Seminars in Arthritis and Rheumatism ] (2015) ]]]–]]]
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Seminars in Arthritis and Rheumatism journal homepage: www.elsevier.com/locate/semarthrit
The economic burden of gout: A systematic review Sharan K. Rai, BSca,b, Lindsay C. Burns, MSca,c, Mary A. De Vera, PhDa,d, Aliya Haji, BSce, Dean Giustini, MLS, MEdf, Hyon K. Choi, MD, DrPHa,f,g,n a
Arthritis Research Canada, Vancouver, British Columbia, Canada Department of Experimental Medicine, University of British Columbia, Vancouver, British Columbia, Canada c Department of Psychology, York University, Toronto, Ontario, Canada d Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada e School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada f Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada g Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA b
a r t i c l e in fo
Keywords: Gout Economics Cost-of-illness Direct cost Indirect cost Health care costs
a b s t r a c t Objective: Gout is a painful and disabling joint disease that constitutes the most common inflammatory arthritis in the US. To clarify the economic impact of gout, we systematically reviewed the literature on the direct and indirect costs associated with this disease. Methods: We conducted a literature search of MEDLINE, EMBASE, International Pharmaceutical Abstracts, NHS Economic Evaluation, and CINAHL databases to identify studies of gout and economics. We systematically reviewed published studies that met our inclusion criteria and extracted and summarized all relevant economic parameters. Reported costs were inflation-adjusted to 2013 US dollars (USD). Results: A total of 15 studies met all eligibility criteria. Three controlled studies reported all-cause total direct costs based on specific populations (i.e., $4733, $16,925, and $18,362 per capita among employed, elderly, and treatment-refractory gout populations, respectively, and $2562, $10,590, and $7188 among corresponding non-gout patients). Two additional studies, although uncontrolled, allowed for estimation of total all-cause direct costs in unselected gout populations ($11,080 and $13,170). Gout-related costs ranged from $172 to $6179, depending on population characteristics. Six studies reported positive associations of direct costs with SUA level, gout attack frequency, or presence of tophi. Four studies reported on indirect costs, which were estimated to be as high as $4341 USD. Conclusion: The available data suggest that gout patients incur substantially greater direct and indirect costs as compared with gout-free individuals among elderly and treatment-refractory gouty patients, whereas the costs are considerably less among younger, employed gouty patients. Further, direct costs increased with worsening disease characteristics. & 2015 Elsevier Inc. All rights reserved.
Introduction Gout is a common and excruciatingly painful inflammatory arthritis associated with hyperuricemia. The prevalence of gout has increased over the past few decades to 3.9% of US adults (8.3 million individuals) [1], which is further complicated by a high level of cardiovascular, metabolic, and renal comorbidities [2]. The pathogenesis of gout is well understood; high levels of circulating
HKC has served on the advisory board for AstraZeneca, and has served as a consultant for AstraZeneca and Takeda Pharmaceuticals. n Corresponding author at: Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. E-mail addresses: [email protected], [email protected] (H.K. Choi). http://dx.doi.org/10.1016/j.semarthrit.2015.02.004 0049-0172/& 2015 Elsevier Inc. All rights reserved.
serum uric acid (SUA) lead to the acute and chronic manifestations of gout via the deposition of monosodium urate crystals in the joints and the soft tissues [3]. Reducing SUA levels effectively “cures” the disease [4], and guidelines including the American College of Rheumatology [5] and the European League Against Rheumatism [6] recommend lowering SUA levels to target levels (o 6 mg/dL or o 5 mg/dL), as well as reducing recurrent attacks, destructive arthropathy, renal disease, and comorbidity. However, gout management remains suboptimal with insufficient SUA lowering [7] and a high rate of recurrent attacks [8,9]. The high prevalence of gout and suboptimal management suggest that its economic impact could potentially be substantial. Indeed, there is a growing body of literature on the costs associated with this disease. A review article estimated the
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economic burden among men to be $27 million (2003 USD) [10]. A more recent review of existing literature reported a revised estimate of the burden of gout to be over $6 billion annually for prevalent cases [11]. To synthesize contemporary evidence on the economic impact of gout, we systematically reviewed the literature on the direct and indirect costs associated with this disease.
Methods Data sources and searches We conducted a literature search of MEDLINE (01 Jan 1946–15 May 2014), EMBASE (01 Jan 1974–15 May 2014), International Pharmaceutical Abstracts (01 Jan 1970–15 May 2014), NHS Economic Evaluation (01 Jan 1995–15 May 2014), and the Cumulative Index to Nursing and Allied Health Literature (01 Jan 1982–15 May 2014) databases. Our search strategies used a combination of controlled terms, subject headings, and keywords to locate studies related to the themes of gout and economics/cost (Supplementary Material). The major search terms and concepts included (but were not limited to) gout, healthcare costs, economics, absenteeism, and productivity loss. We identified additional articles through manual searches of the references in relevant papers. Study selection We reviewed titles and abstracts to identify published studies that met our systematic review inclusion criteria of (1) gout patient population, (2) direct or indirect cost outcome, (3) original research paper, and (4) English language. We excluded nonoriginal literature (e.g., reviews and editorials), economic evaluations (e.g., cost-effectiveness studies), and conference proceedings. Two authors independently reviewed the titles and abstracts of citations identified from the literature search, and discrepancies were resolved by consensus. Abstracts that met our inclusion criteria were forwarded for full-text review. The same two authors independently assessed the selected full-text articles for inclusion on the basis of the eligibility criteria.
Fig. Systematic review study flow.
All reported costs were inflation-adjusted to 2013 US dollars (USD) using the Consumer Price Index unless otherwise specified.
Results Literature search results We identified 1534 articles after the removal of duplicates (Fig.). Following title and abstract review, full-text articles were assessed and excluded for the following reasons: no exposure (i.e., no gout patient population), no outcome (i.e., no direct or indirect cost), incorrect study type (e.g., review article) [10,11], and nonEnglish language. Overall, 15 studies met all eligibility criteria and were included in the systematic review.
Data abstraction and synthesis Study characteristics For each included study, we abstracted the following information: study reference, country, data source, sample size, length of follow-up, costing approach, and direct/indirect costs. With respect to the costing approach, we determined the perspective from which each study was conducted (e.g., societal and payer) [12–14]. Further, we distinguished between studies that referred to a specific country (i.e., nationwide studies) and those that provided information about the mean per patient cost (i.e., per capita studies). Direct costs included those incurred for inpatient stays, outpatient visits (e.g., those to a primary care physician or rheumatologist), emergency department visits, prescription medication, and any additionally reported cost components (e.g., urgent care visits and laboratory and radiology services). Direct costs were further divided into all-cause and gout-related costs, corresponding to those incurred for any reason and those incurred specifically for gout care, respectively. Finally, indirect costs included those incurred for sick days, short-term or long-term disability, and workers' compensation. For studies that reported annual cost estimates stratified by SUA level or gout severity (i.e., gout attack frequency or presence of tophi), we calculated the overall cost of the gout cohort by multiplying the subgroup proportion (N) and its respective cost.
Characteristics for the 15 studies included in the systematic review are shown in Table 1. The majority of studies were conducted in the USA, with one additional study each from Canada [15], Taiwan [16], and Spain [17]. Most studies utilized administrative databases; however, two studies utilized clinic-based samples. Further, 11 studies were conducted from the payer perspective, three from the societal (encompassing both direct and indirect costs) and one from the participant perspective (encompassing lost wages). Finally, 12 studies calculated per capita (i.e., per patient) costs, two studies calculated nationwide costs, and one calculated both costs. Direct costs Overall direct costs of gout patient care We identified 12 studies reporting per capita (i.e., per patient) direct costs; of these, two studies did not report the cost per annum, and instead reported the cost per flare [18,19]. Of the 10 studies reporting annual direct costs, seven were from the US [20–26], and one each from Canada [15], Taiwan [16], and Spain [17]. Six of the US studies reported or allowed for the calculation of total all-cause direct costs [20–25], while one study reported only
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Table 1 Characteristics of studies included in systematic review First author
Year
Country
Data source
Brook et al. [20] Wu et al. [22]
2006 2008
USA USA
Wu et al. [18]
2009
USA
Hanly et al. [15] Halpern et al. [26] Halpern et al. [19] Edwards et al. [29]
2009 2009 2009 2011
Canada USA USA USA
Commercial insurance enrollees Commercial insurance and managed care enrollees Commercial insurance and managed care enrollees Public healthcare plan enrollees Managed care enrollees Managed care enrollees Multicenter rheumatology clinic sample
Chi et al. [16]
2011
Taiwan
Nationwide survey sample
Saseen et al. [24]
2012
USA
Wu et al. [21]
2012
USA
Park et al. [25]
2012
USA
Garg et al. [27] Lynch et al. [23] Sicras-Mainar et al. [17] Li et al. [28]
2013 2013 2013
USA USA Spain
Commercial insurance and Medicare enrollees Commercial insurance and Medicare enrollees Commercial insurance and Medicare enrollees Emergency department database Commercial insurance enrollees Multicenter primary care clinic sample
2013
USA
Ambulatory care databases
a b
Sample size
Follow-up (yr)
Perspective
Cost items
Description of cost
Direct cost
Indirect cost
1171 11,935
1 1
Societal Payer
Yes Yes
Yes No
Per capita Per capita
2237
1
Payer
Yes
No
Per capita
4071 2438 1814 81
5 1 1 1
Yes Yes Yes No
No No No Yes
Per Per Per Per
7691
1
Payer Payer Payer Participant/ family Payer
Yes
No
15,669
1
Payer
Yes
No
Per capita and nationwide Per capita
679
1
Payer
Yes
No
Per capita
352
1
Payer
Yes
No
Per capita
–a 3361 3130
3 1 2
Payer Societal Societal
Yes Yes Yes
No Yes Yes
Nationwide Per capita Per capita
7
Payer
Yes
No
Nationwide
–b
capita capita capita capita
Number of emergency department visits (n ¼ 514,976) reported for which gout was the primary diagnosis over 3 years of follow-up. Number of ambulatory visits (n ¼ 50.1 million) reported related to gout over 7 years of follow-up.
gout-related costs [26] (Table 2). Three of the six studies reported total all-cause direct costs with a gout-free comparison group, one each among employed [20], elderly [22], and treatment-refractory [21] gout populations (i.e., all-cause costs of $4733, $16,925, and $18,362 among gout patients and $2562, $10,590, and $7188 among non-gout patients, respectively) (Table 2(a)). Additionally, one Canadian study reported the cost differential (as opposed to the total cost per group) between gout and gout-free populations to be $134 per month and $8020 (2005/06 CAD) per case over 5 years [15]. Conversely, although a gout-free comparison group was not included, two studies allowed for the calculation of the total all-cause direct cost of an overall unselected gout population (as opposed to stratification by subgroup) [24,25]. Saseen et al. [24] used a US administrative database that included enrollees of commercial insurance as well as Medicare (mean age ¼ 58 years and mean attack frequency ¼ 1.5 attacks per year) and estimated the all-cause annual direct cost of gout patient care to be $11,080 per patient among gout patients across the US (Table 2(b)). Similarly, Park et al. [25] used a Texas claims database (mean age ¼ 61 years and mean SUA level ¼ approx. 8 mg/dL) and
estimated the all-cause annual cost to be $13,170 per patient (Table 2(b)). Among employed populations in the US, the study patients were younger (mean age of 46–50 years) or had less frequent gout attacks per year (weighted mean of 0.4 attacks per year [23]), and the annual direct cost estimates were considerably lower, ranging from $4733 to $9353 per patient (Table 2) [20,23]. In contrast, the all-cause annual direct costs among elderly or treatmentrefractory patient populations were considerably higher. Among elderly gout patients (mean age ¼ 71 years), the annual all-cause cost estimate was $16,925 per patient [22], and among those with treatment-refractory gout, the corresponding cost estimate was $18,362 per patient (Table 2(a)) [21]. These treatment-refractory gout patients experienced a mean of nearly 5 gout attacks per year, and patients were only able to enter the gout cohort if they additionally had a diagnostic code for possible tophi (defined by ICD-9-CM 274.8x). Six studies reported gout-related direct costs. Three of these annual gout-related cost estimates ranged from $433 to $814 per patient in a managed care setting (Table 2(b)) [24–26]. Among an
Table 2 Per Capita studies according to overall gout diagnosis First author
Mean age (yr)
%Male
Population/setting
Total all-cause direct costa Gout patients
Gout-free individuals
Total gout-related direct costa
(a) Studies with a gout comparator group Brook et al. [20] 46 85% Wu et al. [22] 71 74% Wu et al. [21] 50 92%
Employed population Elderly population Treatment-refractory gout
$4733 $16,925 $18,362
$2562 $10,590 $7188
$172 $1006 $6179
(b) Studies without a gout comparator group Lynch et al. [23] 50 83% Saseen et al. [24] 58 77% Park et al. [25] 61 72% Halpern et al. [26] 54 84%
Employed population Commercial insurance and Medicare enrollees Commercial insurance and Medicare enrollees Managed care enrollees
$9353 $11,080 $13,170 –
– – – –
– $433 $444 $814
a
Costs have been inflation-adjusted to 2013 US dollars.
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Table 3 Per capita direct costs according to SUA level or disease severity First author
Cohort
(a) Serum uric acid level Wu et al. [22] o6.0 mg/dL 6–8.99 mg/dL Z9 mg/dL Park et al. [25] o6.0 mg/dL 6–8.99 mg/dL Z9 mg/dL Halpern o6.0 mg/dL et al. [26] 6–8.99 mg/dL Z9 mg/dL
Total all-cause costa
$17,164 $15,666 $21,733 $11,141 $11,930 $17,548 –
Total gout-related costa
$528 $463 $831 $427 $394 $594 $630 $869 $845
(b) Gout attack frequency Wu et al. [21] Z3 attacks Z6 attacks Saseen et al. [24] o3 attacks Z3 attacks Lynch et al. [23] o3 attacks Z3 attacks
$18,362 $26,890 $10,930 $11,379 $9336 $10,102
$6179 $13,164 $199 $902 –
(c) Presence of tophi Wu et al. [22] No tophi Tophi
$16,741 $25,917
–
a
Costs have been inflation-adjusted to 2013 US dollars.
employed (commercially insured) population in the US, the annual gout-related cost estimate was substantially lower, with a weighted annual estimate of $172 (Table 2(a)) [20]. In contrast, the annual gout-related costs among elderly or treatment-refractory patient populations were substantially higher, with estimates of $1006 and $6179, respectively (Table 2(a)) [21,22]. Finally, comorbidity burden was also found to be more prevalent among gout patients with higher SUA levels and more frequent gout attacks; for example, gout patients with SUA Z9 mg/dL or Z3 annual attacks had a higher prevalence of hypertension [21,22,24,25], renal impairment [21,22], chronic kidney disease [24], dyslipidemia [24], and ischemic heart disease [24] than patients with a lower SUA.
Direct costs according to SUA level or gout severity Five studies allowed us to extract the data on the total annual all-cause direct costs associated with SUA level or gout severity (i.e., gout attack frequency and presence of tophi) [21–25]. Patients with worsening disease characteristics incurred more all-cause direct costs as compared with patients with less severe disease (Table 3). For example, Park et al. [25] reported that patients with SUA o 6 mg/dL and Z 9 mg/dL incurred $11,141 and $17,548, respectively, in total all-cause direct costs (Table 3(a)). Another study conducted among an elderly population reported total allcause direct costs of $17,164 and $21,733 among patients with SUA o6 mg/dL and Z9 mg/dL, respectively (Table 3(a)) [22]. Further, total all-cause estimates reached $25,917 and $26,890 among elderly patients with tophi [22] and severe treatment-refractory patients (Z 6 flares per year) [21], respectively (Table 3(b) and (c)). Similar trends were observed for gout-related direct costs, which were reported in five studies (Table 3(a) and (b)) [21,22,24–26]. Three studies evaluated the direct cost incurred during a gout attack [18,19,23]. Two of these studies reported the per attack cost according to stratification by SUA levels [18,19]. Gout patients with higher SUA levels incurred higher costs per attack episode, with gout-related cost estimates reaching $712 per attack for patients with SUA Z9 mg/dL (as compared with up to $303 for those with SUAo 6 mg/dL) [18,19]. Similarly, the third study found that
employed patients with more frequent attacks (i.e., Z3 attacks vs. o3 attacks per year) incurred $833 and $706 during an attack episode, respectively [23]. Nationwide healthcare costs Three studies reported nationwide healthcare costs among gout patients [16,27,28]. Using an emergency department database spanning the US, Garg et al. [27] reported that visits for which gout was the primary indication generated more than $173 million in emergency department charges (median charge $696 per visit) in 2008. Further, using data from two national ambulatory care surveys, Li et al. [28] reported a total of 50.1 million gout-related ambulatory visits in the US from 2002 to 2008 (an average of 7.2 million visits per year), corresponding to a cost of approximately $1 billion annually. Further, 28% of all gout-related visits (approximately 2 million visits per year) were attributable to gout attacks. Lastly, Chi et al. [16] estimated the annual healthcare costs corresponding to inpatient and outpatient care among a representative sample of an elderly Taiwanese gouty population (n ¼ 7691 gout patients Z 65 years of age) to be $14.6 million. Indirect costs We identified four studies that reported costs related to work impairment and productivity loss, three studies from the US [20,23,29], and one from Spain [17]. Of these, only one study reported the annual indirect cost incurred by gout patients alongside a gout-free comparison group, with workers' compensation as the predominant cost driver ($1789 vs. $961 for gout-free individuals) [20]. These gout patients also incurred $868 and $767 for sick leave and short-term disability, respectively, while their gout-free counterparts incurred only $504 and $342 for these cost items [20]. Although a gout-free comparison group was not included, two additional studies reported the indirect costs incurred by a gouty population [23,29]. Lynch et al. [23] reported these costs stratified by attack frequency (i.e., o3 vs. Z 3 annual gout attacks); however, the difference was not significant. Nevertheless, short-term disability was the predominant cost driver among the study's overall gout population. The second study, conducted by Edwards et al. [29], used a clinic-based sample and found that treatment-refractory gout patients incurred $4341 in lost wages. These patients had 8 flares per year, with each flare resulting in approximately 3 days of lost work.
Discussion We aimed to systematically review the literature to date on the costs of gout patient care. Overall, the limited available data suggest that gout patients incurred substantially greater all-cause and gout-specific direct costs and indirect costs as compared with gout-free individuals among elderly and treatment-refractory gouty patients, whereas reported costs were considerably less among employed gouty patients. However, these cost estimates were derived from specific subgroup populations, thus largely precluding comparisons in a general gout population context. Furthermore, both all-cause and gout-related direct costs increased with worsening disease characteristics (i.e., higher SUA levels, greater attack frequency, and tophaceous gout). These data suggest a potential cost benefit to proper disease management and underscore the importance of proper therapeutic approaches to control SUA levels to reduce gout attacks and tophus burden. Of the cost items reported in the included studies, we found that per capita direct costs were the most described, with a large proportion of studies conducted in the US (n ¼ 12 of 15 included studies). Per capita direct costs were reported for a variety of
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specific populations including elderly patients, treatmentrefractory patients, and employed individuals. Although there were several studies of unselected gout populations, their primary aims were to determine correlates of costs (e.g., SUA levels, gout attack frequency, or presence of tophi), and thus they lacked a gout-free comparison group [23–26]. We found that identified studies reported widely varied total cost estimates, likely owing in part to the different populations assessed (e.g., the younger, working population of Brook et al. vs. the elderly population of Wu et al.). Nevertheless, all-cause direct costs were notably substantial, reaching up to $18,362 among treatment-refractory individuals (corresponding to an excess cost of $11,174 as compared with matched gout-free individuals) [21]. Interestingly, gout-specific costs did not account for the entire cost differential, suggesting that the remainder of the excess cost incurred by gout patients may be driven by the care of comorbid conditions, as they were shown to have a higher prevalence of comorbidities as compared with gout-free individuals across included studies [20,22], as well as in other published studies [2,30,31]. Not surprisingly, various studies reported that gout patients incurred greater costs related to these comorbid conditions as compared with gout-free individuals [20,21]. Thus, these data suggest that the care of comorbid conditions may be an important contributor to the overall economic burden of gout. Six studies reported the annual cost of gout care (both all-cause and gout-related) according to either SUA level or disease severity (i.e., gout attack frequency and presence of tophi) in various study populations, including unselected gouty patients. Regardless of the study population assessed, both all-cause and gout-related costs were consistently associated with higher SUA, more gout attacks, and the presence of tophi. While gout-related costs were generally reported to be less than $1000, in the context of severe treatmentrefractory patients, the costs rose to $6179 and $13,164 among patients with Z 3 and Z 6 attacks per year, respectively [21]. These findings are consistent with the general perception that refractory gout care can be quite costly, similar to that of other inflammatory arthropathies [32]. For example, a recent study reported an annual all-cause cost of $7445 (2010 USD) among RA patients [33]. Similar to direct costs, treatment-refractory gout was found to incur a substantial amount of lost wages (i.e., $4341) [29]. Nevertheless, we found data on indirect costs incurred by gout patients to be more scarce, with only four studies identified [17,20,23,29]. Of those, only one study included a gout-free comparison group [20]. Further, these studies utilized employer insurance data and were thus largely unable to account for losses associated with unpaid productivity (e.g., homemaker and volunteer activities), which likely yielded an underestimate of the indirect cost burden associated with gout. Additional research is warranted to further clarify the contribution of lost productivity to the overall economic impact of this disease. The strengths and limitations of our systematic review largely fall into two categories: those attributable to the data available for analysis and those attributable to the techniques generally used to perform the systematic review. Strengths of our study include a systematic approach to synthesizing the available literature on the economic burden of gout through a comprehensive search strategy and updated review [34] of the literature. However, identification and selection of relevant citations may have been limited by publication bias. Further, due to the heterogeneity in cost data across the included studies, a quantitative meta-analysis was not performed. Potential future directions and key gaps in the literature deserve comment. While previous work has described the cost of caring for gout patients largely among specific populations (e.g., elderly patients and treatment-refractory patients), future
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research ought to clarify the costs incurred by gout care in a general population-based setting. In particular, to avoid precluding meaningful comparisons, future studies should include a gout-free comparison group. In addition, to capture potential changes in the costs associated with gout care (i.e., recently diagnosed vs. stable on treatment), analyses conducted over a longer period of followup would also be of value. Further, as the germane economic impact is not adequately reflected in studies limited primarily to medical and pharmacy costs, future work should comprehensively investigate the cost of chronic gout to the employer and to society by estimating the total cost, comprised of both direct and indirect costs. Moreover, future studies ought to estimate the cost associated with the location of care (i.e., primary care physician vs. rheumatology specialty care). As most studies were conducted among US populations, future studies in international settings would also be valuable. Many ongoing studies to determine causality between gout (or hyperuricemia) and the risk of cardiovascular, metabolic, and renal comorbidities should further inform the cost implications of anti-gout measures potentially beyond treating gout. Finally, while the association between the gout severity measures and costs of care are quite suggestive, prospective documentation of cost implications of aggressive antigout measures would be valuable to the field.
Conclusion In conclusion, the available data suggest that gout patients incur substantially greater direct and indirect costs as compared with gout-free individuals, specifically among elderly and treatment-refractory gouty patients, whereas the costs were found to be considerably less among young, employed gouty patients. Furthermore, these direct costs increased with worsening disease characteristics (i.e., higher SUA levels, greater attack frequency, and tophaceous gout). Moreover, the care for comorbid conditions may constitute an important driver for these increased costs. Future research should investigate the economic impact of gout on a population level with an appropriate comparison group, including a comprehensive assessment of indirect costs.
Author contributions SKR and DG developed the search strategies and conducted the literature searches. SKR and LCB screened titles and abstracts for inclusion and extracted the data. SKR, LCB, MDV, and HKC were responsible for data analysis and interpretation. SKR drafted the manuscript. All authors contributed to critical review of the manuscript and have read and approved the final manuscript.
Appendix A. Supporting Information Supplementary material cited in this article is available online at http://dx.doi.org/%2010.1016/j.semarthrit.2015.02.004.
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[20] Brook RA, Kleinman NL, Patel PA, et al. The economic burden of gout on an employed population. Curr Med Res Opin 2006;22:1381–9. [21] Wu EQ, Forsythe A, Guerin A, et al. Comorbidity burden, healthcare resource utilization, and costs in chronic gout patients refractory to conventional uratelowering therapy. Am J Ther 2012;19:e157–66. [22] Wu EQ, Patel PA, Yu AP, et al. Disease-related and all-cause health care costs of elderly patients with gout. J Manag Care Pharm 2008;14:164–75. [23] Lynch W, Chan W, Kleinman N, Andrews LM, Yadao AM. Economic burden of gouty arthritis attacks for employees with frequent and infrequent attacks. Popul Health Manag 2013;16:138–45. [24] Saseen JJ, Agashivala N, Allen RR, et al. 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;51:2004–12. [25] Park H, Rascati KL, Prasla K, McBayne T. Evaluation of health care costs and utilization patterns for patients with gout. Clin Ther 2012;34:640–52. [26] Halpern R, Mody RR, Fuldeore MJ, Patel PA, Mikuls TR. Impact of noncompliance with urate-lowering drug on serum urate and gout-related healthcare costs: administrative claims analysis. Curr Med Res Opin 2009;25:1711–9. [27] Garg R, Sayles HR, Yu F, et al. Gout-related health care utilization in US emergency departments, 2006 through 2008. Arthritis Care Res 2013;65:571–7. [28] Li C, Martin BC, Cummins DF, et al. Ambulatory resource utilization and cost for gout in United States. Am J Pharm Benefits 2013;5:e46–54. [29] Edwards NL, Sundy JS, Forsythe A, Blume S, Pan F, Becker MA. Work productivity loss due to flares in patients with chronic gout refractory to conventional treatment. J Med Econ 2011;14:10–5. [30] Mikuls TR, Farrar JT, Bilker WB, Fernandes S, Schumacher HR Jr, Saag KG. Gout epidemiology: results from the UK General Practice Research Database, 1990– 1999. Ann Rheum Dis 2005;64:267–72. [31] 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;57:109–15. [32] Yelin E, Wanke LA. An assessment of the annual and long-term direct costs of rheumatoid arthritis: the impact of poor function and functional decline. Arthritis Rheum 1999;42:1209–18. [33] Kleinman NL, Cifaldi MA, Smeeding JE, Shaw JW, Brook RA. Annual incremental health benefit costs and absenteeism among employees with and without rheumatoid arthritis. J Occup Environ Med 2013;55:240–4. [34] Trieste L, Palla I, Fusco F, et al. The economic impact of gout: a systematic literature review. Clin Exp Rheumatol 2012;30(Suppl. 73):S145–8.
Contents lists available at ScienceDirect
Seminars in Arthritis and Rheumatism journal homepage: www.elsevier.com/locate/semarthrit
The economic burden of gout: A systematic review Sharan K. Rai, BSca,b, Lindsay C. Burns, MSca,c, Mary A. De Vera, PhDa,d, Aliya Haji, BSce, Dean Giustini, MLS, MEdf, Hyon K. Choi, MD, DrPHa,f,g,n a
Arthritis Research Canada, Vancouver, British Columbia, Canada Department of Experimental Medicine, University of British Columbia, Vancouver, British Columbia, Canada c Department of Psychology, York University, Toronto, Ontario, Canada d Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada e School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada f Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada g Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA b
a r t i c l e in fo
Keywords: Gout Economics Cost-of-illness Direct cost Indirect cost Health care costs
a b s t r a c t Objective: Gout is a painful and disabling joint disease that constitutes the most common inflammatory arthritis in the US. To clarify the economic impact of gout, we systematically reviewed the literature on the direct and indirect costs associated with this disease. Methods: We conducted a literature search of MEDLINE, EMBASE, International Pharmaceutical Abstracts, NHS Economic Evaluation, and CINAHL databases to identify studies of gout and economics. We systematically reviewed published studies that met our inclusion criteria and extracted and summarized all relevant economic parameters. Reported costs were inflation-adjusted to 2013 US dollars (USD). Results: A total of 15 studies met all eligibility criteria. Three controlled studies reported all-cause total direct costs based on specific populations (i.e., $4733, $16,925, and $18,362 per capita among employed, elderly, and treatment-refractory gout populations, respectively, and $2562, $10,590, and $7188 among corresponding non-gout patients). Two additional studies, although uncontrolled, allowed for estimation of total all-cause direct costs in unselected gout populations ($11,080 and $13,170). Gout-related costs ranged from $172 to $6179, depending on population characteristics. Six studies reported positive associations of direct costs with SUA level, gout attack frequency, or presence of tophi. Four studies reported on indirect costs, which were estimated to be as high as $4341 USD. Conclusion: The available data suggest that gout patients incur substantially greater direct and indirect costs as compared with gout-free individuals among elderly and treatment-refractory gouty patients, whereas the costs are considerably less among younger, employed gouty patients. Further, direct costs increased with worsening disease characteristics. & 2015 Elsevier Inc. All rights reserved.
Introduction Gout is a common and excruciatingly painful inflammatory arthritis associated with hyperuricemia. The prevalence of gout has increased over the past few decades to 3.9% of US adults (8.3 million individuals) [1], which is further complicated by a high level of cardiovascular, metabolic, and renal comorbidities [2]. The pathogenesis of gout is well understood; high levels of circulating
HKC has served on the advisory board for AstraZeneca, and has served as a consultant for AstraZeneca and Takeda Pharmaceuticals. n Corresponding author at: Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. E-mail addresses: [email protected], [email protected] (H.K. Choi). http://dx.doi.org/10.1016/j.semarthrit.2015.02.004 0049-0172/& 2015 Elsevier Inc. All rights reserved.
serum uric acid (SUA) lead to the acute and chronic manifestations of gout via the deposition of monosodium urate crystals in the joints and the soft tissues [3]. Reducing SUA levels effectively “cures” the disease [4], and guidelines including the American College of Rheumatology [5] and the European League Against Rheumatism [6] recommend lowering SUA levels to target levels (o 6 mg/dL or o 5 mg/dL), as well as reducing recurrent attacks, destructive arthropathy, renal disease, and comorbidity. However, gout management remains suboptimal with insufficient SUA lowering [7] and a high rate of recurrent attacks [8,9]. The high prevalence of gout and suboptimal management suggest that its economic impact could potentially be substantial. Indeed, there is a growing body of literature on the costs associated with this disease. A review article estimated the
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economic burden among men to be $27 million (2003 USD) [10]. A more recent review of existing literature reported a revised estimate of the burden of gout to be over $6 billion annually for prevalent cases [11]. To synthesize contemporary evidence on the economic impact of gout, we systematically reviewed the literature on the direct and indirect costs associated with this disease.
Methods Data sources and searches We conducted a literature search of MEDLINE (01 Jan 1946–15 May 2014), EMBASE (01 Jan 1974–15 May 2014), International Pharmaceutical Abstracts (01 Jan 1970–15 May 2014), NHS Economic Evaluation (01 Jan 1995–15 May 2014), and the Cumulative Index to Nursing and Allied Health Literature (01 Jan 1982–15 May 2014) databases. Our search strategies used a combination of controlled terms, subject headings, and keywords to locate studies related to the themes of gout and economics/cost (Supplementary Material). The major search terms and concepts included (but were not limited to) gout, healthcare costs, economics, absenteeism, and productivity loss. We identified additional articles through manual searches of the references in relevant papers. Study selection We reviewed titles and abstracts to identify published studies that met our systematic review inclusion criteria of (1) gout patient population, (2) direct or indirect cost outcome, (3) original research paper, and (4) English language. We excluded nonoriginal literature (e.g., reviews and editorials), economic evaluations (e.g., cost-effectiveness studies), and conference proceedings. Two authors independently reviewed the titles and abstracts of citations identified from the literature search, and discrepancies were resolved by consensus. Abstracts that met our inclusion criteria were forwarded for full-text review. The same two authors independently assessed the selected full-text articles for inclusion on the basis of the eligibility criteria.
Fig. Systematic review study flow.
All reported costs were inflation-adjusted to 2013 US dollars (USD) using the Consumer Price Index unless otherwise specified.
Results Literature search results We identified 1534 articles after the removal of duplicates (Fig.). Following title and abstract review, full-text articles were assessed and excluded for the following reasons: no exposure (i.e., no gout patient population), no outcome (i.e., no direct or indirect cost), incorrect study type (e.g., review article) [10,11], and nonEnglish language. Overall, 15 studies met all eligibility criteria and were included in the systematic review.
Data abstraction and synthesis Study characteristics For each included study, we abstracted the following information: study reference, country, data source, sample size, length of follow-up, costing approach, and direct/indirect costs. With respect to the costing approach, we determined the perspective from which each study was conducted (e.g., societal and payer) [12–14]. Further, we distinguished between studies that referred to a specific country (i.e., nationwide studies) and those that provided information about the mean per patient cost (i.e., per capita studies). Direct costs included those incurred for inpatient stays, outpatient visits (e.g., those to a primary care physician or rheumatologist), emergency department visits, prescription medication, and any additionally reported cost components (e.g., urgent care visits and laboratory and radiology services). Direct costs were further divided into all-cause and gout-related costs, corresponding to those incurred for any reason and those incurred specifically for gout care, respectively. Finally, indirect costs included those incurred for sick days, short-term or long-term disability, and workers' compensation. For studies that reported annual cost estimates stratified by SUA level or gout severity (i.e., gout attack frequency or presence of tophi), we calculated the overall cost of the gout cohort by multiplying the subgroup proportion (N) and its respective cost.
Characteristics for the 15 studies included in the systematic review are shown in Table 1. The majority of studies were conducted in the USA, with one additional study each from Canada [15], Taiwan [16], and Spain [17]. Most studies utilized administrative databases; however, two studies utilized clinic-based samples. Further, 11 studies were conducted from the payer perspective, three from the societal (encompassing both direct and indirect costs) and one from the participant perspective (encompassing lost wages). Finally, 12 studies calculated per capita (i.e., per patient) costs, two studies calculated nationwide costs, and one calculated both costs. Direct costs Overall direct costs of gout patient care We identified 12 studies reporting per capita (i.e., per patient) direct costs; of these, two studies did not report the cost per annum, and instead reported the cost per flare [18,19]. Of the 10 studies reporting annual direct costs, seven were from the US [20–26], and one each from Canada [15], Taiwan [16], and Spain [17]. Six of the US studies reported or allowed for the calculation of total all-cause direct costs [20–25], while one study reported only
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Table 1 Characteristics of studies included in systematic review First author
Year
Country
Data source
Brook et al. [20] Wu et al. [22]
2006 2008
USA USA
Wu et al. [18]
2009
USA
Hanly et al. [15] Halpern et al. [26] Halpern et al. [19] Edwards et al. [29]
2009 2009 2009 2011
Canada USA USA USA
Commercial insurance enrollees Commercial insurance and managed care enrollees Commercial insurance and managed care enrollees Public healthcare plan enrollees Managed care enrollees Managed care enrollees Multicenter rheumatology clinic sample
Chi et al. [16]
2011
Taiwan
Nationwide survey sample
Saseen et al. [24]
2012
USA
Wu et al. [21]
2012
USA
Park et al. [25]
2012
USA
Garg et al. [27] Lynch et al. [23] Sicras-Mainar et al. [17] Li et al. [28]
2013 2013 2013
USA USA Spain
Commercial insurance and Medicare enrollees Commercial insurance and Medicare enrollees Commercial insurance and Medicare enrollees Emergency department database Commercial insurance enrollees Multicenter primary care clinic sample
2013
USA
Ambulatory care databases
a b
Sample size
Follow-up (yr)
Perspective
Cost items
Description of cost
Direct cost
Indirect cost
1171 11,935
1 1
Societal Payer
Yes Yes
Yes No
Per capita Per capita
2237
1
Payer
Yes
No
Per capita
4071 2438 1814 81
5 1 1 1
Yes Yes Yes No
No No No Yes
Per Per Per Per
7691
1
Payer Payer Payer Participant/ family Payer
Yes
No
15,669
1
Payer
Yes
No
Per capita and nationwide Per capita
679
1
Payer
Yes
No
Per capita
352
1
Payer
Yes
No
Per capita
–a 3361 3130
3 1 2
Payer Societal Societal
Yes Yes Yes
No Yes Yes
Nationwide Per capita Per capita
7
Payer
Yes
No
Nationwide
–b
capita capita capita capita
Number of emergency department visits (n ¼ 514,976) reported for which gout was the primary diagnosis over 3 years of follow-up. Number of ambulatory visits (n ¼ 50.1 million) reported related to gout over 7 years of follow-up.
gout-related costs [26] (Table 2). Three of the six studies reported total all-cause direct costs with a gout-free comparison group, one each among employed [20], elderly [22], and treatment-refractory [21] gout populations (i.e., all-cause costs of $4733, $16,925, and $18,362 among gout patients and $2562, $10,590, and $7188 among non-gout patients, respectively) (Table 2(a)). Additionally, one Canadian study reported the cost differential (as opposed to the total cost per group) between gout and gout-free populations to be $134 per month and $8020 (2005/06 CAD) per case over 5 years [15]. Conversely, although a gout-free comparison group was not included, two studies allowed for the calculation of the total all-cause direct cost of an overall unselected gout population (as opposed to stratification by subgroup) [24,25]. Saseen et al. [24] used a US administrative database that included enrollees of commercial insurance as well as Medicare (mean age ¼ 58 years and mean attack frequency ¼ 1.5 attacks per year) and estimated the all-cause annual direct cost of gout patient care to be $11,080 per patient among gout patients across the US (Table 2(b)). Similarly, Park et al. [25] used a Texas claims database (mean age ¼ 61 years and mean SUA level ¼ approx. 8 mg/dL) and
estimated the all-cause annual cost to be $13,170 per patient (Table 2(b)). Among employed populations in the US, the study patients were younger (mean age of 46–50 years) or had less frequent gout attacks per year (weighted mean of 0.4 attacks per year [23]), and the annual direct cost estimates were considerably lower, ranging from $4733 to $9353 per patient (Table 2) [20,23]. In contrast, the all-cause annual direct costs among elderly or treatmentrefractory patient populations were considerably higher. Among elderly gout patients (mean age ¼ 71 years), the annual all-cause cost estimate was $16,925 per patient [22], and among those with treatment-refractory gout, the corresponding cost estimate was $18,362 per patient (Table 2(a)) [21]. These treatment-refractory gout patients experienced a mean of nearly 5 gout attacks per year, and patients were only able to enter the gout cohort if they additionally had a diagnostic code for possible tophi (defined by ICD-9-CM 274.8x). Six studies reported gout-related direct costs. Three of these annual gout-related cost estimates ranged from $433 to $814 per patient in a managed care setting (Table 2(b)) [24–26]. Among an
Table 2 Per Capita studies according to overall gout diagnosis First author
Mean age (yr)
%Male
Population/setting
Total all-cause direct costa Gout patients
Gout-free individuals
Total gout-related direct costa
(a) Studies with a gout comparator group Brook et al. [20] 46 85% Wu et al. [22] 71 74% Wu et al. [21] 50 92%
Employed population Elderly population Treatment-refractory gout
$4733 $16,925 $18,362
$2562 $10,590 $7188
$172 $1006 $6179
(b) Studies without a gout comparator group Lynch et al. [23] 50 83% Saseen et al. [24] 58 77% Park et al. [25] 61 72% Halpern et al. [26] 54 84%
Employed population Commercial insurance and Medicare enrollees Commercial insurance and Medicare enrollees Managed care enrollees
$9353 $11,080 $13,170 –
– – – –
– $433 $444 $814
a
Costs have been inflation-adjusted to 2013 US dollars.
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Table 3 Per capita direct costs according to SUA level or disease severity First author
Cohort
(a) Serum uric acid level Wu et al. [22] o6.0 mg/dL 6–8.99 mg/dL Z9 mg/dL Park et al. [25] o6.0 mg/dL 6–8.99 mg/dL Z9 mg/dL Halpern o6.0 mg/dL et al. [26] 6–8.99 mg/dL Z9 mg/dL
Total all-cause costa
$17,164 $15,666 $21,733 $11,141 $11,930 $17,548 –
Total gout-related costa
$528 $463 $831 $427 $394 $594 $630 $869 $845
(b) Gout attack frequency Wu et al. [21] Z3 attacks Z6 attacks Saseen et al. [24] o3 attacks Z3 attacks Lynch et al. [23] o3 attacks Z3 attacks
$18,362 $26,890 $10,930 $11,379 $9336 $10,102
$6179 $13,164 $199 $902 –
(c) Presence of tophi Wu et al. [22] No tophi Tophi
$16,741 $25,917
–
a
Costs have been inflation-adjusted to 2013 US dollars.
employed (commercially insured) population in the US, the annual gout-related cost estimate was substantially lower, with a weighted annual estimate of $172 (Table 2(a)) [20]. In contrast, the annual gout-related costs among elderly or treatment-refractory patient populations were substantially higher, with estimates of $1006 and $6179, respectively (Table 2(a)) [21,22]. Finally, comorbidity burden was also found to be more prevalent among gout patients with higher SUA levels and more frequent gout attacks; for example, gout patients with SUA Z9 mg/dL or Z3 annual attacks had a higher prevalence of hypertension [21,22,24,25], renal impairment [21,22], chronic kidney disease [24], dyslipidemia [24], and ischemic heart disease [24] than patients with a lower SUA.
Direct costs according to SUA level or gout severity Five studies allowed us to extract the data on the total annual all-cause direct costs associated with SUA level or gout severity (i.e., gout attack frequency and presence of tophi) [21–25]. Patients with worsening disease characteristics incurred more all-cause direct costs as compared with patients with less severe disease (Table 3). For example, Park et al. [25] reported that patients with SUA o 6 mg/dL and Z 9 mg/dL incurred $11,141 and $17,548, respectively, in total all-cause direct costs (Table 3(a)). Another study conducted among an elderly population reported total allcause direct costs of $17,164 and $21,733 among patients with SUA o6 mg/dL and Z9 mg/dL, respectively (Table 3(a)) [22]. Further, total all-cause estimates reached $25,917 and $26,890 among elderly patients with tophi [22] and severe treatment-refractory patients (Z 6 flares per year) [21], respectively (Table 3(b) and (c)). Similar trends were observed for gout-related direct costs, which were reported in five studies (Table 3(a) and (b)) [21,22,24–26]. Three studies evaluated the direct cost incurred during a gout attack [18,19,23]. Two of these studies reported the per attack cost according to stratification by SUA levels [18,19]. Gout patients with higher SUA levels incurred higher costs per attack episode, with gout-related cost estimates reaching $712 per attack for patients with SUA Z9 mg/dL (as compared with up to $303 for those with SUAo 6 mg/dL) [18,19]. Similarly, the third study found that
employed patients with more frequent attacks (i.e., Z3 attacks vs. o3 attacks per year) incurred $833 and $706 during an attack episode, respectively [23]. Nationwide healthcare costs Three studies reported nationwide healthcare costs among gout patients [16,27,28]. Using an emergency department database spanning the US, Garg et al. [27] reported that visits for which gout was the primary indication generated more than $173 million in emergency department charges (median charge $696 per visit) in 2008. Further, using data from two national ambulatory care surveys, Li et al. [28] reported a total of 50.1 million gout-related ambulatory visits in the US from 2002 to 2008 (an average of 7.2 million visits per year), corresponding to a cost of approximately $1 billion annually. Further, 28% of all gout-related visits (approximately 2 million visits per year) were attributable to gout attacks. Lastly, Chi et al. [16] estimated the annual healthcare costs corresponding to inpatient and outpatient care among a representative sample of an elderly Taiwanese gouty population (n ¼ 7691 gout patients Z 65 years of age) to be $14.6 million. Indirect costs We identified four studies that reported costs related to work impairment and productivity loss, three studies from the US [20,23,29], and one from Spain [17]. Of these, only one study reported the annual indirect cost incurred by gout patients alongside a gout-free comparison group, with workers' compensation as the predominant cost driver ($1789 vs. $961 for gout-free individuals) [20]. These gout patients also incurred $868 and $767 for sick leave and short-term disability, respectively, while their gout-free counterparts incurred only $504 and $342 for these cost items [20]. Although a gout-free comparison group was not included, two additional studies reported the indirect costs incurred by a gouty population [23,29]. Lynch et al. [23] reported these costs stratified by attack frequency (i.e., o3 vs. Z 3 annual gout attacks); however, the difference was not significant. Nevertheless, short-term disability was the predominant cost driver among the study's overall gout population. The second study, conducted by Edwards et al. [29], used a clinic-based sample and found that treatment-refractory gout patients incurred $4341 in lost wages. These patients had 8 flares per year, with each flare resulting in approximately 3 days of lost work.
Discussion We aimed to systematically review the literature to date on the costs of gout patient care. Overall, the limited available data suggest that gout patients incurred substantially greater all-cause and gout-specific direct costs and indirect costs as compared with gout-free individuals among elderly and treatment-refractory gouty patients, whereas reported costs were considerably less among employed gouty patients. However, these cost estimates were derived from specific subgroup populations, thus largely precluding comparisons in a general gout population context. Furthermore, both all-cause and gout-related direct costs increased with worsening disease characteristics (i.e., higher SUA levels, greater attack frequency, and tophaceous gout). These data suggest a potential cost benefit to proper disease management and underscore the importance of proper therapeutic approaches to control SUA levels to reduce gout attacks and tophus burden. Of the cost items reported in the included studies, we found that per capita direct costs were the most described, with a large proportion of studies conducted in the US (n ¼ 12 of 15 included studies). Per capita direct costs were reported for a variety of
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specific populations including elderly patients, treatmentrefractory patients, and employed individuals. Although there were several studies of unselected gout populations, their primary aims were to determine correlates of costs (e.g., SUA levels, gout attack frequency, or presence of tophi), and thus they lacked a gout-free comparison group [23–26]. We found that identified studies reported widely varied total cost estimates, likely owing in part to the different populations assessed (e.g., the younger, working population of Brook et al. vs. the elderly population of Wu et al.). Nevertheless, all-cause direct costs were notably substantial, reaching up to $18,362 among treatment-refractory individuals (corresponding to an excess cost of $11,174 as compared with matched gout-free individuals) [21]. Interestingly, gout-specific costs did not account for the entire cost differential, suggesting that the remainder of the excess cost incurred by gout patients may be driven by the care of comorbid conditions, as they were shown to have a higher prevalence of comorbidities as compared with gout-free individuals across included studies [20,22], as well as in other published studies [2,30,31]. Not surprisingly, various studies reported that gout patients incurred greater costs related to these comorbid conditions as compared with gout-free individuals [20,21]. Thus, these data suggest that the care of comorbid conditions may be an important contributor to the overall economic burden of gout. Six studies reported the annual cost of gout care (both all-cause and gout-related) according to either SUA level or disease severity (i.e., gout attack frequency and presence of tophi) in various study populations, including unselected gouty patients. Regardless of the study population assessed, both all-cause and gout-related costs were consistently associated with higher SUA, more gout attacks, and the presence of tophi. While gout-related costs were generally reported to be less than $1000, in the context of severe treatmentrefractory patients, the costs rose to $6179 and $13,164 among patients with Z 3 and Z 6 attacks per year, respectively [21]. These findings are consistent with the general perception that refractory gout care can be quite costly, similar to that of other inflammatory arthropathies [32]. For example, a recent study reported an annual all-cause cost of $7445 (2010 USD) among RA patients [33]. Similar to direct costs, treatment-refractory gout was found to incur a substantial amount of lost wages (i.e., $4341) [29]. Nevertheless, we found data on indirect costs incurred by gout patients to be more scarce, with only four studies identified [17,20,23,29]. Of those, only one study included a gout-free comparison group [20]. Further, these studies utilized employer insurance data and were thus largely unable to account for losses associated with unpaid productivity (e.g., homemaker and volunteer activities), which likely yielded an underestimate of the indirect cost burden associated with gout. Additional research is warranted to further clarify the contribution of lost productivity to the overall economic impact of this disease. The strengths and limitations of our systematic review largely fall into two categories: those attributable to the data available for analysis and those attributable to the techniques generally used to perform the systematic review. Strengths of our study include a systematic approach to synthesizing the available literature on the economic burden of gout through a comprehensive search strategy and updated review [34] of the literature. However, identification and selection of relevant citations may have been limited by publication bias. Further, due to the heterogeneity in cost data across the included studies, a quantitative meta-analysis was not performed. Potential future directions and key gaps in the literature deserve comment. While previous work has described the cost of caring for gout patients largely among specific populations (e.g., elderly patients and treatment-refractory patients), future
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research ought to clarify the costs incurred by gout care in a general population-based setting. In particular, to avoid precluding meaningful comparisons, future studies should include a gout-free comparison group. In addition, to capture potential changes in the costs associated with gout care (i.e., recently diagnosed vs. stable on treatment), analyses conducted over a longer period of followup would also be of value. Further, as the germane economic impact is not adequately reflected in studies limited primarily to medical and pharmacy costs, future work should comprehensively investigate the cost of chronic gout to the employer and to society by estimating the total cost, comprised of both direct and indirect costs. Moreover, future studies ought to estimate the cost associated with the location of care (i.e., primary care physician vs. rheumatology specialty care). As most studies were conducted among US populations, future studies in international settings would also be valuable. Many ongoing studies to determine causality between gout (or hyperuricemia) and the risk of cardiovascular, metabolic, and renal comorbidities should further inform the cost implications of anti-gout measures potentially beyond treating gout. Finally, while the association between the gout severity measures and costs of care are quite suggestive, prospective documentation of cost implications of aggressive antigout measures would be valuable to the field.
Conclusion In conclusion, the available data suggest that gout patients incur substantially greater direct and indirect costs as compared with gout-free individuals, specifically among elderly and treatment-refractory gouty patients, whereas the costs were found to be considerably less among young, employed gouty patients. Furthermore, these direct costs increased with worsening disease characteristics (i.e., higher SUA levels, greater attack frequency, and tophaceous gout). Moreover, the care for comorbid conditions may constitute an important driver for these increased costs. Future research should investigate the economic impact of gout on a population level with an appropriate comparison group, including a comprehensive assessment of indirect costs.
Author contributions SKR and DG developed the search strategies and conducted the literature searches. SKR and LCB screened titles and abstracts for inclusion and extracted the data. SKR, LCB, MDV, and HKC were responsible for data analysis and interpretation. SKR drafted the manuscript. All authors contributed to critical review of the manuscript and have read and approved the final manuscript.
Appendix A. Supporting Information Supplementary material cited in this article is available online at http://dx.doi.org/%2010.1016/j.semarthrit.2015.02.004.
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