The DAS28 in rheumatoid arthritis and fibromyalgia patients

B. F. Leeb, I. Andel, J. Sautner, T. Nothnagl and B. Rintelen

HUMANIS Klinikum Lower Austria, Lower Austrian Center for Rheumatology, Stockerau, Austria.

Correspondence to: B. F. Leeb, Second Department of Medicine, HUMANIS Klinikum 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
 
Objective. To compare the DAS28 (Disease Activity Score including a 28-joint count) values of rheumatoid arthritis (RA) and fibromyalgia (FM) patients, and to establish whether high pain levels and impaired mood influence DAS28 values.

Methods. DAS28 values were calculated in 62 consecutive patients with RA and in 26 patients suffering from FM. Values for DAS28 scores as well as for the single items of the patient cohorts were compared using Student's t-tests. To evaluate the item weighting and internal consistency of the total score factor analysis was performed and Cronbach's alpha calculated.

Results. RA patients showed a mean DAS28 score of 4.23 (±1.2; range 0.77–7.46) and in FM patients the mean DAS28 came to 4.04 (±1.13; range 1.19–6.28). DAS28 values of RA and FM patients were not significantly different statistically. Comparing the single components of the score, however, highly significant differences (P<0.0005) occurred between RA and FM patients. Cronbach's alpha for the DAS28 in RA patients amounted to 0.7329, indicating high internal consistency, whereas in FM patients it was 0.4832.

Conclusion. The DAS28, as expected, proved to be inappropriate to express disease activity in FM patients. DAS28 values for expressing disease activity in RA patients may be flawed by coexisting FM and should therefore be regarded with caution as high pain levels more than impaired mood may lead to higher total scores.

KEY WORDS: Rheumatoid arthritis, Fibromyalgia, Disease activity measurement


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Monitoring and documenting disease activity in rheumatoid arthritis (RA) in daily practice should be easy and not time-consuming to perform. Moreover, it should provide the physician with enough information to enable treatment decision-making. The American College of Rheumatology (ACR) response criteria or the Disease Activity Score (DAS, DAS28) and consequently the European League Against Rheumatism response criteria (EULARC), which all are well described and validated, are usually used to record disease activity and the therapeutic efficacy respectively [1–3].

As the ACR response criteria give relative results with respect to a baseline observation, there is consensus that they do not meet the needs of daily rheumatological practice [4]. The DAS28, consisting of four items, namely the number of swollen and tender joints (SJC, TJC), the visual analogue scale of patients' assessment of their general health (VAS-GH), and the erythrocyte sedimentation rate (ESR) in the first hour, gives an absolute number reflecting disease activity. Therefore it may constitute a tool for daily practice despite the fact that in order to apply it an electronic device is necessary to calculate the complicated formula of the DAS28.

Fibromyalgia (FM) frequently accompanies RA (in up to one in seven cases) and this is known to result in higher measures of disease activity and functional capability [5, 6]. Moreover, disease activity measures for the spondyloarthropathies (SpA), such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), have recently been described to reach similar values in SpA and FM patients [7].

Although the DAS28 is validated only for RA, we wanted to answer the question as to what kind of influence high pain levels and impaired mood—being part of FM, obviously—may exert on DAS28 levels in the light of decision-making in the course of RA. Here we report the initial results, which in our opinion may help provide a somewhat more differentiated, but also more realistic, view of the DAS28 value as a tool for decision-making in the treatment of RA in daily practice.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Sixty-two consecutive patients with RA according to the ARA criteria [8] and 26 patients suffering from FM according to the ACR classification criteria [9] were seen in the out-patient clinic during weeks 41, 42, 43 and 44 of 2002. All patients gave their written informed consent to be enrolled into this observational study according to the Declaration of Helsinki. The design of the study has been approved by the local ethics committee.

Each patient was assessed by the DAS28 and the DAS28-3 (including only TJC, SJC and ESR). RA patients fulfilling the classification criteria for FM at the time of the assessment were not enrolled into this study. Demographic data are given in Table 1.


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TABLE 1. Demographic data for the patients

 
All RA patients were on disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate, leflunomide, sulphasalazine, chloroquine, cyclosporin A only in combination, etanercept and anakinra, or on combination DMARD therapy. Sixty-five per cent of the patients were on prednisolone (between 2.5 and 12.5 mg daily). All patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) on an on-demand basis. Fifty-five per cent of the RA patients were additionally treated with analgesics such as acetaminophen or opioids.

The demographic data of the FM patient group are also shown in Table 1. Drug therapy comprised analgesics, such as opioids and acetaminophen, NSAIDs and antidepressants; none of these patients were on corticoids or DMARDs.

Statistical analysis
DAS28 values in both patient groups were assessed for normal distribution by the Kolmogorov–Smirnov test. Consequently DAS28 scores as well as the single items of the patient cohorts were compared using Student's t-tests. Cronbach's alpha, as a measure of internal consistency, was calculated for DAS28 values in the two patient groups; values greater than 0.7 are commonly regarded as markers of high reliability. Additionally, exploratory factor analysis [principal component analysis (PCA)] was performed in order to reveal the dimensionality of the score in the two patient cohorts and to investigate factor loading respectively.


    Results
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 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Patients were well matched for age and gender (see Table 1). No statistically significant differences could be found between female and male RA and FM patients with respect to VAS-GH, which in part reflects pain status.

DAS28 values of the two patient groups were found to be normally distributed according to the Kolmogorov–Smirnov test (z = 0.548; z = 0.591). Therefore DAS28 values are presented as means±standard error of the mean (SEM) and the range. RA patients showed a mean DAS28 score of 4.23 (SEM ±1.20; range 0.77–7.46); in FM patients the mean DAS28 amounted to 4.04 (SEM ±1.13; range 1.19–6.28) and failed to demonstrate a statistically significant difference (P = 0.599) (see Fig. 1).



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FIG. 1. DAS28 values of FM and RA patients including the normal distribution curve.

 
Comparing the values of the single items of the total score between the two patient groups, however, statistically significant differences were revealed for TJC, SJC, ESR and VAS-GH, despite the fact that the global scores were statistically not significantly different, as shown in Table 2.


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TABLE 2. Mean values of DAS28 and the single items in the two patient groups

 
The item weighting and dimensionality of the score were assessed by correlation analysis as well as PCA. As shown in Table 3 in both patient groups, the total DAS28 correlated best with TJC. High correlations were also seen for SJC and the total score in RA, but obviously not for FM patients. Interestingly, the correlation between VAS-GH and the total score was lower in FM patients than in RA patients, while somewhat surprisingly for both patient groups the influence of the ESR upon the total score was similar.


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TABLE 3. Correlation coefficients (Spearman's rho) of the single items to the total DAS28 for RA and FM patients

 
Factor analysis revealed that the DAS28 constitutes a mono-component measure in RA, while in FM two components could be seen to contribute to the total score; item loading is given in Table 4. As can be seen in Table 4, in FM patients TJC and VAS-GH contribute similarly to the total score, while the second component consists of the inflammatory markers ESR and SJC. In RA, TJC and SJC contribute most, followed by VAS-GH, with the ESR contributing least to the total DAS28.


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TABLE 4. Weighting of the single items of the DAS28 in RA and FM patients

 
Cronbach's alpha, a measure of the reliability of mono-component scores, for the DAS28 in RA patients amounted to 0.724, indicating high reliability. In contrast, but as expected, alpha totalled 0.483 in FM patients, indicating a reasonable difference in reliability and internal consistency for RA and FM patients.

As another possible method of finding out to what extent VAS-GH is responsible for the DAS28 values of the FM patients within the range of the RA population, we also calculated the DAS28-3, comprising TJC, SJC and ESR, for both patient groups. The mean DAS28-3 in RA patients was 4.23 (±0.2; 0–7.59) and in FM patients 3.55 (±0.26; 0.68–5.24). The correlation between the two DAS values was striking for both patient groups (r = 0.964 for FM; r = 0.983 for RA), and consequently no statistically significant difference between the DAS28-3 in RA and FM patients could be found (P = 0.136). Calculating Cronbach's alpha for both patient cohorts, the DAS28-3 was seen to be of lower internal consistency ({alpha} = 0.6666 for RA; {alpha} = 0.3855 for FM).


    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
At first sight we found no significant differences between the DAS28 values of RA and FM patients. However, as expressed by the low internal consistency of the DAS28 in FM patients, the DAS28 proved to be inappropriate for monitoring disease activity in FM patients, as expected.

Despite the lack of a significant difference between the total scores, the mean values of the single items of the DAS28 were significantly different in RA patients in comparison with the FM group and showed significant differences with respect to item weighting.

Unsurprisingly, since FM represents a non-inflammatory disorder, the ESR and the SJC were within the normal range in those patients, resulting in a two-dimensionality of the DAS28. As expected for FM patients, who were suffering from a disorder caused by altered pathways of pain processing resulting in impaired sleep and chronic fatigue, the VAS-GH values and the TJC were far higher than in RA [10]. The significantly different VAS-GH levels of FM were to be expected, whereas the difference in TJC was somewhat surprising. It is well known that one feature of FM is a particularly decreased pain threshold, which may constitute the main reason for the differences in observed TJC. FM constitutes one of only a few syndromes defined by the presence of both spontaneous and evoked pain. While the issues associated with the evaluation of spontaneous pain are shared with all chronic pain syndromes, the issues associated with the evaluation of evoked pain sensitivity seem to be specific to FM [11].

Regardless of the differences with respect to the single items, the DAS28 total was almost equal in RA and FM patients, as was the DAS28-3, but at a lower reliability level for RA. Therefore the difference in VAS-GH between the two patient groups cannot be declared responsible for the similarities of the DAS28 levels. It is of great interest that despite normal ESRs and the lack of joint swelling in FM patients, DAS28 values resulted in a range of at least moderate RA disease activity according to the EULAR response criteria [3]. It seems clear that presence of joint tenderness is the prime contributing parameter to the DAS28 values in FM patients.

Internal consistency testing revealed reasonable reliability of DAS28 levels in RA, whereas values in FM patients cannot be regarded as reliable. Therefore the possibility of describing FM activity—whether by the means of the DAS28 or the DAS28-3—cannot be derived from the results of this study. Factor analysis, as given above, indicates that the DAS28, even in RA patients, does not constitute a strict one-dimensional score; TJC, SJC and VAS-GH are of a similar weight in the total score, in contrast to the ESR.

Disease activity of isolated RA is thought to mean mostly inflammatory activity, whereas disease activity in FM can only be described by subjective parameters, such as pain and/or impaired mood, which lead to significant DAS28 levels in these patients, but without reliability as the inflammatory component is lacking.

Moreover, Cronbach's alpha values indicate that the sensitivity and specificity of the DAS28 is, as expected, highly dependent upon the proven diagnosis of RA. However, the total score may be flawed by coexisting illnesses such as FM or, for example, infections, which may cause elevations of the ESR or decreased general health—a finding which is in line with the results of measurement of spondyloarthropathy indices in FM patients described recently [7].

With regard to the wide range of single components at very similar levels of the total scores, the DAS28 cannot be regarded as a unique tool for decision-making in RA therapy, because changes in the total score may be generated by fluctuation of very different items covering inflammatory activity, pain and general health. In particular, pain and general health, representing the most and third most important factors for the total DAS28, can be influenced by various other factors such as those of a psychological nature or concomitant diseases. It clearly makes a difference whether a patient has average elevations of all items or pronounced ones of single parameters leading to comparable values of the total score.

Thus, particularly DAS28 values in RA patients with coexisting FM, which is frequently the case [5, 6], should be regarded with caution since high pain levels, far more than impaired mood, may lead to higher total scores, which in such cases may indicate increased FM activity rather than RA activity. However, the total score constitutes a very significant alert, which should initiate considerations about the therapeutic regime, if significant changes as expressed by the EULAR response criteria occur. If this is the case, however, any decisions should be taken with more attention paid to the single items than to the total DAS28, as coexisting or newly developed diseases may alter it as shown above for FM. The clinical decision should be based on the values and relationships of the single parameters since the DAS28 for individual patients cannot replace careful inquiry, examination and clinical thinking [12]

In conclusion, the DAS28 constitutes a useful tool for monitoring RA patients. Stable low values for the DAS28 can be regarded as indicators of an uncomplicated course of RA. Significant increases, however, must be assessed with respect to the changes in the single items and possibly coexisting or newly occurring diseases.

The authors have declared no conflicts of interest.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

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Submitted 3 May 2004; revised version accepted 21 June 2004.