The course of rheumatoid arthritis and predictors of psychological, physical and radiographic outcome after 5 years of follow-up

T. Uhlig, L M. Smedstad, P. Vaglum1, T. Moum1, N. Gérard2 and T. K. Kvien

Department of Rheumatology, Diakonhjemmet Hospital, Box 23 Vinderen, N-0319 Oslo,
1 Department of Behavioural Sciences in Medicine, University of Oslo, Box 1111 Blindern, N-0317 Oslo, Norway and
2 School of Public Health, University of Nancy, Box 184, F-54505 Nancy, France


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Objective. To examine the course of RA over 5 yr and identify predictors of psychological, physical and radiographic outcome.

Patients and methods. Out of 238 patients with rheumatoid arthritis of no more than 4 (mean 2.2) yr duration, 182 (76%) completed a clinical examination with follow-up at 1, 2, and 5 yr. The course of the disease was assessed by measures of psychological and physical health status, disease process and radiographic damage.

Results. Over 5 yr we observed at a group level a stable disease course for measures of disease process, psychological and physical health status. Radiographic damage progressed. Health status and radiographic damage after 5 yr were predicted by the baseline measures for the respective outcome. Physical function was also predicted by age and by psychological status when the physical dimension of the Arthritis Impact Measurement Scales was chosen as outcome variable. Erythrocyte sedimentation rate and presence of rheumatoid factor predicted radiographic progression.

Conclusions. The 5 yr course of RA was characterized by preserved health status measures and clinically preserved disease process measures, whereas joint damage progressed steadily. Outcomes after 5 yr can be predicted partly by certain measures at baseline.

KEY WORDS: Rheumatoid arthritis, Prospective study, HAQ, AIMS, Radiographic damage, Prognostic factors, Prognosis, Psychological distress, Physical disability, Health status measures.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
The natural course of rheumatoid arthritis (RA) is characterized by increasing morbidity and excess mortality [1]. The long-term course over >=15 yr has been examined in only a few studies [2, 3], and even reports on a follow-up of >=5 yr are relatively scarce. Patients with varying follow-up periods have been included in many studies.

Psychological distress is recognized as a major problem in patients with RA and other chronic diseases. Nevertheless, few studies have explored psychological measures over time [4], as predictors of outcome [5] or in attempts to predict psychological distress in RA [6, 7]. Predictors of psychological health status after >=5 yr of follow-up have not yet been described.

More data are available on prognostic markers of physical and radiographic outcome, but the results have varied to some extent across studies. In some studies gender [810], age at onset [3, 8], or level of education [9] was associated with physical outcome after at least 5 yr, while the presence of rheumatoid factor (RF) was confirmed as a predictor of poor outcome in a great number of studies [2, 1014]. Studies including functional capacity at baseline have identified the baseline level of disability as the most consistent predictor of deterioration in physical function over time [2, 3, 8, 9, 11, 14, 15].

Disease activity [12, 13, 1619] or radiographic status at baseline [1620, 20, 21] are recognized as predictive factors for radiographic damage after >=5yr of follow-up. There has been controversy regarding the importance of demographic factors [12, 20], so it is still relevant to examine the importance of clinical and demographic features for the prediction of physical and radiographic outcome in RA.

This 5-yr longitudinal study examined the course and outcome of RA in a cohort of 238 patients with disease of short duration. We assessed measures of psychological as well as physical health status, markers of disease process and radiographic damage by performing waves of data collection at baseline and after 1, 2 and 5 yr. Additional aims were to explore differences in disease course according to gender, presence of RF and presence of radiographic abnormalities. Finally, we wanted to identify independent predictors of psychological, physical and radiographic status at 5 yr of follow-up.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Patients
Patients with a clinical diagnosis of RA with a maximum duration of 4 yr, seen one or more times at the Oslo City Department of Rheumatology or at the Akershus County Department of Rheumatology, were invited to participate in this study. Criteria of entry and exclusion were set by the EURIDISS project (European Research on Incapacitating Diseases and Social Support) [22], of which this study was a part. The sampling procedure, as well as the sample, has been described in detail elsewhere [23]. In short, patients were recruited from files of patients examined earlier at one of the two rheumatology out-patient departments. The inclusion criteria were as follows: residence in the study area, age 20–70 yr, diagnosis of RA according to the 1987 American Rheumatism Association revised criteria (ACR) [24] and a disease duration at inclusion of no more than 4 yr. Exclusion criteria were the presence of other incapacitating diseases, stage-IV Steinbrocker functional class [25] or expected loss to follow-up (e.g. moving home). Of 326 consecutive patients invited, 268 (82%) were willing to participate. Thirty of the 268 patients were excluded, of whom 21 did not meet four of the seven ACR criteria [24] at the time of inclusion, six planned to move to another region and three were immigrants with severe communication problems in the Norwegian language. Two hundred and thirty-eight patients (175 females, 63 males) were included in the study. Mean age was 52.2 yr (S.D. 13.0), mean disease duration was 2.2 years (S.D. 1.27, range 0–4) and 68% were RF-positive.

Of the 238 patients included at baseline, 227 (95.4%) completed the follow-up examination at 1 yr, 216 (90.8%) completed the follow-up examination at 2 yr and 182 (76.5%) were re-examined at the 5-yr follow-up, providing data from all four waves of data collection. Reasons for the loss of 56 patients to the final follow-up were reluctance to participate further (n = 39), moving out of the area (n = 5) and death (n = 12). The response rate was 81.2% over 5 yr when deceased patients were considered. Patients completing the 5-yr follow-up were younger than the non-completers (P = 0.01) but comparable for all other demographic and disease-specific features (Table 1Go). All patients received routine combined care from a rheumatologist or a general practitioner independently of the scheduled observational study visits. Patients were followed clinically by a rheumatologist as medically indicated, usually twice a year if they used a disease-modifying anti-rheumatic drug (DMARD).


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TABLE 1. Baseline characteristics of completers, non-completers and living non-completers at 5 yr of follow-up

 

Assessments
Patients were assessed clinically at baseline and after 1, 2 and 5 yr. Each patient was evaluated with a medical examination, including the Ritchie articular index [26], and grip strength (kg, average of right and left arms). The clinical examination was performed by a rheumatologist at baseline and after 1 and 2 yr (L.M.S.), and after 5 yr (T.U.). A test of inter-examiner agreement [27] between the two physicians in 10 RA patients showed a moderate value for tender joints (kappa value 0.45).

Blood samples were taken for the analysis of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Analyses of IgM-RF were performed at baseline for all patients, using WHO international standard reference preparations [28].

Radiographs of the hands could be evaluated in 205 patients at baseline, 195 patients after 2 yr and 149 patients after 5 yr of follow-up. Grading of joint damage was performed according to the Sharp method [29], using the modification by van der Heijde et al. [30]. In this method, 16 areas for erosions and 15 for joint-space narrowing are considered in each hand. With an erosion score per joint ranging from 0 to 5 and a score for joint space narrowing ranging from 0 to 4, the maximum total score for both hands is 280. All radiographs were read sequentially and scored by the same observer (N.G.), who recorded the total modified Sharp score, without entering scores for individual joints (erosions and joint space narrowing) into the database.

After the examination, the patients filled in self-report instruments without assistance. The procedure by which the instruments were translated has been described elsewhere [23, 31].

The Arthritis Impact Measurement Scales (AIMS) is a multidimensional health status instrument used widely in arthritis patients. It consists of nine scales: mobility, physical activity, dexterity, household activities, activities of daily living, social activities, anxiety, depression, and pain. A three-component model of AIMS health status was used which included physical disability (the five physically orientated AIMS scales), psychological status (anxiety and depression) and pain [32]. The scores for each individual scale are transformed to a 0–10 scale on which higher scores represent more severe dysfunction. They are then added and divided by 5 or 2 for the components physical disability and psychological status, respectively. The AIMS was used to measure psychological distress. The psychometric properties of the instrument have been examined extensively [33, 34]. However, the AIMS depression scale has not been validated in relation to diagnostic interviews, although strong correlations have been reported between this scale and the Center of Epidemiological Studies—Depression measure [35]. The patients' global assessment of the impact of arthritis was assessed by one item from the AIMS on a scale from 0 to 10 [34].

The Health Assessment Questionnaire (HAQ) examines disability within eight dimensions of daily living [36]. The item with the highest score within each dimension—weighted by the use of aids or instruments—is selected, and a sum score (range 0–3) is computed as the average of the eight dimensions. The psychometric properties of the original HAQ as a measure of disability in arthritis have been examined extensively [35, 37]. The HAQ has been validated in Swedish, which is very similar to the Norwegian language [38].

The questionnaire also included RA history (medication, complications) and a list of co-morbidities. The investigator recorded current and previous medication. Education was recorded, coded according to the International Standard Classification of Education [39], and then recorded to a three-point scale.

Data analysis
The two-tailed t-test was applied for comparisons of continuous variables and Pearson's {chi}2 test for categorical variables. A 5% level of significance was chosen for all analyses. The data were analysed using the SPSS/PC software version 8.0.

Repeated measures analysis of variance (ANOVA) was used to explore the effect of time on measures of outcome and to compare subgroup differences. Repeated ANOVA was used to process data from all four examinations, thereby adding to the statistical strength.

Many variables were not normally distributed. We were concerned to ensure the validity of the parametric tests that were used, and we therefore also transformed the observed values into ranks for variables that were not normally distributed (e.g. the HAQ and AIMS scores). No important differences in results were noted. The non-transformed data are presented for ease of interpretation.

The scores for psychological, physical and radiographic status at the 5-yr follow-up were dichotomized and bivariate associations were calculated. For the psychological dimension a cut-off of 3.0 was chosen to indicate psychological distress, corresponding to the proposal to consider scores of >3.0 on the AIMS depression scale as the threshold for possible depression [35]. A cut-off point of 1.0 was chosen for the final HAQ score to indicate at least moderate disability [9]. For AIMS physical this level was set to 2.0. The modified Sharp score was dichotomized at 30, and scores >30 were considered as indicating radiographic damage.

Candidate predictive variables at baseline were required to generate a significant (P < 0.15) value in bivariate analysis to be selected for stepwise multivariate analysis. The dependent variables were psychological status, physical function (AIMS physical or HAQ) and radiographic damage, measured after 5 yr of follow-up. Multivariate analyses were performed both with dichotomized (logistic regression) and continuous (linear regression) dependent variables. Similar results were obtained for the two types of analysis, and results for linear regression are presented. For stepwise forward regression, the candidate variable most strongly correlated with functional or radiographic status was selected first, then the variable providing the most additional information when combined with the first, and so on. The R2 value is the percentage of the variation in the dependent variable that can be explained by variation in the independent variables of the regression.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
We observed a generally stable course of RA regarding functional measures in the 182 patients completing the 5-yr follow-up. There were no significant changes in psychological status over time in the group, and scores for the health status measures of physical function were mainly unchanged. Radiographic damage, however, had deteriorated by 2 and 5 yr of follow-up (Table 2Go). More patients were using corticosteroids at the 5-yr follow-up than at baseline (Pearson {chi}2 = 36.2, P < 0.001).


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TABLE 2. Study variables among 182 RA patients over 5 yr of follow-up

 
Possible subgroup differences in the follow-up results for psychological status, physical status and radiographic damage were explored by subdividing the material according to gender (Fig. 1Go), presence of RF (Fig. 2Go) and radiographic abnormalities at study entry (Fig. 3Go). When we adjusted for the respective baseline values of the outcome variables examined, radiographic progression differed between patients with and without RF, and between those with and without radiographic abnormalities at baseline (both P < 0.001, repeated measures ANOVA). When we corrected for baseline differences there was no apparent effect of gender, RF status or radiographic status on psychological or physical status over time. However, females, RF-positive individuals and patients with X-ray abnormalities tended to have higher (i.e. more disabling) scores for health status measures at baseline and later during the study.



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FIG. 1. Scores for psychological and physical health status and radiographic damage (mean and 95% confidence interval) in males and females.

 


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FIG. 2. Scores for psychological and physical health status and radiographic damage (mean and 95% confidence interval) in patients with and without RF.

 


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FIG. 3. Scores for psychological and physical health status and radiographic damage (mean and 95% confidence interval) in patients with and without radiographic abnormalities at baseline.

 
In bivariate analyses, several baseline variables were associated with psychological distress (AIMS psychological >3.0), physical disability (HAQ >1.0 or AIMS physical >2.0) and with radiographic damage (modified Sharp score >30) at the 5-yr follow-up (Table 3Go).


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TABLE 3. Possible predictors at baseline for psychological distress (AIMS psychological >3.0), disability (HAQ >1.0, AIMS physical >2.0) and radiographic damage (Sharp score >30) after 5 yr (means and t-tests for continuous variables, % and {chi}2 test for counts)

 
In linear regression analyses, outcomes for psychological and physical health status as well as radiographic damage at the 5-yr follow-up were best predicted by their respective baseline values (Table 4Go). Physical disability was also predicted by high age at onset, while physical disability when measured with AIMS was also independently predicted by psychological health status at baseline. Radiographic damage was predicted by radiographic baseline value, by ESR and to a minor degree by RF-positivity. Gender, grip strength and pain were not independent predictors of disability or radiographic damage. Physical function was not an independent predictor of radiographic damage, nor could disability be predicted by radiographic damage at baseline. If ESR was replaced by CRP in the multivariate analysis, a statistically significant but weaker association with progression of radiographic damage was also observed.


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TABLE 4. Significant predictors of psychological health status (AIMS psychological), physical health status (HAQ, AIMS physical) and radiographic damage (Modified Sharp score) after 5 yr of follow-up, using multiple linear regression analysis

 
For radiographic outcome after 5 yr, 64% of the variance could be accounted for by baseline variables with significant contributions to the model. The corresponding values for physical function and psychological status were 38 and 32% respectively.


    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
This study, with four waves of data collection over 5 yr, demonstrated a generally benign course of RA at the group level, with stable disease process and health status measures. This stable course was also revealed in patients grouped according to gender, RF and radiographic status at baseline. In spite of this favourable clinical course, joint damage progressed steadily.

Unchanged psychological health status has also been reported by Meenan et al. [4] and unchanged helplessness scores by Callahan et al. [5] after 5 yr of follow-up. Hawley and Wolfe [6] found stable AIMS scores for anxiety and depression in 400 patients over an average of 3.1 yr. While studies on longitudinal outcome have reported a deterioration in physical capacity after 15 yr [2] or 20 yr [3], some newer reports in line with the present study indicate a more benign course [4, 9, 13, 15, 40, 41].

The present data revealed slightly diverging results for HAQ and AIMS physical dimension: the HAQ scores remained stable while the AIMS mean scores deteriorated slightly, but statistically significantly, from 1.92 to 2.16 during the 5-yr follow-up. This discrepancy between the two health status instruments for physical function may indicate higher responsiveness for AIMS physical than HAQ in longitudinal observational studies.

The present study (Table 2Go; Figs 1Go–3Go, bottom panels) and other studies have demonstrated progression of structural damage in the face of preserved functional health status [5, 20, 42]. This dissociation reflects the probability that the pathological process in RA and disease-modifying anti-rheumatic treatments exert different effects on the domains of disease outcome, thus leading to a poor correlation between functional and radiological measures. Another possible explanation is related to the properties of self-reported measures of health status. The radiologist may, on the contrary, be more concerned with joint damage accumulating over time.

One of the major challenges for the clinician is to predict disease course when facing a patient with RA at an early stage. There is now a growing body of data from cohorts with >= 5 yr of follow-up [43] which provides information on predictors of disease course in various domains [44]. While these results are often presented in separate reports, multinational pooling of data may increase the power [45]. Table 5Go gives an overview of predictors identified for psychological, physical and radiographic outcomes in studies of RA with <5 yr duration at baseline and a longitudinal follow-up of at least 5 yr. This study, in line with others in which baseline measurements were considered [3, 810, 14, 1721], demonstrated that the best predictors for physical and psychological health status as well as radiographic damage were the respective baseline measures (Table 4Go).


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TABLE 5. Predictors of poor functional and radiographic outcome after at least 5 yr of follow-up in RA with disease duration of <5 yr at baseline

 
Psychological baseline status was the only independent predictor of psychological health status after 5 yr of follow-up (Table 4Go), even though a wide spectrum of demographic and clinical variables was examined. Similar results have been reported by Hawley and Wolfe [6], who found no associations between change in disease variables and anxiety or depression over a mean follow-up of 3.1 yr. Previous studies have indicated that psychological distress seems to be mediated to a large degree through disease variables in RA such as pain, disability and fatigue [6, 46].

The 5-yr change in AIMS measures of physical function was predicted by psychological status at baseline, in line with a report by Wolfe and Cathey [15], who found psychological variables useful for the prediction of physical outcome. A predictive value of high age for poor functional outcome in this study is supported [3, 8, 14, 15] by other studies. Female sex was not a prognostic marker for poor functional outcome in this study (Fig. 1Go, middle; Table 4Go), in line with other [12], but not all [8, 9], reports. Some studies, like ours (Fig. 2Go, middle; Table 4Go) have found no evidence of independent prediction of RF-positivity [9, 15] or of ESR or other indicators of disease activity [3, 8, 9, 1214] for poor outcome. Others have identified RF [2, 3, 12, 14] as independent predictors of physical function. Taking this and other reports together, age and, most likely, an indicator of the disease process may be considered as predictors for longitudinal change in physical function, while the roles of RF-seropositivity, gender and psychological distress are not clear.

Radiographic status at baseline was not an independent predictor of physical disability 5 yr later (Fig. 3Go, middle; Table 4Go), though clear bivariate associations were found (Table 3Go). Only a few previous studies have examined radiographic status at baseline and functional outcome, and they have found no clear association in bivariate [11, 48] or multivariate [9] analyses. Thus, taking all studies together, damage and functional status can be considered as independent measures of disease progression in RA.

Radiographic damage at follow-up was closely related to damage at baseline; this was also found by Fex et al. [20] but not by Möttonen et al. [18]. Laboratory markers of inflammation and RF-positivity at baseline (Fig. 2Go, bottom; Table 4Go) predicted change in radiographic damage. This confirms other reports identifying RF at baseline [1214, 1719] and laboratory markers of inflammation [14, 17, 19, 20] as important predictors of radiographic outcome. Patients without RF had little chance to develop radiographic damage (Fig. 2Go, bottom) and lack of radiographic abnormality at study entry made it unlikely that these would develop during the next 5 yr (Fig. 3CGo). We found ESR to be a stronger predictor than CRP, while others have found a better correlation between radiographic progression and CRP than with ESR [49].

This study shows that predictors of the disease course may help the clinician in reaching a therapeutic decision. As an illustration, only one of the present 26 RF-negative patients who had normal joint radiographs at a mean of 2.2 yr after disease onset had developed radiographic damage 5 yr later, with a Sharp score of >30. For many patients the disease will continue to remain benign, and treatment should be tailored individually according to predictors of course and outcome. Furthermore, our results support the observation that radiographic progression and functional health status are dissociated outcomes, at least early in the disease course. This apparent paradox may be due to different effects of the pathological process or treatment on the various domains of disease outcome.


    Acknowledgments
 
Supported in part by grants from The Research Council of Norway, Lions Clubs International (MD 104 Norway), The Norwegian Rheumatism Association, The Norwegian Women's Public Health Association, Trygve Gythfeldt and Wife's Legacy, Grethe Harbitz Legacy, Marie and Else Mustad's Legacy and the European Community BMH4-CT96–1580 (EURIDISS) from the DG XII. We are indebted to our research nurses Ingerid Müller and Catherine Planke for their assistance in the collection of data. We also thank medical student Espen Haavardsholm for data entry.


    Notes
 
Correspondence to: T. Uhlig. Back


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

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Submitted 5 May 1999; revised version accepted 10 January 2000.