The patient's perspective and rheumatoid arthritis disease activity indexes

B. F. Leeb, I. Andel, S. Leder, B. A. Leeb and B. Rintelen

Second Department of Medicine, Humanisklinikum Lower Austria, Lower Austrian Center for Rheumatology, Stockerau, Austria.

Correspondence to: B. F. Leeb, Second Department of Medicine, Humanisklinikum Lower Austria Lower Austrian Center for Rheumatology, A-2000 Stockerau, Landstrasse 18, Austria. E-mail: leeb.khstockerau{at}aon.at


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Background. Monitoring disease activity in rheumatoid arthritis (RA) patients by composite indexes is regarded as obligatory when following the recent recommendations for therapy. Whether these recommendations and the patient's perspective are in congruence is a crucial question with respect to the patient's compliance. The aim of the study was to obtain information on the patient's perspective with respect to the disease activity indexes used most often.

Methods. Two hundred and seven RA patients (157 female, 50 male; mean age 59.03 yr, 17–86 yr) were enrolled in this cross-sectional evaluation. The patients’ satisfaction [PATSAT (Austrian school mark system) 1 = excellent to 5 = unsatisfactory] and the patients’ attitude to therapy (PATATT 1 = reduction, 2 = no change, 3 = increase) were assessed and related to the 28-joint Disease Activity Score (DAS28), the Simplified Disease Activity Index (SDAI) and the Modified Health Assessment Questionnaire (M-HAQ). Statistical evaluation was carried out by applying the Mann–Whitney U test, calculating {chi}2 and ANOVA.

Results. According to the DAS28 and the M-HAQ, patients were at a moderately active disease stage and had low functional deficiency. PATSAT was significantly correlated to the disease activity indexes (all PS ≤ 0.002). The mean DAS28 (2.56) at PATSAT 1 was within the remission range, whereas at PATSAT 5 a mean of 5.52 indicated highly active disease. PATATT was found to be related to PATSAT, but did not completely parallel it. Reduction of therapy was intended at a mean DAS28 of 2.87, whereas a request for an increase did not occur before a mean DAS28 of 4.92.

Conclusion. The patients’ therapeutic attitudes are somewhat in line with their satisfaction, which mirrors disease activity to a great extent, though not with the common therapeutic recommendations. The DAS28 proved to be superior to both other indexes taking account of the patient's perspective. These results may provide guidance in patient care and education as well as therapeutic strategies.

KEY WORDS: Rheumatoid arthritis, Disease activity measurement, Patient's perspective


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
‘An improved HAQ score may not mean that the areas important to the patient have improved’ [1] and this may likewise be the case for composite disease activity indexes, such as the Disease Activity Index including an 28-joint count (DAS28), and the simplified Disease Activity Index (SDAI) [2, 3].

These composite indexes for the evaluation of disease activity, a combination of surrogates related directly to the inflammatory events, such as joint counts and the acute-phase response, have been successfully used over the past decade, particularly in clinical trials [2, 4]. A numerical measure, as provided by the DAS28 and the European League Against Rheumatism (EULAR) response criteria (EULARC), as well as the SDAI, gives the opportunity of comparing the disease status of patient groups as well as of individual patients [2–4].

The EULARC define disease activity stages and the significance of a therapeutic response on the basis of the DAS28 as follows: values below 2.6 indicate a remission-like disease stage; values between 2.6 and 3.2 indicate low; between 3.2 and 5.1 moderate; and greater than 5.1 high rheumatoid arthritis (RA) activity. A DAS28 reduction of more than 1.2 is regarded as describing a good response, while a reduction of 0.6–1.2 indicates a moderate response in case of moderate or low disease activity [4].

The SDAI is a composite index resulting from the addition of the swollen joint score (SJC) and the tender joint score (TJC) of an 28-joint count, as well as C-reactive protein (CRP, mg/dl), the visual analogue scale (VAS) of the patient's general health (VAS-GH) and the VAS of physician's assessment (VAS-PH). The SDAI proved to be highly correlated to the DAS28, but the SDAI-derived disease activity categories (SDAIAC) are significantly different from the respective categories as expressed by the EULARC [3, 5].

These indexes are widely recommended for disease activity monitoring in clinical practice. Achieving low disease activity, at best a remission-like state, is regarded as essential in improving prognosis [6].

Recently, there has been some discussion about the relevance of such indices with respect to daily practice, taking into account the patient's position [7]. In daily life, the decision to change the therapeutic regimen can only be made together with each single patient, and not without considering the patient's thoughts and perspectives. What good is a scientifically well-founded decision if the patient is not ready to follow the recommendations? Thus, in most cases in daily practice, therapeutic decisions are based on some kind of compromise between physician and patient.

Almost all therapeutic recommendations were established—by physicians—on the basis of disease activity or outcome measures, which do not incorporate parameters such as patient satisfaction or his/her willingness to change therapy [6, 8]. Moreover, composite scores, such as the Disease Activity Score (DAS28) the Simplified Disease Activity Index (SDAI) and the Modified Health Assessment Questionnaire (M-HAQ), may be influenced by coexisting diseases, such as infections or fibromyalgia, which accompanies RA relatively frequently [9, 10]. In addition, the patient's individual perspective of the disease may be influenced by various—not necessarily directly disease-dependent and not only rational—factors, but obviously not exclusively by current disease activity.

The reason for conducting this observational investigation was a question that is often discussed but rarely answered: are the patient's perspectives and thoughts about their disease and its activity in keeping with the commonly applied (and primarily physician-generated) disease activity measures and therapeutic recommendations? And if so, to what extent is one of the commonly applied disease activity indexes, such as the DAS28 or the M-HAQ, and also the new SDAI, superior to the others with respect to the patient's perspective? [2, 3, 11]. Consequently, will patients follow their physicians’ therapeutic recommendations willingly, or will the physicians have to reckon with often difficult discussions?

Therefore, in order to obtain better information about patients’ attitudes and thoughts, it seemed worthwhile to make an attempt to investigate relations between disease activity measures and patient satisfaction, as well as patient willingness to change the therapeutic regimen. Ideally the physician's tools to measure disease activity and the patient's opinion about his or her situation should be congruent. However, to our knowledge, the clearly crucial degree of congruence has not yet been elucidated for the tools to measure disease activity that are used most often.

Here we report the results of an investigation performed in a conventional rheumatology out-patient clinic, comparing disease activity measures with patient satisfaction and patients’ requests for a decrease, an increase, or no change in their therapeutic regimen.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Patients
Two hundred and seven out-patients (157 female, 50 male; mean age 59.03 yr; 17–86 yr), all fulfilling the 1987 ARA classification criteria of RA [12]), were enrolled in the cross-sectional evaluation from March to November 2003. All patients gave written informed consent to be enrolled in this observational study, according to the Declaration of Helsinki. The design of the study was approved by the local ethics committee. In addition to giving their consent, patients had to be regular control patients of our out-patient clinic.

All the demographic details of the study participants, which are shown in Table 1, as well as their actual medication were recorded at the time of inclusion. Assessment of patients according to the DAS28 [2] and the SDAI [3], comprising swollen and tender joint counts, CRP, erythrocyte sedimentation rate and VAS values for patient's and physician's global assessments, is part of the routine monitoring programme. Additionally, patients were asked to complete the M-HAQ questionnaire [11]. Moreover, patients rated their current satisfaction with their disease state according to the Austrian school mark system (PATSAT: 1 = excellent, 2 = good, 3 = average, 4 = moderate, 5 = unsatisfactory). The Austrian school mark system resembles a Likert scale and is well established; therefore misinterpretations by the patients are highly unlikely. Simultaneously, patients were asked for their therapeutic attitude (PATATT), whether they wanted to reduce (=1) or increase (=3) their medication, or whether they wanted their medication to remain unchanged (=2).


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TABLE 1. Patients’ demographic data

 
PATSAT and PATATT constituted the primary variables. The disease activity measures applied, namely the DAS28, the SDAI and the M-HAQ, were compared at the different levels of PATSAT, and also with PATATT. Besides the comparison of the entire patient population, patient categories according to their disease activity were established. With respect to the EULARC [4], the SDAIAC [3] and the functional disability according to the M-HAQ, respectively [13], patients were divided into those with low (=1; DAS28<3.2; SDAI<20, M-HAQ<0.38), moderate (=2; DAS28 3.2–5.1, SDAI 20–40, M-HAQ 0.38–1.5) and high (=3; DAS28>5.1, SDAI>40, M-HAQ>1.5) disease activity or functional disability.

Statistical analysis
DAS28, SDAI and M-HAQ-values and values of patient satisfaction are given as mean ± S.D., as departures from normality do not play a role in larger samples, given the central limit theorem. Spearman's {rho} was applied for correlation analysis between the disease activity parameters.

Wherever two variables were compared with one another, the Mann–Whitney U test was used. P values below 0.05 were regarded as statistically significant. ANOVA was applied for assessment of disease activity indices and their single components at different levels of PATSAT and PATATT. The value of {chi}2 was calculated to estimate the relationship of PATSAT and PATATT and to assess the relationship between the disease activity categories and the patients’ satisfaction and attitude.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
The demographic data as well as the RA-specific characteristics of the 207 patients investigated are given in Table 1. Two hundred and two of the 207 (97.5%) patients were on therapy with disease-modifying anti-rheumatic drugs (DMARDs), comprising methotrexate (10–25 mg weekly; n = 92; 44%), sulphasalazine (n = 36; 17%), antimalarials (n = 41; 20%), leflunomide (n = 21; 10%), etanercept (n = 6; 3%) and OM-89 (n = 7; 3%); 27 patients were on combination DMARD therapy. One hundred and ten patients (53.1%) had additional therapy with corticosteroids (1.25–17.5 mg prednisolone equivalent daily), and all patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) on demand.

The disease activity indexes and PATSAT and PATATT showed no significant relationship with age, gender, type of DMARD therapy or disease duration. The disease activity parameters were highly correlated with one another (all PS<0.001).

In the 207 patients assessed, their mean (±S.D.) satisfaction score (possible scores, 1–5) was 2.52 ± 1.02, the mean DAS28 to 3.73 ± 1.56, SDAI 14.55 ± 11.0 and M-HAQ 0.62 ± 0.66. Thus, the overall patient satisfaction in the population investigated was between good and average, at moderate disease activity according to the EULARC, at low disease activity as expressed by the SDAIAC, and at mild functional disability according to the M-HAQ. [3, 4, 12]. In 2003 a total of 1239 DAS28 and SDAI values in 513 patients (including the population investigated here) was obtained in our out-patients clinic. The mean DAS28 was 3.69 the mean SDAI was 14,2. Therefore, the population investigated can be regarded as highly representative of all the RA patients we are taking care of.

The mean values for the disease activity indices at the five levels of PATSAT are given in Table 2. Interestingly, the mean values for the DAS28 at the five levels of patient satisfaction mirrored the EULARC impressively [4], finding those patients expressing excellent satisfaction (mean DAS28 = 2.56) in a remission-like stage and those expressing good satisfaction (mean DAS28 = 3.05) at low disease activity, whereas the moderately satisfied and unsatisfied patients were found at high disease activity (mean DAS28 values >5.1). Such a clear relationship could not be found for the SDAIAC, where a value up to 20 indicates low disease activity, between 20 and 40 medium, and greater than 40 high disease activity [3]. Applying ANOVA and the Bonferroni correction, the mean values of the disease activity indices were significantly different at the five levels of PATSAT at P<0.05.


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TABLE 2. Means of the disease activity indexes at the five levels of patient satisfaction

 
Of the 207 patients, 55 patients (26.6%) expressed a wish for an increase in their medication, while 57 (27.5%) wanted to reduce their medication, and 95 patients (45.9%) wanted their therapeutic regimen to remain unchanged. The mean values of the disease activity parameters and the medians for patient satisfaction are given in Table 3. DAS28 and SDAI levels in patients wishing a decrease in therapy and those intending no change of their therapeutic regime were statistically significant different according to the Mann–Whitney U test (P = 0.008 and P = 0.004, respectively), while PATSAT (P = 0.065) and M-HAQ (P = 0.348) levels were not. DAS28, SDAI and M-HAQ-levels as well as PATSAT were highly statistically significantly different in patients expressing their wish for an increase in therapy and both other groups (all PS<0.0001) (Fig. 2).


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TABLE 3. Patient satisfaction and the disease activity indexes at the three stages of patients' attitude to therapy (mean ± S.D.)

 


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FIG. 2. Cross-tabs to demonstrate the relationship between PATSAT and RA disease activity as expressed by the EULARC [RA activity (DAS)], the SDAI activity categories [RA activity (SDAI)] and functional disability as expressed by the M-HAQ (M-HAQ disability).

 
Applying the {chi}2 test, a highly significant relationship between PATSAT and PATATT could be found ({chi}2 = 51.175; P < 0.0001) (Fig. 1).



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FIG. 1. Cross-tab to demonstrate the relationship between PATSAT and PATATT.

 
Applying ANOVA, the single items of the composite scores, namely VAS-GH, VAS-PH, TJC and SJC were significantly different at the different levels of PATSAT and PATATT (P = 0.014 to P < 0.0001), whereas CRP values were not (P = 0.106 and P = 0.614) (Table 4).


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TABLE 4. The single components of the DAS28 and SDAI at the five levels of patient satisfaction (mean ± S.D.)

 
On categorizing patients into those with low, medium and high disease activity or functional disability respectively, with respect to the to the EULARC [4], the SDAIAC [3] and the M-HAQ [12], PATSAT and PATATT were highly significantly different between the three categories (all PS<0.0001). The respective cross tabs, however, revealed substantial differences between the EULARC and the SDAIAC. In relation to PATSAT and PATATT, a substantially greater number of patients had low disease activity stage according to the SDAIAC than according to the EULARC, as well as in comparison with functional disability categories, as expressed by the M-HAQ (Fig. 2). This finding indicates difficulties with respect to the direct comparability of single DAS28 values and SDAI values, as described before [5].


    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
The question, frequently discussed in daily routine but not in clinical trials, concerning the degree of congruence between patients’ thoughts about their disease and its activity and the commonly applied disease activity measures was the reason for performing this observational investigation. As the disease activity indexes and the therapeutic recommendation are both primarily physician-generated, this question implies patients’ perspectives on therapeutic decisions. Moreover, it also relates to possible differences in the definition of response by physicians and patients. Additionally, answers to this question are crucial for the transferability of clinical trial results into daily practice. There is also a need for information on whether, from the patient's viewpoint, one of the commonly applied disease activity indexes is superior to the other.

As an approach to answering this question, the term ‘patient satisfaction with the actual disease stage’ was invented, in order to be easily understood and scored by the patients. At first view, the congruence between patient satisfaction and the disease activity indexes was found to be higher than initially expected. The corresponding DAS28 levels at the five different levels of patient satisfaction impressively mirror the disease activity categories of the EULARC, with the DAS28 in completely satisfied patients within the remission range and subsequently the level in unsatisfied patients in the range of high disease activity [4]. Similarly, patient satisfaction has been shown to impressively echo functional deficiencies, as expressed by the M-HAQ [13]. However, applying the SDAIAC, the degree of congruence is considerably lower, showing the unsatisfied patients in the medium disease activity category [3]. Anyway, disease activity categorizing constitutes the disadvantage of the SDAI compared with the DAS28, as previously described [5] and proven here.

Do patients assess their perspective and attitude to therapy on the same basis as physicians? It was impossible to answer to this question in the affirmative. Whereas PATSAT and PATATT were found to be related, the levels of disease activity at which patients desire an increase in their therapy do not meet established recommendations of acceptable disease activity [6, 8], as was found to be the case for PATSAT. Patients consider a reduction in their medication at a disease activity level at which physicians, following the recommendations, would even propose a further increase in therapy to achieve remission [6, 8]. Moreover, despite relatively low satisfaction (between good and average), and at a moderate disease activity (DAS28 3.52), patients wanted their therapy to remain unchanged, whereas physicians would recommend a change (in most cases an increase) at such disease activity to achieve a remission-like state. In addition, patients did not express a wish for an increase in treatment before having reached a level of reasonably high disease activity (DAS28 4.92). However, this situation constitutes the only one in which patients and physicians think congruently.

For all these reasons, it is evident that patients think in a different way, with respect to therapeutic strategies, than physicians do. Therefore, some discussion must be expected, as patients’ thresholds for therapeutic changes are definitely different from physicians’ recommendations [6, 8]. Thus, there must be other equally important reasons for a patient to define his position with respect to treatment, and these might be lack of awareness of the disease's course in particular, fear of side-effects, or, on occasion, simply resignation. Particularly, this observation gives evidence for an urgent need for more patient information about the disease and the therapeutic possibilities, to further decrease patients’ thresholds. Raising awareness will only be reached by enhanced educational efforts.

The question of which disease activity index, of those investigated here, is superior to another may be answered as follows. The DAS28 and the SDAI seem to express disease activity with similar accuracy, given by the high correlation of the absolute values. However, the SDAI values are clearly not normally distributed, in contrast to the DAS28 values, with a shift to the lower disease activity range. Therefore, the predominant, and perhaps sole, difference between the DAS28 and the SDAI, when considering also the patient's position, constitutes disease activity categorizing [5]. Definitions of disease activity based on the DAS28 come appreciably closer to the patients’ position than those made on the basis of the SDAI. The M-HAQ covers different issues than both other indexes; however, its congruence with patients’ perspectives is almost comparable to that of the DAS28. Taking into account the patient's position, it may be regarded as an appropriate tool with which to monitor disease activity [14]. This finding is in line with reports that scores for functional disability in RA patients are rather correlated at higher levels with pain scores than with radiographic scores [15].

This study was limited by the facts that it was performed in a single centre within a relatively small region and that the study population in general, although being representative of the centre's entire RA patient population, was mildly to moderately diseased, as can be seen by the relatively low number of patients on combination or anti-cytokine-therapy. Additionally, the measures to assess the patients’ perspective, namely PATSAT and PATATT, have not yet been validated completely. For further validation, we would propose to include the patients’ perspective, particularly the patients’ therapeutic attitude, into clinical trials as well as into multicentre observational investigations.

The results obtained should result in some concern about the interaction between patients and physicians as well as about the transferability of recommendations, established on the basis of clinical trial results, in daily rheumatological practice. Asking for patients’ satisfaction provides a possible way to get an impression about disease activity and constitutes an easy tool to assess the accuracy of disease activity indices. Moreover, it gives an estimate of possible difficulties in persuading a patient about a therapeutic change. As patients’ attitudes to therapeutic choices depend on disease activity (though obviously they are also influenced by factors other than disease activity), it could constitute an independent measure of therapeutic success.

In summary, some discrepancies occurred with respect to the physicians’ and patients’ perspectives on disease activity and its scoring as well as therapeutic strategies. Some problems in convincing a patient of the desirability of an increase in his or her therapeutic regimen can be expected in cases of low disease activity. Nevertheless, the incongruencies between the patients’ perspectives and the physician-generated disease activity indexes were less than initially expected. The results obtained can be regarded as being in line with preceding comparisons of patients’ and physicians’ assessments of disease activity and functionality [16–18]. Physicians can be relatively safe to monitor RA activity when using the commonly applied indexes, especially the DAS28 and the M-HAQ, to monitor RA activity, even taking account the patients’ perspectives. The best possible congruence between the patient's thoughts and evidence-based therapeutic recommendations can be regarded as the primary requirement in order to achieve the patient's best possible compliance and thereby an optimum outcome.

The authors have declared no conflicts of interest.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

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Submitted 21 July 2004; revised version accepted 15 October 2004.



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