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Abstract
Background New strategies and options for the treatment of rheumatoid arthritis (RA) have evolved during the past decade. A study was undertaken to investigate to what extent this influenced daily rheumatological care and how this translates into clinical and patient-reported outcomes.
Methods Data from a total of 38 723 outpatients with RA enrolled in the National Database of the German Collaborative Arthritis Centres in the years 1997–2007 were analysed. The cross-sectional annual data were compared to detect time trends.
Results Between 1997 and 2007 the prescription of combinations of traditional disease-modifying antirheumatic drugs (DMARDs) increased from 8% of all patients to 23%; biological agents were prescribed to 16% of patients with RA in 2007. The mean disease activity (DAS28) fell from 4.5 to 3.4 (median 4.5–3.2). The percentage of patients with low disease activity (DAS28 <3.2) increased significantly from 23% to 49%. The proportion of patients with ≥6 swollen joints fell from 43.1% in 1997 to 8.1% in 2007 and, in those with ≥6 tender joints, from 46.3% to 15.8%. There was a large decrease in the total annual number of days of sick leave due to the rheumatic condition from 27.2 to 8.8 days per gainfully employed person. This reduction is far beyond the decline in the general population. There was also a tendency to higher participation in the work force, specifically in older patients, reflecting the trend seen in the general population.
Conclusions The intensity of drug treatment in patients with RA has increased during the past 7 years. This has been accompanied by not only a decrease in disease activity but also a considerable reduction of economic losses due to sick leave and permanent work disability.
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Introduction
During the past decade, treatment in rheumatology has fundamentally changed owing to the availability of novel therapeutic options as well as improved treatment strategies for patients with rheumatoid arthritis (RA) and other inflammatory rheumatic diseases. Many studies have convincingly shown that early initiation and timely escalation of treatment with conventional disease-modifying antirheumatic drugs (DMARDs) and the initiation of treatment with biological agents (usually after failure of conventional DMARDs) can significantly improve the prognosis of patients with RA.1,–,5 However, little is known of the extent to which these new treatment options and strategies have entered routine rheumatological care and how the clinical and social outcomes of patients treated today have changed compared with earlier times.
German rheumatology has a 17-year tradition of ongoing monitoring of patients with inflammatory rheumatic diseases. In 1993 the National Database of the German Collaborative Arthritis Centres was established. Since then, more than 15 000 patients have been recorded each year. The database provides information on trends in treatment, outcomes and burden of disease in patients seen by rheumatologists.
In the past, results from the National Database were reported on treatment and outcomes,6,–,9 the burden of illness,10 11 developments of employment12 and on the cost of illness.13 In this paper we analyse recent trends in treatment and outcomes based on data from the years 1997–2007.
Methods
The National Database of the German Collaborative Arthritis Centres was established in 1993 as a long-term monitoring system for patients treated in rheumatology care units in Germany. The objective is to provide rheumatology data on deficits and trends in healthcare, on variations in healthcare provision, outcomes of care and costs of rheumatic diseases.
The database contains data from outpatients with an inflammatory disease who were treated in the participating rheumatology units. These units comprise university departments, departments of rheumatology at general hospitals and rheumatologists in private practices. Once a year the clinical status (physician-derived data) and a patient questionnaire of each outpatient are recorded. Owing to financial restrictions, the data collection is limited to once-yearly. The follow-up documentation is done at a regular visit which comes closest to the month of the documentation in the previous year.
From 1993 to 2004 the data were collected via paper-based forms and sent to the German Rheumatism Research Centre for further data processing. In 2005 we switched to a system with electronic data entry by the rheumatologists and paper-based data from the patients. A study nurse feeds the patient-reported data into an IT system. The changeover to a system of electronic data entry required financial support for study nurses in the rheumatology units which could only be provided for a limited number of sites. Eighteen large rheumatology units, representative of the spectrum of all previously participating sites, continued to contribute. Despite the loss of a considerable number of participating centres, the number of patients recorded annually only decreased from 25 000 to 17 000. This high number of cases still allows a detailed description of the healthcare situation in Germany.
The changeover to IT-based data collection produced a number of difficulties in the participating units, therefore the data from 2005 and 2006 have to be interpreted with some caution. In 2007 the data do again reflect the full spectrum of patients seen in the units.
The clinical dataset recorded in patients with RA remained the same over the years and included the following parameters: onset of symptoms, diagnosis and comorbidity, current treatment, treatment during the past 12 months, 28-joint disease activity score (DAS28) and Steinbrocker's functional class.14 Patients provided information on the utilisation of health services, social and family status, employment situation (including sickness absence during past 12 months) and indicators of quality of life (pain, general health, functional status). Global health was recorded on a 5-point Likert scale until 1999 and on a 0–10 rating scale thereafter. The data before 2000 are therefore not comparable and are not reported. Disability was recorded using the Hannover Functional Status Questionnaire (FFbH), an 18-item scale of activities of daily living. The FFbH is comparable to the Health Assessment Questionnaire (HAQ) but is used more frequently in Germany. The two disability scales are highly correlated (r=0.87). FFbH values can be translated into HAQ values.15
In this paper we report treatment and outcome data for patients with RA for the years 1997–2007. In order to avoid bias due to practice variation, we included only patients from those rheumatology units which participated in all respective years. The number of patients included in the analysis is therefore lower than the total number of patients with RA enrolled. However, these patients reflect the developments seen in the entire dataset. We see a trend towards increasing age and increasing disease duration in the entire dataset as well as in the data presented here. This can be explained by the high proportion of patients in long-term care. Between 52% and 69% of the patients in the individual years had been seen in the documenting unit in the previous year.
In order to relate the employment rates of the patients with RA in our database to the general population rates, we calculated standardised rates weighted by age, gender and calendar year, thus taking into account the skewed age and sex distribution of patients with RA. Owing to low numbers of cases in younger age groups, standardisation could only be performed for the age groups 40–54 and 55–64 years.
To test for time trends, a simple trend test based on mean square successive differences was performed.16 Levels of resulting p values are shown in the tables. No adjustment for multiple testing was made.
Results
In the years 1997–2007, the numbers of patients with RA who were enrolled in the database by the selected units varied between 4020 in 2004 (last year using paper-based forms) and 2549 in 2005 (first year with electronic data entry, table 1). In 2005 and 2006, the numbers of patients recorded were relatively low due to initial problems caused by the changeover to electronic recording. In 2007, almost the same number of cases was reached as in the paper-based years. In the individual years, 76–79% of the patients were women and the mean age was 59.6–62.3 years with a tendency towards increasing age. There was also a slight tendency towards increasing disease duration owing to the significant increase in the percentage of patients with a disease duration of >10 years.
Characteristics of patients included in the analysis
Disease activity and patient-reported outcomes
The mean (median) DAS28 decreased from 4.5 (4.5) in 1997 to 3.4 (3.2) in 2007 (table 2). The percentage of patients with low disease activity (DAS28 <3.2) increased significantly from 23% to 49%, whereas the percentage of patients with high disease activity (DAS28 >5.1) decreased noticeably from 36% to 10%; 29% of the patients seen in 2007 were in DAS28 remission. In patients with disease duration up to 2 years, the percentage of patients in remission was 33%.
Clinical and patient derived outcomes
A decrease in the mean DAS28 scores could be seen in patients irrespective of whether they had a short, medium or long disease duration (figure 1). For patients with a disease duration ≤2 years the mean score decreased from 4.9 to 3.2, while in those with a long disease duration the mean score decreased from 4.7 to 3.5. In 2007, patients with a disease duration of <2 years and those with a disease duration of more than 2–10 years had a mean DAS28 of about 3.2, which is the threshold for low disease activity. This improvement in the DAS28 corresponds to a significant decrease in the mean number of swollen joints and in the percentage of patients with ≥6 swollen or tender joints. Mean C reactive protein levels fell from 2.4 to 1.1 mg/l in all patients with RA from 1997 to 2007.
Mean 28-joint disease activity score (DAS28) in patients with rheumatoid arthritis by disease duration, 1997–2007.
However, despite the clear improvements in physician-derived assessments, independent of disease duration the patient-reported outcomes did not show much improvement. The mean pain level, the percentage of patients with severe pain (≥7 on a rating scale of 0–10) and the mean global health assessment remained unchanged. The mean functional status improved only marginally, independent of disease duration (table 2).
Drug treatment
Table 3 shows the spectrum of DMARDs and other drug prescriptions for the rheumatic disease. Between 13% and 19% of the patients did not receive DMARD treatment (conventional or biological) at the time of documentation. In 1997, 21% of these patients were in DAS28 remission, and this proportion increased to 31% in 2007. Patients without DMARDs who were not in remission had more comorbidities such as renal or liver disease, gastrointestinal disorders, diabetes or cardiovascular disease. Between 4% and 8% of the patients were on prednisone monotherapy. Over the years, a continuous decrease in monotherapy and an increase in combination DMARD therapy was observed with 23% of patients receiving DMARD combination therapy in 2007. With regard to individual drugs, methotrexate (MTX) remained the anchor drug over the years. Many of the patients were on continuous treatment; the continuation rates of MTX in individual patients were 55% over 5 years. Biological agents were prescribed to 1.5% of the patients in 2000 and to 16.2% in 2007. Antimalarial drugs and sulfasalazine were mainly used in combination with MTX. Leflunomide had a share of 12%. The use of COX2 inhibitors rose to 20% in 2003 and then fell to 8%, which was not compensated for by the slow increase in the use of non-selective non-steroidal anti-inflammatory drugs.
Current drug treatment 1997–2007
Hospitalisation
The percentage of patients who received inpatient treatment at least once a year remained relatively stable at 16–19% of all outpatients (table 4). However, the mean cumulative annual duration of stay in hospitals decreased from 26 days in 1997 to 15 days in 2007. For all patients, this corresponds to a decrease in the annual per capita hospital days from 4.9 to 2.5 days.
Healthcare utilisation and work participation
Sick leave
Gainfully employed patients showed a decrease in sickness absence (table 4). The percentage of employed persons with at least one phase of sick leave due to the rheumatic condition in the preceding year decreased from 39% to 27% between 1997 and 2007 and the mean duration of sick leave decreased from 71 to 33 days. This resulted in a decline in the total number of days on sick leave per employed person of 68% (from 27.2 in 1997 to 8.8 in 2007). A less pronounced reduction in sick leave was also seen in the general population, with the total number of sickness absence days (for any reason) per employed compulsorily insured person decreasing by 30% from 18.4 days in 1997 to 12.8 days in 2007.17 18
Employment
In 1997, 37% of women and 47% of men with RA aged 18–64 years were in gainful employment compared with 46% of women and 57% of men in 2007. In those aged 55–64 years, the percentage of patients still in gainful employment rose from 22% to 30% for women and from 37% to 44% for men. When our data were standardised with the age and sex distribution of the general population, there was a total increase of 7% in the employment rates in this age group (from 31% to 38%). At the same time, higher employment rates were also seen in the general population of Germany; in persons aged 55–64 the employment rate increased by 14% (from 38% to 52%) between 1997 and 2007.
Between 1997 and 2007 the employment rate for those aged 40–54 years increased from 53% to 65% (table 4) for women and from 61% to 73% for men with RA. For this age group we observed the same trend in the general population for women, while the employment rate of men remained almost stable during this period.
In the age group 55–64 years, the percentage of patients with RA still in gainful employment rose from 23% to 31% for women and from 38% to 46% for men. During this time, the mean days of sick leave per employed patient decreased from 27.2 to 8.8 days. In the general population the proportion of working persons increased by about the same degree (from 29% to 44% for women and from 48% to 60% for men).
Discussion
Our analysis shows a constant decline in disease activity, paralleled by an increase in work participation (reduction of sick leave as well as increase in the percentage of gainfully employed persons) of patients with RA treated in German rheumatology units over the past 11 years. At the same time, we observed an increasing intensity of treatment, reflected by increasing use of DMARD combinations and of new therapeutic options such as biological agents.
Moreover, we observed a significant decrease in the proportion of patients who had ≥6 swollen or tender joints. Most of the contemporary clinical trials require this criterion for patient inclusion. In 2007, only 8% of the patients in daily care would have fulfilled the swollen joint criterion and 16% the tender joint criterion.
Our data coincide with reports from other datasets that have reported an improvement in earlier years. Pincus et al19 compared two smaller cohorts of patients seen between 1984 and 1986 (1985 cohort, n=125) or between 1999 and 2001 (2000 cohort, n=150). The mean DAS28 score decreased from 5.7 to 4.4 in the 2000 cohort. At the start of our observation in 1997, the mean DAS28 score was 4.5, with a constant decrease thereafter. The mean swollen joint count in the study by Pincus et al decreased from 12 to 5 in 2000 compared with a decrease from 4.8 to 1.4 in our data. The treatment data for the year 2000 shown by Pincus et al19 are in part comparable with our 2000 data (13% of patients with RA in the Pincus et al study were without DMARDs at documentation vs 15% in our study, 10% vs 4% were treated with glucocorticoids only, 77% vs 55% received MTX, 6% vs 2% used biological agents). Combinations of MTX with other DMARDs were given to 11% of the patients in the 2000 cohort in the study by Pincus et al and all DMARD combinations (the majority with MTX) added up to 12% in 2001 in our study.
There have been several reports indicating that RA might have become a milder disease in more recent years. Bergström et al20 compared two cohorts in Malmö, Sweden and observed a decrease in disease activity and disability between 1978 and 1995. The increasing intensity of treatment (68% on DMARDs in 1995 vs 51% in 1978) was paralleled by a significant improvement in the Ritchie articular index and the Steinbrocker functional class.
Uhlig et al21 investigated patient-reported outcomes in four cohorts from the Oslo Arthritis Register in 1994, 1996, 2001 and 2004 and found improvement in function, pain and quality of life. However, similar to our data, there was almost no improvement in mean pain intensity between 1996 and 2004 (37.7 and 34.5 on a 0–100 visual analogue scale).
Data from the QUEST-RA study, which compared selected rheumatology sites in 21 countries, showed a mean use of MTX of 63% and of biological agents of 19% between 2005 and 2007.22 This is similar to our data, with 56% of the patients on MTX and 16% on biological agents. Glucocorticoids were used on average by 49% of the patients in the QUEST-RA database and by 54% of the patients in our study. In sum, our data reflect current treatment strategies applied in most countries.
The trend towards more aggressive treatment and better clinical results concerning disease activity is evidently continuing. Our data show that this is accompanied by better outcomes in terms of work force participation. There was a general change in the early retirement policy in Germany at the beginning of this century, leading to a considerable increase in the employment rates of older persons in the population from 2004 onwards. Patients with RA have increased their work participation in a comparable manner to other persons whose retirement in the past may have occurred for a variety of medical and non-medical reasons. In addition, employed patients with RA had a significant decline in sickness absence. Owing to increasing unemployment rates and fear of job loss, sickness absence in Germany has declined in general. It is not self-evident that this also holds true for chronically ill patients. The greater decrease in sick leave in patients with RA compared with the general population is therefore remarkable.
Moreover, we noticed that there is a disconnection between the constant improvement in physician-observed clinical outcomes and the almost unchanged subjective ratings of the patients. A similar observation was made by Welsing et al23 who compared four subcohorts of the Nijmegen early RA cohort according to the date of inclusion (1985–1990 to 2000–2005). In this dataset the DAS28 decreased over the first 5 years from 5.7 to 4.8 and the swollen and tender joint counts and mean erythrocyte sedimentation rate showed significant improvement. Nevertheless, the self-ratings of pain and global well-being did not improve over time with the mean global well-being worsening from 43.6 to 49.2 on a 0–100 scale (in our data it was 4.5 on a 0–10 scale in 2000 and 4.6 in 2007) and the mean pain score was 45.3 in the oldest cohort and 47.6 in the most recent cohort (4.7 and 4.5 in our data). Likewise, Pincus et al19 showed that, between 1985 and 2000, the pain score did not change to the same extent as physician-rated disease activity; the mean pain score only decreased from 52 to 49 on a 0–100 scale.
We cannot rule out the possibility that the lack of improvement in the pain scores in our dataset might also be a result of the considerably more restrictive prescription of selective and non-selective non-steroidal antirheumatic drugs since 2004. However, the detachment of physician- and patient-reported outcomes has been a constant trend over many years and was reflected in several datasets. The most plausible explanation is a change in the expectations of the patients. Over the years, patients' knowledge of the possibilities of modern rheumatology has increased steadily and the expectations of both physicians and patients are higher today than 10 years ago. It might well be that patients today are less satisfied with small improvements, and many of them expect a complete release from their symptoms. When these expectations are not met, patients' frustration might be greater than it used to be in the past, despite clinical improvement. As a consequence, when comparing cross-sectional data over longer time periods, it might be advisable to concentrate on physician-rated outcomes as well as ‘objective’ parameters such as employment.
Acknowledgments
The authors acknowledge the invaluable contributions and the enthusiasm of all German consultant rheumatologists who contributed data of their patients with inflammatory rheumatic diseases to the national database since 1993. In particular, the authors would like to acknowledge the significant contributions of those rheumatologists whose data were included in the current analysis R Alten (Berlin), G Hoese (Stadthagen), K Karberg (Berlin), A Krause (Berlin), U von Hinüber and W Demary (Hildesheim), H H Peter (Freiburg), M Schneider (Düsseldorf) and S Wassenberg (Ratingen). The authors gratefully acknowledge the assistance from Katja Thiele, Andrea Pfäfflin and Sascha Bischoff, German Rheumatism Research Centre.
References
Footnotes
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Funding The national database received research grants from the German Federal Ministry of Health (FB2-433346-8/13; 1993–1999), from the German Ministry of Education and Research within the Competence Network Rheumatology (01GI0344/3; 1999–2007), from the Association of German Collaborative Arthritis Centres (2007–2009), and from a consortium of the following pharmaceutical companies who have supported the database since 2007 via joint, unconditional grants to the Rheuma-Akademie of the German Society for Rheumatology: Abbott, Actelion, BMS, Essex, Medac, Merck, MSD, Pfizer, Roche, Sanofi-Aventis, UCB and Wyeth. The principal investigators have full academic freedom in study conduct, data analysis and publication of results.
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Competing interests None.
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Ethics approval This study was conducted with the approval of the Charité Medical School.
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Provenance and peer review Not commissioned; externally peer reviewed.
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