1. Higgins JP, Altman DG. Chapter 8: Assessing risk of bias in included studies. . In: Higgins JP, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 [updated February 2008]. www.cochrane‐handbook.org. The Cochrane Collaboration, 2008.
Hirsch 2008
    1. Hirsch JD, Lee SJ, Terkeltaub R, Khanna D, Singh J, Sarkin A, et al. Evaluation of an instrument assessing influence of Gout on health‐related quality of life. Journal of Rheumatology 2008;35(12):2406‐14. - PubMed
Janssens 2008
    1. Janssens HJ, Lucassen PL, Laar FA, Janssen M, Lisdonk EH. Systemic corticosteroids for acute gout. Cochrane Database of Systematic Reviews 2008, Issue 2008(2):CD005521. - PMC - PubMed
Larsen 1977
    1. Larsen A, Dale K, Eek M. Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films. Acta Radiologic Diagnosis (Stockholm) 1977;18(4):481–91. - PubMed
Saag 2006
    1. Saag KG, Choi H. Epidemiology, risk factors, and lifestyle modifications for gout. Arthritis Res Ther 2006;8 Suppl 1:S2. - PMC - PubMed
Schlesinger 2006
    1. Schlesinger N, Schumacher R, Catton M, Maxwell L. Colchicine for acute gout. Cochrane Database of Systematic Reviews 2006, Issue (4):CD006190. - PubMed
Schumacher 2009
    1. Schumacher HR, Jr, Taylor WJ, Edwards NL, Grainger R, Schlesinger N, Dalbeth N, et al. Outcome domains for studies of acute and chronic gout. OMERACT 9. Journal of Rheumatology 2009;36(10):2342‐5. - PubMed
Schunemann 2008
    1. Schünemann HJ, Oxman AD, Higgins JP, Vist GE, Glasziou P, Guyatt GH. Chapter 11: Presenting results and ‘Summary of findings tables'. In: Higgins JP, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 500 [updated February 2008]. The Cochrane Collaboration. www.cochrane‐handbook.org, 2008.
Schunemann 2008a
    1. Schünemann HJ, Oxman AD, Higgins JP, Vist GE, Glasziou P, Guyatt GH. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JP, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 500 [updated February 2008]. The Cochrane Collaboration. www.cochrane‐handbook.org, 2008.
Sharp 1971
    1. Sharp JT, Lidsky MD, Collins LC, Moreland J. Methods of scoring the progression of radiologic changes in rheumatoid arthritis. Correlation of radiologic, clinical and laboratory abnormalities. Arthritis & Rheumatism 1971;14(6):706–20. - PubMed
So 2008
    1. So A. Developments in the scientific and clinical understanding of gout. Arthritis Research and Therapy 2008;10(5):221. - PMC - PubMed
Sundy 2007
    1. Sundy JS, Ganson NJ, Kelly SJ, Scarlett EL, Rehrig CD, Huang W, et al. Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinant mammalian urate oxidase in patients with refractory gout. Arthritis and Rheumatism 2007;56(3):1021‐8. - PubMed
Sundy 2008
    1. Sundy JS, Becker MA, Baraf HS, Barkhuizen A, Moreland LW, Huang W, et al. Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol‐conjugated uricase) in patients with treatment‐failure gout: Results of a phase II randomized study. Arthritis and Rheumatism 2008;58(9):2882‐91. - PubMed
Terkeltaub 2003
    1. Terkeltaub RA. Clinical practice. Gout. New England Journal of Medicine 2003;349(17):1647‐55. - PubMed
Wallace 1977
    1. Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yu TF. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis and Rheumatism 1977;20(3):895‐900. - PubMed
Yue 2008
    1. Yue CS, Huang W, Alton M, Maroli AN, Waltrip RW, Wright D, et al. Population pharmacokinetic and pharmacodynamic analysis of pegloticase in subjects with hyperuricemia and treatment‐failure gout. Journal of Clinical Pharmacology 2008;48(6):708‐18. - PubMed

Publication types

MeSH terms