Comorbidity Burden in Trial-Aligned Patients with Established Gout in Germany, UK, US, and France: a Retrospective Analysis

Fredrik Nyberg, Laura Horne, Robert Morlock, Javier Nuevo, Chris Storgard, Lalitha Aiyer, Dionne M Hines, Xavier Ansolabehere, Pierre Chevalier, Fredrik Nyberg, Laura Horne, Robert Morlock, Javier Nuevo, Chris Storgard, Lalitha Aiyer, Dionne M Hines, Xavier Ansolabehere, Pierre Chevalier

Abstract

Introduction: Patients with gout have numerous comorbidities. We aimed to estimate the prevalence and incidence rates of renal and cardiovascular morbidities in trial-aligned patients with established gout in Germany (DE), the United Kingdom (UK), the United States (US), and France (FR).

Methods: This longitudinal cohort study used retrospective data from IMS Disease Analyzer™ (DE, FR), Clinical Practice Research Datalink-Hospital Episode Statistics (UK), and IMS' PharMetrics Plus database linked with outpatient laboratory results (US). Included patients were ≥18 years at index date (January 1, 2010; all dates +1 year for FR), with continuous enrollment during the pre-index year, had "prevalent established gout" determined by data in the pre-index year, and ≥1 documented visit after index date; additional inclusion/exclusion criteria were aligned with recent gout clinical trials. Look-back for comorbidity prevalence extended to January 1, 2003 (US: January 1, 2009). Follow-up for incidence extended from index date to at most March 26, 2013 (FR: May 31, 2014). Events of interest were identified by diagnostic codes and/or laboratory data.

Results: The trial-aligned cohorts included 35,118 (DE), 24,607 (UK), 121,591 (US), and 17,338 (FR) patients. Among renal conditions, baseline diagnosis of chronic kidney disease/renal failure was most prevalent in the UK followed by DE; abnormal serum creatinine was most prevalent in the UK. Hypertension was the most prevalent cardiovascular diagnosis in all countries, followed by ischemic heart disease (IHD) and myocardial infarction. Incidence rates (per 100 patient-years) for new/worsening renal impairment ranged from 1.67 (DE) to 4.34 (US) and for nephrolithiasis diagnosis from 0.31 (FR) to 3.79 (US). The incidence rates for hypertension diagnosis were highest among cardiovascular-related events, ranging from 3.23 (UK) to 20.27 (US), followed by IHD.

Conclusions: Patients with established gout such as those included in gout trials have a high burden of established morbidity and new diagnoses of morbid events. Consideration of comorbidities, which greatly exacerbate disease burden, is important in gout management.

Funding: AstraZeneca.

Keywords: Cardiovascular; Comorbidities; European Union; Gout; Incidence; Prevalence; Renal; Serum uric acid; United States.

Figures

Fig. 1
Fig. 1
Longitudinal cohort study design. DE Germany, UK United Kingdom, US United States, FR France
Fig. 2
Fig. 2
Patient attrition. aAssessed in the 1-year pre-index period. DE Germany, UK United Kingdom, US United States, FR France

References

    1. Cea Soriano L, Rothenbacher D, Choi HK, Garcia Rodriguez LA. Contemporary epidemiology of gout in the UK general population. Arthritis Res Ther. 2011;13(2):R39. doi: 10.1186/ar3272.
    1. Richette P, Bardin T. Gout. Lancet. 2010;375(9711):318–328. doi: 10.1016/S0140-6736(09)60883-7.
    1. Wertheimer A, Morlock R, Becker MA. A revised estimate of the burden of illness of gout. Curr Ther Res Clin Exp. 2013;75:1–4. doi: 10.1016/j.curtheres.2013.04.003.
    1. Zhang W, Doherty M, Bardin T, et al. 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):1312–1324. doi: 10.1136/ard.2006.055269.
    1. Gustafsson D, Unwin R. The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. BMC Nephrol. 2013;14:164. doi: 10.1186/1471-2369-14-164.
    1. Martillo MA, Nazzal L, Crittenden DB. The crystallization of monosodium urate. Curr Rheumatol Rep. 2014;16(2):400. doi: 10.1007/s11926-013-0400-9.
    1. Perez-Ruiz F, Dalbeth N, Bardin T. A review of uric acid, crystal deposition disease, and gout. Adv Ther. 2015;32(1):31–41. doi: 10.1007/s12325-014-0175-z.
    1. Boss GR, Seegmiller JE. Hyperuricemia and gout. Classification, complications and management. N Engl J Med. 1979;300(26):1459–1468. doi: 10.1056/NEJM197906283002604.
    1. Kannangara DR, Ramasamy SN, Indraratna PL, et al. Fractional clearance of urate: validation of measurement in spot-urine samples in healthy subjects and gouty patients. Arthritis Res Ther. 2012;14(4):R189. doi: 10.1186/ar4020.
    1. Jordan KM, Cameron JS, Snaith M, et al. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of gout. Rheumatology (Oxford) 2007;46(8):1372–1374. doi: 10.1093/rheumatology/kem056a.
    1. Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431–1446. doi: 10.1002/acr.21772.
    1. Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken). 2012;64(10):1447–1461. doi: 10.1002/acr.21773.
    1. European Medicines Agency. European public assessment report (EPAR) for Zurampic. EMA Web site. Available from: . Last accessed May 5, 2016.
    1. Shen Z, Rowlings C, Kerr B, et al. Pharmacokinetics, pharmacodynamics, and safety of lesinurad, a selective uric acid reabsorption inhibitor, in healthy adult males. Drug Des Devel Ther. 2015;9:3423–3434. doi: 10.2147/DDDT.S85193.
    1. US Food and Drug Administration. FDA approves Zurampic to treat high blood uric acid levels associated with gout. U S FDA Web site. Available from: . Last accessed May 5, 2016.
    1. Choi HK, Ford ES, Li C, Curhan G. Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 2007;57(1):109–115. doi: 10.1002/art.22466.
    1. Choi HK, Ford ES. Prevalence of the metabolic syndrome in individuals with hyperuricemia. Am J Med. 2007;120(5):442–447. doi: 10.1016/j.amjmed.2006.06.040.
    1. Clarson LE, Hider SL, Belcher J, Heneghan C, Roddy E, Mallen CD. Increased risk of vascular disease associated with gout: a retrospective, matched cohort study in the UK Clinical Practice Research Datalink. Ann Rheum Dis. 2015;74(4):642–647. doi: 10.1136/annrheumdis-2014-205252.
    1. Jing J, Kielstein JT, Schultheiss UT, et al. Prevalence and correlates of gout in a large cohort of patients with chronic kidney disease: the German Chronic Kidney Disease (GCKD) study. Nephrol Dial Transplant. 2014;30(4):613–621. doi: 10.1093/ndt/gfu352.
    1. Juraschek SP, Kovell LC, Miller ER, III, Gelber AC. Association of kidney disease with prevalent gout in the United States in 1988–1994 and 2007–2010. Semin Arthritis Rheum. 2013;42(6):551–561. doi: 10.1016/j.semarthrit.2012.09.009.
    1. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Ann Rheum Dis. 2015;74(4):661–667. doi: 10.1136/annrheumdis-2013-204463.
    1. Lopez-Suarez A, Elvira-Gonzalez J, Bascunana-Quirell A, et al. Serum urate levels and urinary uric acid excretion in subjects with metabolic syndrome. Med Clin (Barc). 2006;126(9):321–324. doi: 10.1157/13085753.
    1. Nakagawa T, Hu H, Zharikov S, et al. A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol. 2006;290(3):F625–F631. doi: 10.1152/ajprenal.00140.2005.
    1. Puig JG, Martinez MA. Hyperuricemia, gout and the metabolic syndrome. Curr Opin Rheumatol. 2008;20(2):187–191. doi: 10.1097/BOR.0b013e3282f4b1ed.
    1. Saseen JJ, Agashivala N, Allen RR, Ghushchyan V, Yadao AM, Nair KV. Comparison of patient characteristics and gout-related health-care resource utilization and costs in patients with frequent versus infrequent gouty arthritis attacks. Rheumatology (Oxford) 2012;51(11):2004–2012. doi: 10.1093/rheumatology/kes183.
    1. Primatesta P, Plana E, Rothenbacher D. Gout treatment and comorbidities: a retrospective cohort study in a large US managed care population. BMC Musculoskelet Disord. 2011;12:103. doi: 10.1186/1471-2474-12-103.
    1. Knake C, Stamp L, Bahn A. Molecular mechanism of an adverse drug-drug interaction of allopurinol and furosemide in gout treatment. Biochem Biophys Res Commun. 2014;452(1):157–162. doi: 10.1016/j.bbrc.2014.08.068.
    1. Richette P, Frazier A, Bardin T. Pharmacokinetics considerations for gout treatments. Expert Opin Drug Metab Toxicol. 2014;10(7):949–957. doi: 10.1517/17425255.2014.915027.
    1. Ryu HJ, Song R, Kim HW, et al. Clinical risk factors for adverse events in allopurinol users. J Clin Pharmacol. 2013;53(2):211–216. doi: 10.1177/0091270012439715.
    1. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Comorbidities in patients with gout prior to and following diagnosis: case–control study. Ann Rheum Dis. 2014;75(1):210–217. doi: 10.1136/annrheumdis-2014-206410.
    1. Bardin T, Keenan R, Khanna P, et al. Lesinurad, a selective uric acid reabsorption inhibitor, in combination with allopurinol: results from a phase III study in gout patients having an inadequate response to standard of care (CLEAR 2) Ann Rheum Dis. 2015;74(Suppl 2):545. doi: 10.1136/annrheumdis-2015-eular.1238.
    1. Saag K, Fitz-Patrick D, Kopicko J, et al. Lesinurad, a selective uric acid reabsorption inhibitor, in combination with allopurinol: results from a phase III study in gout patients having an inadequate response to standard of care (CLEAR 1) Ann Rheum Dis. 2015;74(Suppl 2):540.
    1. Kostev K, Dippel FW, Bierwirth R. Resource consumption and costs of treatment in patients with type 1 diabetes under intensified conventional therapy under German real-life conditions. J Diabetes Sci Technol. 2013;7(3):736–742. doi: 10.1177/193229681300700319.
    1. Rathmann W, Kostev K, Gruenberger JB, Dworak M, Bader G, Giani G. Treatment persistence, hypoglycaemia and clinical outcomes in type 2 diabetes patients with dipeptidyl peptidase-4 inhibitors and sulphonylureas: a primary care database analysis. Diabetes Obes Metab. 2013;15(1):55–61. doi: 10.1111/j.1463-1326.2012.01674.x.
    1. Gallagher AM, van Staa TP, Murray-Thomas T, et al. Population-based cohort study of warfarin-treated patients with atrial fibrillation: incidence of cardiovascular and bleeding outcomes. BMJ Open. 2014;4(1):e003839. doi: 10.1136/bmjopen-2013-003839.
    1. Bergvall N, Petrilla AA, Karkare SU, et al. Persistence with and adherence to fingolimod compared with other disease-modifying therapies for the treatment of multiple sclerosis: a retrospective US claims database analysis. J Med Econ. 2014;17(10):696–707. doi: 10.3111/13696998.2014.940422.
    1. Bergvall N, Lahoz R, Reynolds T, Korn JR. Healthcare resource use and relapses with fingolimod versus natalizumab for treating multiple sclerosis: a retrospective US claims database analysis. Curr Med Res Opin. 2014;30(8):1461–1471. doi: 10.1185/03007995.2014.915802.
    1. Curtis JR, Schabert VF, Yeaw J, et al. Use of a validated algorithm to estimate the annual cost of effective biologic treatment for rheumatoid arthritis. J Med Econ. 2014;17(8):555–566. doi: 10.3111/13696998.2014.914031.
    1. Grandfils N, Detournay B, Attali C, et al. Glucose lowering therapeutic strategies for type 2 diabetic patients with chronic kidney disease in primary care setting in france: a cross-sectional study. Int J Endocrinol. 2013;2013:640632. doi: 10.1155/2013/640632.
    1. Misery L, Ansolabehere X, Grandfils N, Georgescu V, Taieb C. Nine-year follow-up of children with atopic dermatitis by general practitioners. Dermatology. 2014;228(4):344–349. doi: 10.1159/000358296.
    1. Daskalopoulou SS, Tzovaras V, Mikhailidis DP, Elisaf M. Effect on serum uric acid levels of drugs prescribed for indications other than treating hyperuricaemia. Curr Pharm Des. 2005;11(32):4161–4175. doi: 10.2174/138161205774913309.
    1. Kim SC, Schmidt BM, Franklin JM, Liu J, Solomon DH, Schneeweiss S. Clinical and health care use characteristics of patients newly starting allopurinol, febuxostat, and colchicine for the treatment of gout. Arthritis Care Res (Hoboken). 2013;65(12):2008–2014. doi: 10.1002/acr.22067.
    1. Karis E, Crittenden DB, Pillinger MH. Hyperuricemia, gout, and related comorbidities: cause and effect on a two-way street. South Med J. 2014;107(4):235–241. doi: 10.1097/SMJ.0000000000000082.
    1. Riedel AA, Nelson M, Wallace K, Joseph-Ridge N, Cleary M, Fam AG. Prevalence of comorbid conditions and prescription medication use among patients with gout and hyperuricemia in a managed care setting. J Clin Rheumatol. 2004;10(6):308–314. doi: 10.1097/01.rhu.0000147049.12220.32.
    1. Perez-Ruiz F, Martinez-Indart L, Carmona L, Herrero-Beites AM, Pijoan JI, Krishnan E. Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout. Ann Rheum Dis. 2014;73(1):177–182. doi: 10.1136/annrheumdis-2012-202421.
    1. Rathmann W, Funkhouser E, Dyer AR, Roseman JM. Relations of hyperuricemia with the various components of the insulin resistance syndrome in young black and white adults: the CARDIA study. Coronary Artery Risk Development in Young Adults. Ann Epidemiol. 1998;8(4):250–261. doi: 10.1016/S1047-2797(97)00204-4.
    1. Vuorinen-Markkola H, Yki-Jarvinen H. Hyperuricemia and insulin resistance. J Clin Endocrinol Metab. 1994;78(1):25–29.
    1. Abbott RD, Brand FN, Kannel WB, Castelli WP. Gout and coronary heart disease: the Framingham Study. J Clin Epidemiol. 1988;41(3):237–242. doi: 10.1016/0895-4356(88)90127-8.
    1. Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation. 2007;116(8):894–900. doi: 10.1161/CIRCULATIONAHA.107.703389.
    1. Krishnan E, Baker JF, Furst DE, Schumacher HR. Gout and the risk of acute myocardial infarction. Arthritis Rheum. 2006;54(8):2688–2696. doi: 10.1002/art.22014.
    1. Kuo CF, Yu KH, See LC, et al. Risk of myocardial infarction among patients with gout: a nationwide population-based study. Rheumatology (Oxford) 2013;52(1):111–117. doi: 10.1093/rheumatology/kes169.
    1. Clarson L, Chandratre P, Hider S, et al. Increased cardiovascular mortality associated with gout: a systematic review and meta-analysis. Eur J Prev Cardiol. 2015;22(3):335–343. doi: 10.1177/2047487313514895.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi