The costs of rheumatoid arthritis (RA) are increasing because of the introduction and increasing use of biologic therapy. Biologic agents are effective but expensive, and there are almost no data to measure their impact on costs among RA patients in the community. In a sense, with the introduction of biologic therapy everything is new: RA costs have to be measured all over again to account for these agents. Additionally, costs are a changing target; if the prevalence of biologic therapy use increases, costs estimated today or in the past (1–14) may not be valid after a few years.
Lubeck (1) reviewed 10 studies on the costs of RA and noted that hospitalization costs were generally ≥60% of direct medical costs, with a single exception (9), and that drug costs were <25% of total direct medical costs. Pugner et al (15) reviewed cost studies (2–10) performed between 1978 and1998. They reported that the mean annual direct cost of RA was $5,425 per patient when expressed in 1998 US dollars. The median percentage of costs attributed to hospitalization in their review was 47%, and the percentage attributed to drugs was 16%. Gabriel and colleagues reported average annual direct medical charges to be $3,802 in 357 patients with RA and $2,654 in 5,730 patients with osteoarthritis (13); a random subset of patients was used to estimate charges for prescription medications in that study. Newhall-Perry et al studied the costs of RA in 150 seropositive patients during the first 5 years of illness and found the average total cost of the disease to be $2,400 per year (11). Lanes and colleagues reported on RA costs among health maintenance organization (HMO) patients from 1993 to 1994 (9). The average annual costs were $2,162, and 16% of the costs were for hospitalization. The study by Lanes et al is the only previous study in which drug costs were found to be the predominant cost in RA.
The study that is perhaps most germane to the current report is that by Yelin and Wanke (12). In 1999, they reported on 272 patients who were followed up continuously in 1995 and 1996. The average annual direct medical costs from a societal perspective were $8,501. Drugs constituted 18.2% and hospitalization accounted for 61.8% of total costs. The authors point out that hospital charges in California for that study may not be representative of hospital costs generally, and they prepared a second set of estimates based on a discount of 50% for hospital costs; this was discussed in their text though not included in the statistical tables. Applying the 50% discount would reduce the total cost from $8,501 to $5,876; both numbers are relevant in comparing the current report with the data of Yelin and Wanke.
Herein we describe the direct medical costs for persons with RA, encompassing costs no matter who incurs them (societal perspective), and identify predictors of these costs. We report that drugs are the predominant cost factor in RA, and that total costs are considerably greater than in studies performed prior to the introduction of biologic agents. In addition, we report the quantitative effect of a wide variety of predictors on future costs.
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- PATIENTS AND METHODS
The results of this study indicate that the mean direct medical care costs in RA are at least $9,519 per year. Of the total costs, drug costs account for 66% and hospital costs for 17%. The drug costs are driven predominantly by biologic therapy. Approximately 25% of patients received biologic therapy, and the direct annual medical care cost for those receiving biologic agents was $12,852 greater than that for those not receiving these agents. Patients with RA with poor function incur substantially higher drug and hospitalization costs. Increased education, income, and majority ethnic status were all associated with increased drug costs but not with hospitalization costs.
As expected, our direct medical care cost estimates in RA are substantially higher than cost estimates before the biologic therapy era (1–14). As noted above, the low end of annual direct medical costs before the biologic therapy era ranged between $2,162 and $3,802 ($3,802 as charges rather than costs) (9, 11, 13), with an overall average annual direct cost of $5,425 reported in Pugner et al's 2000 review of previous cost studies (2–10, 15). The previous estimate closest to ours was that of Yelin and Wanke (12). They reported the annual total direct medical care costs for their 272 northern California RA patients to be $8,501 in 1995–1996. Discounting their hospital costs by 50% as they recommended ($5,876), subtracting their costs due to travel, paid help, and medical devices that we did not measure in our study ($5,682), and taking into account inflation, their total annual cost would be $6,414.This is similar to our result of $5,850 from a Monte Carlo simulation using their study's characteristics (average age, sex, ethnicity, disease duration, pain scale, HAQ, comorbidities, and no biologic agents).
Nevertheless, the 50% reduction in hospital costs suggested by Yelin and Wanke still does not make the Medicare costs used in our study equivalent to their hospitalization costs. In addition, the mean duration of disease among participants in their study at its conclusion was 17.9 years, as opposed to 15.0 years in the current report. The risk of total joint replacement has been shown to increase with time at a rate of ∼1.1% per year of RA (45). The net results of the simulation studies and these additional differences suggest strongly that the actual findings of Yelin and Wanke's study and our study are essentially equivalent, except for the addition of biologic therapy.
Medical care costs appear to be primarily driven by drug costs in the biologic therapy era. Before the biologic therapy era, studies showed hospitalization costs to generally account for ≥60% of direct medical costs, and drug costs for ≤20%. In contrast, our results show the reverse of these proportions between the two costs. While this change is primarily due to the high cost of biologic agents, it remains possible that hospitalization costs may be reduced by more effective treatments with biologic agents.
A number of factors could influence drug costs in the future. The most probable determinant of future drug costs is an increase in the proportion of patients receiving biologic therapies, driven in part by the acceptability of the drugs and the expected introduction of new biologic agents in 2003 and after. However, there might be factors working to decrease these current costs. It is possible that the introduction of competing biologic agents might lead to a reduction in charges for these drugs. Additionally, accumulating experience with biologic agents is likely to lead to insurance companies' requiring more sharing of costs by patients, with the result that fewer patients may be able to afford the medications. A further consideration is that severity screening might lead to a reduction in the number of patients eligible to receive biologic therapy.
To account for these possibilities, we have performed Monte Carlo simulation studies using the data in this report. With the data from Table 8 and Figure 3, it is possible to predict costs based on the increase or decrease in drug costs as well as the prevalence of biologic therapy use in the community. One example for doing this that might be germane to the current report involves dosing with infliximab. As noted in Patients and Methods, if the dose of infliximab were increased in clinical practice to 5 mg/kg rather than the ∼4 mg/kg caused by rounding to the nearest 100 mg (using the remainder of the vial), there would be an increase in infliximab costs of 25% and an overall increase in costs of 10.9%. If this were done in half of the infliximab-treated patients, costs would increase by ∼5.5%. From Table 8 and Figure 3, a 5.5% increase in drug costs can be extrapolated easily to obtain a new estimate of total medical costs. When new estimates of total costs are obtained, the standardized cost coefficients (Table 3) can be applied to obtain updated estimates of variable contributions to costs.
The key clinical factors in predicting future costs are functional disability and comorbidity. In fact, these variables dominate the individual sociodemographic variables. It does not matter whether the HAQ or the SF-36 PCS is used to measure functional status since both function equally well; however, no other clinical or demographic variables approach their predictive strength. A 1-unit difference in the HAQ score predicts a $1,447 difference in total costs over the next 6 months (Table 3), and in a multivariable model it predicts a $1,041 difference (Table 6). A 1-unit difference in these 2 variables combined predicts $1,313 (95% confidence interval $1,163, $1,463) in future costs. Comorbidity is not difficult to measure by questionnaire, and HAQ measurement is simple. Therefore, these 2 tools can provide a rapid and reliable measure of future costs. The RADAI (25), an instrument that is as effective as American College of Rheumatology improvement criteria (46) in clinical trials, does not predict total costs well. This is an indication that function, rather than clinical activity, is the key factor in RA costs.
Some of the factors that predict individual cost components are of interest. Hospitalization costs (Table 7) are essentially predicted by the HAQ score, comorbidity, and sex, but outpatient costs are responsive to a very different set of variables. In addition to the HAQ score, the RADAI and depression are predictors of outpatient costs (of almost equal importance), and comorbidity is an even stronger predictor than the RADAI and depression scores. Education and income are also predictors of costs for outpatient care. Drug costs (Table 5) were influenced somewhat by insurance. HMO patients and the uninsured had lower costs and were least likely to be receiving anti-TNF therapy. In contrast, Medicaid patients had higher costs. Drug costs also increased with RA duration during the first 10 years of illness, and drug costs for non-Hispanic white patients were $443 greater per 6 months than for minority patients.
We believe our results break new ground in several ways. First, the study measures costs in a representative sample in an era of biologic therapy where the major determinant of cost is the biologic therapy itself. Such data have not been available previously. Second, it provides a wide variety of predictor variables in the area of clinical and sociodemographic factors. Third, it provides detailed cost measurements from a very large contemporary sample of 7,527 RA patients and 25,050 observations in a 3-year period.
There are a number of potential limitations to this study. We obtained costs for drugs from the Federal Upper Limit or wholesale rates according to Drug Topics Red Book, and actual costs in practice may be higher. This is also the case for nondrug costs, for which we used Medicare rates. We used these rates so standard, comparable, and nationally recognized methods could be applied. At the time of the preparation of the manuscript we were unable to obtain information on infliximab dose by patient self-report, and it is possible we may have underestimated usage. However, if more accurate data become available, Table 8 and Figure 3 can be used to provide updated cost estimates. Participants in longitudinal studies may differ systematically from nonparticipants in terms of social, demographic, and disease severity characteristics. Disease is slightly more severe in nonparticipants, but nonparticipants may have less access to insurance or may have other reasons to use fewer drugs. The effect of nonparticipation cannot be fully described, but it is likely to be small. In addition, because of the national nature of our study and use of specialty and nonspecialty physicians by the patients, we were unable to measure travel costs. Finally, the data from this study should be used with caution in predicting cost changes associated with particular treatments, since we did not specifically evaluate treatment-related cost changes.
In summary, current direct medical cost estimates in RA are substantially higher than cost estimates before the biologic therapy era, and costs are now driven predominantly by drug costs, primarily for biologic agents. RA patients with poor function continue to incur substantially higher costs, as do those with comorbid conditions, and sociodemographic characteristics also play an important role in determining costs.