See related editorial by Uhlig, <http://arthritis-research.com/content/12/2/114>

Introduction
============

Work disability is a major consequence of rheumatoid arthritis (RA) \[[@B1]-[@B4]\].  Although RA is cumulative over time, 20% to 30% of patients become permanently work-disabled in the first 2 to 3 years of the disease \[[@B5]\].  Rapid remission in early disease appears to be a beneficial strategy against work disability in RA \[[@B6]\]. 

The availability of biologic agents during the past decade has led to expectations of reduced work disability rates in RA \[[@B7]\], according to observations in clinical trials \[[@B8]-[@B12]\].  However, reports of clinical cohorts indicate that work disability remains a major problem in RA \[[@B13]-[@B16]\].  Possible explanations are that the timing of biologic agents after joint damage is seen may be too late in many cases or that the use of biologic agents is unusual in many countries for financial reasons or both \[[@B17]\]. 

The risk of work disability in RA is associated not only with traditional articular, radiographic, and laboratory measures of disease activity and severity but as much or more with demographic, socioeconomic, vocational, functional, and social policy variables \[[@B1],[@B18]\].  Although work disability is one of the most important outcomes in RA, cultural and economical differences between societies \[[@B19]\] may compromise its value as an outcome measure. 

Most studies concerning work disability in RA have been conducted in North America and Western Europe, and little is known about the employability of RA patients in other countries.  A multinational database, Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) \[[@B20],[@B21]\], was established to assess 100 unselected consecutive RA patients per clinic in different countries, including countries outside Western Europe and North America.  In June 2009, the QUEST-RA database included 8,039 patients from 86 clinics in 32 countries.  The QUEST-RA database was analyzed for work status at the onset of RA and discontinuation of work due to RA, as recalled by the patients.  Current clinical status of patients who continued to work or who had stopped working in high-gross domestic product (high-GDP) and low-GDP countries was analyzed. 

Materials and methods
=====================

Establishment of database
-------------------------

QUEST-RA was established in 2005 with the objectives to promote quantitative assessment in usual rheumatology care and to develop a baseline cross-sectional database of consecutive RA patients seen outside of clinical trials in regular care in many countries.  Three or more rheumatologists were asked to enroll 100 consecutive unselected patients in each country \[[@B20]\].  As of June 2009, the program enrolled 8,039 patients from 86 sites in 32 countries, including Argentina, Brazil, Canada, Denmark, Egypt, Estonia, Finland, France, Germany, Greece, Hungary, India, Ireland, Italy, Japan, Kenya, Kosovo, Latvia, Lithuania, Morocco, The Netherlands, Norway, Poland, Romania, Russia, Serbia, Spain, Sweden, Turkey, United Arab Emirates, the UK, and the US \[[@B21]\]. 

Ethics committee approvals
--------------------------

The study was carried out in compliance with the Declaration of Helsinki.  Ethics committees or internal review boards of participating institutes approved the study, and written informed consent was obtained from the patients. 

Physician assessment measures
-----------------------------

All patients were assessed according to a standard protocol to evaluate RA (SPERA) \[[@B22]\].  The physician review included four RA Core Data Set measures: a formal examination of swollen joints (swollen joint count using 28 joints, or SJC28) and tender joints (tender joint count using 28 joints, or TJC28), global estimate of disease activity, and erythrocyte sedimentation rate (ESR).  Rheumatoid factor (RF) positivity according to local reference values was reported as well as whether the patient had radiographic erosions.  All courses of disease-modifying antirheumatic drugs (DMARDs) and biologic agents were listed.  The number of DMARDs over disease course was calculated. 

Patient self-report questionnaire measures
------------------------------------------

Patients completed a 4-page self-report questionnaire, which included three RA Core Data Set measures - physical function, pain, and patient global estimate (PTGL) - as well as demographic data, fatigue, and psychological distress.  A standard Health Assessment Questionnaire (HAQ) \[[@B23]\] assesses physical function in activities of daily living and has four response categories: 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do.  Visual analog scales (VASs) (0 = best to 10 = worst) were completed for pain, fatigue, and PTGL.  Psychological distress was queried as the capacity to cope with sleep, stress, anxiety, and depression in the HAQ format with response options 0 to 3 (seen above) for each question.  The mean of the responses of these four questions was calculated for PS-HAQ (Psychological HAQ) of 0 to 3 \[[@B24]\]. 

Data concerning work or disability status were based on a patient self-report questionnaire that included queries about work status at the time of the first symptoms of RA and currently and that had the following response alternatives: working full-time, working part-time, unemployed, student, homemaker, retired, and disabled.  Full-time workers, part-time workers, students, and unemployed individuals were classified as working in these analyses as these groups had the potential to be employed in the workforce.  Homemakers, retirees, and disabled individuals were classified as non-working, although individuals in these groups may perform valuable non-paid work.  Patient self-perceived work disability was queried with the questions, \'Are you work-disabled because of RA?\' (with response options \'yes\' or \'no\') and \'If so, since when?\'

Gross domestic product
----------------------

The GDP of each country in 2005 was obtained from a database of the International Monetary Fund \[[@B25]\] and is expressed in units of 1,000 US dollars (USD) per capita.  GDP ranged from 3.5 to 49K USD but was either less than 11K USD or greater than 24K USD in all countries.  In this report, the 16 countries with a GDP per capita of greater than 24K USD are classified as \'high-GDP\' whereas the 16 countries with a GDP per capita of less than 11K USD are classified as \'low-GDP\'. 

Statistical methods
-------------------

Descriptive results are presented as mean, median, and percentages.  The disease activity score using 28 joint counts (DAS28) \[[@B26]\] was calculated from the formula 0.56\*v(TJC28) + 0.28\*v(SJC28) + 0.70\*ln(ESR) + 0.014\*(PTGL) and ranged from 0 to 9.1 (low to high).  Comparisons of demographic variables, clinical characteristics, RA disease activity measures, and treatment-related variables were performed using parametric and non-parametric tests for continuous variables and the chi-square test for categorical variables.  Kaplan-Meier statistics were applied; those who reached age 65 after the onset of RA were censored at that date. 

Regressions were performed to analyze which demographic and clinical measures were independently significant to identify work disability status.  Variables in the model included age, sex, education level, HAQ physical function, radiographic erosions, RF, ESR, and SJC28.  Data of all individuals from all countries were pooled together; regressions were performed in four independent categories for all countries: in low-GDP countries, with onset prior to 2000 and after 2000, and in high-GDP countries, with onset prior to 2000 and after 2000.  The year 2000 was chosen as a milestone because the first biologic agent for treatment of RA was approved in 1999. 

Results
=======

Patients
--------

The mean age of 8,039 patients in the QUEST-RA database, from 86 clinics in 32 countries, was 55 years; 80% were females, and the mean disease duration was 11 years (Table [1](#T1){ref-type="table"}).  Patients in low-GDP countries were younger and were more likely to be female and have RF and radiographic erosions compared with those in high-GDP countries, as described in detail previously \[[@B27]\].  Patients in low-GDP countries had statistically significantly higher disease activity levels of all individual RA Core Data Set measures, including physician-derived measures and patient self-report scores, compared with patients in high-GDP countries.  The number of DMARDs taken, and especially the percentage of patients who had ever taken biologic agents, differed significantly, with 31% in high-GDP countries and 9.4% in low-GDP countries (Table [1](#T1){ref-type="table"}). 

###### 

Patient and disease characteristics in 8,039 patients in the QUEST-RA study in countries with a high (\>24K USD) or low (\<11K USD) GDP

                                             All patients                   
  ------------------------------------------ -------------- ------- ------- ----------
  Number                                     8,039          4,235   3,804   
  Patient characteristics                                                   
    Female, percentage                       80%            76%     85%     \< 0.001
    Age in years, mean                       55             58      52      \< 0.001
    Disease duration in years, mean          11             11      11      NS
    Rheumatoid factor-positive, percentage   75%            73%     77%     \< 0.001
    Erosive disease, percentage              63%            59%     67%     \< 0.001
  Disease activity measures                                                 
    DAS28 (0 to 9.1), mean                   4.4            3.7     5.2     \< 0.001
    ESR, median                              25             18      33      \< 0.001
    SJC (0 to 28), median                    2              1       4       \< 0.001
    TJC (0 to 28), median                    4              2       9       \< 0.001
    Physician global (0 to 10), median       2.5            1.7     3.9     \< 0.001
  Patient self-report                                                       
    HAQ physical function (0 to 3), median   0.88           0.75    1.3     \< 0.001
    Pain VAS (0 to 10), median               4.1            3.2     4.7     \< 0.001
    Patient global VAS (0 to 10), median     4.2            3.2     4.8     \< 0.001
    Fatigue VAS (0 to 10), median            4.5            3.8     5.0     \< 0.001
    Psychological HAQ (0 to 3), mean         0.84           0.73    0.99    \< 0.001
  Treatment-related variables                                               
    Number of DMARDs ever taken, mean        2.7            2.8     2.5     \< 0.001
    Biologics ever, percentage of patients   23%            31%     9.4%    \< 0.001

^a^Unadjusted *P*values are presented.  DAS28, disease activity score using 28 joint counts; DMARD, disease-modifying antirheumatic drug; ESR, erythrocyte sedimentation rate; GDP, gross domestic product; HAQ, Health Assessment Questionnaire; NS, not significant; QUEST-RA, Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis; SJC, swollen joint count; TJC, tender joint count; USD, US dollars; VAS, visual analog scale. 

Work status at baseline
-----------------------

At the time of first symptoms, 68% of patients who were 65 years old or younger, including 85% of men (57% to 100% among countries) and 64% of women (19% to 83%), reported that they were working (Table [2](#T2){ref-type="table"}).  Among women, the proportion working at onset ranged from greater than 80% in Sweden, Finland, Estonia, and Lithuania to not more than 50% in Turkey, Kosovo, Morocco, Greece, and Egypt (Table [2](#T2){ref-type="table"}). 

###### 

Percentage of patients who were younger than 65 years old and working at the onset of symptoms in the QUEST-RA study in 32 countries

                    Percentage working^a^at onset          
  ----------------- ------------------------------- ------ -----
  Sweden            88%                             90%    88%
  Finland           83%                             86%    84%
  Estonia           83%                             82%    83%
  Lithuania         82%                             85%    83%
  UK                80%                             90%    82%
  Latvia            79%                             100%   83%
  USA               79%                             93%    83%
  France            78%                             86%    80%
  Denmark           76%                             93%    80%
  Hungary           75%                             73%    75%
  Brazil            73%                             83%    73%
  Germany           72%                             89%    75%
  Canada            65%                             89%    70%
  Argentina         64%                             100%   67%
  Russia            63%                             96%    69%
  India             62%                             93%    67%
  Poland            61%                             78%    63%
  Japan             60%                             85%    64%
  The Netherlands   60%                             82%    67%
  Ireland           59%                             91%    71%
  UAE               59%                             100%   64%
  Spain             57%                             85%    65%
  Serbia            56%                             70%    57%
  Italy             54%                             82%    60%
  Egypt             50%                             73%    51%
  Greece            49%                             73%    55%
  Morocco           42%                             100%   48%
  Kosovo            23%                             57%    28%
  Turkey            19%                             66%    25%
  Norway            NA                              NA     NA
  Total             64%                             85%    68%

NA, not applicable; QUEST-RA, Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis; UAE, United Arab Emirates.  ^a^Defined in Materials and methods. 

Rate of work disability
-----------------------

A third of the patients (37%) who were younger than 65 years old and working at the onset of symptoms reported that they subsequently became work-disabled because of RA, over the median (interquartile range) observation period of 9 (4 to 16) years.  Among 1,754 patients whose symptoms had begun during the 2000s and were working at the baseline, the rates of probability (95% confidence interval) to continue working were 80% (78% to 82%) at 2 years and 68% (65% to 71%) at 5 years, in a similar pattern to women and men in high-GDP and low-GDP countries (Figure [1](#F1){ref-type="fig"}). 

![** Kaplan-Meier probability to continue work in women and men who were diagnosed with rheumatoid arthritis in the 2000s in countries with a high or low gross domestic product (GDP)**.  USD, US dollars.](ar2951-1){#F1}

Clinical status variables in people younger than 65 years old who were working versus those who had stopped working
-------------------------------------------------------------------------------------------------------------------

People who had stopped working had poorer clinical status according to all disease activity and patient self-report measures compared with people who were working (Table [3](#T3){ref-type="table"}).  Although better clinical status was seen in patients who were working than in those who were not working within high-GDP countries and within low-GDP countries, patients who were working in low-GDP countries had significantly better clinical status according to most measures than patients in high-GDP countries who had stopped working (Table [3](#T3){ref-type="table"}).  Among patients who were younger than 65 years old at the evaluation visit and reported that they are working, the current mean HAQ levels in high-GDP versus low-GDP countries were 0.43 versus 0.82 in men and 0.62 versus 0.95 in women.  The mean DAS28 values in high-GDP versus low-GDP countries were, respectively, 3.1 versus 4.6 in men and 3.4 versus 4.8 in women (Figure [2](#F2){ref-type="fig"}), indicating that women continue working at higher disability and disease activity levels compared with men. 

![** Disease activity (DAS28) and physical function (HAQ) in men and women who were younger than 65 years old and continued working in high-GDP and low-GDP countries**.  CI, confidence interval; DAS28, disease activity score using 28 joint counts; GDP, gross domestic product; HAQ, Health Assessment Questionnaire.](ar2951-2){#F2}

###### 

Patient and disease characteristics in 5,493 individuals younger than 65 years who are working or not working in the QUEST-RA study in countries with a high (\>24K USD) or low (\<11K USD) GDP

                                            Individuals younger than 65 years old                                                                 
  ----------------------------------------- --------------------------------------- ------- ---------- ------- ------- ---------- ------- ------- ----------
  Number                                    2,590                                   2,903              1,436   1,347              1,154   1,556   
  Patient characteristics                                                                                                                         
   Females, percentage                      76%                                     85%     \< 0.001   72%     81%     \< 0.001   82%     89%     \< 0.001
   Age in years, mean                       46                                      52      \< 0.001   47      54      \< 0.001   45      50      \< 0.001
   Disease duration in years, mean          8.3                                     11      \< 0.001   8.7     12      \< 0.001   7.8     11      \< 0.001
   Rheumatoid factor-positive, percentage   72%                                     75%     0.004      70%     75%     0.001      75%     76%     0.64
   Erosive disease, percentage              53%                                     65%     \< 0.001   51%     62%     \< 0.001   56%     69%     \< 0.001
  Disease activity measures                                                                                                                       
   DAS28 (0 to 9.1), mean                   4.0                                     4.6     \< 0.001   3.3     3.9     \< 0.001   4.8     5.2     \< 0.001
   ESR, median                              20                                      26      \< 0.001   14      18      \< 0.001   28      32      \< 0.001
   SJC (0 to 28), median                    2                                       3       \< 0.001   1       2       \< 0.001   3       4       0.002
   TJC (0 to 28), median                    3                                       5       \< 0.001   1       2       \< 0.001   7       8       \< 0.001
   Physician global (0 to 10), median       2.1                                     2.8     \< 0.001   1.5     1.9     \< 0.001   3.0     3.8     \< 0.001
  Patient self-report                                                                                                                             
   HAQ physical function (0 to 3), median   0.63                                    1.1     \< 0.001   0.50    0.88    \< 0.001   0.88    1.3     \< 0.001
   Pain VAS (0 to 10), median               3.2                                     4.5     \< 0.001   2.3     3.8     \< 0.001   4.2     4.9     \< 0.001
   Patient global VAS (0 to 10), median     3.3                                     4.6     \< 0.001   2.4     3.6     \< 0.001   4.3     5.0     \< 0.001
   Fatigue VAS (0 to 10), median            3.9                                     4.8     \< 0.001   3.2     4.2     \< 0.001   4.5     5.2     \< 0.001
   Psychological HAQ (0 to 3), mean         0.79                                    0.94    \< 0.001   0.60    0.82    \< 0.001   0.87    1.1     \< 0.001
  Treatment-related variables                                                                                                                     
   Number of DMARDs ever taken, mean        2.42                                    2.73    \< 0.001   2.6     3.1     \< 0.001   2.2     2.4     \< 0.001
   Biologics ever, percentage of patients   22%                                     21%     0.60       32%     35%     0.12       8.5%    9.0%    0.65

^a^Unadjusted *P*values are presented.  DAS28, disease activity score using 28 joint counts; DMARD, disease-modifying antirheumatic drug; ESR, erythrocyte sedimentation rate; GDP, gross domestic product; HAQ, Health Assessment Questionnaire; QUEST-RA, Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis; SJC, swollen joint count; TJC, tender joint count; USD, US dollars; VAS, visual analog scale. 

Differences in drug treatments
------------------------------

Among individuals who were younger than 65 years old at the evaluation, the rates of use of biologic agents were higher in those who had discontinued versus continued working and were 39% versus 32% in high-GDP countries and 13% versus 8.3% in low-GDP countries. 

Identifiers of work disability
------------------------------

A series of logistic regressions was performed to analyze the independent capacity of age, sex, education, RF, radiographic erosions, HAQ physical function, ESR, and SJC28 to identify people who reported that they were work-disabled due to RA (Table [4](#T4){ref-type="table"}).  In the entire database, HAQ physical function, radiographic erosions, and sex were the three significant variables in these regressions (Table [4](#T4){ref-type="table"}). 

###### 

Regression analyses to identify work disability status in 5,493 individuals younger than 65 years in the QUEST-RA study in 32 countries with a high (\>24K USD) or low (\<11K USD) GDP

  ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
  Type of country   Onset of RA   Sex, male     Age           Education lowest 2/3   RF-positive, ever   Erosion-positive, ever   HAQ           ESR           SJC28         Constant
  ----------------- ------------- ------------- ------------- ---------------------- ------------------- ------------------------ ------------- ------------- ------------- ----------
  All countries                   1.46\         0.99\         1.36\                  1.10\               1.74\                    2.76\         1.00\         0.99\         0.13
                                  (1.26-1.68)   (0.99-1.0)    (1.21-1.54)            (0.96-1.26)         (1.53-1.96)              (2.53-3.01)   (0.99-1.00)   (0.98-1.00)   

  Low-GDP           Pre-2000      2.04\         0.98\         1.22\                  1.52\               1.97\                    2.65\         1.00\         0.98\         0.32
                                  (1.38-3.02)   (0.97-0.99)   (0.95-1.58)            (1.12-2.08)         (1.40-2.76)              (2.19-3.19)   (0.99-1.00)   (0.96-1.01)   

                    Post-2000     1.26\         1.00\         1.65\                  1.07\               2.10\                    2.33\         1.00\         0.98\         0.07
                                  (0.92-1.74)   (0.99-1.01)   (1.27-2.14)            (0.82-1.42)         (1.64-2.69)              (1.93-2.81)   (0.99-1.01)   (0.95-1.00)   

  High-GDP          Pre-2000      1.41\         0.99\         1.40\                  0.89\               1.12\                    2.94\         1.00\         1.00\         0.25
                                  (1.10-1.79)   (0.98-1.00)   (1.13-1.73)            (0.70-1.14)         (0.89-1.42)              (2.52-3.43)   (0.99-1.01)   (0.98-1.02)   

                    Post-2000     1.71\         0.99\         1.43\                  0.99\               1.16\                    2.89\         1.00\         1.02\         0.15
                                  (1.29-2.26)   (0.98-1.00)   (1.09-1.87)            (0.75-1.30)         (0.90-1.50)              (2.36-3.54)   (0.99-1.01)   (0.99-1.05)   
  ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Odds ratios (95% confidence intervals) are presented.  ESR, erythrocyte sedimentation rate; GDP, gross domestic product; HAQ, Health Assessment Questionnaire; QUEST-RA, Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis; RA, rheumatoid arthritis; RF, rheumatoid factor; SJC28, swollen joint count using 28 joints; USD, US dollars. 

Discussion
==========

The multinational QUEST-RA study provides several important observations concerning work-related outcomes in RA: (a) work disability rates remain high among patients with RA during this millennium; (b) major differences are seen in the proportion of women and men working at the onset of RA in different countries; (c) people continue working in low-GDP countries with levels of disease activity as high as or higher than those of work-disabled people with RA in high-GDP countries; and (d) in both high-GDP and low-GDP nations, the most significant identifier of work disability is the HAQ functional disability score. 

Work disability rates remain high among patients with rheumatoid arthritis during this millennium
-------------------------------------------------------------------------------------------------

The availability of biologic agents over the past decade has increased expectations of reduced work disability rates in RA \[[@B7]\], based on results of clinical studies \[[@B8]-[@B11]\].  However, reports based on clinical cohorts have not indicated major effects of biologic agents on patients\' work status \[[@B13]-[@B15]\].  The timing of treatment with biologic agents may not be optimal in many situations, and biologic agents are used infrequently in many countries for financial reasons (Tables [1](#T1){ref-type="table"} and [3](#T3){ref-type="table"}) \[[@B17]\].  In QUEST-RA, a greater proportion of those who had discontinued versus continued working had taken biologic agents.  Perhaps the early use of biologic agents will be associated with prevention of work disability in the future.  However, at this time in actual clinics, the use of biologic agents appears to be primarily a surrogate for disease severity.  In an ideal world, a reduction of work disability rates in RA patients might be achieved by initiating early and aggressive treatment within some weeks or months of the first symptoms \[[@B28]\].  The Finnish Rheumatoid Arthritis Combination Trial (FIN-RACo) \[[@B6]\] documented that early remission is critical concerning subsequent work or disability status: All patients who were in remission 6 months after baseline continued to work at 5 years compared with less than 80% with ACR20 (American College of Rheumatology 20% improvement criteria) and ACR50 responses and less than 50% with less than ACR20 responses \[[@B6]\].  FIN-RACo also indicated that traditional DMARDs, without biologic agents, can prevent work disability in early RA. 

Work disability as an outcome measure of rheumatoid arthritis
-------------------------------------------------------------

It has become a fashion to use work disability-related outcome measures in the trials of biologic agents.  Reports from clinical trials of biologic agents appear to be based on a traditional \'biomedical model\' \[[@B29]\] view that work disability is a direct consequence of severe disease activity and damage.  Previous studies document that mean levels of clinical variables in RA patients who were work-disabled in Finland indicated better clinical status than RA patients who were working in the US, and this difference was explained by different social policies regarding work disability \[[@B19]\].  In QUEST-RA, disease activity and disability levels were as high in working people in low-GDP countries as in work-disabled people in high-GDP countries.  Thus, the QUEST-RA data extend evidence that macroeconomic variables influence an individual\'s work status to a greater degree than an individual\'s disease activity.  The majority of patients with RA are women, a low proportion of whom are employed in certain countries at disease onset.  In the present study, women continued working with higher scores of disease activity and functional disability compared with men (Figure [2](#F2){ref-type="fig"}).  Cultural and socioeconomic differences between societies affect work disability as an outcome measure.  In the RA population, losses in household productivity may be a more important matter than disability at paid work; household productivity is affected many-fold compared with paid productivity \[[@B30]\]. 

The HAQ functional disability score as the most significant identifier of work disability was confirmed in the QUEST-RA database including different countries and cultures in addition to what has been observed in Western countries \[[@B31],[@B32]\].  In addition to disease activity and damage, variables such as age, sex, education, occupation, duration of disease, functional status, family, physical demand, and time control issues at work have an impact on work status \[[@B1],[@B33]\].  In one study, if scores were known for physical function, occupation, age, and duration of disease, other clinical status measures, including joint counts, radiographs, and laboratory tests, did not add to the explanation of a patient\'s work or disability status \[[@B34]\]. 

Limitations
-----------

This study has several limitations.  First, cross-sectional QUEST-RA data cannot provide detailed analysis of all work disability-related issues such as specified instruments concerning work disability/participation but rather provide an overview across various countries.  The short 4-page patient questionnaire did not include a question about workload, for example, to analyze in this multinational setting whether, as has been suggested \[[@B35]\], work disability is a consequence of mismatch between an individual\'s functional capacity (HAQ) and work requirements.  Second, some of the patients have a long disease duration and might not fully remember their work history.  Therefore, recall bias may be one of the limitations of this study.  Third, a limited number of patients were included per country.  Nonetheless, results were quite similar among clinics within each country \[[@B20]\].  Fourth, it is possible that only RA patients with poor clinical status visit clinics in low-GDP countries and that patients with better status in high-GDP countries seek medical care.  While this possibility cannot be excluded, the study was designed to incorporate a cross-section of patients seen in various countries.  Nevertheless, the QUEST-RA results illustrate the potential value of collaborative databases, with identical database content and architecture, to provide an opportunity to study associations between disease characteristics, therapies, and outcomes at many sites in many countries with different cultural and socioeconomic environments.  Work disability accounts for a major fraction of the costs of RA to both patients and societies.  Improved work disability outcomes in RA will require attention to social, economic, and political issues and wider physician and public education in addition to improved medical management of the disease. 

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. 

Abbreviations
=============

ACR20: American College of Rheumatology 20% improvement criteria; DAS28: disease activity score using 28 joint counts; DMARD: disease-modifying antirheumatic drug; ESR: erythrocyte sedimentation rate; FIN-RACo: The Finnish Rheumatoid Arthritis Combination Trial; GDP: gross domestic product; HAQ: Health Assessment Questionnaire; ln: logarithm; PTGL: patient global estimate of disease activity; QUEST-RA: Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis; RA: rheumatoid arthritis; RF: rheumatoid factor; SJC28: swollen joint count using 28 joints; TJC28: tender joint count using 28 joints; USD: US dollars. 

Competing interests
===================

One or more authors of this article have received reimbursements, fees, or funding from the following pharmaceutical companies: Abbott (Abbott Park, IL, USA), Allergan, Inc. (Irvine, CA, USA), Amgen (Thousand Oaks, CA, USA), Bristol-Myers Squibb Company (Princeton, NJ, USA), Chelsea Therapeutics, Inc. (Charlotte, NC, USA), GlaxoSmithKline (Uxbridge, Middlesex, UK), Jazz Pharmaceuticals (Palo Alto, CA, USA), Merrimack Pharmaceuticals, Inc. (Cambridge, MA, USA), MSD (Whitehouse Station, NJ, USA), Pfizer Inc (New York, NY, USA), Pierre Fabre Medicament (Boulogne Cedex, France), Roche (Basel, Switzerland), sanofi-aventis (Paris, France), Schering-Plough Corporation (Kenilworth, NJ, USA), UCB (Brussels, Belgium), and Wyeth (Madison, NJ, USA). 

Authors\' contributions
=======================

TS, HK, and TP contributed to study design and analyses.  The entire QUEST-RA study group contributed to data collection and preparation of the manuscript.  All authors read and approved the final manuscript. 

Acknowledgements
================

QUEST-RA Investigators:

Argentina: Sergio Toloza, Santiago Aguero, Sergio Orellana Barrera, Soledad Retamozo, Hospital San Juan Bautista, Catamarca; Paula Alba, Cruz Lascano, Alejandra Babini, Eduardo Albiero, Hospital of Cordoba, Cordoba. 

Brazil: Geraldo da Rocha Castelar Pinheiro, Universidade do Estado do Rio de Janeiro, Rio de Janeiro; Licia Maria Henrique da Mota, Hospital Universitário de Brasília; Ines Guimaraes da Silveira, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre; FAC Rocha, Universidade Federal do Ceará, Fortaleza; Ieda Maria Magalhães Laurindo, Universidade Estadual de São Paulo, São Paulo. 

Canada: Juris Lazovskis, Riverside Professional Center, Sydney, NS. 

Denmark: Merete Lund Hetland, Lykke Ørnbjerg, Copenhagen Univ Hospital at Hvidovre and Glostrup, Hvidovre; Kim Hørslev-Petersen, King Christian the Xth Hospital, Gråsten; Troels Mørk Hansen, Lene Surland Knudsen, Copenhagen Univ Hospital at Herlev, Herlev. 

Egypt: Hisham Hamoud, Mohamad Sobhy, Ahmad Fahmy, Mohamad Magdy, Hany Aly, Hatem Saeid, Ahmad Nagm, Al-Azhar University, Cairo; Nihal A Fathi, Assiut University Hospital, Assiut; Esam Abda, Zahra Ebraheam, Abo Sohage University Hospital, Sohage. 

Estonia: Raili Müller, Reet Kuuse, Marika Tammaru, Riina Kallikorm, Tartu University Hospital, Tartu; Tony Peets, Kati Otsa, Karin Laas, East-Tallinn Central Hospital, Tallinn; Ivo Valter, Center for Clinical and Basic Research, Tallinn. 

Finland: Heidi Mäkinen, Jyväskylä Central Hospital, Jyväskylä, and Tampere University Hospital, Tampere; Kai Immonen, Sinikka Forsberg, Jukka Lähteenmäki, North Karelia Central Hospital, Joensuu; Reijo Luukkainen, Satakunta Central Hospital, Rauma. 

France: Laure Gossec, Maxime Dougados, University René Descartes, Hôpital Cochin, Paris; Jean Francis Maillefert, Dijon University Hospital, University of Burgundy, and INSERM U887, Dijon; Bernard Combe, Hôpital Lapeyronie, Montpellier; Jean Sibilia, Hôpital Hautepierre, Strasbourg. 

Greece: Alexandros A Drosos, Sofia Exarchou, University of Ioannina, Ioannina; H M Moutsopoulos, Afrodite Tsirogianni, School of Medicine, National University of Athens, Athens; Fotini N Skopouli, Maria Mavrommati, Euroclinic Hospital, Athens. 

Germany: Gertraud Herborn, Rolf Rau, Siegfrid Wassenberg, Evangelisches Fachkrankenhaus, Ratingen; Rieke Alten, Christof Pohl, Schlosspark-Klinik, Berlin; Gerd R Burmester, Bettina Marsmann, Charite - University Medicine Berlin, Berlin. 

Hungary: Pál Géher, Semmelweis University of Medical Sciences, Budapest; Bernadette Rojkovich, Ilona Újfalussy, Polyclinic of the Hospitaller Brothers of St. John of God in Budapest, Budapest. 

Ireland: Barry Bresnihan, St. Vincent University Hospital, Dublin; Patricia Minnock, Our Lady\'s Hospice, Dublin; Eithne Murphy, Claire Sheehy, Edel Quirke, Connolly Hospital, Dublin; Joe Devlin, Shafeeq Alraqi, Waterford Regional Hospital, Waterford. 

India: Amita Aggarwal, Department of Immunology, Lucknow; Sapan C Pandya, Vedanta Institiute of Medical Sciences, Ahmedabad; Banwari Sharma, Department of Immunology, Jaipur Hospital. 

Italy: Massimiliano Cazzato, Stefano Bombardieri, Santa Chiara Hospital, Pisa; Gianfranco Ferraccioli, Alessia Morelli, Catholic University of Sacred Heart, Rome; Maurizio Cutolo, University of Genova, Genova; Fausto Salaffi, Andrea Stancati, University of Ancona, Ancona. 

Japan: Hisashi Yamanaka, Ayako Nakajima, Institute of Rheumatology, Tokyo Women\'s Medical University, Tokyo; Wataru Fukuda, Department of Rheumatology, Kyoto First Red Cross Hospital, Kyoto; Eisuke Shono, Shono Rheumatism Clinic, Fukuoka. 

Kenya: G Omondi Oyoo, Kenyatta Hospital, Nairobi. 

Kosovo: Sylejman Rexhepi, Mjellma Rexhepi, Rheumatology Department, Pristine. 

Latvia: Daina Andersone, Pauls Stradina Clinical University Hospital, Riga. 

Lithuania: Sigita Stropuviene, Jolanta Dadoniene, Institute of Experimental and Clinical Medicine at Vilnius University, Vilnius; Asta Baranauskaite, Kaunas University Hospital, Kaunas. 

Morocco: Najia Hajjaj-Hassouni, Karima Benbouazza, Fadoua Allali, Rachid Bahiri, Bouchra Amine, El Ayachi Hospital Mohamed Vth Souissi University, Rabat. 

The Netherlands: Johannes WG Jacobs, Suzan MM Verstappen, University Medical Center Utrecht, Utrecht; Margriet Huisman, Femke Bonte-Mineur, Sint Franciscus Gasthuis, Rotterdam; Monique Hoekstra, Medisch Spectrum Twente, Enschede. 

Norway: Glenn Haugeberg, Hilde Gjelberg, Eirik Wilberg, Sørlandet Hospital, Kristiansand. 

Poland: Stanislaw Sierakowski, Medical University in Bialystok, Bialystok; Maria Majdan, Medical University of Lublin, Lublin; Wojciech Romanowski, Poznan Rheumatology Center in Srem, Srem; Witold Tlustochowicz, Military Institute of Medicine, Warsaw; Danuta Kapolka, Silesian Hospital for Rheumatology and Rehabilitation in Ustron Slaski, Ustroñ Slaski; Stefan Sadkiewicz, Szpital Wojewodzki im. Jana Biziela, Bydgoszcz; Danuta Zarowny-Wierzbinska, Wojewodzki Zespol Reumatologiczny im. dr Jadwigi Titz-Kosko, Sopot. 

Romania: Ruxandra Ionescu, Denisa Predeteanu, Spitalul Clinic Sf Maria, Bucharest; Lia Georgescu, Spitalul Cinic Judetean de Urgenta Mures, Targu Mures; Rodica Marieta Chirieac, Codrina Ancuta, Gr.  T. Popa University of Medicine and Pharmacy Iasi, Iasi. 

Russia: Dmitry Karateev, Elena Luchikhina, Institute of Rheumatology of Russian Academy of Medical Sciences, Moscow; Natalia Chichasova, Moscow Medical Academy, Moscow; Vladimir Badokin, Russian Medical Academy of Postgraduate Education, Moscow. 

Serbia: Vlado Skakic, Aleksander Dimic, Jovan Nedovic, Aleksandra Stankovic, Rheumatology Institut, Niska Banja. 

Spain: Antonio Naranjo, Carlos Rodríguez-Lozano, Hospital de Gran Canaria Dr. Negrin, Las Palmas; Jaime Calvo-Alen, Hospital Sierrallana Ganzo, Torrelavega; Miguel Belmonte, Hospital General de Castellón, Castellón. 

Sweden: Eva Baecklund, Dan Henrohn, Uppsala University Hospital, Uppsala; Rolf Oding, Margareth Liveborn, Centrallasarettet, Västerås; Ann-Carin Holmqvist, Hudiksvall Medical Clinic, Hudiksvall. 

Turkey: Feride Gogus, Gazi University Medical Faculty, Ankara; Recep Tunc, Meram Medical Faculty, Konya; Selda Celic, Cerrahpasa Medic Faculty, Istanbul. 

United Arab Emirates: Humeira Badsha, Dubai Bone and Joint Center, Dubai; Ayman Mofti, American Hospital Dubai, Dubai. 

UK: Peter Taylor, Catherine McClinton, Charing Cross Hospital, London; Anthony Woolf, Ginny Chorghade, Royal Cornwall Hospital, Truro; Ernest Choy, Stephen Kelly, Kings College Hospital, London. 

USA: Theodore Pincus, Vanderbilt University, Nashville, TN; Yusuf Yazici, NYU Hospital for Joint Diseases, New York, NY; Martin Bergman, Taylor Hospital, Ridley Park, PA; Jurgen Craig-Müller, CentraCare Clinic, St. Cloud, MN. 

Study Center: Tuulikki Sokka, Hannu Kautiainen, Jyväskylä Central Hospital, Jyväskylä, and Medcare Oy, Äänekoski, Finland; Christopher Swearingen, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Theodore Pincus, New York University Hospital for Joint Diseases, New York, NY, USA. 

Funding sources: Abbott provided an unrestricted grant to establish the study and to cover printing and mailing expenses to participating rheumatologists but did not participate in conducting the study, analyzing data, or writing reports. 

TS has received grants from Central Finland Health Care District and Heinola Rheumatism Foundation Hospital (EVO grants). 

Ethics committee approvals: the study was carried out in compliance with the Declaration of Helsinki.  Ethics committees or internal review boards of participating institutes approved the study, and informed consent was obtained from the patients.