Developing a framework for the implementation of recommendations for lifestyle factors for people with RMDs across Europe: assessment of current materials and implementation needs.

Lifestyle factors (such as diet, physical activity or smoking habits, among others) are known to influence the progression of rheumatic and musculoskeletal diseases (RMDs). Despite contemporary improvements in RMD care, the management of lifestyle factors is suboptimal. In the context of a recent European Alliance of Associations for Rheumatology (EULAR) task force, existing informative materials regarding lifestyle factors for people with RMDs were collected from national organisations across European countries. Current materials show important limitations in terms of coverage, literature support and access, which may make the implementation of successful interventions difficult. In the present viewpoint, a roadmap to cover these gaps at the European level with the recent EULAR recommendations on lifestyle factors is discussed from an implementation perspective. This analysis may pave the ground for future implementation endeavours at the European level related to non-pharmacological interventions that may also be applicable beyond rheumatology.

Influence of Social Support, Financial Status, and Lifestyle on the Disparity Between Inflammation and Disability in Rheumatoid Arthritis.

OBJECTIVE: To investigate how social support, financial status, and lifestyle influence the development of excess disability in rheumatoid arthritis (RA). METHODS: Data were obtained from the Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort study of people with RA. A previous analysis identified groups with similar inflammation trajectories but markedly different disability over 10 years; those in the higher disability trajectory groups were defined as having "excess disability." Self-reported data regarding contextual factors (social support, financial situation, lifestyle) were obtained from participants, and they completed patient-reported outcome measures (pain, fatigue, anxiety, depression) at baseline. The direct effect of the contextual factors on excess disability and the effect mediated by patient-reported outcome measures were assessed using structural equation models. Findings were validated in 2 independent data sets (Norfolk Arthritis Register [NOAR], Early Rheumatoid Arthritis Network [ERAN]). RESULTS: Of 538 included ESPOIR participants (mean age ± SD 48.3 ± 12.2 years; 79.2% women), 200 participants (37.2%) were in the excess disability group. Less social support (ß = 0.17 [95% confidence interval (95% CI) 0.08, 0.26]), worse financial situation (ß = 0.24 [95% CI 0.14, 0.34]), less exercise (ß = 0.17 [95% CI 0.09-0.25]), and less education (ß = 0.15 [95% CI 0.06, 0.23]) were associated with excess disability group membership; smoking, alcohol consumption, and body mass index were not. Fatigue and depression mediated a small proportion of these effects. Similar results were seen in NOAR and ERAN. CONCLUSION: Greater emphasis is needed on the economic and social contexts of individuals with RA at presentation; these factors might influence disability over the following decade.

A Systematic Review of Productivity in Economic Evaluations of Workplace Interventions: A Need for Reporting Criteria?

BACKGROUND: Rheumatic and musculoskeletal diseases (RMDs) are understood to reduce levels of paid productivity. Productivity, including absenteeism and presenteeism, is arguably an important factor for consideration in economic evaluations of workplace interventions for RMDs (WPI-RMDs). Existing methods available to quantify and value absenteeism and presenteeism are heterogeneous and produce estimates that vary substantially across studies. To date, there has been no systematic summary of the reporting quality of methods used to quantify paid productivity included in economic evaluations of WPI-RMDs. OBJECTIVE: The aim of this systematic review was twofold. First, the review was conducted to understand if, and how, the impact of WPI-RMDs on productivity was considered and incorporated in published economic evaluations. Second, we aimed to assess the reporting quality of productivity in published economic evaluations of WPI-RMDs and determine the need for a published set of reporting guidelines for productivity. METHODS: This systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic review published in 2008 that focused on the cost effectiveness of WPIs, with limited information on productivity, was updated from 2007 to July 2018. A global search was conducted using three online databases: MEDLINE (1946 to August 2018, week 2), EMBASE (1974 to 10 July 2018); and EconLit (1886 to July 2018). The studies were double-screened by four independent reviewers. Data extraction was conducted using a bespoke data extraction table. RESULTS: Twenty-one economic evaluations of WPI-RMDs were identified. All studies evaluated absenteeism, but only five reported on levels of presenteeism. The methods used to identify and measure absenteeism were fairly consistent; however, methods used to identify and measure presenteeism, and value absenteeism and presenteeism, varied across studies. Two studies may have potentially double-counted productivity in their economic evaluations of WPI-RMDs. The results of this systematic review identified key elements potentially useful as a starting point to inform reporting quality guidelines for productivity. CONCLUSIONS: Variation in the methods used to quantify productivity and how it is reported in economic evaluations suggests the need for specific published reporting guidelines for productivity. The development of standardised reporting guidelines for the identification, measurement, and valuation of absenteeism and presenteeism in economic evaluations may help reduce variation in the methods and promote transparency.

Validity of a two-component imaging-derived disease activity score for improved assessment of synovitis in early rheumatoid arthritis.

OBJECTIVES: Imaging of joint inflammation provides a standard against which to derive an updated DAS for RA. Our objectives were to develop and validate a DAS based on reweighting the DAS28 components to maximize association with US-assessed synovitis. METHODS: Early RA patients from two observational cohorts (n = 434 and n = 117) and a clinical trial (n = 59) were assessed at intervals up to 104 weeks from baseline; all US scans were within 1 week of clinical exam. There were 899, 163 and 183 visits in each cohort. Associations of combined US grey scale and power Doppler scores (GSPD) with 28 tender joint count and 28 swollen joint count (SJC28), CRP, ESR and general health visual analogue scale were examined in linear mixed model regressions. Cross-validation evaluated model predictive ability. Coefficients learned from training data defined a re-weighted DAS28 that was validated against radiographic progression in independent data (3037 observations; 717 patients). RESULTS: Of the conventional DAS28 components only SJC28 and CRP were associated with GSPD in all three development cohorts. A two-component model including SJC28 and CRP outperformed a four-component model (R2 = 0.235, 0.392, 0.380 vs 0.232, 0.380, 0.375, respectively). The re-weighted two-component DAS28CRP outperformed conventional DAS28 definitions in predicting GSPD (Δtest log-likelihood <-2.6, P < 0.01), Larsen score and presence of erosions. CONCLUSION: A score based on SJC28 and CRP alone demonstrated stronger associations with synovitis and radiographic progression than the original DAS28 and should be considered in research on pathophysiological manifestations of early RA. Implications for clinical management of RA remain to be established.

Conceptual model for the health technology assessment of current and novel interventions in rheumatoid arthritis.

The objective of this study was to evaluate current approaches to economic modeling in rheumatoid arthritis (RA) and propose a new conceptual model for evaluation of the cost-effectiveness of RA interventions. We followed recommendations from the International Society of Pharmacoeconomics and Outcomes Research-Society of Medical Decision Making (ISPOR-SMDM) Modeling Good Research Practices Task Force-2. The process involved scoping the decision problem by a working group and drafting a preliminary cost-effectiveness model framework. A systematic literature review (SLR) of existing decision-analytic models was performed and analysis of an RA registry was conducted to inform the structure of the draft conceptual model. Finally, an expert panel was convened to seek input on the draft conceptual model. The proposed conceptual model consists of three separate modules: 1) patient characteristic module, 2) treatment module, and 3) outcome module. Consistent with the scope, the conceptual model proposed six changes to current economic models in RA. These changes proposed are to: 1) use composite measures of disease activity to evaluate treatment response as well as disease progression (at least two measures should be considered, one as the base case and one as a sensitivity analysis); 2) conduct utility mapping based on disease activity measures; 3) incorporate subgroups based on guideline-recommended prognostic factors; 4) integrate realistic treatment patterns based on clinical practice/registry datasets; 5) assimilate outcomes that are not joint related (extra-articular outcomes); and 6) assess mortality based on disease activity. We proposed a conceptual model that incorporates the current understanding of clinical and real-world evidence in RA, as well as of existing modeling assumptions. The proposed model framework was reviewed with experts and could serve as a foundation for developing future cost-effectiveness models in RA.

Rheumatoid arthritis and work: The impact of rheumatoid arthritis on absenteeism and presenteeism.

For patients with rheumatoid arthritis (RA), being in paid work is very important, and it increases self-esteem and financial independence. Although the management of RA has changed in the last 15 years to early aggressive treatment and the introduction of biologic treatments, many patients still have to take sick leave or even stop working because of their RA (i.e., absenteeism). For those remaining in paid work, patients may experience problems due to RA resulting in productivity loss while at work (i.e., presenteeism). The costs attributed to absenteeism and presenteeism (i.e., indirect costs) have been estimated to be very high, and they even exceed direct costs. However, there is no consensus on how to calculate these costs. This manuscript examines the relationship between the use of biologic therapy and absenteeism, with a focus on sick leave, and on presenteeism, and it provides an overview of indirect costs of absenteeism and presenteeism in those treated with biologic therapies.

Direct health costs of inflammatory polyarthritis 10 years after disease onset: results from the Norfolk Arthritis Register.

OBJECTIVES: To explore the change in direct medical costs associated with inflammatory polyarthritis (IP) 10 to 15 years after its onset. METHODS: Patients from the Norfolk Arthritis Register who had previously participated in a health economic study in 1999 were traced 10 years later and invited to participate in a further prospective questionnaire-based study. The study was designed to identify direct medical costs and changes in health status over a 6-month period using previously validated questionnaires as the primary source of data. RESULTS: A representative sample of 101 patients with IP from the 1999 cohort provided complete data over the 6-month period. The mean disease duration was 14 years (SD 2.1, median 13.6, interquartile range 12.6-15.4). The mean direct medical cost per patient over the 6-month period was £1496 for IP (inflated for 2013 prices). This compared with £582 (95% CI £355-£964) inflated to 2013 prices per patient with IP 10 years earlier in their disease. The increased cost was largely associated with the use of biologics in the rheumatoid arthritis subgroup of patients (51% of total costs incurred). Other direct cost components included primary care costs (11%), hospital outpatient (19%), day care (12%), and inpatient stay (4%). CONCLUSION: The direct healthcare costs associated with IP have more than doubled with increasing disease duration, largely as a result of the use of biologics. The results showed a shift in the direct health costs from inpatient to outpatient service use.

The association between low socioeconomic status with high physical limitations and low illness self-perception in patients with juvenile idiopathic arthritis: results from the Childhood Arthritis Prospective Study.

OBJECTIVE: To examine the association between socioeconomic status (SES) and delay to a pediatric rheumatology clinic, disease severity, and illness perception in patients with juvenile idiopathic arthritis in England. METHODS: Using the Index of Multiple Deprivation, 923 consecutive children from the Childhood Arthritis Prospective Study were assigned to SES groups: high-SES (19.1%), middle-SES (44.5%), or low-SES (36.4%). At baseline, disease activity was assessed, and the Childhood Health Assessment Questionnaire (C-HAQ), the Illness Perception Questionnaire, and the Child Health Questionnaire, version Parent Form 50, were completed. Linear median regression analyses or zero-inflated negative binominal (ZINB) regression analyses were used. RESULTS: Delay to first pediatric rheumatology consultation was the same between the 3 SES groups. Although disease activity scores assessed by the pediatric rheumatologist did not differ between the 3 SES groups, persons in the low-SES group recorded higher C-HAQ scores compared to the high-SES group (zero-inflated part of ZINB odds ratio 0.28 [95% confidence interval (95% CI) 0.14, 0.55], count part of ZINB ß 0.26 [95% CI 0.05, 0.48]). Parents with low SES also reported more often that their children's school work or activities with friends had been limited. Furthermore, the low-SES group had a worse perception about the consequences of the disease and the effect of treatment than those in the high-SES group. CONCLUSION: Patients from a low-SES background report more problems with daily activities and have a lower perception of the consequences of the disease than patients from a high-SES background, warranting special attention from a multidisciplinary team.

Health Assessment Questionnaire disability progression in early rheumatoid arthritis: systematic review and analysis of two inception cohorts.

OBJECTIVE: The Health Assessment Questionnaire is widely used for patients with inflammatory polyarthritis (IP) and its subset, rheumatoid arthritis (RA). In this study, we evaluated the progression of HAQ scores in RA (i) by systematically reviewing the published literature on the methods used to assess changes in functional disability over time and (ii) to study in detail HAQ progression in two large prospective observational studies from the UK. METHODS: Data from two large inception cohorts, ERAS and NOAR, were studied to determine trajectories of HAQ progression over time by applying latent class growth models (LCGMs) to each dataset separately. Age, sex, baseline DAS28, symptom duration, rheumatoid factor, fulfilment of the 1987 ACR criteria and socio-economic status (SES) were included as potential predictors of HAQ trajectory subgroup membership. RESULTS: The literature search identified 49 studies showing that HAQ progression has mainly been based on average changes in the total study population. In the HAQ progression study, a LCGM with four HAQ trajectory subgroups was selected as providing the best fit in both cohorts. In both the cohorts, older age, female sex, longer symptom duration, fulfilment of the 1987 ACR criteria, higher DAS28 and lower SES were associated with increased likelihood of membership of subgroups with worse HAQ progression. CONCLUSION: Four distinct HAQ trajectory subgroups were derived from the ERAS and NOAR cohorts. The fact that the subgroups identified were nearly identical supports their validity. Identifying distinct groups of patients who are at risk of poor functional outcome may help to target therapy to those who are most likely to benefit.

Economic consequences and potential benefits.

Patients with established rheumatoid arthritis (RA) may incur important resource utilisation and work productivity loss, resulting in high costs of illness. Impairment in physical function, which increases with disease duration, is the main variable driving all aspects of these costs. The large variation of costs across administrations is a complex issue and results not only from differences in access to and provision of care but also from absolute differences in the prices for health-care or loss of paid work. Despite the major effects of biologicals on almost all aspects of health, the literature shows that in established RA, the cost-utility ratios are high when compared to adjusting or switching non-biological disease-modifying anti-rheumatic drugs (DMARD) sequences. Until the prices of the biologicals can be reduced, the challenge for optimising the use of biologicals in treatment sequences in RA is to improve selection of patients that would be unresponsive to non-biological DMARDs in an early phase of the disease and identification of patient groups in which biologicals can be successfully stopped.

Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA study.

INTRODUCTION: Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. METHODS: The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. RESULTS: At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score. CONCLUSIONS: Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.

Exploring the validity of estimating EQ-5D and SF-6D utility values from the health assessment questionnaire in patients with inflammatory arthritis.

BACKGROUND: Utility scores are used to estimate Quality Adjusted Life Years (QALYs), applied in determining the cost-effectiveness of health care interventions. In studies where no preference based measures are collected, indirect methods have been developed to estimate utilities from clinical instruments. The aim of this study was to evaluate a published method of estimating the EuroQol-5D (EQ-5D) and Short Form-6D (SF-6D) (preference based) utility scores from the Health Assessment Questionnaire (HAQ) in patients with inflammatory arthritis. METHODS: Data were used from 3 cohorts of patients with: early inflammatory arthritis (<10 weeks duration); established (>5 years duration) stable rheumatoid arthritis (RA); and RA being treated with anti-TNF therapy. Patients completed the EQ-5D, SF-6D and HAQ at baseline and a follow-up assessment. EQ-5D and SF-6D scores were predicted from the HAQ using a published method. Differences between predicted and observed EQ-5D and SF-6D scores were assessed using the paired t-test and linear regression. RESULTS: Predicted utility scores were generally higher than observed scores (range of differences: EQ-5D 0.01 - 0.06; SF-6D 0.05 - 0.10). Change between predicted values of the EQ-5D and SF-6D corresponded well with observed change in patients with established RA. Change in predicted SF-6D scores was, however, less than half of that in observed values (p < 0.001) in patients with more active disease. Predicted EQ-5D scores underestimated change in cohorts of patients with more active disease. CONCLUSION: Predicted utility scores overestimated baseline values but underestimated change. Predicting utility values from the HAQ will therefore likely underestimate the QALYs of interventions, particularly for patients with active disease. We recommend the inclusion of at least one preference based measure in future clinical studies.

Functional Health Assessment Questionnaire (HAQ) and Psychological HAQ Are Associated with and Predicted by Different Factors in Rheumatoid Arthritis.

OBJECTIVE: To evaluate the association between clinical, demographic, and psychological factors and the functional Health Assessment Questionnaire (HAQ) and psychological HAQ (PSHAQ) in patients with rheumatoid arthritis (RA). METHODS: After a mean followup time of 7 years after diagnosis, 112 patients with RA were asked to fill out the HAQ and the PSHAQ. Several clinical variables [erythrocyte sedimentation rate (ESR), visual analog scale (VAS) pain, VAS general well-being, Thompson joint score, and morning stiffness] had been assessed at diagnosis and at followup. In addition, the Impact of Rheumatic diseases on General health and Lifestyle questionnaire, comprising different domains of psychological distress, was assessed at diagnosis. Spearman correlations were calculated to determine associations between functional HAQ and clinical and psychological variables at baseline and to determine the associations between clinical variables and the HAQ and PSHAQ score at followup. Univariate logistic regression analyses were performed to identify possible predictors at diagnosis for a worse HAQ score and PSHAQ score (score > 1) at followup. RESULTS: At followup the functional HAQ score was associated with all clinical variables, whereas the PSHAQ was only associated with more subjective patient related variables (VAS pain, VAS general well-being, and morning stiffness). The final model of the multivariate regression analyses to predict a worse HAQ score at followup only included worse functional ability [odds ratio (OR) 2.63, 95% confidence interval (CI) 1.30-5.32, p = 0.007]. Anxiety (OR 1.13, 95% CI 1.03-1.24, p = 0.007) and a lower ESR value (OR 0.98, 95% CI 0.96-1.00, p = 0.05) assessed at diagnosis were included into the final model as predictors for a high PSHAQ score. CONCLUSION: Overall, the HAQ score, reflecting limitations of daily functioning, is a good representation of disease activity at diagnosis and after a mean disease duration of 7 years, whereas PSHAQ is not.