Decreases in Rates of Hospitalizations For Manifestations of Severe Rheumatoid Arthritis,

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1 ARTHRITIS & RHEUMATISM Vol. 50, No. 4, April 2004, pp DOI /art , American College of Rheumatology Decreases in Rates of Hospitalizations For Manifestations of Severe Rheumatoid Arthritis, Michael M. Ward Objective. To determine whether the rates of hospitalization for 4 manifestations of severe rheumatoid arthritis (RA), which are used as indicators of long-term health outcomes, have changed from 1983 to Methods. Data on all patients with RA who were hospitalized with rheumatoid vasculitis or to undergo splenectomy for Felty s syndrome, cervical spine fusion for myelopathy, or total knee arthroplasty at hospitals in California were abstracted from a state hospitalization database. Changes in rates of hospitalization from 1983 to 2001 were examined in this serial cross-sectional study. Results. Rates of hospitalization for rheumatoid vasculitis and splenectomy in Felty s syndrome decreased progressively over time. The risk of hospitalization for rheumatoid vasculitis was one-third lower in than in The risk of hospitalization for splenectomy in Felty s syndrome was 71% lower in than in There were no significant decreases in the rates of hospitalization for cervical spine surgery or total knee arthroplasty (primary and revision), although in there was a reversal of the trend of increasing rates of total knee arthroplasty. The risk of hospitalization for primary total knee arthroplasty was significantly lower in than in (rate ratio 0.90, 95% confidence interval ; P < ). Conclusion. Rates of hospitalization for rheumatoid vasculitis and splenectomy in Felty s syndrome have decreased over the past 19 years, and there has Michael M. Ward, MD, MPH: National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland. Address correspondence and reprint requests to Michael M. Ward, MD, MPH, NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases/IRP, Building 10, Room 9S205, 10 Center Drive, MSC 1828, Bethesda, MD wardm1@mail.nih.gov. Submitted for publication September 8, 2003; accepted in revised form January 7, been a recent decrease in the rates of primary total knee arthroplasty in patients with RA. Although several factors may account for these decreases, these findings suggest that since the early 1980s, the long-term health outcomes of patients with RA have improved. During the late 1980s, the strategy for the treatment of rheumatoid arthritis (RA) evolved from an approach that emphasized the selective use of diseasemodifying medications for patients with entrenched synovitis and evidence of joint damage, to one that emphasized the consistent use of disease-modifying medications in almost all patients from the onset of joint inflammation (1 4). This change in treatment philosophy was not based on direct comparisons of the efficacy of these strategies, but rather was motivated by the recognition that joint damage occurs early in RA, that the health outcomes of patients treated using the previous strategy were generally poor, and that diseasemodifying medications were safer than previously thought (5 10). Recently, the findings from several short-term controlled trials and observational studies have suggested that treatment with disease-modifying medications initiated early in the course of RA leads to improved control of joint inflammation, less joint damage, and better health compared with the outcomes following even short delays in treatment (11 18). However, it is unclear whether this change in treatment strategy has been accompanied by improvement in the long-term health outcomes of patients with RA. The effectiveness of the new treatment strategy in improving long-term health outcomes would be supported by evidence of a decrease in the manifestations of severe RA, particularly ones that develop later in the course of the illness. Such manifestations include cervical spine instability with myelopathy, knee arthritis requiring arthroplasty, Felty s syndrome requiring splenectomy, and rheumatoid vasculitis, each of which may be a consequence of ineffective treatment (19). This 1122

2 HOSPITALIZATIONS IN RA 1123 study examined the hypothesis that there has been a decrease in the rates of hospitalization for these manifestations of RA from 1983 to 2001, using a populationbased registry of hospitalizations in California. PATIENTS AND METHODS Source of data. Patients with RA were identified through a computerized search of data files compiled by the California Office of Statewide Health Planning and Development (OSHPD). All acute-care, nonfederal hospitals in California are mandated to provide this agency with discharge abstracts on each hospitalization. The discharge abstracts include information on patient age, sex, race, the principal diagnosis (defined as the condition chiefly responsible for the hospitalization) and up to 24 additional diagnoses, the principal procedure (defined as the procedure performed for definitive treatment and most related to the principal diagnosis) and up to 10 additional procedures, type of admission (elective, urgent, or emergency), length of stay, and disposition. Diagnoses and procedures are coded using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes (20). The abstracts do not include information on the admitting physician. The average number of hospitalizations in the data files was 3.65 million per year. Before OSHPD data are released publicly, the data are subjected to several hundred reliability and validity checks, and data fields with error rates of 0.1% or higher are returned to hospitals for correction (21,22). Reabstraction studies that have compared OSHPD data files with original medical records have found specificities for diagnoses ranging from 0.98 to 1.00, and sensitivities for diagnoses ranging from 0.88 to 1.00 (23 25). Because these data are based in part on those used for billing purposes, there is near-complete recording of major surgical procedures, although recording of minor procedures such as blood transfusions is less complete (23 25). To protect patient confidentiality, the data are anonymous, so validation of specific diagnoses and procedures in this study could not be performed. Data on all hospitalizations of patients with RA age 18 years or older were abstracted from 1983 (the first year of the database) to 2001 (the most recent year with complete data). The unit of analysis was the hospitalization, rather than the individual patient, because unique patient identifiers were not included in the database prior to 1991 or in Hospitalizations in rehabilitation facilities were excluded, because these would not represent new surgeries or new episodes of vasculitis. Hospitalizations that resulted from interhospital transfers were counted only once. Hospitalizations that listed diagnoses of other connective tissue diseases in addition to RA were excluded, to provide a diagnostically homogeneous group. Manifestations of severe RA. Four manifestations of RA were studied: rheumatoid vasculitis, splenectomy for treatment of Felty s syndrome, cervical fusion for treatment of myelopathy, and total knee arthroplasty. These manifestations were chosen because they indicate severe RA and represent, in part, the failure of antirheumatic treatment to adequately control RA. Hospitalization is required for the 3 surgical procedures, and patients with rheumatoid vasculitis are often hospitalized. Therefore, a hospitalization database can be used to capture changes in the frequency of each condition. Hospitalizations of interest were identified by the ICD-9-CM codes of the discharge diagnoses and procedures. Because there is no unique ICD-9-CM code for rheumatoid vasculitis, a hospitalization was considered to indicate rheumatoid vasculitis if the discharge diagnosis codes included those for RA (714.0) and either arteritis (447.6), mononeuritis multiplex (354.5 or any combination of 354.1, 354.2, 354.3, 354.8, 354.9, 355.0, 355.2, 355.3, 355.4, 355.7, , 355.8, or 355.9), peripheral neuropathy due to connective tissue disease (357.1), gangrene (785.4) in the absence of peripheral vascular disease due to diabetes mellitus (250.7), or chronic leg ulcers (707.1). Patients with chronic leg ulcers were included only if there was also a procedure code indicating the administration of intravenous chemotherapy (99.25) in the absence of malignancy ( ). To test this scheme, 2 medical records technicians were asked to code independently 10 discharge summaries of patients with clinical diagnoses of rheumatoid vasculitis (which represented all audited hospitalizations of patients with rheumatoid vasculitis in the Arthritis, Rheumatism, and Aging Medical Information System for the past 7 years). Based on the ICD-9-CM codes assigned by the technicians to these hospitalizations, all 10 hospitalizations would have been captured as rheumatoid vasculitis using this coding scheme. Hospitalizations of patients with Felty s syndrome were included if the diagnosis codes included Felty s syndrome (714.1) and the procedure codes included splenectomy (41.5). Hospitalizations of patients with RA and cervical myelopathy were identified by diagnosis codes of RA (714.0) and either myelopathy or paralysis (336.3, 336.8, 336.9, , or 344.9), along with a procedure code for cervical fusion (81.01 or from 1983 to 1989; 81.01, 81.02, or from 1990 to 2001). Hospitalizations for cervical fusion alone, without diagnoses codes indicating myelopathy or paralysis, were not included. Hospitalizations for total knee arthroplasty were included if the diagnosis codes included RA (714.0) and the procedure codes included total knee arthroplasty (81.41 from 1983 to 1989; or from 1990 to 2001). Primary arthroplasty and revision arthroplasty were not differentiated in the ICD-9-CM prior to Rates of primary total knee arthroplasty (procedure code 81.54) were examined as a separate outcome for the years Knee arthroplasty was studied because it is a commonly performed procedure and is more specifically associated with RA-related joint damage than with total hip arthroplasty (26). Because RA is more common in older persons and because these manifestations usually develop later in RA, these manifestations were rare in patients younger than age 40 years. For example, only 3.5% of hospitalizations for rheumatoid vasculitis, 4.1% of hospitalizations for splenectomy in Felty s syndrome, 3.5% of hospitalizations for cervical fusion, and 4.2% of total knee arthroplasties occurred in patients younger than age 40 years. In younger individuals, some of these manifestations may be consequences of juvenile RA. To increase the specificity of the analyses to complications of RA, analyses were limited to hospitalizations of patients who were age 40 years or older.

3 1124 WARD Table 1. Demographic characteristics of patients hospitalized with each manifestation of rheumatoid arthritis in California, * All years Vasculitis Total no. 3,897 1,050 1, Age years 867 (22.2) 269 (25.6) 200 (18.0) 204 (21.0) 194 (25.4) years 1,099 (28.2) 312 (29.7) 342 (30.8) 258 (26.6) 187 (24.5) 70 years and older 1,931 (49.5) 469 (44.7) 569 (51.2) 508 (52.4) 385 (50.1) Women 2,948 (75.6) 764 (72.8) 845 (76.1) 749 (77.2) 590 (77.0) Men 949 (24.4) 286 (27.2) 266 (23.9) 221 (22.8) 176 (23.0) White 2,965 (76.1) 872 (83.1) 867 (78.0) 733 (75.6) 493 (64.4) Black 284 (7.3) 56 (5.3) 83 (7.5) 83 (8.5) 62 (8.1) Hispanic 453 (11.6) 84 (8.0) 118 (10.6) 120 (12.4) 131 (17.1) Other 195 (5.0) 38 (3.6) 43 (3.9) 34 (3.5) 80 (10.4) Splenectomy in Felty s syndrome Total no Age years 37 (31.4) 11 (25.0) 13 (31.0) 7 (36.8) 6 (46.1) years 46 (39.0) 20 (45.4) 17 (40.5) 6 (31.6) 3 (23.1) 70 years and older 35 (29.6) 13 (29.6) 12 (28.5) 6 (31.6) 4 (30.8) Women 65 (55.1) 26 (59.1) 25 (59.5) 9 (47.4) 5 (38.5) Men 53 (44.9) 18 (40.9) 17 (40.5) 10 (52.6) 8 (61.5) White 107 (90.7) 38 (86.4) 37 (88.1) 19 (100) 13 (100) Black 2 (1.7) 1 (2.3) 1 (2.4) 0 0 Hispanic 5 (4.2) 3 (6.8) 2 (4.7) 0 0 Other 4 (3.4) 2 (4.5) 2 (4.7) 0 0 Cervical spine fusion in myelopathy Total no Age years 30 (36.1) 6 (30.0) 8 (40.0) 8 (28.6) 8 (53.3) years 18 (21.7) 6 (30.0) 4 (20.0) 7 (25.0) 1 (6.7) 70 years and older 35 (42.2) 8 (40.0) 8 (40.0) 13 (46.4) 6 (40.0) Women 58 (69.9) 15 (75.0) 12 (60.0) 19 (67.9) 12 (80.0) Men 25 (30.1) 5 (25.0) 8 (40.0) 9 (32.1) 3 (20.0) White 56 (67.5) 12 (60.0) 14 (70.0) 20 (71.4) 10 (66.7) Black 6 (7.2) 4 (20.0) 0 2 (7.1) 0 Hispanic 12 (14.5) 3 (15.0) 4 (20.0) 4 (14.3) 1 (6.7) Other 9 (10.8) 1 (5.0) 2 (10.0) 2 (7.1) 4 (26.6) Total knee arthroplasty Total no. 16,133 3,523 4,077 4,781 3,752 Age years 4,694 (29.1) 1,005 (28.5) 1,149 (28.2) 1,406 (29.4) 1,134 (30.2) years 5,485 (34.0) 1,356 (38.5) 1,438 (35.3) 1,585 (33.2) 1,106 (29.5) 70 years and older 5,954 (36.9) 1,162 (33.0) 1,490 (36.5) 1,790 (37.4) 1,512 (40.3) Women 12,941 (80.2) 2,806 (79.6) 3,251 (79.7) 3,820 (79.9) 3,064 (81.7) Men 3,192 (19.8) 717 (20.4) 826 (20.3) 961 (20.1) 688 (18.3) White 11,793 (73.1) 2,808 (79.7) 3,152 (77.3) 3,446 (72.1) 2,387 (63.6) Black 986 (6.1) 207 (5.9) 251 (6.2) 308 (6.4) 220 (5.9) Hispanic 2,099 (13.0) 297 (8.4) 442 (10.8) 719 (15.0) 641 (17.1) Other 1,255 (7.8) 211 (6.0) 232 (5.7) 308 (6.4) 504 (13.4) Primary total knee arthroplasty Total no. 10,124 3,214 3,526 3,384 Age years 2,969 (29.3) 875 (27.2) 1,067 (30.3) 1,027 (30.3) years 3,275 (32.3) 1,121 (34.9) 1,144 (32.4) 1,010 (29.9) 70 years and older 3,880 (38.3) 1,218 (37.9) 1,315 (37.3) 1,347 (39.8) Women 8,179 (80.8) 2,590 (80.6) 2,822 (80.0) 2,767 (81.8) Men 1,945 (19.2) 624 (19.4) 704 (20.0) 617 (18.2) White 7,076 (69.9) 2,438 (75.9) 2,505 (71.0) 2,133 (63.0) Black 614 (6.1) 190 (5.9) 231 (6.6) 193 (5.7) Hispanic 1,541 (15.2) 384 (12.0) 558 (15.8) 599 (17.7) Other 893 (8.8) 202 (6.2) 232 (6.6) 459 (13.6) * Values are the no. (%) of patients. The time periods for primary total knee arthroplasty differ from the others, as follows: the all years period is , and the other 3, from left to right, are , , and , respectively.

4 HOSPITALIZATIONS IN RA 1125 To determine whether changes in the rates of hospitalization might reflect changes in antirheumatic treatment strategies, or whether they reflected changes in the use of hospital care since 1983, rates of hospitalization for 2 conditions not related to RA were also examined: cerebrovascular accidents (ICD-9-CM codes ) and atrial fibrillation (ICD-9-CM code ). Statistical analysis. Annual rates of each type of hospitalization were computed using the yearly count of hospitalizations as the numerator and the number of patients with RA living in California in each year as the denominator. Estimates of the number of patients with RA in California were derived by applying age-, sex-, and ethnicity-specific prevalences of RA to yearly estimates of the population of California. Prevalences of RA were based on an analysis of the Third National Health and Nutrition Examination Survey (NHANES-III), a population-based assessment of the health of Americans conducted by the US National Center for Health Statistics from 1988 to 1994 (27). In this analysis, prevalences of RA were computed for women and men in 3 ethnic groups (white, black, and Mexican-American) and 3 age groups (40 59 years, years, and 70 years and older). Prevalences in the year age group were based on subjects reports of a physician-based diagnosis of RA along with a current prescription for a disease-modifying medication or prednisone. Prevalences for the 2 older age groups were based on fulfillment of the American College of Rheumatology (formerly, the American Rheumatism Association) classification criteria for RA (28), using data from medical examinations that included examination of peripheral joints for features of RA. Joint examinations were not performed in NHANES-III subjects younger than age 60 years. Census data from the California Department of Finance Demographic Research Unit were used to provide yearly estimates of the population of California, stratified by age group, sex, and ethnicity (29). These estimates were multiplied by the age- and sex-specific prevalences of RA among whites and blacks as reported in the NHANES-III, to derive estimates of the number of whites and blacks with RA in California in each year from 1983 to Estimates of the number of RA patients of Hispanic ethnicity in California were based on the prevalence of RA in Mexican-Americans reported in the NHANES-III, and the number of RA patients in California who were of an ethnicity other than white, black, or Hispanic was based on the prevalence of RA in whites reported in the NHANES-III. Crude rates were standardized to the age, sex, and ethnic distribution of the RA population in To provide more stable estimates of hospitalization rates, rates were also computed by pooling events in 4 approximately equal time intervals: , , , and Poisson regression models were used to estimate rate ratios for hospitalization in each time period, using the rates in the interval as the reference group. These models tested whether the risk of hospitalization for each manifestation of severe RA in , , and was different from the rate of hospitalization in These models were adjusted for age group, sex, and ethnicity. P values (2-tailed) of less than or equal to 0.05 were considered statistically significant. Analyses were performed using SAS programs (version 8.2; SAS Institute, Cary, NC). Figure 1. Annual rates of hospitalization for rheumatoid vasculitis per 100,000 persons with rheumatoid arthritis from 1983 to Rates are presented as 3-year weighted moving averages. Two sensitivity analyses were performed to determine the effect of varying estimates of the prevalence of RA on changes in the rates of hospitalizations over time. First, analyses were repeated using only hospitalizations of patients age 60 years or older, since RA prevalence estimates for these age groups were based on physical examination in the NHANES-III. Second, analyses were done using estimates of RA prevalence that were projected to decrease by 20% from 1983 to RESULTS Rates of hospitalization. From 1983 to 2001, there were 3,897 hospitalizations of patients with rheumatoid vasculitis, 118 hospitalizations for splenectomy in patients with Felty s syndrome, 83 hospitalizations for cervical spine fusion in patients with RA and myelopathy, and 16,133 hospitalizations for total knee arthroplasty (primary and revision) in patients with RA age 40 years or older. From 1990 to 2001, there were 10,124 hospitalizations for primary total knee arthroplasty in patients with RA age 40 years or older. Most of the hospitalized patients were white women, although men comprised a substantial proportion of the patients with Felty s syndrome who underwent splenectomy (Table 1). The rate of hospitalization for rheumatoid vasculitis, adjusted for patient age, sex, and ethnicity, decreased from 170 per 100,000 persons with RA in 1983 to 99 per 100,000 persons with RA in 2001 (Figure 1). The risk of hospitalization for rheumatoid vasculitis was 33% lower in than in (adjusted rate ratio 0.67, 95% confidence interval ; P ) (Table 2). The adjusted annual rate of hospitalization for splenectomy in patients with Felty s syndrome decreased from 8.0 per 100,000 persons with RA in 1983 to 1.0 per

5 1126 WARD Table 2. Age-, sex-, and ethnicity-adjusted rates of hospitalization and associated rate ratios for manifestations of rheumatoid arthritis and for cerebrovascular accidents and atrial fibrillation, by multiyear interval* Vasculitis Total no. 1,050 1, Adjusted rate (95% CI) ( ) ( ) ( ) 97.8 ( ) Adjusted rate ratio (95% CI) 1.00 (reference) 0.94 ( ) 0.74 ( ) 0.67 ( ) P Splenectomy in Felty s syndrome Total no Adjusted rate (95% CI) 6.1 ( ) 5.3 ( ) 2.3 ( ) 1.8 ( ) Adjusted rate ratio (95% CI) 1.00 (reference) 0.87 ( ) 0.37 ( ) 0.29 ( ) P Cervical spine fusion in myelopathy Total no Adjusted rate (95% CI) 2.9 ( ) 2.5 ( ) 3.2 ( ) 1.8 ( ) Adjusted rate ratio (95% CI) 1.00 (reference) 0.86 ( ) 1.06 ( ) 0.63 ( ) P Total knee arthroplasty (primary and revision) Total no. 3,523 4,077 4,781 3,752 Adjusted rate (95% CI) ( ) ( ) ( ) ( ) Adjusted rate ratio (95% CI) 1.00 (reference) 1.02 ( ) 1.09 ( ) 0.98 ( ) P Cerebrovascular accident Total no ,071 1,655 1,667 Adjusted rate (95% CI) ( ) ( ) ( ) ( ) Adjusted rate ratio (95% CI) 1.00 (reference) 1.21 ( ) 1.70 ( ) 2.00 ( ) P Atrial fibrillation Total no Adjusted rate (95% CI) 61.2 ( ) 73.4 ( ) ( ) ( ) Adjusted rate ratio (95% CI) 1.00 (reference) 1.18 ( ) 1.62 ( ) 2.10 ( ) P * 95% CI 95% confidence interval. 100,000 persons with RA in 2001 (Figure 2). The risk of hospitalization for splenectomy among patients with Felty s syndrome was 71% lower in than in (adjusted rate ratio 0.29, 95% confidence interval ; P ) (Table 2). In contrast, there was no significant decrease in the rate of hospitalization for cervical spine surgery among patients with myelopathy, although there was a trend toward lower rates in more recent years (Figure 3). The adjusted rate of hospitalization for cervical spine Figure 2. Annual rates of hospitalization for splenectomy in Felty s syndrome per 100,000 persons with rheumatoid arthritis from 1983 to Rates are presented as 3-year weighted moving averages. Figure 3. Annual rates of hospitalization for cervical spine fusion in patients with myelopathy and rheumatoid arthritis per 100,000 persons with rheumatoid arthritis from 1983 to Rates are presented as 3-year weighted moving averages.

6 HOSPITALIZATIONS IN RA 1127 Figure 4. Annual rates of hospitalization for total knee arthroplasty (primary and revision) (}) per 100,000 persons with rheumatoid arthritis from 1983 to 2001, and for primary total knee arthroplasty ( ) from 1990 to Rates are presented as 3-year weighted moving averages. surgery in myelopathy was 3.7 per 100,000 persons with RA in 1983 and 2.5 per 100,000 persons with RA in 2001, but the small number of hospitalizations each year resulted in rates that were quite variable. The risk of hospitalization for cervical spine fusion among patients with myelopathy was 37% lower in than in , but this decrease was not statistically significant (Table 2). Rates of hospitalizations for total knee arthroplasty (primary and revision) increased from 1983 to 1997, from 473 per 100,000 to 580 per 100,000 persons with RA, but decreased steadily from 1997 to 2001 (Figure 4). Although the risk of hospitalization for total knee arthroplasty in was not significantly lower than in , there was, in , a reversal of the increased rates of total knee arthroplasty seen in (Table 2). When the rates of hospitalization for primary total knee arthroplasty were examined separately, these rates also increased from 1990 to 1997 (from 486 per 100,000 persons with RA to 530 per 100,000 persons with RA), and then decreased to 390 per 100,000 persons with RA in 2001 (Figure 4). The risk of hospitalization for primary total knee arthroplasty was 10% lower in than in (adjusted rate ratio 0.90, 95% confidence interval ; P ) (Table 3). Rates of hospitalizations for cerebrovascular accidents and atrial fibrillation in patients with RA increased over time (Table 2). These findings suggest that the decreased rates of hospitalization for manifestations of severe RA were not due to changes in the use of hospital care from 1983 to 2001, but rather were specific to manifestations of RA. Sensitivity analyses. Results were similar when the analyses were restricted to hospitalizations of patients ages 60 years or older (Tables 4 and 5). In analyses in which the prevalence of RA was projected to have decreased by 20% from 1983 to 2001, results for hospitalizations for vasculitis, splenectomy, and cervical spine surgery were similar to the base case (Table 4). These findings indicate that changes in the prevalence of RA over time are unlikely to account for the decreases in hospitalization rates that were observed. However, rates of knee arthroplasty (primary and revision) were sensitive to an assumption that the prevalence of RA has decreased over time, with significantly higher risk in than in under this assumption. For primary total knee arthroplasty, assumption of an 11% decrease in the prevalence of RA from 1990 to 2001 reduced the association present in the base case (Table 5). However, even with this assumption, there was, in , a reversal of the increased risk of primary total knee arthroplasty present in Assuming a 5% decrease in the prevalence of RA from 1990 to 2001, the risk of hospitalization for primary total knee arthroplasty in was significantly lower than in (adjusted rate ratio 0.93, 95% confidence interval ; P 0.02). DISCUSSION In this population-based study, rates of hospitalization for rheumatoid vasculitis and for splenectomy among patients with Felty s syndrome decreased significantly from the early 1980s to Rates of hospital- Table 3. Age-, sex-, and ethnicity-adjusted rates of hospitalization and associated rate ratios for primary total knee arthroplasty, by multiyear interval* Total no. 3,214 3,526 3,384 Adjusted rate (95% CI) ( ) ( ) ( ) Adjusted rate ratio (95% CI) 1.00 (reference) 1.03 ( ) 0.90 ( ) P * 95% CI 95% confidence interval.

7 1128 WARD Table 4. Adjusted rate ratios and 95% confidence intervals for hospitalizations for manifestations of rheumatoid arthritis (RA) by multiyear interval, among the subgroup of patients age 60 years and older and in analyses in which the prevalence of RA was projected to decrease by 20% from 1983 to Age 60 years or older Vasculitis 1.00 (reference) 1.04 ( ) 0.81 ( ) 0.71 ( ) P Splenectomy in Felty s syndrome 1.00 (reference) 0.81 ( ) 0.33 ( ) 0.23 ( ) P Cervical spine surgery in myelopathy 1.00 (reference) 0.75 ( ) 1.12 ( ) 0.45 ( ) P Total knee arthroplasty (primary and revision) 1.00 (reference) 1.05 ( ) 1.14 ( ) 1.05 ( ) P Prevalence of RA decreased by 20% from 1983 to 2001 Vasculitis 1.00 (reference) 0.99 ( ) 0.83 ( ) 0.79 ( ) P Splenectomy in Felty s syndrome 1.00 (reference) 0.91 ( ) 0.41 ( ) 0.34 ( ) P Cervical spine fusion in myelopathy 1.00 (reference) 0.91 ( ) 1.18 ( ) 0.74 ( ) P Total knee arthroplasty (primary and revision) 1.00 (reference) 1.08 ( ) 1.22 ( ) 1.15 ( ) P ization for cervical spine fusion in patients with RA and myelopathy, a rare occurrence (30,31), were also 37% lower in than in There was also evidence, in recent years, of a reversal of the trend of increasing rates of total knee arthroplasty in patients with RA that had occurred from 1983 to In addition, there was a significant decrease in the rates of primary total knee arthroplasty in compared with the rates in the early 1990s. These decreases were not mirrored by the rates of hospitalization for conditions unrelated to RA, and were unlikely to be explained by decreases in the prevalence of RA (32,33). The decreases in hospitalizations for manifestations of severe RA suggest that the long-term health outcomes of patients with RA have improved over the past 19 years. These results are consistent with those from other reports that have described temporal trends in the severity of RA. Comparisons of patients treated in the late 1980s or mid-1990s with patients treated in the same clinics years earlier have demonstrated less functional disability and less radiographic damage in the more recent cohorts (34 36). Patients in these more recent cohorts had received more treatment with disease-modifying medications. However, some evidence also suggests that the severity of RA, as reflected by the prevalence of subcutaneous rheumatoid nodules, radiographic bone erosions, and serum rheumatoid factor, might have been decreasing prior to the more widespread use of disease-modifying medications (32,37). Studies of temporal changes in the clinical manifestations of RA that are based on cohorts of patients seen at particular clinics are difficult to interpret, because observed changes in severity may be due to differences in the types of patients seen by a particular group of physicians over time, rather than being true changes in the severity of the disease. The likelihood of selection bias increases with the length of time over which changes are studied. Use of a population-based registry permits the study of changes in RA severity over Table 5. Adjusted rate ratios and 95% confidence intervals for hospitalizations for primary total knee arthroplasty by multiyear interval, among the subgroup of patients age 60 years and older and in analyses in which the prevalence of rheumatoid arthritis (RA) was projected to decrease by 11% from 1990 to Age 60 years or older Primary total knee arthroplasty 1.00 (reference) 1.01 ( ) 0.92 ( ) P Prevalence of RA decreased by 11% from 1990 to 2001 Primary total knee arthroplasty 1.00 (reference) 1.07 ( ) 0.99 ( ) P

8 HOSPITALIZATIONS IN RA 1129 long periods while avoiding selection bias or confounding by changes in referral patterns over time. However, use of a hospitalization registry limited the markers of RA severity that could be studied to manifestations of RA that required, or often needed, hospitalization. These manifestations included 2 articular complications, cervical spine instability with myelopathy requiring cervical fusion and knee arthritis requiring arthroplasty, and 2 extraarticular manifestations of severe RA, rheumatoid vasculitis and Felty s syndrome requiring splenectomy. Antirheumatic treatment can effectively treat rheumatoid vasculitis and improve the neutropenia and reduce the likelihood of infections in Felty s syndrome. Significant decreases were observed in the rates of hospitalization for rheumatoid vasculitis, splenectomy in patients with Felty s syndrome, and primary total knee arthroplasty. The decrease in the rates of knee arthroplasties is particularly noteworthy, given that rates of this procedure among Medicare recipients have more than doubled from 1988 to 2000 (38). Another populationbased study has also recently reported a decrease in total joint arthroplasty among patients with RA diagnosed since 1985, compared with those diagnosed earlier (39). Although there was a decrease in the rates of cervical spine surgery in patients with myelopathy, this change was not statistically significant, possibly due to the infrequent occurrence of this complication and the low statistical power. Factors other than a change in RA severity may have contributed to the decreases in the rates of hospitalizations that were observed. Greater emphasis on outpatient treatment may have accounted for some of the decrease in hospitalizations of patients with rheumatoid vasculitis, and the introduction of hematopoietic growth factors is likely to have contributed to a decreased need for splenectomy in patients with Felty s syndrome. Changes in the surgical management of patients with RA who have unstable cervical spines may have led to less use of surgery, even though recent studies advocate the use of stabilization surgery earlier than has been common practice (30,31). Furthermore, decreased patient demand for total knee arthroplasty or decreases in recommendations for arthroplasty might have occurred, although this explanation seems unlikely. Changes in medical insurance coverage or expansions in managed care are unlikely to explain the findings, since similar results were present among those age 60 years or older, of whom 86% were insured by Medicare. The fact that there were decreases in the rates of hospitalization for several different articular and extraarticular manifestations of severe RA suggests that these decreases are related to changes in the severity of RA. Although the decreases occurred during a time when the use of disease-modifying medications in RA increased (4,40), the data set did not include information on medication use, and a direct association between prior or current use of disease-modifying medications and changes in RA severity could not be made. However, rates for most manifestations first demonstrated significant decreases in or This time course is consistent with an effect of increased use of disease-modifying medications in the late 1980s and early 1990s, allowing for diffusion of the new treatment strategy (and therefore decreases in the number of new patients with RA who might develop these complications) and attrition in the number of patients treated using the previous strategy who might have been destined for total knee arthroplasty or cervical spine fusion despite any more recent changes in treatment. Another limitation of the data set was that attribution of the complication to RA was not made. This limitation applies mainly to total knee arthroplasty, the need for which, in some patients, may have been due to osteoarthritis rather than RA. However, inclusion of any cases that were not complications of RA would decrease the likelihood that changes in rates would be detected. In addition, for many years, the data set did not include identifiers of repeat hospitalizations in individual patients. For manifestations that might entail more than 1 hospitalization per patient, such as rheumatoid vasculitis, and less often, total knee arthroplasty, our analysis based on changes in the number of hospitalizations would underestimate decreases in the number of patients with these manifestations. These limitations mean that the decreases in hospitalization rates are conservative estimates of the changes in the number of patients with manifestations of severe RA. Finally, because the data were anonymous, we could not independently validate the diagnoses. However, previous validation studies of this data source demonstrated high accuracy (23 25). Data abstracting and coding errors could be present, but improvements in coding accuracy over time would be expected to identify more patients with RA in more recent years, rather than fewer. The increases in hospitalization rates for atrial fibrillation and cerebrovascular disease among patients with RA merit further investigation. The decrease in hospitalization rates for manifestations of severe RA predated the widespread use of anti tumor necrosis factor medications and other new

9 1130 WARD antirheumatic medications. Available data also suggest that the use of disease-modifying medications is largely limited to patients treated by rheumatologists (4,41,42). Few patients with RA who are not treated by rheumatologists are prescribed disease-modifying medications, but these patients are at risk for development of the manifestations of severe RA described herein. As the use of both conventional and biologic antirheumatic medications becomes more prevalent and these medications are used more consistently throughout the course of RA, further improvements in the health outcomes of patients with RA might be anticipated. Less physical disability, decreased need for joint surgery, and decreases in the excess mortality of patients with RA may be the most useful indicators of these improvements. REFERENCES 1. Wilske K, Healey L. Remodeling the pyramid: a concept whose time has come. J Rheumatol 1989;16: Bensen WG, Adachi JD, Tugwell PX. 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