Rheumatoid arthritis is already expensive during the first year of the disease (the Swedish TIRA project)

E. Hallert1,2, M. Husberg3, D. Jonsson3 and T. Skogh1,2

1 Department of Clinical Medicine, Örebro University, 2 Division of Rheumatology, Department of Molecular and Clinical Medicine and 3 Centre for Medical Technology Assessment, Department of Health and Society, Linköping University, Sweden.

Correspondence to: T. Skogh, Rheumatology Unit, Department of Clinical Medicine, University Hospital of Örebro, SE-701 85 Örebro, Sweden. E-mail: thomas.skogh{at}lio.se


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Objective. To calculate direct and indirect costs in early rheumatoid arthritis (RA) and to characterize patients generating high and low costs respectively.

Methods. Two hundred and ninety-seven patients with recent-onset (≤12 months) RA were recruited. Clinical/laboratory data and ‘health assessment questionnaire’ (HAQ) were registered at inclusion and after 3, 6 and 12 months. After 6 and 12 months, the patients completed a questionnaire concerning health-care utilization and days lost from work. A cut-off point for direct costs was set at 34 000 Swedish kronor ({euro}3675) defining one-third of the patients as a high-cost group and two-thirds as low-cost group. Indirect costs were calculated for patients aged <65 yr.

Results. Two hundred and eleven patients completed the HAQ on both occasions. Indirect costs exceeded direct costs by a factor of 2.3. Sixty three per cent experienced work disability during the first year and were identified as the ‘high-indirect-cost group’. Indirect costs accounted for >70% of total costs. Direct costs included ambulatory health care (76%), hospitalization (12%) and medication (9%). Men aged ≥65 yr had low costs compared with younger men and women of all ages. In multiple logistic regression tests, HAQ, high levels of IgM rheumatoid factor (IgM RF) and poor hand function increased the odds of entering the high-direct-cost group, and poor hand function and pain increased the odds of entering the high-indirect-cost group.

Conclusions. Substantial costs were incurred during the first year after diagnosis of early RA, mainly due to work disability. Indirect costs were two to three times higher than direct costs. High levels of IgM RF, high HAQ score, poor hand function and pain increased the odds of entering high-cost groups.

KEY WORDS: Early rheumatoid arthritis, Outcome, Indirect costs, Direct costs, Cost of illness


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Arthritis is a major cause of disability and is associated with a decline in quality of life, reduced ability to work and increased health care utilization [1–5]. In Sweden, with a population of 9 million, the total annual costs of rheumatoid arthritis (RA) were estimated in 1994 to be about 3 billion Swedish kronor (SEK) ({euro}350 million) [6]. Previous studies have reported that health-care costs for RA patients are almost three times greater than for an age- and sex-matched population [7–10]. Several studies have been carried out to analyse the direct and indirect costs of RA over a longer period, but only a few have described the costs during the first year of disease. Newhall-Perry et al. [11] reported that early RA is associated with higher costs than disease of longer duration. In the very short perspective (6 months), the cost of recent-onset RA has been found to be similar to that of other arthritides [12]. While Lapsley et al. [13] reported that the total costs of RA increase with the duration of the disease, Merkesdal et al. [14] found that indirect costs in early RA were equal to those in advanced disease. Van Jaarsveld et al. [5] reported that patients with high disease activity exhibited significantly higher costs than did patients with low disease activity, but found no correlation between direct costs and disease duration. The present study was done to investigate direct and indirect cost during the first year after diagnosis of recent-onset (<1 yr) RA and to examine whether or not the costs were related to baseline disease activity and functional disability. Further, we aimed to identifying characteristics of the group of patients which generated the highest direct and indirect costs.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Patients
All patients participated in a prospective cohort of recent-onset RA, i.e. ‘the Swedish TIRA’ study [15]. TIRA is the Swedish acronym for ‘early intervention in rheumatoid arthritis’, where the involvement of nurses, physiotherapists and occupational therapists is considered in addition to the interventions administrated by physicians. The subjects were enrolled from January 1996 to April 1998 from 10 rheumatology units in southeast Sweden corresponding to a catchment area of a million inhabitants. All patients fulfilled at least four of seven criteria according to the 1987 revised ACR criteria [16] or had suffered from morning stiffness (60 min or more as judged by the patients), symmetrical joint affection and arthritis in small joints (fingers/hands/wrists/toes). The duration of the disease (i.e. onset of joint swelling) was ≤12 months at inclusion. Patients with seronegative psoriasis or any other inflammatory rheumatic disease, serious liver or renal disease were excluded. Three hundred and twenty patients diagnosed with RA were enrolled. 23 (7%) dropped out during the first year; in one case the diagnosis was revised, two moved from the area, two died and 18 did not want to participate further for various reasons.

Disease
Clinical and laboratory data were collected at inclusion and after 3, 6 and 12 months. The number of swollen and tender joints was registered on a 28-joint score [17]. The average duration of morning stiffness for the last week was estimated by the patient. The physician's global assessment of disease activity (PGA) was scored at 0–4, (0 = no activity, 1 = low activity, 2 = moderate activity, 3 = high activity, 4 = very high activity). Erythrocyte sedimentation rate (ESR) and plasma C-reactive protein (CRP) were analysed at all visits. Disease activity was also assessed by calculating the 28-joint count disease activity score (DAS-28) as described by Prevoo et al. [17]. Routine laboratory analyses were performed at the local hospital laboratories. Isotype-specific (IgM and IgA) rheumatoid factors (RF) and antibodies to cyclic citrullinated peptide (anti-CCP) were analysed by enzyme-linked immunosorbent assays (ELISA) (AutozymeTM RF, IgM and IgA respectively, Cambridge Life Sciences, Cambridge, UK; Immunoscan RA CCP2, Eurodiagnostica, Arnhem, The Netherlands). The cut-off limits for positive IgM and IgA RF (34 and 15 U/ml respectively) were based upon the 95 percentile in 100 healthy blood donors. The cut-off limit for anti-CCP antibodies was set at 25 U/ml as suggested by the manufacturer (at this level none of the 80 sera from healthy blood donors turned out positive).

Function, pain and general health
Tests of physical function were performed using a range-of-movement index designated ‘signs of functional impairment’ (SOFI), including assessment of hand function, upper limb function and lower limb function [18]. The score range is 0–16 for hands and lower limbs and 0–12 for upper limbs, higher scores indicating increasing disability. Walking time was measured by asking the patient to walk 20 m as fast as possible. The Swedish version of the Health Assessment Questionnaire (HAQ) was used [19]. The patients were also asked how much pain they had felt on average during the last week. This was estimated on a 100 mm visual-analogue scale (VAS) ranging from 0 (no pain at all) to 100 (worst possible pain). General health was estimated in the same manner, 0 representing ‘best possible well-being’ and 100 ‘worst possible well-being’.

Medication
On-going, instituted and withdrawn medication with disease-modifying anti-rheumatic drugs (DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and analgesics was registered at all visits.

Health utilization and productivity loss
Six and 12 months after inclusion, the patients completed a self-administered questionnaire designed to obtain information about general health and health-care services. They were asked about utilization of health services over the most recent 6 months. This included the number of out-patient visits to a physician and other health-care professionals (i.e. physiotherapist (PT), occupational therapist (OT), nurse, social worker) as well as hospitalization and surgery caused by the rheumatic disease. The patients also reported detailed information regarding medication prescribed to treat the arthritis and/or its complications. The cost of drug safety monitoring was also calculated. The usage of non-prescription medication and complementary therapy such as homeopathy, chiropractics and herbal treatments was also reported. The patients were asked to report the number of days lost from work due to illness and rehabilitation. Costs were calculated using a human capital approach, taking into account all costs that arise from loss of productivity in subjects of working age (18–65 yr), who were unable to work due to the disease.

Direct costs
Direct costs refer to the resources used in medical care and include all health-care utilization, treatments and medication. A distinction was made between disease-specific and non-disease-related resource use and all analyses were limited to care for treatment of the arthritis. Unit costs for visits to physicians and other health professionals were rated using tariffs from the Swedish Federation of County Councils [20]. During the first year all patients had three visits each to physician, nurse, PT and OT, in total 12 visits. To facilitate calculation of the direct costs, a standard cost was calculated for an ambulatory visit to a physician or other health professional including all costs such as laboratory analyses and diagnostic tests, X-ray, etc. A visit to a physician was estimated to cost 2100 SEK ({euro}227) and to a health professional 700 SEK ({euro}76). Costs for hospitalization were calculated in the same manner, estimating a day in hospital to cost 2800 SEK ({euro}302). The costs for surgery, including total costs for surgical interventions, were calculated according to the NordDRG system [21]. Pharmaceutical costs were calculated using market wholesale prices. Costs of complementary medicine were estimated by the patient. Non-medical costs, such as adaptations at home, assistive devices and transportation costs, were not included in the present study.

Indirect costs
Loss of productivity was calculated using the number of days lost from paid work, as reported by the patients. The number of days was recalculated to equal full-time days. The cost of 1 month's full-time work was calculated using an average of the gross income of all gainfully employed Swedish full-time workers and corresponds to 30 000 SEK ({euro}3243) (including taxes and other fees). The cost applied to one working day was 30 000/30 SEK = 1000 SEK. Days of inability to perform work were estimated similarly for those with paid work and those with early retirement due to arthritis. Eight patients (6%) were, however, already early retired at inclusion, possibly due to matters other than arthritis. Mortality costs, i.e. the present value of lost production due to premature death caused by illness, were not calculated. Intangible costs, such as deteriorated quality of life, foregone leisure-time and reliance on other people were not assessed in the present study. Costs were compared between men and women and between patients aged below and above 65 yr. Each patient's questionnaire was reviewed to reduce the risk of errors in the data collection. All costs in the present study are presented in SEK and are adjusted to 2001 values, using the consumer price index and expressed in Euros. The annual average in 2001 was {euro}1 = 9.25 SEK = US$ 0.89.

Ethical considerations
All patients gave written informed consent to participate. The study protocol was approved by the local ethics committees associated with the participating hospitals.

Statistical analyses
Demographic and clinical characteristics are presented using descriptive statistics. All values are expressed as mean and standard deviation (S.D.) unless otherwise stated. Costs are reported in SEK per year. With the aim of identifying subgroups of patients who contributed disproportionately to high direct costs, the patients were divided into high-cost groups and low-cost groups. A cut-off point for direct costs was set at 34 000 SEK/yr ({euro}3675), defining one-third of the patients as the high-direct-cost group and two-thirds as the low-direct-cost group. Indirect costs were calculated for those aged below 65 yr. Thirty seven per cent of the patients aged less than 65 yr had no indirect costs and were identified as the low (=no) indirect-cost group. The remaining 63% belonged to the high-indirect-cost group. Tests of statistical significance were performed using Student's t-test or the Mann–Whitney U-test when appropriate. The {chi}2 test and Fisher's exact test were used to test differences in proportions. Multivariate logistic regression tests were used with high direct costs and high indirect costs as dependent variables. All tests were two-tailed and P<0.05 was considered to be statistically significant. The statistical calculations were performed using the statistical package for the social sciences (SPSS) version 11.5 for Windows.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Clinical variables
At the time of this investigation, 211 patients (71%), 146 women and 65 men, had completed both health utility questionnaires (6 and 12 months after diagnosis). Baseline characteristics were similar for responders and non-responders, except for non-responders reporting a longer duration of morning stiffness (P = 0.03) and worse function of lower limbs (P = 0.01) (data not shown). Demographic and clinical variables for the total study group are presented in Table 1.


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TABLE 1. Demographic and clinical variables for all patients at inclusion and differences between women and men

 
Most patients had a disease duration of <6 months at the time point of study entry. The patients had active arthritis with elevated laboratory markers of inflammation and an average DAS-28 of 5.3. Two hundred patients (95%) fulfilled at least four of seven ACR criteria. On average, the patients fulfilled 4.5 ACR criteria and the mean HAQ score was 0.9. Men were older on average and more affected regarding function of the upper limbs, but nevertheless assessed better well-being than did women. Isotype-specific RF tests were available in 173 patients (82%), 124 women and 49 men. In total 75% were IgM RF-positive with no statistically significant difference between women (76%) and men (69%). Seventy-two per cent of the 173 patients were IgA RF-positive; 71% for women and 76% for men (not significant; n.s.). Anti-CCP tests were available in 159 patients (75%), of which 64% were positive, with no difference between the 113 women and the 46 men (63 and 67% respectively). The mean serum autoantibody levels (U/ml) were IgM RF 225, IgA RF 83 and anti-CCP antibodies 398, with no significant differences between women and men.

Direct costs
Contact with health-care workers
The average annual direct cost was 35 694 SEK ({euro}3858), range 12 600–276 093 SEK ({euro}1362–29 843). All patients had a minimum of three visits to a physician, and PT and/or OT, and nurse. This included the baseline visit as well as the 3- and 6-month visits. The mean number of visits was 31 (range 12–110). Women had significantly more visits to the physician (P = 0.006) and a higher usage of complementary medicine (P<0.0001) compared with men. Women had higher costs for hospitalization than did men: 5427 vs 1249 SEK ({euro}587 vs {euro}135). The costs were, however, highly skewed and no statistical difference was found (Mann–Whitney) (Table 2).


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TABLE 2. Costs during the first year after diagnosis (in SEK)

 
The ambulatory care visits together accounted for 76.1% of the direct costs and medication for 9.4%. The proportion of the direct costs for the total group is shown in Fig. 1. Thirty-eight per cent of the costs for health professionals were related to nurse visits and included drug toxicity monitoring.



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FIG. 1. Pie chart illustrating the distribution of direct costs. The costs for health professionals (48%) consisted of nurse visits (18%), mainly due to drug toxicity monitoring, and of visits to physiotherapists and occupational therapists (30%).

 
Hospitalization and surgery
Hospitalization accounted for 11.6% of the direct costs. Nineteen patients (9%) were hospitalized, 17 patients for 1–28 days and two patients for 41 and 43 days respectively, thus substantially contributing to the mean costs. All hospital admissions were related to the disease or its complications. Six patients had surgery during the first year and two of them had two operations each (bilateral carpal tunnel release). One patient had a total hip arthroplasty and the remaining five had minor hand surgery such as carpal tunnel release and tendo-synovectomies. The median costs for hospitalization and surgery were nil due to the skewed distribution.

Medication
All patients except three were prescribed drugs during the first year to a mean cost of 3347 SEK, range 0–34 833 SEK ({euro}362, range {euro}0–3765). Medication costs accounted for 9.4% of the direct costs. The costs for monitoring of side-effects are included in the ambulatory care visits. Twelve months after inclusion, 147 patients (69.8%) took DMARDs, most frequently methotrexate. NSAIDs were prescribed to 124 (58.7%), analgesics to 59 (27.9%) and glucocorticosteroids to 74 patients (35.1%).

Complementary medicine
Fifty-six patients (26.5%) reported use of complementary medicine. This comprised visits to complementary health-care providers and purchase of complementary care drugs with costs ranging between 46 SEK ({euro}5) and 7300 SEK ({euro}789). Women had a significantly higher usage of complementary medicine than men (P<0.0001).

Patients with high direct costs
With the aim of identifying subgroups of patients who contributed disproportionately to high direct costs, the patients were divided into a high-direct-cost group and a low-direct-cost group. A cut-off point was set at 34 000 SEK/yr ({euro}3675/yr), defining one-third of the patients as the high-direct-cost group and two-thirds as the low-direct-cost group. The high-cost group consisting of 72 patients, 53 women and 19 men, was compared with the low-cost group, consisting of 139 patients, 92 women and 47 men. At inclusion, the high-cost group had significantly worse functional ability as measured by HAQ. They also had worse hand function, walked more slowly and assessed more pain than patients belonging to the low-cost group (Table 3). Seventy-two per cent (83/115) of the patients in the low-cost group were IgM RF positive and 79% (45/58) were positive in the high-cost group (n.s.). Seventy-one per cent were IgA RF positive in the low-cost group and 75% in the high-cost group (n.s.). Anti-CCP tests were positive in 62% of the low-cost group and in 68% in the low-cost group (n.s.). There was no difference between high-cost men and high-cost women at baseline, except for women assessing significantly (P = 0.008) worse well-being (VAS 50 mm) than men (VAS 34 mm). Men in the high-cost group, compared with men in the low-cost group, were significantly younger (51 vs 63 yr, P = 0.001), and had worse hand function (4.6 vs 2.7 at inclusion, P = 0.008). Women in the high-cost group, compared with women in the low-cost group, had significantly worse functional ability (HAQ 1.1 vs 0.8, P = 0.004), worse hand function (3.3 vs 2.0, P = 0.003), assessed more pain (56 vs 45, P = 0.009) and had higher DAS-28 (5.6 vs 5.1, P = 0.03) (data not shown). Men aged 65 yr or more had very low direct costs compared with younger men and with women of all ages.


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TABLE 3. Disease activity and functional disability at inclusion and after 1 year for patients with annual direct cost <34 000 SEK and for patients with annual direct cost >34 000 SEK and differences between low-cost and high-cost groups at inclusion and at follow-up. Abbreviations as Table 1

 
Since the disease activity probably changes during the first year after diagnosis due to therapy, the variables were also compared after 1 yr. The differences between high- and low-cost groups had increased substantially and highly significant differences were seen in all variables (Table 3).

Variables associated with high costs (P value <0.2) were selected from the univariate analysis and entered in a forward stepwise regression model with high direct costs as the dependent variable. Variables with no influence on the dependent variable were removed from the model by stepwise regression leaving HAQ, IgM RF and SOFI hand function in the final model. As seen in Table 4, HAQ was a significant predictor of high direct costs [odds ratio (OR) 3.348, 95% confidence interval (CI) 1.6–6.8, P<0.001], IgM RF gave OR 1.002 (95%CI 1.0–1.003, P = 0.045) and SOFI hand function gave OR 1.177 (95%CI 1.0–1.37, P = 0.033). The percentage correctly predicted was 71.5%.


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TABLE 4. Univariate and multivariate logistic regression of potential variables associated with high direct costs. Abbreviations as Table 1

 
Indirect costs
The average indirect cost was 80 728 SEK/month ({euro}8726), the indirect costs thus accounting for almost 70% of the total costs, although only 67% of the patients were below the age of 65 and subsequently contributed to the indirect costs.

Patients with high indirect costs
Seventy patients (33%) were aged ≥65 yr and did not contribute to the indirect costs. At inclusion, 71 patients (50%) were working, 62 were on sick-leave (44%) and eight (6%) were work disabled and early retired. After 1 yr 50 patients (35%) were still working, while patients on sick-leave had increased to 74 (53%) and 17 (12%) were early retired. Seven of the 17 early-retired patients were on sick-leave for part of the year before receiving full early retirement. Thus 82 patients were on sick-leave during the year with an average of 170 sick-leave days, corresponding to approximately 6 months (including non-working days). The patients were divided into two groups. Fifty-two patients with no indirect costs were identified as the low (=no) indirect-cost group and the remaining 89 patients were the high-indirect-cost group.

The high-indirect-cost group was compared with the low (no) indirect-cost group. At inclusion the high-indirect-cost group had worse hand function (3.3 vs 1.5, P<0.0001) and assessed more pain (54 vs 41, P = 0.004) compared with the low (no) indirect-cost group (Table 5). Seventy-eight per cent of the patients in the low-cost group were IgM RF positive and 84% in the high-cost group (n.s.). Seventy-four per cent were IgA RF positive in the low-cost group and 77% in the high-cost group (n.s.). Anti-CCP tests were positive in 68% of the low-cost group and in 72% in the high-cost group (n.s.). A comparison of mean values at baseline between men in the high-cost group and women in the high-cost group showed no differences between the groups. There was no difference between men in the high-cost group and men in the no-cost group. The women, however, differed from each other in the two groups. In the high-cost group, women had significantly worse hand function than in the no-cost group, 3.0 vs 1.4 (P<0.0001) and assessed more pain, 53 vs 42 (P = 0.02) (data not shown). All variables were also compared after 1 yr. In contrast to the increasing differences appearing in the high- and low-direct-cost groups, all variables were similar in high- and low-indirect-cost groups, except for pain and well-being, HAQ-score, upper limb function and DAS-28 (Table 5).


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TABLE 5. Disease activity and functional disability at inclusion and after 1 year for patients with and without indirect costs and differences between low- and high-cost groups at inclusion and at follow-up. Abbreviations as Table 1

 
Applying the same model as above in a forward stepwise regression model, using high indirect costs as the dependent variable, SOFI hand function and pain remained significant, indicating that poor hand function increased the probability of achieving high indirect costs (OR 1.338, 95%CI 1.1–1.6, P = 0.002) and pain increased the odds by OR 1.017 (95%CI 1–1.03; P = 0.035). The percentage of correct predictions was 66.7% (Table 6).


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TABLE 6. Univariate and multivariate logistic regression of potential variables associated with high indirect costs. Abbreviations as Table 1

 

    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
The present study reflects the situation in Sweden in 1996–1999. With the more and more aggressive early treatment approach [22, 23] and the introduction of new biological anti-rheumatic treatment modalities [24], the strategies have changed dramatically and continue to do so. The results of the present investigation may be used as a reference for future studies on health economy in early RA. We found that considerable costs, both direct and indirect, were incurred within the first year of the disease. The costs for health-care visits and medication made up for 86% of the total direct costs. Hospitalization and surgery accounted for only 14%, which is not surprising since the vast majority of the patients were treated as out-patients. This reduces costs substantially, compared with the days when hospitalizations were commonplace, accounting for about 40–60% of total direct costs [8, 25, 26].

The various structures of the health-care systems in different countries taken together with methodological differences in calculating costs make comparisons between different studies difficult. Bearing this in mind, some comparisons can still be made.

In the present study, the mean annual direct cost for recent-onset RA during the first year after diagnosis was 35 694 SEK ({euro}3858). This is in accordance with two recent studies from Sweden and Spain [12, 27]. Others have reported higher direct costs ranging from 5600 to 11 500 US dollars (1996 values) ({euro}6320 and {euro}12 980 adjusted to 2001 values) [5, 7, 8, 10, 28, 29] while other studies report lower costs ranging from 2400 to 3200 US dollars (1996) ({euro}2700–3610 adjusted to 2001 values) [9, 11, 30–32]. Since this was an on-going prospective study and the patients were checked up according to a study protocol (i.e. at inclusion and after 3, 6 and 12 months), the number of visits to a physician, PT, OT, nurse and social worker may have been slightly higher than otherwise, which could thus have increased the direct costs. Despite the short disease duration, one total joint replacement and seven minor operations were performed during the first year following diagnosis in our study. In the study by Newhall-Perry et al. [11] the disease duration was shorter (6 months) and no surgery was performed during the first year.

The total cost of medication cannot solely be ascribed to the costs for the drugs, but also to therapeutic and drug safety monitoring. In the present study, medication accounted for only 9.4% of the total direct costs, which is low compared with the results of others who have reported 16–62% [11, 28, 30–33]. We have, however, included all costs for drug safety monitoring in the cost for nurse visits. Eighteen per cent of the costs consisted of nurse visits, corresponding to a mean annual cost of 6464 SEK. For comparison with other studies, these costs could be added to medication costs, giving a mean cost of 9811 SEK, corresponding to 27% of direct costs. This is in accordance with the results of Prashker and Meenan [34], who reported that the cost of drugs themselves accounted for only one-third of the total drug costs during the first 6 months, whereas later on, when the monitoring frequency was lowered, the costs were considerably reduced.

Twenty-six and a half per cent of our patients reported use of complementary health care during the first year of RA, which can be compared with 24% during 6 yr in the study of van Jaarsveld et al. [5]. Buchbinder et al. [35], on the other hand, reported that over 80% of RA patients had used complementary medicine at some time during the year that passed. The explanation for this great difference is not immediately obvious, but may possibly be sought in how ‘complementary medicine’ is regarded and defined in different communities.

The fact that men above the age of 65 had very low direct costs compared with younger men and compared with women of all ages was unexpected. This could not be explained by differences in disease activity/severity in the older men, except possibly from a slightly better walking ability compared with women above the age of 65 (P = 0.007) and an insignificantly lower co-morbidity than women.

The indirect costs in the present study, i.e. costs due to work disability, amounted to 80 728 SEK ({euro}8726), exceeding direct costs by 2.3 times. Indirect costs differ widely between previous studies (12 000–210 000 SEK; {euro}1297–22 700) depending on which patients are included and the duration of illness. Some studies report indirect costs that are much higher than ours [7, 14], whereas others report lower indirect costs [9, 11, 12, 31]. Like our findings, some studies have revealed that the indirect costs exceed direct costs substantially [7, 9, 27, 36], while others have found no difference between direct and indirect costs [11, 12, 31, 37]. In a recent Swedish study [9], the mean direct cost, referring to the price level of 1997, was 14 394 SEK, range 5407–36 986 ({euro}1618, range {euro}608–4158, adjusted to 2001 values) and indirect costs 43 766 SEK, range 0–136 500 ({euro}4920, range {euro}0–15 344 adjusted to 2001 values). This is lower than in our study, but the relation between direct and indirect costs was, however, almost the same [9]. Using the Markov model, both direct and indirect costs were shown to increase steadily with increasing severity of the disease [9, 38]. Leardini et al. [36] reported that direct and indirect costs increased very significantly as the disease worsened. In another recent Swedish study on very early (≤3 months) arthritis, the total costs during the first 6 months after diagnosis were $4385 in RA [12]. This corresponds to an annual cost of {euro}9853, half of which were direct costs, i.e. the same magnitude as in the present study. However, the indirect costs were about twice as large in the present study as in the study by Söderlin et al. [12]. The reasons for this discrepancy may be sought in the higher mean age of the patients in their study as well as in the shorter disease duration and the shorter follow-up time. In a recent Spanish study, the average total annual costs of $10 419 ({euro}11 627) attributed 70% to indirect costs [27], and correspond to the findings in the present study. There is a discrepancy between men and women with respect to gross national income. We have, however, chosen to calculate the same average gross income for everybody, regardless of gender or occupation, in order primarily not to focus on the differences in salary.

Functional disability, as assessed by HAQ, was the best predictor of high direct costs, which is in accordance with previous reports [4, 5, 8, 14, 26, 31, 37, 39, 40]. Singh et al. [41] reported that changes in disability, especially early in the disease, are strongly predictive of direct costs over the following years. In the present study, poor hand function was the best predictor of high indirect costs. Seropositivity with regard to IgM RF, IgA RF or anti-CCP antibodies did not turn out to be predictors of high costs. High levels of IgM RF, however, increased the odds of entering a high-cost group.

In the present study, the calculations were limited to costs directly related to RA. In addition, however, substantial costs must be anticipated, e.g. due to co-morbidity associated to RA, including adverse events of the medication. A recent study by Ruof et al. [42] reported that non-RA-related costs accounted for 39.4% of the total direct costs. The major costs were non-RA-related drugs and non-RA-related hospital admissions with diseases of the circulatory system and neoplasms being the most common diagnoses.

A limitation of the present study is that non-medical costs such as costs of assistive devices, house adaptations, transportation cost, etc. have not been calculated. This would presumably have added substantial expenditure to the total direct costs. A previous study calculated that non-medical costs accounted for 45% of the total direct costs [5]. The longitudinal prospective design of the present study is a big strength compared with most other studies, which have been cross-sectional.

To conclude, high direct and indirect costs were incurred during the first year of the disease. Indirect costs were 2.3 times higher than the direct costs. The costs for health-care visits and medication made up 86% of the total, while hospitalization and surgery only accounted for 14%. Women had significantly more visits to the physician and used more complementary health care than did men. Men above the age of 65 had very low direct costs compared with younger men and with women of all ages. Functional disability and a high level of IgM RF increased the odds of achieving high direct costs, while poor hand function and pain increased the odds of achieving indirect costs. Since disease activity correlates with functional disability, early targeted interventions are important to control disease. This is likely not only to decrease morbidity, mortality and increase health-related quality of life, but also to save costs both for the patient and for society.


    Acknowledgments
 
We thank Ingrid Thyberg, Ylva Billing and all TIRA partners at the rheumatology units in Eskilstuna, Jönköping, Kalmar, Lindesberg, Linköping, Motala, Norrköping, Oskarshamn, Västervik and Örebro for excellent cooperation. This study was supported by The Medical Research County Council of South-East Sweden (FORSS), the Swedish Rheumatism Association, The Swedish Research Council (project K2003–74VX-14594–01A), King Gustaf V 80-year Foundation and The National Board of Health and Welfare.

The authors have declared no conflicts of interest.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

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Submitted 8 March 2004; revised version accepted 21 June 2004.