Monika Hifinger

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.

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.

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

Patients’ preferences and economic considerations play an important role in treatment decisions: a discrete choice experiment among rheumatologists

Objective. To evaluate to what extent rheumatologists consider economic aspects and patients’ preferences when choosing drug treatments in patients with active RA. Methods. In a discrete choice experiment, rheumatologists were asked to choose between two unlabelled drug treatment options for a hypothetical RA patient with moderate disease activity who failed two synthetic DMARDs. Attributes and levels of drug treatments were selected based on existing literature, rheumatologists’ opinion and expert consensus. This resulted in five attributes each described by three levels: efficacy (level of improvement and achieved state on DAS28), safety (probability of a serious adverse event), patients’ preference (level of agreement), annual medication costs and cost-effectiveness (incremental cost-effectiveness ratio). An efficient experimental design generated 14 treatment choices and a random parameter logit model estimated the relative importance of attributes. Results. Sixty-three rheumatologists from the Netherlands contributed to the analysis; 44% were female and mean (S.D.) age was 49 (8) years. Drug efficacy had the strongest relative contribution to the drug choice (44%) followed by medication costs (24%), patients’ preference (17%) and cost-effectiveness (14%). Patients’ preferences were most relevant when patients disliked a proposed treatment. The risk of serious but uncommon or rare side effects only played a minor role in the treatment choice (1%). Conclusion. In addition to drug efficacy, rheumatologists account for economic aspects and for patients’ preferences when deciding on drugs. Decisions are more influenced by absolute costs than relative cost-effectiveness and by patients’ disliking as opposed to favouring the treatment.

OP0284 Comparability of The Health Assessment Questionnaire between Countries: Psychometric Examination of Cross-National Measurement Equivalence

Background The HAQ disability index is the most widely used measure of function in rheumatological conditions. Translated versions of thr original HAQ and several revisions are increasingly used to make comparisons between countries in epidemiological studies. Such comparisons assume cross-national measurement equivalence. That is, total scores are not biased due to responses to individual items being influenced by subtle differences in interpretation across languages or cultures. Despite its wide use, this measurement property has not been tested across a wide range of countries. Objectives To examine the cross-national measurement equivalence of four versions of the HAQ: modified HAQ (MHAQ), multidimensional HAQ (MDHAQ), functional HAQ (FNHAQ) and HAQ-II. Methods Data are from the QUEST-RA cross-sectional survey of 10,150 patients with RA from 34 countries (74% female, mean age 55 years). Respondents completed an item pool of 33 items, excluding devices, relating to the original HAQ and four revisions. Item response theory (IRT) models were estimated. Likelihood ratio tests compared models for each HAQ version fixing IRT parameters to be the same across all countries (equivalent) or estimating separate parameters for each country (non-equivalent). Further analysis with Bayesian multiple-group IRT models identified items with non-equivalent IRT parameters for each country using an alignment method. Results All versions of the HAQ exhibited good psychometric properties with a single latent disability variable explaining around two-thirds of the variance in item responses. Compared to other versions, the HAQ-II exhibited greater precision (i.e. reliability) in differentiating between people with low levels of disability. For each version of the HAQ the non-equivalent model provided a significantly better fit compared to the equivalent model (all p<0.001), indicating comparisons of scores across countries are biased. Further analysis indicated this non-equivalence across countries was generally due to differences in the level of disability required to respond positively to an item, rather than variation in an items ability to discriminate level of disability. Examining the aligned means for each country using the limits of agreement method (Figure) indicated that the overall impact of non-equivalence was likely to be minimal for most countries and that scores for the MHAQ were least affected. Scores for Russia, Serbia and Morocco were overestimated, and Egypt underestimated. Conclusions All versions of the HAQ have good psychometric properties. Due to differences in item interpretation across translations, caution should be taken when drawing inferences about disability levels across countries. For most countries such inferences are likely to be valid due to the relatively low level of bias introduced by individual items. Although measurement properties at the individual level are more favourable for the HAQ-II, it is more prone to bias in cross-national comparisons where the MHAQ may be favoured. Disclosure of Interest None declared

Influence of disease activity on RA treatment choices in countries with restricted access to expensive, innovative drugs: a discrete choice experiment among rheumatologists

Objective To assess the influence of disease activity of patients with rheumatoid arthritis on treatment choices of rheumatologists in countries with restricted access to expensive, innovative drugs. Methods Rheumatologists from Hungary, Romania and UK were invited to complete two consecutive discrete choice experiments with hypothetical drug treatments for two different patient profiles: high and moderate disease activity. Rheumatologists were asked to choose repeatedly between two unlabelled treatment options that differed in five attributes: efficacy (expected improvement and achieved disease activity state), safety (probability of serious adverse events), patients preference (level of agreement), total medication costs and cost-effectiveness. A heteroscedastic discrete choice model using interaction terms between attribute levels and patient profiles (binary variable) was used to assess the preferences of rheumatologists towards each attribute and the influence of the patient profile. Results Overall, 148 rheumatologists completed the survey (46% females, mean age 49 years, 49% academic). For both patient profiles, efficacy dominated the treatment choice over patients preference, safety and economic aspects. However, for patients with high compared with moderate disease activity, the importance of drug efficacy significantly increased (from 48% for moderate to 57% for high disease activity), whereas the importance of patients preference significantly decreased (from 15% to 11%). No significant differences were observed for economic and safety considerations. Conclusion Rheumatologists were willing to give up some efficacy to account for patients preference when choosing treatments for patients with moderate compared to high disease activity. Disease activity however did not influence importance of economic aspects in treatment choices.

SAT0080 Equivalence of Different Versions of The Health Assessment Questionnaire (HAQ) across Socio-Economic Factors in The Multi-National Quest-RA Study

Background Several studies reported socio-economic (SE) gradients in physical function as assessed by HAQ. It is however not known whether this reflects true differences in physical function among socio-economic groups, or whether differential interpretation of HAQ items across SE groups biases item responses. Objectives To investigate differential item functioning (DIF) across SE factors (age, gender, education and work status) when assessing physical function in RA patients across the different composite HAQ scores. Methods Data from the Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA), comprising 8,891 patients from 30 countries (mean age 55 years, 81% females) were used. Physical function in daily activities was assessed using a set of 30 individual items from the different HAQ versions (Stanford HAQ, HAQ-II, modified HAQ (MHAQ) and multi-dimensional HAQ (MDHAQ)). SE factors comprised age, gender, education (years), and work status (yes or no). DIF was investigated using item response theory models implemented in a latent variable modelling framework, with models equivalent to ordinal logistic regressions having answers on each HAQ as outcome and SE factors as well as the latent trait function as predictors. Scores for 4 composite HAQs were recalculated and adjusted for DIF by methods similar as above, but simultaneous modelling all previously identified items exhibiting DIF. To assess the impact of DIF on associations between SE factors and composite HAQ scores, multilevel mixed effect linear regression models were estimated with individuals nested in country. Models were adjusted for SE factors, disease activity score in 28 joints (DAS28)) and a comorbidity index (Rheumatic diseases comorbidity index (RDCI)). Changes in the strength of association between SE-factors and HAQ or for DIF-adjusted HAQ were investigated by comparing β-coefficient of the SE factors in the models. Results Relevant DIF (defined as OR >1.1 or <0.90, (Δ≥10%)) in HAQ items was found for the SE factors age (n=13 items), gender (n=26 items) and work status (n=20 items), whereas education influenced only few items (n=7) (table) (table). Adjustment of composite HAQs for DIF resulted in an increase of HAQ scores, indicating influence of individual item DIF on the composite scores (table). In regression models all SE factors remained significantly related to all composite HAQ before or after adjusting for DIF. Changes in coefficients of regression models were overall negligible, except for gender (all HAQ versions). β-coefficients for gender increased by up to 0.07 (70% coefficient change), indicating several items have for women a different meaning, independent of their underlying level of functional limitation. Conclusions Relevant measurement bias across SE factors was found for a number of individual HAQ items. In composite HAQ scores, some evidence for measurement issues remains. Although not having a major impact in terms of measurement of physical function, there is some need for caution when comparing HAQ between males and females. Disclosure of Interest None declared