Anna Forsythe

Tophi and frequent gout flares are associated with impairments to quality of life, productivity, and increased healthcare resource use: Results from a cross-sectional survey

BackgroundThe prevalence of gout is increasing, and most research on the associated burden has focused on serum urate (sUA) levels. The present study quantifies the impact of the presence of tophi and frequency of acute gout attacks on health-related quality of life (HRQOL), productivity, and healthcare resource utilization.MethodsPatients with self-reported gout (n = 620; 338 in US and 282 across France, Germany, and UK) were contacted based on inclusion in the 2010 US and EU National Health and Wellness Surveys (Kantar Health) and the Lightspeed Research ailment panel. Respondents were categorized into mutually-exclusive groups based on number of gout flares experienced in the past 12 months (0/don’t recall, 1–2, 3, 4–5, 6+), current presence of tophi (none, 1+, or not sure), and sUA level awareness (yes, no). HRQOL (SF-12v2), healthcare provider visits in the last 6 months, and work productivity and activity impairment (WPAI) were compared across groups.ResultsMost patients were males, mean age of 61 years, who reported experiencing at least one acute gout flare in the past 12 months, and 12.3% (n = 76) reported presence of tophi. Among the 27.7% (n = 172) of patients who were aware of their sUA levels, higher sUA was associated with more flares and tophi. Decreased HRQOL was associated with more frequent flares and presence of tophi. In multivariable models predicting outcomes based on presence of tophi and number of flares, both flares (≥4) and tophi (≥1) were associated with HRQOL decrements on physical and mental component summary scores and health utilities (all p < 0.05), after adjustment for age, gender, and time since diagnosis. Flares were also associated with greater activity impairment.ConclusionsImpairments associated with gout flares and presence of tophi, across patients in the US and EU, underscore the importance of effective management of this potentially curable condition.

Chronic gout: epidemiology, disease progression, treatment and disease burden

Abstract Background: Gout is a painful and disabling inflammatory arthritis of increasing prevalence associated with hyperuricemia and the deposition of monosodium urate crystals in soft tissues and joints. Diagnosed gout cases have been estimated at 2.13% of the 2009 US population. The highest incidence occurs in the 65+ year age group, with males more than twice as likely to be afflicted as females. Objective: To present the epidemiology of chronic gout and to discuss its disease burden. Methods: This commentary is based on expert opinion and supplemented with published/presented information identified through PubMed and rheumatology associations. Results: The steady rise of diagnosed gout cases can generally be linked to an aging population with multiple comorbidities, the use of certain prescription medications, and changes in diet and lifestyle. Progression to chronic gout has numerous causes such as poor compliance with, ineffectiveness of, or inability to tolerate prescribed regimens. Despite the availability of urate-lowering therapies (ULT), patients may either have contraindications to them or may not adequately respond. Patients with high flare frequency, tophi, and the inability to maintain serum urate levels below 6 mg/dL with ULT can be categorized as having chronic gout that is refractory, with a substantial disease burden. Based on lack of therapeutic options for urate-lowering for patients with chronic gout refractory to conventional therapy, the economic burden of this small but substantial population contributes disproportionately to the overall economic burden of chronic gout. Recent availability of gout-specific ICD-9-CM codes capturing the cost intense and impactful aspects of the disease – flares and tophi – is likely contribute to understanding the full health economic burden in gout. Conclusion: The impact of chronic gout, especially if refractory to treatment, on functionality, productivity, quality of life and health care costs can be substantial and is deserving of future research.

Improved Health-related Quality of Life and Physical Function in Patients with Refractory Chronic Gout Following Treatment with Pegloticase: Evidence from Phase III Randomized Controlled Trials

Objective. To assess the efficacy of pegloticase on pain, physical function, and health-related quality of life (HRQOL) in patients with refractory chronic gout. Methods. Subjects in 2 replicate, 6-month, randomized controlled phase III trials received intravenous infusions of pegloticase 8 mg twice monthly (biweekly group), pegloticase alternating with placebo (8-mg monthly group), or placebo. Medical Outcomes Study Short Form-36 (SF-36), Health Assessment Questionnaire-Disability Index (HAQ-DI), patient global assessment of disease activity (PtGA), and pain by visual analog scale were completed at weeks 1 (baseline), 13, 19, and 25. Prespecified pooled analyses of patient-reported outcomes were performed by combining values for each treatment group (biweekly treatment, monthly treatment, and placebo) at Week 25. Results. Of 212 patients enrolled, 157 (74.1%) completed treatment. At entry, mean age was 55.4 years (range 23–89 yrs) and mean plasma uric acid was 9.7 mg/dl; most were male (81.6%) and white (67.5%). Subjects reported an average of 9.8 flares in the previous 18 months. Baseline SF-36 physical component summary (PCS) scores were > 1.5 SD below US normative values. At Week 25, mean changes from baseline in PtGA, pain, HAQ-DI, and PCS scores were statistically significant and exceeded minimum clinically important differences (MCID) in the biweekly treatment group, compared with little to no improvement in placebo group. Statistically significant improvements greater than or equal to MCID were reported in 6 of 8 SF-36 domains. Monthly pegloticase resulted in significantly improved PtGA, HAQ-DI, PCS, and 3 SF-36 domains. Conclusion. Pegloticase therapy resulted in statistically significant and clinically meaningful improvements in PtGA, pain, physical function, and HRQOL.

Validation of pain and patient global scales in chronic gout: data from two randomised controlled trials

Objective To assess validity of pain and patient global scales in gout. Methods The authors used data from pegloticase clinical trials in chronic refractory gout to examine the validity of visual analogue scale (VAS) pain, Short-Form 36 (SF-36) bodily pain subscale and VAS patient global assessment (all scales 0–100). Convergent/divergent validity with clinical characteristics was tested by using Spearmans correlation coefficient. For discriminant ability, the authors compared the change at 6 months between placebo and pegloticase arms and calculated effect size (ES) and standardised response mean (SRM). Results 212 patients (mean age, 55.4 years, 82% men; 73% with tophaceous gout) provided data. VAS pain was statistically significantly correlated with tender joints (r=0.42), swollen joints (r=0.30), SF-36 physical (r=−0.56) and Mental Component Summary (r=−0.36) and Health Assessment Questionnaire scores (r=0.54; all p-values <0.0001), but not disease duration (r=−0.01; p=0.84), gout flares (r=0.12; p=0.08), comorbidities (r=0.05; p=0.47) or plasma urate (r=0.01; p=0.89). Similar and significant correlation coefficients with tender and swollen joints were noted for VAS patient global assessment (r=0.35 and 0.23; p<0.0012 for both) and SF-36 pain subscale (r=−0.27 and −0.19; p<0.006 for both). Pegloticase group had significantly more improvement than placebo at 6 months, mean (SD): VAS pain, −9.2 (29.3) versus 1.9 (26.4), p=0.0002; SF-36 pain, 14.6 (25.6) versus −0.04 (21.1), p<0.0001; and patient global, −9.3 (26.5) versus 3.4 (22.8), p<0.0001. ES and SRMs in pegloticase group were as follows: VAS pain, 0.34 and 0.30; SF-36 pain, 0.69 and 0.57; patient global, 0.49 and 0.44. Conclusion VAS pain, SF-36 pain and patient global VAS are valid outcome measures in patients with chronic gout.

FRI0387 Pain, health-related quality of life and health status in GOUT in europe

Background Gout is an increasingly prevalent rheumatic disease (with acute and chronic components) which is associated with significant reduction in Health-Related Quality of Life (HRQoL)1,2. Although much of this impairment results from associated comorbidities1,2 recent expert consensus has emphasised the importance of measuring pain as a key patient reported outcome (PRO) in chronic gout3. Thus there remains a need to assess the independent impact of pain in gout populations. Objectives To measure quantitatively the impact of pain, with particular reference to severe daily pain and chronic gout, on HRQoL in Western Europe using data from the National Health and Wellness Survey (NHWS). Methods NHWS is a syndicated, annual and biannual, nationally representative, cross-sectional, internet-based study of the healthcare attitudes, behaviors, and characteristics of adults. Data from over 57,000 respondents in the UK, France, Spain, Germany, and Italy, collected in 2010 was utilized. Respondents reporting physician-diagnosed gout in the prior 12 months were identified (n=756). Details of pain severity and frequency in the previous 30 days were recorded along with demographic and socio-economic characteristics and comorbidities. HRQoL was assessed using the SF-12 instrument (version 2, with a focus on the physical and mental component summary scores; PCS and MCS). Health state utilities were captured with the SF-6D scoring algorithm and self-reported health status (first item of SF-12 questionnaire). Multivariate regression analysis was performed to assess the contribution of severe daily gout pain vs other (non-gout) pain using a reference a group of patients diagnosed with gout who were pain-free. Results The overall annual prevalence of gout in adults for the 5 countries was 1.28%. Among those diagnosed with gout, 34.89% reported experiencing pain in the last 30 days (vs. 19.95% of controls in the NHWS cohort who did not report gout; p<0.05); 25.08% (vs. 16.74% of controls; p<0.05) of patients with pain reported severe pain (equivalent to approximately 8% of the gout population), and 22.93% (vs. 13.47% of controls; p<0.05) reported severe daily pain. Compared with the reference group of persons with gout not reporting pain, the effect of severe daily pain on PCS (-15.29; 95% CI -17.6, -13.0) and MCS (-5.35; 95% CI -8.1, -2.6) was significant. It was substantially greater than other pain (severe non-daily pain, moderate pain, mild pain) which were collapsed into a single variable (PCS: -6.0; 95% CI -7.5, -4.5). The impact of other pain experience on MCS was not significant. The influence of pain on SF-6D utilities was also striking; for daily severe pain the deficit was -0.17 (95% CI -0.20, -0.14) while other pain generated a deficit of -0.05 (95% CI -0.07, -0.03). Conclusions A survey of patient-reported pain in patients diagnosed with gout in Western Europe has demonstrated that daily pain is a characteristic of chronic gout, and is associated with substantial deficits in HRQoL and self-reported health status. The estimate that 1 in 5 gout patients experience moderate or severe daily pain, presents an important challenge for physicians. References Roddy E et al. Rheumatol 2007; 46:1441-6. Singh JA et al. Ann Rheum Dis 2008; 67(9):1310-6. Singh JA et al. J Rheumatol 2011; 38:1452-7. Disclosure of Interest P. Langley Consultant for: Novartis, Pfizer, Kantar Health, Grunenthal, Johnson and Johnson, Shire, Bayer, Savient, G. Nuki Consultant for: Ardea, Menarini, Novartis, Savient, Paid Instructor for: Ipsen, Menarini, A. Forsythe Shareholder of: Savient, Novartis, Employee of: Novartis

Mapping AcroQoL scores to EQ-5D to obtain utility values for patients with acromegaly

Abstract Aims: To estimate a preference-based single index for the disease-specific instrument (AcroQoL) by mapping it onto the EQ-5D to assist in future economic evaluations. Materials and methods: A sample of 245 acromegaly patients with AcroQoL and EQ-5D scores was obtained from three previously published European studies. The sample was split into two: one sub-sample to construct the model (algorithm construction sample, n = 184), and the other one to confirm it (validation sample, n = 61). Various multiple regression models including two-part model, tobit model, and generalized additive models were tested and/or evaluated for predictive ability, consistency of estimated coefficients, normality of prediction errors, and simplicity. Results: Across these studies, mean age was 50–60 years and the proportion of males was 36–59%. At overall level the percentage of patients with controlled disease was 37.4%. Mean (SD) scores for AcroQoL Global Score and EQ-5D utility were 62.3 (18.5) and 0.71 (0.28), respectively. The best model for predicting EQ-5D was a generalized regression model that included the Physical Dimension summary score and categories from questions 9 and 14 as independent variables (Adj. R2 = 0.56, with mean absolute error of 0.0128 in the confirmatory sample). Observed and predicted utilities were strongly correlated (Spearman r = 0.73, p < .001) and paired t-Student test revealed non-significant differences between means (p > .05). Estimated utility scores showed a minimum error of ≤10% in 45% of patients; however, error increased in patients with an observed utility score under 0.2. The model’s predictive ability was confirmed in the validation cohort. Limitations and conclusions: A mapping algorithm was developed for mapping of AcroQoL to EQ-5D, using patient level data from three previously published studies, and including validation in the confirmatory sub-sample. Mean (SD) utilities index in this study population was estimated as 0.71 (0.28). Additional research may be needed to test this mapping algorithm in other acromegaly populations.