Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial.

BACKGROUND: In the UK, gout management is suboptimum, with only 40% of patients receiving urate-lowering therapy, usually without titration to achieve a target serum urate concentration. Nurses successfully manage many diseases in primary care. We compared nurse-led gout care to usual care led by general practitioners (GPs) for people in the community. METHODS: Research nurses were trained in best practice management of gout, including providing individualised information and engaging patients in shared decision making. Adults who had experienced a gout flare in the previous 12 months were randomly assigned 1:1 to receive nurse-led care or continue with GP-led usual care. We assessed patients at baseline and after 1 and 2 years. The primary outcome was the percentage of participants who achieved serum urate concentrations less than 360 µmol/L (6 mg/dL) at 2 years. Secondary outcomes were flare frequency in year 2, presence of tophi, quality of life, and cost per quality-adjusted life-year (QALY) gained. Risk ratios (RRs) and 95% CIs were calculated based on intention to treat with multiple imputation. This study is registered with www.ClinicalTrials.gov, number NCT01477346. FINDINGS: 517 patients were enrolled, of whom 255 were assigned nurse-led care and 262 usual care. Nurse-led care was associated with high uptake of and adherence to urate-lowering therapy. More patients receiving nurse-led care had serum urate concentrations less than 360 µmol/L at 2 years than those receiving usual care (95% vs 30%, RR 3·18, 95% CI 2·42-4·18, p<0·0001). At 2 years all secondary outcomes favoured the nurse-led group. The cost per QALY gained for the nurse-led intervention was £5066 at 2 years. INTERPRETATION: Nurse-led gout care is efficacious and cost-effective compared with usual care. Our findings illustrate the benefits of educating and engaging patients in gout management and reaffirm the importance of a treat-to-target urate-lowering treatment strategy to improve patient-centred outcomes. FUNDING: Arthritis Research UK.

Economic Impact of Adherence to Pain Treatment Guidelines in Chronic Pain Patients.

OBJECTIVES: This research compared health care resource use (HCRU) and costs for pharmacotherapy prescribing that was adherent vs nonadherent to published pain management guidelines. Conditions included osteoarthritis (OA) and gout (GT) for nociceptive/inflammatory pain, painful diabetic peripheral neuropathy (pDPN) and post-herpetic neuralgia (PHN) for neuropathic pain, and fibromyalgia (FM) for sensory hypersensitivity pain. METHODS: This retrospective cohort study used claims from MarketScan Commercial and Medicare Databases identifying adults newly diagnosed with OA, GT, pDPN, PHN, or FM during July 1, 2006, to June 30, 2013, with 12-month continuous coverage before and after initial (index) diagnosis. Patients were grouped according to their pharmacotherapy pattern as adherent, nonadherent, or "unsure" according to published pain management guidelines using a claims-based algorithm. Adherent and nonadherent populations were compared descriptively and using multivariate statistical analyses for controlling bias. RESULTS: Final cohort sizes were 441,465 OA, 76,361 GT, 10,645 pDPN, 4,010 PHN, and 150,321 FM, with adherence to guidelines found in 51.1% of OA, 25% of GT, 59.5% of pDPN, 54.9% of PHN, and 33.5% of FM. Adherent cohorts had significantly (P < 0.05) fewer emergency department (ED) visits and lower proportions with hospitalizations or ED visits. Mean health care costs increased following diagnosis across all conditions; however, adherent cohorts had significantly lower increases in adjusted costs pre-index to postindex (OA $5,286 vs $9,532; GT $3,631 vs $7,873; pDPN $9,578 vs $16,337; PHN $2,975 vs $5,146; FM $2,911 vs $3,708; all P < 0.001; adherent vs nonadherent, respectively). CONCLUSIONS: Adherence to pain management guidelines was associated with significantly lower HCRU and costs compared with nonadherence to guidelines.

Work disability in gout: a population-based case-control study.

OBJECTIVES: To examine the extent and cost of work disability among patients with gout compared with matched population controls and to analyse predictors of work disability. METHODS: A regional cohort study using data from Swedish national and regional registries from January 2000 through December 2012, including 4571 patients with gout of working age, with a first recorded diagnosis of gout in the years 2003-2009 and 22 482 population controls, matched by age, sex and place of residence. Differences in baseline characteristics (educational level, income, previous employment and comorbidities) and the number of work-loss days (absenteeism) due to sick leave and disability pension for 3 years after identification were calculated. Predictors for new-onset work absenteeism (>90 days/year) in a subset were determined by conditional logistic regression. RESULTS: Patients with gout (median age 53 years) had significantly more comorbidities, lower income and lower level of education than matched controls. The average work absentee rate during the 3-year follow-up period was higher among patients with gout than controls, 22% and 14%, respectively (P<0.0001). New-onset absenteeism was in multivariate analyses significantly predicted by gout (OR 1.47; 95% CI 1.23 to 1.75). Other variables independently related to new-onset absenteeism were education ≤12 years, previous unemployment and history of sick leave, in addition to several comorbidities (renal disease, cardiovascular disease, alcohol abuse and obesity). CONCLUSIONS: Gout is associated with substantially higher work absenteeism and costs for society due to productivity loss, after adjusting for associated comorbidities and socioeconomic differences. Whether more intensive treatment of gout is cost-effective needs to be addressed in future studies.

Impact of Non-Adherence and Flare Resolution on the Cost-Effectiveness of Treatments for Gout: Application of a Linked Pharmacometric/Pharmacoeconomic Model.

BACKGROUND: Dual urate-lowering therapy (ULT) with lesinurad in combination with either allopurinol or febuxostat is an option for patients with gout unsuccessfully treated on either monotherapy. Treatment failure is often a result of poor medication adherence. Imperfect adherence in clinical trials may lead to biased estimates of treatment effect and confound the results of cost-effectiveness analyses. OBJECTIVES: To estimate the impact of varying medication adherence on the cost effectiveness of lesinurad dual therapy and estimate the value-based price of lesinurad at which the incremental cost-effectiveness ratio is equal to £20,000 per quality-adjusted life-year (QALY). METHODS: Treatment effect was simulated using published pharmacokinetic-pharmacodynamic models and scenarios representing adherence in clinical trials, routine practice, and perfect use. The subsequent cost and health impacts, over the lifetime of a patient cohort, were estimated using a bespoke pharmacoeconomic model. RESULTS: The base-case incremental cost-effectiveness ratios comparing lesinurad dual ULT with monotherapy ranged from £39,184 to £78,350/QALY gained using allopurinol and £31,901 to £124,212/QALY gained using febuxostat, depending on the assumed medication adherence. Results assuming perfect medication adherence imply a per-quarter value-based price of lesinurad of £45.14 when used in dual ULT compared with allopurinol alone and £57.75 compared with febuxostat alone, falling to £25.41 and £3.49, respectively, in simulations of worsening medication adherence. CONCLUSIONS: The estimated value-based prices of lesinurad only exceeded that which has been proposed in the United Kingdom when assuming both perfect drug adherence and the eradication of gout flares in sustained treatment responders.

The Duality of Economic Issues With Medication Non-adherence in Patients With Inflammatory Arthritis.

PURPOSE OF REVIEW: In this review, we synthesize current data on non-adherence across inflammatory arthritides and explore (1) the effects of economic factors on non-adherence and (2) the impacts of non-adherence on economic outcomes. RECENT FINDINGS: Recent evidence demonstrates medication non-adherence rates as high as 74% in ankylosing spondylitis (AS), 90% in gout, 50% in psoriatic arthritis (PsA), 75% in systemic lupus erythematosus (SLE), and 82% in rheumatoid arthritis (RA). The effects of socioeconomic factors have been studied most in RA and SLE but with inconsistent findings. Nonetheless, the evidence points to having prescription coverage and costs of treatment as important factors in RA and education as an important factor in SLE. Limited data in AS and gout, and no studies of the effects of socioeconomic factors in PsA, show knowledge gaps for future research. Finally, there is a dearth of data with respect to the impacts of non-adherence on economic outcomes.

Reductions in Use of Colchicine after FDA Enforcement of Market Exclusivity in a Commercially Insured Population.

BACKGROUND: A brand-name version of colchicine (Colcrys) was introduced after its manufacturer conducted a clinical trial in acute gout patients, leading to higher prices for this drug. OBJECTIVE: We analyzed the impact of the new single-source colchicine product on prescribing and patient health spending as well as incidence rates of potentially dangerous concomitant use of clarithromycin and cyclosporine after formal FDA approval. DESIGN/PARTICIPANTS: We conducted a retrospective cohort study of UnitedHealth-affiliated enrollees newly diagnosed with gout or FMF. MAIN MEASURES: Among gout and FMF patients separately, we assessed linear trends in colchicine prescriptions, prescription drug costs, and total health care costs from 2009 to September 2010 (market exclusivity announced) compared to January 2011 (market exclusivity enforced) through 2012. Next, we estimated trends in co-prescription within 15 days of clarithromycin, azithromycin (indicated on the Colcrys label for use in place of clarithromycin), and cyclosporine. KEY RESULTS: Among gout patients, before Colcrys' market exclusivity, the odds of receiving colchicine within 30 days of gout diagnosis increased 1.4 %/month (OR: 1.014, 95 % CI: 1.011-1.018). Following FDA action, the odds decreased by 0.5 %/month (OR: 0.995, 95 % CI: 0.992-0.999) (p < 0.001). Similarly, among FMF patients, odds of initiating colchicine changed from an increase of 2.8 %/month to a decrease by 7.6 %/month (p = 0.01). Patients receiving colchicine experienced increases in average monthly prescription drug costs ($418 vs. $651, p < 0.001) and health care costs ($3,406 vs. $3,534, p < 0.001). Incidence rates of colchicine/clarithromycin co-prescription before and after FDA action did not change, while co-prescription of colchicine/cyclosporine increased after introduction of Colcrys [-0.75 monthly change in patients (95 % CI: -1.07, -0.43) vs. 0.13 (95 % CI: -0.16, 0.42), p < 0.001]. CONCLUSIONS: The FDA's actions were associated with a reduction in colchicine initiation and an increase in patient spending. By contrast, we did not observe any association with improvements in avoidance of potentially dangerous co-prescriptions.

Cost-effectiveness of allopurinol and febuxostat for the management of gout.

BACKGROUND: Gout is the most common inflammatory arthritis in the United States. OBJECTIVE: To evaluate the cost-effectiveness of urate-lowering treatment strategies for the management of gout. DESIGN: Markov model. DATA SOURCES: Published literature and expert opinion. TARGET POPULATION: Patients for whom allopurinol or febuxostat is a suitable initial urate-lowering treatment. TIME HORIZON: Lifetime. PERSPECTIVE: Health care payer. INTERVENTION: 5 urate-lowering treatment strategies were evaluated: no treatment; allopurinol- or febuxostat-only therapy; allopurinol-febuxostat sequential therapy; and febuxostat-allopurinol sequential therapy. Two dosing scenarios were investigated: fixed dose (80 mg of febuxostat daily, 0.80 success rate; 300 mg of allopurinol daily, 0.39 success rate) and dose escalation (≤120 mg of febuxostat daily, 0.82 success rate; ≤800 mg of allopurinol daily, 0.78 success rate). OUTCOME MEASURES: Discounted costs, discounted quality-adjusted life-years, and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: In both dosing scenarios, allopurinol-only therapy was cost-saving. Dose-escalation allopurinol-febuxostat sequential therapy was more costly but more effective than dose-escalation allopurinol therapy, with an incremental cost-effectiveness ratio of $39 400 per quality-adjusted life-year. RESULTS OF SENSITIVITY ANALYSIS: The relative rankings of treatments did not change. Our results were relatively sensitive to several potential variations of model assumptions; however, the cost-effectiveness ratios of dose escalation with allopurinol-febuxostat sequential therapy remained lower than the willingness-to-pay threshold of $109 000 per quality-adjusted life-year. LIMITATION: Long-term outcome data for patients with gout, including medication adherence, are limited. CONCLUSION: Allopurinol single therapy is cost-saving compared with no treatment. Dose-escalation allopurinol-febuxostat sequential therapy is cost-effective compared with accepted willingness-to-pay thresholds. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

The economic impact of gout: a systematic literature review.

This article performs a systematic literature review of the last decade studies assessing the economic impact of gout. The literature review confirms the fact that gout reduces productivity and increases annual total healthcare costs, since care of gout absorbs relevant amounts of healthcare resources. One important aspect to be considered is represented by prevention and monitoring of the disease after the diagnosis, as gout is sometimes underestimated by patients and this leads to a reduced adherence to follow up and to treatment with consequences on the disease course and outcome. In fact, the lack of prevention and the scarce adherence to monitoring increase the number and costs of hospitalisation. Prevention, monitoring the level of sUA and using a urate-lowering therapy appear to have a central role for controlling gout and reducing hospitalisation, with positive advantages in terms of healthcare costs and healthcare utilisation. One limitation on the analysis of gout related costs, however, resides in the fact that the majority of the retrieved studies are retrospective and the definition of the economic impact of the disease is made difficult by differences in inclusion criteria, costs assessment, use of gout-related healthcare resources.

Comorbidity burden, healthcare resource utilization, and costs in chronic gout patients refractory to conventional urate-lowering therapy.

Patients with chronic gout refractory to conventional urate-lowering therapy have high rates of flares and incidence of tophi, which impose a significant disease and potentially economic burden. This study examined healthcare resource use and costs stratified by disease burden. Adult patients diagnosed with gout (ICD-9-CM:274.xx) and having had ≥3 flares defined by clinical surrogates within a 12-month period were selected for the case cohort from the Thomson MarketScan databases (2003/Q3-2008/Q3). Only patients who had received allopurinol treatment and a diagnosis of tophi (ICD-9-CM:274.8x) at any time before the first flare (index date) or within 12 months postindex were included and were matched in a 1:1 ratio with control gout-free subjects. The comorbidity burden, healthcare resource use, and annual healthcare costs (2008 US$) in the 12-month postindex period were compared between both cohorts using regression models adjusted for demographic characteristic and stratified for patients with ≥6 flares. A total of 679 gout patients met the inclusion criteria for the study and had a higher prevalence of comorbidities than their matched controls. Gout cohort had a significantly higher incidence of emergency room, hospitalizations, outpatient visits, and other medical services than did their matched controls (all comparisons, uncorrected P < 0.01). After adjusting for baseline characteristics, the refractory gout cohort incurred an incremental total annual healthcare cost of $10,222 where 40% of the annual medical cost was for gout-related care compared with control cohort (P < 0.01). Patients with refractory gout have a significant economic burden compared with a gout-free population.

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.

BACKGROUND: The 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. METHODS: Patients 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. RESULTS: Most 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. CONCLUSIONS: Impairments 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.

Healthcare burden of in-hospital gout.

The disease burden of inpatient gout has not been reported. Using a discharge diagnosis database and individual case record review, 77 patients who developed acute gout complicating a hospital admission for another reason were identified between January 2001 and April 2010 at The Townsville Hospital. A control group of 28 301 cases with identical principal diagnoses were similarly ascertained, along with a subgroup of 231 cases matched for age, gender and ethnicity. Patients with an admission complicated by acute gout stayed 6 days longer in hospital than matched control patients (9 days vs 3 days, P = 0.0005) with the same principal diagnoses and demographics. Patients with an attack of gout were more likely to be older, male or indigenous. Early diagnosis and appropriate treatment may help to reduce the healthcare costs of this overlooked disease.

Payer decision-making with limited comparative and cost effectiveness data: the case of new pharmacological treatments for gout.

CONTEXT: The need for comparative effectiveness (CE) data continues to grow, fuelled by market demand as well as health reform. There may be an assumption that new drugs result in improved efficacy compared with the standard of care, therefore warranting premium prices. Gout treatment has recently become controversial, as expensive new drugs enter the market with limited CE data. METHODS: The authors reviewed published clinical trials and conducted a cost effectiveness analysis on a new drug (febuxostat) versus the standard (allopurinol) to illustrate the limitations in using these data to inform evidence-based decision-making. FINDINGS: Although febuxostat trials included allopurinol as a comparator, methodological limitations make comparative effectiveness evaluations difficult. However, when available trial data were input to a decision analytic model, the authors found that a significant reduction in febuxostat cost would be required in order for it to dominate allopurinol in cost effectiveness analysis. This case exemplifies the challenges of using clinical trial data in comparative and cost effectiveness analyses.

Model-based cost-effectiveness analyses comparing combinations of urate lowering therapy and anti-inflammatory treatment in gout patients.

OBJECTIVES: To assess the cost-effectiveness of various combinations of urate lowering therapy (ULT) and anti-inflammatory treatment in the management of newly diagnosed gout patients, from the Dutch societal perspective. METHODS: A probabilistic patient-level simulation estimating costs and quality-adjusted life years (QALYs) comparing gout and hyperuricemia treatment strategies was performed. ULT options febuxostat, allopurinol and no ULT were considered. Flare treatments naproxen, colchicine, prednisone, and anakinra were considered. A Markov Model was constructed to simulate gout disease. Health states were no flare, and severe pain, mild pain, moderate pain, or no pain in the presence of a flare. Model input was derived from patient level clinical trial data, meta-analyses or from previously published health-economic evaluations. The results of probabilistic sensitivity analyses were presented using incremental cost-effectiveness ratios (ICERs), and summarized using cost-effectiveness acceptability curves (CEACs). Scenario analyses were performed. RESULTS: The ICER for allopurinol versus no ULT was €1,381, when combined with naproxen. Febuxostat yielded the highest utility, but also the highest costs (€4,385 vs. €4,063 for allopurinol), resulting in an ICER of €25,173 when compared to allopurinol. No ULT was not cost-effective, yielding the lowest utility. For the gout flare medications, comparable effects on utility were achieved. Combined with febuxostat, naproxen was the cheapest option (€4,404), and anakinra the most expensive (€4,651). The ICER of anakinra compared to naproxen was €818,504. Colchicine and prednisone were dominated by naproxen. CONCLUSION: Allopurinol and febuxostat were both cost-effective compared to No ULT. Febuxostat was cost-effective in comparison with allopurinol at higher willingness-to-pay thresholds. For treating gout flares, colchicine, naproxen and prednisone offered comparable health economic implications, although naproxen was the favoured option.

Healthcare-related impact of gout in hospitalized patients in Spain.

To analyze the epidemiology, clinical features and costs of hospitalized patients with gout during the last decade in Spain. Retrospective observational study based on data from the Minimum Basic Data Set (MBDS) from the Spanish National Health Service database. Patients ≥ 18 years with any gout diagnosis at discharge who had been admitted to public or private hospitals between 2005 and 2015 were included. Patients were divided in two periods: p1 (2005-2010) and p2 (2011-2015) to compare the number of hospitalizations, mean costs and mortality rates. Data from 192,037 patients with gout was analyzed. There was an increase in the number of hospitalized patients with gout (p < 0.001). The more frequent comorbidities were diabetes (27.6% of patients), kidney disease (26.6%) and heart failure (19.3%). Liver disease (OR 2.61), dementia (OR 2.13), cerebrovascular diseases (OR 1.57), heart failure (OR 1.41), and kidney disease (OR 1.34) were associated with a higher mortality risk. Women had a lower risk of mortality than men (OR 0.85). General mortality rates in these hospitalized patients progressively increased over the years (p < 0.001). In addition, costs gradually rose, presenting a significant increase in p2 even after adjusting for inflation (p = 0.001). A progressive increase in hospitalizations, mortality rates and cost in hospitalized patients with gout was observed. This harmful trend in a preventable illness highlights the need for change and the search for new healthcare strategies.

Serious Infections in Patients With Gout in the US: A National Study of Incidence, Time Trends, and Outcomes.

OBJECTIVE: To study the epidemiology of serious infections in patients hospitalized with gout. METHODS: We identified patients with gout hospitalized with a primary diagnosis of pneumonia, sepsis/bacteremia, urinary tract infection (UTI), skin and soft tissue infections (SSTIs), or opportunistic infections (OIs) in a US National Inpatient Sample from 1998 to 2016 and examined factors associated with utilization and mortality. RESULTS: We noted 1,140,085 hospitalizations of patients with serious infections and gout (11% of all hospitalizations of patients with gout; 1998-2000 [8.9%], 2015-2016 [14.5%]). Compared to patients without gout, patients with gout hospitalized with serious infections were older (median age 65 versus 74 years), more of them had a Charlson-Deyo comorbidity index score ≥2 (42% versus 65%), and fewer were female (53% versus 35%) or non-White (40% versus 35%), respectively. The most common infection was pneumonia (52%) in 1998-2000 and sepsis (52%) in 2015-2016. Median hospital charges and hospital stays were higher for patients with sepsis and OIs in 2015-2016 ($41,000-$42,000; 5.1-5.5 days) versus those with UTI, pneumonia, or SSTIs ($15,000-$17,000; 3.0-3.9 days). Compared to patients with sepsis, the multivariable-adjusted odds of health care utilization and in-hospital mortality were significantly lower for patients with UTI, SSTIs, and pneumonia, and non-home discharge or in-hospital mortality were lower in patients with OIs. Among patients hospitalized with infections, older age, Medicaid coverage, a higher Charlson-Deyo comorbidity index score, Black race, and Northeast and nonrural hospital location were associated with significantly higher health care utilization and mortality, while female sex, Medicare insurance, and lower income were associated with higher utilization. CONCLUSION: Given an increasing rate of serious infections, especially sepsis and pneumonia, in individuals with gout, development of effective interventions targeting factors associated with health care utilization and mortality will improve outcomes and reduce burden.

Cost-Effectiveness of Colchicine Prophylaxis for Gout Flares When Commencing Allopurinol.

OBJECTIVE: Colchicine prophylaxis to prevent gout flares when commencing urate-lowering therapy is recommended by international rheumatology society guidelines. Whether this is a cost-effective intervention is currently unknown. Our objective was to perform a cost-effectiveness analysis using both a US cost input model and an Australian cost input model. METHODS: This cost-effectiveness analysis was completed from the point of view of the third-party payer. We used a 2-arm decision tree with 1 arm commencing allopurinol with no colchicine prophylaxis and the other with colchicine prophylaxis. Model inputs were drawn from published literature where available. We completed a univariate and probabilistic sensitivity analysis to confirm the robust nature of the modeling. The time frame for the model was 6 months. RESULTS: The colchicine prophylaxis arm resulted in a cost of $1,276 and 0.49 quality-adjusted life-years (QALYs), while in the placebo arm the cost was $516 and 0.47 QALYs, with an incremental cost-effectiveness ratio of $34,004 per QALY gained. In Australia, where cost of colchicine was much lower, the colchicine arm dominated the placebo ($208 [Australian] in the colchicine arm versus $415 [Australian] in the placebo). Univariate and probability sensitivity analysis demonstrated that results were robust to changes in input parameters. In the probabilistic sensitivity analysis, the probability of colchicine prophylaxis being the most cost-effective option was 93% in the US and 100% in the Australian setting. CONCLUSION: Colchicine prophylaxis to prevent gout flares while commencing allopurinol in gout is very cost-effective.

Out-of-pocket spending among a cohort of Australians living with gout.

OBJECTIVE: To measure the direct and indirect out-of-pocket (OOP) costs borne by Australians with gout. METHODS: A cross-sectional, Australia-wide, web-based survey was conducted over 12 months between May 2017 and April 2018. Participants were recruited via advertisements in doctors' clinics and healthcare organizations' websites, and social media platforms such as Facebook and Twitter. Survey questions collected information about participants' OOP spending on direct medical and non-medical gout-related healthcare costs. Participant demographics, gout status, healthcare sought, workdays lost to due gout and health-related quality of life were also collected. RESULTS: Seventy-nine patients with gout completed the survey; 70 (89%) were male, and on average were 56 (SD 16) years of age and had gout for 14 (SD 12) years. For this cohort, the median total OOP direct medical cost was AU$200 per year (interquartile range [IQR]: AU$60-AU$570). Sixty (76%) people with gout reported being affected by gout during work; however, only 0.25 (IQR: 0-3) days of work (approximately $60) were lost due to gout in a year. Nine percent (n = 7) of participants experienced cost-related treatment attrition and 33% reported economic hardship (n = 26). Participants who experienced economic hardship or cost-related treatment attrition had higher median total gout-related direct costs than those who did not. CONCLUSION: In Australia, gout has an OOP financial cost and reduces work productivity. The presence of cost-related treatment attrition among people with gout indicates that financial costs may be a significant barrier to seeking treatment for a subset of patients with gout.

Combining Model-Based Clinical Trial Simulation, Pharmacoeconomics, and Value of Information to Optimize Trial Design.

The Bayesian decision-analytic approach to trial design uses prior distributions for treatment effects, updated with likelihoods for proposed trial data. Prior distributions for treatment effects based on previous trial results risks sample selection bias and difficulties when a proposed trial differs in terms of patient characteristics, medication adherence, or treatment doses and regimens. The aim of this study was to demonstrate the utility of using pharmacometric-based clinical trial simulation (CTS) to generate prior distributions for use in Bayesian decision-theoretic trial design. The methods consisted of four principal stages: a CTS to predict the distribution of treatment response for a range of trial designs; Bayesian updating for a proposed sample size; a pharmacoeconomic model to represent the perspective of a reimbursement authority in which price is contingent on trial outcome; and a model of the pharmaceutical company return on investment linking drug prices to sales revenue. We used a case study of febuxostat versus allopurinol for the treatment of hyperuricemia in patients with gout. Trial design scenarios studied included alternative treatment doses, inclusion criteria, input uncertainty, and sample size. Optimal trial sample sizes varied depending on the uncertainty of model inputs, trial inclusion criteria, and treatment doses. This interdisciplinary framework for trial design and sample size calculation may have value in supporting decisions during later phases of drug development and in identifying costly sources of uncertainty, and thus inform future research and development strategies.

Febuxostat for gout.

Around 1.4% of the UK population have gout, the prevalence of which increases with age to around 3% in women and 7% in men aged over 75 years. Acute gout is intensely painful and can reduce patients' quality of life. It occurs when the serum uric acid concentration (SUA) rises (hyperuricaemia) and persists above the solubility threshold of monosodium urate (400 micromol/L [6.8 mg/dL]), leading to urate crystal formation that causes arthritis, gouty tophi (nodules) in subcutaneous tissues and renal calculi. The mainstay of treatment for chronic gout is allopurinol, which inhibits xanthine oxidase (an enzyme involved in the production of uric acid in the body). However, this drug has to be stopped in a minority of patients due to rashes or hypersensitivity. Febuxostat (Adenuric - Menarini/Ipsen), another xanthine oxidase inhibitor, is a newly licensed treatment for chronic hyperuricaemia in conditions where urate deposition has occurred. Here we consider its place for patients with gout.