Raye H. Brooks

Prediction of Long-Term Mortality in Patients with Rheumatoid Arthritis according to Simple Questionnaire and Joint Count Measures

Rheumatoid arthritis is a chronic disease that affects 0.5% to 1% of the U.S. population [1]. Although population studies identify many people who meet classification criteria for rheumatoid arthritis [2, 3] and have a self-limited process [4-7], most patients seen in clinical settings have a progressive chronic disease, with radiographic damage [8-11], frequent work disability [12, 13], incremental functional declines [13-15], and increased mortality rates [16-18]. Higher mortality rates in rheumatoid arthritis were described initially in 1953 [19] and in all subsequent published clinical series [6, 16, 20]. However, estimation of mortality rates according to quantitative data has not been incorporated into the standard assessment of individual patients with rheumatoid arthritis, as has advanced clinical assessment in other chronic diseases, notably cardiovascular [21] and neoplastic diseases [22]. One reason for the relative absence of quantitative prediction of mortality in rheumatoid arthritis is that traditional clinical measures with documented prognostic value for mortality [13, 18, 23] appear too complex for routine clinical use, whereas global, radiographic, and laboratory data have not yet provided comparable prognostic utility for mortality. Studies during the last decade indicate that simple quantitative clinimetric [24] measures, including questionnaires to assess activities of daily living that include only 20 [25] or 8 [26] activities and joint counts that include 36 [27] or 28 [28] joints, provide valid and reliable data to assess clinical status in patients with rheumatoid arthritis. These measures can be ascertained in usual clinical practice in 10 to 15 minutes and provide information comparable to more elaborate traditional measures, which may involve 70 or more activities of daily living [13] or joints [28]. Most studies of these simplified measures have been cross-sectional, and relatively little information is available about their prognostic value over long periods. We have reported that mortality rates over 9 years in a cohort of patients with rheumatoid arthritis are increased compared with expected rates [13, 18] and are similar to most previous series from rheumatology settings [16]. Increased mortality rates, which were not seen over the first 2 to 3 years after baseline, were predicted over 5 years or longer by more severe clinical involvement at baseline and were comparable to other chronic diseases in certain patients. Clinimetric measures that predicted increased mortality rates included joint counts, functional status questionnaires, and other clinical measures, as well as age and formal education level [13, 18, 29]. In this report, we extend these studies to analyze whether simplified questionnaires and joint counts, which can be obtained in 10 to 15 minutes in a physicians office, provide effective data to identify increased probability of mortality over the subsequent 15 years in individual patients. Methods Patients Seventy-five patients with rheumatoid arthritis were evaluated during the fall of 1973. The patients included 53 women and 22 men (73 white and 2 black persons). The mean age at baseline in 1973 was 54.7 years, the mean duration of disease was 11.2 years, and the mean formal education level was 10.9 years. The mean joint count level was 16.2 of 50 joints, the mean morning stiffness was 82.1 minutes, and 12.3% of the patients had cardiovascular disease (in addition to hypertension). Mean values for baseline measures of functional capacity were as follows: Questionnaire responses about activities of daily living were 88.3% of activities done with ease; grip strength was 99.2 mm Hg; modified walking time was 18.5 seconds; the button test was 76.6 seconds; and the disease adjustment score was 1.8 [13, 18]. The standardized mortality ratio was 1.62 at 15 years. That is typical of series of patients with rheumatoid arthritis, as were the findings that rheumatoid arthritis was listed on only 14 of 34 death certificates and the overall similarity of attributed causes of death to those in the general population [6, 16]. The demographic composition and baseline values for patients in this study were similar to those seen in 155 other consecutive patients with rheumatoid arthritis studied at Vanderbilt University from 1982 to 1984 [13]. Evidence has been presented that patients seen in private rheumatology practices are similar to patients seen at medical centers [30], although it is not known whether patients seen by rheumatologists may differ from patients seen by nonspecialist physicians. All 75 patients who were studied in 1973 were accounted for 15 years later in 1988. Protocol for Baseline Evaluation The baseline evaluation in 1973 included assessment of demographic, clinical, articular, questionnaire, and functional capacity variables. Demographic variables at baseline included age, sex, and level of formal education. Clinical variables included 1) duration of disease [the years from disease onset to 1973 as reported by the patient and recorded by a physician]; 2) morning stiffness [the number of minutes from awakening to optimal status for that day]; 3) treatments [parenteral gold salts and oral corticosteroids]; and 4) comorbid cardiovascular disease (including diseases other than hypertension only). Articular variables were based on a joint count in which swelling, limited motion, and deformity were recorded for each of 70 joints in each patient, and any abnormality was scored as an involved joint. The standard joint count studied as potentially prognostic for mortality included 50 joints: 8 distal interphalangeal joints in the hand, 10 proximal interphalangeal joints in the hand, 10 metacarpophalangeal joints in the hand, 2 shoulder, 2 knee, 2 hip, 2 ankle, 2 wrist, 2 elbow, and 10 metatarsophalangeal joints in the feet. Certain analyses were directed at the prognostic value of reduced joint counts for mortality for 15 years. A 36 joint count [27] did not include shoulder or hip joints, distal interphalangeal joints in the hand, or metacarpophalangeal joints in the thumb. A 28 joint count [28] did not include hip or ankle joints, distal interphalangeal joints in the hand, or metatarsophalangeal joints in the foot. A 12 joint count included only 8 metacarpophalangeal joints (not including the thumb), the shoulders, and the knees; a count of 6 joints included only shoulders, knees, and hips. Survival rates were also analyzed according to baseline involvement of 0, 1, or 2 knees. Two questionnaire measures of functional status were obtained. 1. Activities of daily living: An interviewer reviewed a list of 87 activities with each patient, and the patient was asked to rate his or her performance into one of three categories, able to do with ease = 1; able to do with some help = 2; and unable to do = 3. Certain activities were irrelevant to certain patients (for example, use of cane or wheelchair), resulting in patients being asked a variable number of questions between 74 and 87 (mean, 82.9). Overall functional capacity was calculated by determining the percentage of activities that the patient was able to do with ease and calculating the mean score. In order to analyze the prognostic value of a decreased number of items, survival was also analyzed according to only 20 or 8 of these activities, to simulate the 20-item Stanford Health Assessment Questionnaire (HAQ) [25] and the 8-item modified version of this questionnaire (MHAQ) [26]. Responses in the initial review had been obtained by an observer rather than by self-report as in the contemporary questionnaires. 2. Adjustment scale: Three questions were asked in a self-report format at baseline in 1973: 1) Do you feel all is being done that can be done for your care?; 2) Do you feel you have been well educated on how to live with your condition?; 3) Do you neglect medicine or treatment because of the expense? A score of 1 was assigned for a yes response to the first two questions and a no response to the third question. The total adjustment score, therefore, ranged from 0 to 3. Three physical measures of functional status [31] were obtained. 1. Grip strength: A blood pressure cuff was inflated to 30 mm Hg, and the patient was asked to squeeze it as hard as he or she could. The test was repeated three times for each hand, and the score recorded was the mean of these six measures. 2. Modified walking time: The standard procedure, in which the patient is asked to walk at a normal pace for 7.6 metres (25 feet) [31], was modified in the 1973 evaluation by having the patient get up from a chair before walking and sit in a chair at the conclusion of the 25-foot walk. The score was recorded in seconds. 3. Button test: A standard button board (J. A. Preston, Clifton, New Jersey) was used. The patient was asked to unbutton five buttons and then button them as quickly as he or she could, using the dominant hand only, unlike the present method [31]. The score was recorded in seconds [32]. Trivial differences in values of tests of functional capacity that were previously reported [13] resulted from small amounts of missing data found after that report was published. The baseline evaluation 15 years earlier had included more quantitative data than are usually collected in the care of patients with rheumatoid arthritis but unfortunately had not included the American Rheumatism Association Criteria for rheumatoid arthritis [2, 3] or the formal American Rheumatism Association Functional Class [33]. Most patients had a complete blood count, but only a few patients had assessments of erythrocyte sedimentation rate or tests for rheumatoid factor; therefore, meaningful analyses according to baseline laboratory data could not be done. Statistical Analysis The data were analyzed using the BMDP [34] and SAS [35] statistical software packages. Standard mortality ratios were computed by comparison to age- and sex-specific U.S. mortality [

Self-Report Questionnaire Scores in Rheumatoid Arthritis Compared with Traditional Physical, Radiographic, and Laboratory Measures

STUDY OBJECTIVE To assess whether scores on a simple self-report questionnaire to depict the clinical status of patients with rheumatoid arthritis are correlated with traditional measures of physical, radiographic, laboratory, functional, and global status. DESIGN The self-report questionnaire was administered at the same time the following variables were assessed: American Rheumatism Association functional class, joint count, hand radiograph, erythrocyte sedimentation rate, rheumatoid factor titer, walking time, grip strength, button test, and global self-assessment. SETTING University rheumatology clinic, the rheumatology clinic of a Veterans Administration hospital, and a private rheumatology practice. PATIENTS The study included 259 patients who met the criteria of the American Rheumatism Association for a diagnosis of definite or classic rheumatoid arthritis. INTERVENTIONS Standard rheumatologic care for patients with rheumatoid arthritis. MEASUREMENTS AND MAIN RESULTS Self-report questionnaire scores were significantly correlated with the joint count, radiographic score, erythrocyte sedimentation rate, grip strength, button test, walking time, American Rheumatism Association functional class, and global self-assessment. Patients were categorized into five questionnaire score categories of 1.00, indicating no dysfunction, and 1.01 to 1.50, 1.51 to 2.00, 2.01 to 3.00, and 3.01 to 4.00, indicating progressive dysfunction. In these five categories, more than ten involved joints were seen in 11%, 37%, 67%, 79%, and 100% of patients, respectively, and erythrocyte sedimentation rates greater than 20 mm/h in 29%, 49%, 64%, 74%, and 85% of patients, respectively. Similar results were seen for other physical and radiographic measures. The questionnaire score was as effective in explaining other measures of clinical status as was any other available measure. CONCLUSIONS A simple self-report questionnaire provides information similar to many traditional measures in rheumatoid arthritis and appears to be an attractive, cost-effective approach to assessing and monitoring quantitatively the status of an individual patient.

Associations of HLA-DR4 with rheumatoid factor and radiographic severity in rheumatoid arthritis

Possible associations between HLA-DR4 and laboratory, radiographic, joint count, functional, and demographic measures of clinical status were analyzed in 154 white patients with rheumatoid arthritis. Overall, 65 percent of the patients were HLA-DR4 positive, similar to other series. HLA-DR4 was associated significantly with the presence of rheumatoid factor and more severe radiographic changes. HLA-DR4 was not associated with significant differences in demographic, joint count, or functional measures of clinical status. HLA-DR1 was not associated significantly with differences in the presence of rheumatoid factor, radiographic changes, or other measures of clinical status. Selective associations of HLA-DR4 with rheumatoid factor and radiographic scores were more marked in men than in women. Patients who were putatively homozygous for HLA-DR4 were all seropositive and had more severe radiographic changes than patients who were heterozygous for HLA-DR4.

Combination treatment of severe rheumatoid arthritis with cyclosporine and methotrexate for forty-eight weeks: an open-label extension study. The Methotrexate-Cyclosporine Combination Study Group.

OBJECTIVE To determine whether the clinical benefit and favorable safety profile previously noted with the combination of cyclosporine (CSA) and methotrexate (MTX) given for 24 weeks in patients with rheumatoid arthritis (RA) would be maintained for a further 24 weeks, and whether the addition of CSA in patients who had previously been randomized to receive placebo + MTX would result in clinical benefit. METHODS Eligible subjects from the initial study (weeks 0-24), in which the addition of placebo or CSA to MTX therapy was compared in patients with RA that was partially responsive to MTX, were enrolled. Patients who had received CSA + MTX continued this regimen for a further 24 weeks (weeks 24-48) (group 1; n = 48), and patients who had initially received placebo + MTX now received CSA + MTX for 24 weeks (weeks 24-48) (group 2; n = 44), in an open-label extension study. The primary outcome measures were the number of tender joints, number of swollen joints, physician and patient global assessments, pain, functional disability as measured by the modified Health Assessment Questionnaire, and erythrocyte sedimentation rate. RESULTS Of the 92 patients enrolled, 80 (87%) completed the extension study. In patients in group 1, the clinically and statistically significant improvement in response outcomes previously noted at week 24, ranging from 25% to 50%, was maintained through week 48. In patients in group 2, the addition of CSA resulted in significant clinical improvement. By week 48, most outcome measures in group 2 patients were similar to those in group 1 patients. CSA treatment resulted in a small increase in serum creatinine levels, but only 1 patient was withdrawn from the study for this reason. CONCLUSION The clinical improvement previously observed in patients treated with the CSA + MTX combination for 24 weeks was maintained for 24 subsequent weeks, without serious adverse effects, and was also observed in the patients whose treatment was switched from placebo + MTX to CSA + MTX.

Bony ankylosis in rheumatoid arthritis: Associations with longer duration and greater severity of disease

Hand and wrist radiographs of 203 patients with rheumatoid arthritis were examined for bony ankylosis. Forty-eight patients (23.6%) showed ankylosis, including 34 with more than one joint fused. The distribution of ankylosed joints was 32.4% midcarpal, 29.5% common carpometacarpal, 15.8% radiocarpal, 15.8% proximal interphalangeal, and 6.5% metacarpophalangeal. Patients with ankylosis had significantly higher radiographic erosion, joint space narrowing, and malalignment scores than those without ankylosis (all P less than .001). Patients with ankylosis had significantly longer duration of disease (P less than .001) and physical examinations showed more limited motion and deformity (both P less than .001). More patients with ankylosis had subcutaneous nodules (P less than .05). Functional testing with grip strength and the button test revealed poorer performance in patients with ankylosis (both P less than .001). Questionnaires revealed patients with ankylosis had more difficulty with activities of daily living (P less than .001) and had more limited activity (P less than .01); physicians estimated more limited functional capacity (P less than .001). Thus, radiographic bony ankylosis was a relatively common feature of rheumatoid arthritis, and a marker of patients whose disease was clinically, radiographically, and functionally more severe.

IgM-rheumatoid factor and responses to second-line drugs in rheumatoid arthritis

We have examined the relationship between IgM-rheumatoid factor (RF) and responses to second-line drugs in patients with rheumatoid arthritis (RA). Patients with active RA who were beginning treatment with gold, methotrexate or both were studied. Clinical responses were assessed with ESR, joint count, grip strength and activities of daily living questionnaire scores. Production of IgM-RF by peripheral blood mononuclear cellsin vitro and plasma levels of IgM-RF were measured by ELISA. Overall, 31 of 44 patients completing more than 6 months treatment improved including 10 treated with gold, 12 with MTX and 9 with both. Production of IgM-RF by peripheral blood mononuclear cells was decreased by 59% in patients who improved on treatment, but increased 2-fold in the unimproved group. Plasma levels of IgM-RF were decreased from 121 to 66 μg/ml in the improved group after 6 months of treatment, with similar decreases seen for each of the three treatments. In contrast, plasma IgM-RF levels in the unimproved group did not decrease until 1 year of treatment was completed. Nine patients converted to seronegativity, and all but one of these were in the improved group. The results suggest that IgM-RF is correlated with responses to second-line drug in RA patients.