P. Putrik

Inequities in access to biologic and synthetic DMARDs across 46 European countries

Objectives We investigated access to biologic and synthetic disease modifying drugs (bDMARDs and sDMARDs) in patients with rheumatoid arthritis (RA) across Europe. Methods A cross-sectional study at national level was performed in 49 European countries. A questionnaire was sent to one expert, addressing the number of approved and reimbursed bDMARDs and sDMARDs, prices and co-payments, as well as acceptability of bDMARDs (barriers). Data on socio-economic welfare (gross domestic product per capita (GDP), health expenditure, income) were retrieved from web-based sources. Data on health status of RA patients were retrieved from an observational study. Dimensions of access (availability, affordability and acceptability) were correlated with the countrys welfare and RA health status. Results In total, 46 countries (94%) participated. Six countries did not reimburse any of the five sDMARDs surveyed, and in ten countries no bDMARDs were reimbursed. While the price of annual treatment with an average sDMARD was never higher than GPD, the price of one year treatment with a bDMARD exceeded GPD in 26 countries. Perceived barriers for access to bDMARDs were mainly found among financial and administrative restrictions. All dimensions of access were positively correlated with the countrys economic welfare (coefficients 0.69 to 0.86 for overall access scores). Conclusions Patients with RA in lower income European countries have less access to bDMARDs and sDMARDs, with particularly striking unaffordability of bDMARDs in some of these countries. When accepting that sDMARDs and bDMARDs are equally needed across countries to treat RA, our data point to inequities in access to pharmacological treatment for RA in Europe.

Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country's wealth?

Objectives To explore criteria regulating treatment with reimbursed biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) across Europe and to relate criteria to indicators of national socioeconomic welfare. Methods A cross-sectional study among 46 European countries. One expert from each country completed a questionnaire on criteria regulating the start, maintenance/stop and switch of reimbursed bDMARDs. A composite score was developed to evaluate the level of restrictions in prescription of a first bDMARD (0=highly restricted, 5=most liberal). The level of restrictiveness was correlated with national socioeconomic welfare indicators. Results In 10 countries (22%), no bDMARD was reimbursed. Among 36 countries with at least one biologic reimbursed, 23(64%) had no requirement for disease duration to initiate a biologic. Half of the countries required a failure of two synthetic DMARDs to qualify for therapy. 31 countries specified a minimum level of disease activity to be fulfilled and in 20 (56%) countries cut-off for disease activity score with 28-joint assessment was higher than 3.2. Four countries (11%) had the maximum composite score (most liberal) and 20 (56%) scored between 0 and 2 (more restrictive). Criteria for initiation of a bDMARD were negatively associated with countries’ socioeconomic welfare (−0.34 to −0.64), and a moderate positive correlation was found between the composite score and welfare indicators (0.59–0.72). Only some countries had regulations for stopping (n=14(39%)) or switching (n=19(53%)). Conclusions Clinical criteria regulating prescription of bDMARDs in RA differ significantly across Europe. Countries with lower socioeconomic welfare tend to have stricter eligibility criteria, pointing to inequities in access to treatment.

Lower education and living in countries with lower wealth are associated with higher disease activity in rheumatoid arthritis: results from the multinational COMORA study

Objectives To investigate the relationship of socioeconomic status (SES) on an individual and country level with disease activity in rheumatoid arthritis (RA) and explore the mediating role of uptake of costly biological disease-modifying antirheumatic drugs (bDMARDs) in this relationship. Methods Data from a cross-sectional multinational study (COMOrbidities in RA) were used. Contribution of individual socioeconomic factors and country of residence to disease activity score with 28-joint assessment (DAS28) was explored in regression models, adjusting for relevant clinical confounders. Next, country of residence was replaced by gross domestic product (GDP) (low vs high) to investigate the contribution of SES by comparing R2 (model fit). The mediating role of uptake of bDMARDs in the relationship between education or GDP and DAS28 was explored by testing indirect effects. Results In total, 3920 patients with RA were included (mean age 56 (SD 13) years, 82% women, mean DAS28 3.7 (1.6)). After adjustment, women (vs men) and low-educated (vs university) patients had 0.35 higher DAS28. Adjusted country differences in DAS28, compared with the Netherlands (lowest DAS28), varied from +0.2 (France) to +2.4 (Egypt). Patients from low GDP countries had 0.98 higher DAS28. No interactions between individual-level and country-level variables were observed. A small mediation effect of uptake of bDMARDs in the relationship between education and DAS28 (7.7%) and between GDP and DAS28 (6.7%) was observed. Conclusions Female gender and lower individual or country SES were independently associated with DAS28, but did not reinforce each other. The association between lower individual SES (education) or lower country welfare (GDP) with higher DAS28 was partially mediated by uptake of bDMARDs.

In wealthier countries, patients perceive worse impact of the disease although they have lower objectively assessed disease activity: results from the cross-sectional COMORA study

Objectives To investigate patterns in patient-reported and physician-reported disease outcomes in patients with rheumatoid arthritis (RA) from countries with different level of socioeconomic development. Methods Data from a cross-sectional multinational study (COMOrbidities in RA) were used. Contribution of socioeconomic welfare (gross domestic product (GDP); low vs high) of country of residence to physician-reported (tender joint count, swollen joint count (SJC), erythrocyte sedimentation rate, disease activity score based on 28 joints assessment (DAS28)-3v based on these three components and physician global assessment) and patient-reported (modified Health Assessment Questionnaire (mHAQ), patient global assessment and fatigue) disease outcomes was explored in linear regressions, adjusting for relevant confounders. Results In total, 3920 patients with RA from 17 countries (30 to 411 patients per country) were included, with mean age of 56 years (SD13) and 82% women. Mean SJC varied between 6.7 (Morocco) and 0.9 (The Netherlands), mean mHAQ ranged between 0.7 (Taiwan) and 1.5 (The Netherlands). Venezuela had the lowest (1.7) and the Netherlands the highest score on fatigue (5.0). In fully adjusted models, lower GDP was associated with worse physician-reported outcomes (1.85 and 2.84 more swollen and tender joints, respectively, and 1.0 point higher DAS28-3v), but only slightly worse performance-based patient-reported outcome (0.15 higher mHAQ), and with better evaluation-based patient-reported outcomes (0.43 and 0.97 points lower on patient global assessment and fatigue, respectively). Conclusions In patients with RA, important differences in physician-reported and patient-reported outcomes across countries were seen, with overall a paradox of worse physician-reported outcomes but better patient-reported outcomes in low-income countries, while results indicate that these outcomes in multinational studies should be interpreted with caution. Research on explanatory factors of this paradox should include non-disease driven cultural factors influencing health.

Impact of socioeconomic gradients within and between countries on health of patients with rheumatoid arthritis (RA): Lessons from QUEST RA

In this chapter, we discuss challenges in collecting data on outcomes of patients who receive usual rheumatology care. We present results of the multinational Quantitative Monitoring of Patients with Rheumatoid Arthritis (QUEST RA) study which is a successful example of quantitative clinical measuring of RA as part of routine clinical care in a large number of centres across more than 30 countries. We further elaborate on what we can learn from these data about inequalities and inequities, both within and between countries. Frameworks to understand socioeconomic determinants of health are presented and, in addition to the QUEST RA data, the literature is summarised to provide further evidence on how socioeconomic determinants can contribute to health disparities of patients within and between countries.

In rheumatoid arthritis, country of residence has an important influence on fatigue: results from the multinational COMORA study

OBJECTIVES To investigate the relationship between country of residence and fatigue in RA, and to explore which country characteristics are related to fatigue. METHODS Data from the multinational COMORA study were analysed. Contribution of country of residence to level of fatigue [0-10 on visual analogue scale (VAS)] and presence of severe fatigue (VAS ⩾ 5) was explored in multivariable linear or logistic regression models including first socio-demographics and objective disease outcomes (M1), and then also subjective outcomes (M2). Next, country of residence was replaced by country characteristics: gross domestic product (GDP), human development index (HDI), latitude (as indicator of climate), language and income inequality index (gini-index). Model fit (R(2)) for linear models was compared. RESULTS A total of 3920 patients from 17 countries were included, mean age 56 years (s.d. 13), 82% females. Mean fatigue across countries ranged from 1.86 (s.d. 2.46) to 4.99 (s.d. 2.64) and proportion of severe fatigue from 14% (Venezuela) to 65% (Egypt). Objective disease outcomes did not explain much of the variation in fatigue ([Formula: see text] = 0.12), while subjective outcomes had a strong negative impact and partly explained the variation in fatigue ([Formula: see text]= 0.27). Country of residence had a significant additional effect (increasing model fit to [Formula: see text] = 0.20 and [Formula: see text] = 0.36, respectively). Remarkably, higher GDP and better HDI were associated with higher fatigue, and explained a large part of the country effect. Logistic regression confirmed the limited contribution of objective outcomes and the relevant contribution of country of residence. CONCLUSION Country of residence has an important influence on fatigue. Paradoxically, patients from wealthier countries had higher fatigue.

Less educated and older patients have reduced access to biologic DMARDs even in a country with highly developed social welfare (Norway): results from Norwegian cohort study NOR-DMARD

OBJECTIVE To explore whether age, gender or education influence the time until initiation of the first bDMARD in patients with RA. METHODS Data from the Norwegian Register of DMARDs collected between 2000 and 2012 were used. Only DMARD-naïve patients with RA starting their first conventional synthetic DMARD were included in the analyses. The start of the first bDMARD was the main outcome of interest. Cox regression analyses were used to explore the impact of education, age and gender on the start of a first bDMARD, adjusting for confounders, either at baseline or varying over time (time-varying model). RESULTS Of 1946 eligible patients [mean (s.d.) age: 55 (14) years, 68% females], 368 (19%) received a bDMARD during follow-up (mean 2.6 years). In the baseline prediction model, older age [Hazard Ratio (HR) 0.97, 95% CI: 0.96, 0.98], lower education [HR = 0.76 and 0.68 for low and intermediate education levels vs college/university education, respectively (P = 0.01)] and female gender [only in the period 2000-03, HR = 0.61 (95% CI: 0.41, 0.91)] were associated with a lower hazard ratio to start a bDMARD. The time-varying model provided overall consistent results, but the effect of education was only relevant for older patients (>57 years) and became more pronounced by the end of the decade. CONCLUSIONS Less educated and older patients have disadvantages with regard to access to costly treatments, even in a country with highly developed welfare like Norway. Females had lower access in the beginning of the 2000s, but access had improved by the end of the decade.

FRI0082 In Addition to Individual Demographic and Clinical Measures, Levels of Fatigue Are Dependent on Country of Residence. An Analysis among 3920 Patients from 17 Countries (The Comora Study)

Background For patients with rheumatoid arthritis (RA), fatigue is an important aspect of disease which impacts quality of life. However the complex relationship between fatigue and either disease-related or external factors remains unclear. Country of residence as a surrogate for a variety of cultural, economic, climatological and linguistic aspects might play a role, but this has never been formally explored. Objectives To investigate how country of residence influences level of fatigue in addition to socio-demographic and objective disease- characteristics. Methods Data from a multi-national study were used (COMORA). Fatigue was measured using 0-10 VAS scale. A multivariable linear regression model (outcome fatigue) was computed using manual forward selection. Contribution of socio-demographic factors (age, gender, education, marital status, work status), comorbidities (Wolfe-Michaud index), smoking status, clinical disease characteristics (tender and swollen joints (TJC, SJC), erosions in hands or feet (yes/no), erythrocyte sedimentation rate) and medication (all type of DMARDs, steroids and NSAIDs) was tested. Country of residence was added using the country with the highest level of fatigue (Netherlands) as reference. In a second step, sensitivity analyses were developed replacing country of residence by country specific variables including gross domestic product (GPD), human development index (HDI), a climate indicator (latitude) and income inequality (gini index). Results 3920 patients from 17 countries (range: 30 to 411, mean age 56 years (SD 13), 82% female). Mean fatigue across countries was 4.13 (SD 2.8). 32.8% of all patients had fatigue scores >5. In multi-variable regression, female gender (βf=1=0.72, CI 0.50/0.93) and a higher comorbidity score (β=0.30, CI 0.24/0.37) were associated with higher fatigue. TJC and SJC had limited influence on fatigue with higher contribution of TJC (βTJC=0.14, CI 0.12/0.16 and βSJC=0.05, CI 0.25/0.79). When adding country, the contribution was significant and increased the overall model fit (Δ R2=0.07). Country differences in fatigue varied between -3.9 for Venezuela vs Netherlands (NL) and -0.6 (Italy vs NL) after adjustment for individual factors. When country was replaced by GDP, HDI, latitude or gini index, only GPD and HDI index contributed significantly. The overall model improvement was lower compared to country (R2 GDP=0.14, R2 HDI=0.18, R2 country=0.20). Interactions were not significant. Conclusions While individual demographics and objective clinical measures of disease have only a small influence on the experience of fatigue, the country of residence adds substantially. Economic and development status of the country only explain small parts of the variation among countries. More research is needed to identify other relevant cultural (attitudes, believes), climatological or linguistic aspects that could explaining fatigue. Disclosure of Interest M. Hifinger Employee of: Hexal AG, Germany (inactive employment, maternity leave), P. Putrik: None declared, S. Ramiro: None declared, A. Keszei: None declared, I. Hmamouchi: None declared, M. Dougados: None declared, L. Gossec: None declared, A. Boonen: None declared DOI 10.1136/annrheumdis-2014-eular.2098

Socioeconomic inequities in perceived health among patients with musculoskeletal disorders compared with other chronic disorders: results from a cross-sectional Dutch study.

Objectives To explore the impact of socioeconomic factors on physical and mental health of patients with musculoskeletal disorders (MSKDs) and compare it across patients with other disorders. Methods A representative sample of the Dutch population (n=8904) completed a survey on sociodemographics, physician-diagnosed (co-) morbidities, and physical (physical component summary, PCS) and mental (mental component summary, MCS) subscales of SF-12 (outcome variables). Regression models were computed first in the total group of patients with MSKDs, with education, age, gender, origin and place of residence as independent variables, and, second, in individuals expected to have paid work, adding a variable on social status. Models were repeated for five other subgroups of chronic disorders (cardiovascular (CVD), diabetes, cancer, mental and respiratory) and for healthy individuals. Results MSKDs confirmed by a physician were reported by 1766 (20%) participants (mean age 59 years, 38% male), 547 (6%) respondents reported to have diabetes, 1855 (21%) CVD, 270 (3%) cancer, 526 (6%) mental disorders, 679 (8%) respiratory disorders and 4525 (51%) did not report any disease. In patients with MSKDs, (primary school vs university education (−5.3 (PCS) and −3.3 (MCS)) and having a state subsidy vs paid work (−5.3 (PCS) and −4.7 (MCS)) were consistently associated with worse physical and mental health. Gender was only relevant for PCS (female vs male −2.1). Comparable differences in health by education and social status were observed in the other diseases, except for cancer. Conclusions Education and social status in MSKD have the same strong and independent association with health as in other chronic diseases. These health gradients are unfair and partly avoidable, and require consorted attention and action in and outside healthcare.

Impact of Chronic Diseases and Multimorbidity on Health and Health Care Costs: The Additional Role of Musculoskeletal Disorders

Chronic diseases are increasingly prevalent and often occur as multimorbidity. This study compares the impact of musculoskeletal disorders (MSKDs) on health and health care costs with other chronic diseases, and assesses the additional impact of MSKDs on these outcomes when occurring as part of multimorbidity.