Uricases: Reversing Evolution to Treat Gout
The instructive BMJ review on the management of gout overlooks the use of exogenous uricases in the treatment of the crystal arthropathy(1).
Exogenous uricases mimic physiological uricases found in most other species but lost by humans during evolution(2). The enzymes metabolise uric acid to allantoin which is much more soluble than the former and is excreted in the urine(2). There is thus no accumulation of uric acid. Uricases include pegloticase and rasburicase; the former used in the treatment of gout and the latter used principally to prevent the sequelae of hyperuricaemia in tumour lysis syndrome(2). Pegloticase is produced from genetically modified E coli(2,3). It is administered twice-weekly by intravenous injection in a healthcare setting(3).
The European League against Rheumatism, in its most recent guidance on gout issued in 2016, advocates the use of pegloticase for refractory gout (3). The uricase has a similar indication in the USA and is approved by the USA Food and Drug Administration for this purpose(4). Similarly the American College of Rheumatology medication guideline offers it as an option in those who fail to respond to xanthine oxidase inhibitors, allopurinol and febuxostat(5). An International Consensus statement from the global rheumatology community came to a similar conclusion in 2014(6). In the same year a Cochrane review identified pegloticase as beneficial in the management of tophi in gout(7).
The main risks of use identified, are allergy following the formation of antibodies against the enzyme and also transient exacerbation of gout symptoms. It is contraindicated in those with glucose-6-phosphate dehydrogenase deficiency. In this context it may trigger severe haemolysis and methaemoglobinaemia(2,3). Those at high risk of this metabolic disorder, such as patients of African and Mediterranean ancestry require screening prior to initiation of this medication. The drug manufacturer relinquished its marketing authorisation in the EU in 2016 following initial authorisation by the European Medicines Agency in 2013(8). However, globally pegloticase remains potentially an important tool in the therapeutic repertoire for intransigent gout.
(1) Drug and Therapeutics Bulletin. Latest guidance on the management of gout. BMJ. 2018 Jul 18;362:k2893.
(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; 8:379-388
(3) Richette P, Doherty M, Pascual E, Barskova V, Becce F, Castañeda-Sanabria J, Coyfish M, Guillo S, Jansen TL, Janssens H, Lioté F, Mallen C, Nuki G, Perez-Ruiz F, Pimentao J, Punzi L, Pywell T, So A, Tausche AK, Uhlig T, Zavada J, Zhang W, Tubach F, Bardin T. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017 Jan;76(1):29-42. doi: 10.1136/annrheumdis-2016-209707
(6) Multinational evidence-based recommendations for the diagnosis and management of gout: integrating systematic literature review and expert opinion of a broad panel of rheumatologists in the 3e initiative. Sivera F, Andrés M, Carmona L, Kydd AS, Moi J, Seth R, Sriranganathan M, van Durme C, van Echteld I, Vinik O, Wechalekar MD, Aletaha D, Bombardier C, Buchbinder R, Edwards CJ, Landewé RB, Bijlsma JW, Branco JC, Burgos-Vargas R, Catrina AI, Elewaut D, Ferrari AJ, Kiely P, Leeb BF, Montecucco C, Müller-Ladner U, Ostergaard M, Zochling J, Falzon L, van der Heijde DM. Ann Rheum Dis. 2014 Feb;73(2):328-35.
(7) Sriranganathan MK, Vinik O, Bombardier C, Edwards CJ. Interventions for tophi in gout. Cochrane Database Syst Rev. 2014 Oct 20;(10):CD010069.
Competing interests: No competing interests