The Disease Activity Score in 28 joints in rheumatoid arthritis and psoriatic arthritis patients

INTRODUCTION

Psoriatic arthritis (PsA) constitutes the second most destructive arthritis, with a milder course on average than rheumatoid arthritis (RA) (1). However, management of PsA frequently requires the application of treatment regimes comparable with RA treatment (2). In contrast to RA, however, a disease-specific activity score for PsA is lacking, although several response criteria, mainly the Psoriatic Arthritis Response Criteria (PsARC) or the modified American College of Rheumatology (ACR) response criteria, are applied in clinical trials to record disease activity and therapeutic efficacy, respectively (3-5). These tools give relative results with respect to a baseline observation, which is why they are considered not to meet the needs of daily rheumatologic practice as the ACR response criteria in RA (6).

The Disease Activity Score including a 28-joint count (DAS28) and the European League Against Rheumatism response criteria are widely used to record disease activity and therapeutic response in patients with RA (7). The DAS28 was developed and validated for patients with RA, and in addition to disease activity it also reflects the patient's satisfaction with reasonable accuracy (8). This composite index comprises 4 items, namely, swollen joint count (SJC), tender joint count (TJC), a visual analog scale (VAS) of the patient's assessment of general health (GH), and erythrocyte sedimentation rate (ESR; first hour), which are also part of the ACR response criteria and the PsARC (4, 5). The DAS28 was developed for a general sample of patients with RA, and primarily for the reason of item weighting the following complicated formula was established: DAS28 = 0.56 × √(tender28) + 0.28 × √(swollen28) + 0.70 × ln(ESR) + 0.014 × GH.

Disease activity measures of spondylarthritides, such as the Bath Ankylosing Spondylitis Disease Activity Index, were recently described to express activity of psoriatic spondylarthritis exclusively, but not activity of PsA with peripheral joint involvement (9). Although validated only for RA, the DAS28 and the original DAS (also including the feet) have already been applied in PsA clinical trials as secondary efficacy criteria. Therefore, there are considerations for also using the scale in daily routine for disease activity assessment (10-13).

Two body compartments, namely, the skin and the joints, are commonly involved in PsA; therefore, for the DAS28 to be applicable in PsA, it is crucial to determine to what degree weighting of the single items will be different in RA and PsA and, if item weighting is comparable, whether the single items load on the same factors. Furthermore, PsA occurs as an oligoarticular disease far more often than RA, and other features not covered by the DAS, such as enthesitis, dactylitis, and spondylitis, are of particular importance with respect to disease activity. Therefore the overall DAS28 levels achievable by patients with PsA in comparison with patients with RA are of interest.

To this end, we cross-sectionally compared DAS28 values and the single items in patients with RA and PsA to assess possible differences with respect to the instrument's statistical properties. The results could provide an answer to the question of whether the DAS28 can be applied in the same way as in RA to measure PsA activity.

PATIENTS AND METHODS

During the last quarter of 2003, 85 consecutive patients with PsA (27 women and 58 men, median age 52.11 years, range 31–79 years) were seen in the outpatient clinic and were enrolled in this observation. Two groups of patients with RA were recruited as controls. A total of 85 age- and sex-matched outpatients with RA, according to the ACR (formerly the American Rheumatism Association) criteria (14), who presented during the same period as patients with PsA, were recruited as the first control cohort (RA1). The first 85 patients with RA seen in September/October 2003 (except RA1 patients) constituted the second consecutively chosen control group (RA2). The demographic data of the patients investigated are shown in Table 1. The RA2 cohort was statistically significantly different from both other patient cohorts with respect to age and sex distribution, but not disease duration. Patients had to give their informed consent to be enrolled and the local ethics committee approved the study design. Patients with RA and additional psoriasis as well as RA and PsA patients who fulfilled the classification criteria for fibromyalgia at the assessment were excluded from the observation, because the DAS28 could be flawed by coexisting fibromyalgia (15).

Fifty-nine (69.4%) patients with PsA were taking disease-modifying antirheumatic drugs (DMARDs), namely, methotrexate, leflunomide, cyclosporin A, and infliximab; 47 (55.3%) patients with PsA were additionally treated with low-dose corticosteroids (<10 mg/day of prednisolone). Additional drug therapy included nonsteroidal antiinflammatory drugs (NSAIDs) on an on-demand basis and analgesics, such as opioids or acetaminophen. Moreover, local skin treatment comprising corticosteroid ointments or calcitriol preparations was administered in 65 (76.5%) patients. All but 4 patients with RA (all in the RA1 group) were taking DMARDs, such as methotrexate, leflunomide, sulfasalazine, chloroquine, cyclosporin A, etanercept, and anakinra, or were taking combination DMARD therapy; 65% of the patients were taking corticosteroids (between 2.5 and 12.5 mg daily) and all patients were treated with NSAIDs on an on-demand basis. Of the patients with RA, 55% were taking additional analgesics such as acetaminophen or opioids. Each patient was assessed by the DAS28, comprising SJC, TJC, ESR, and VAS GH (0–100-mm VAS) (16).

RESULTS

DAS28 values were normally distributed in all 3 patient groups. Therefore DAS28 values are presented as means and ranges. Patients with PsA had a mean DAS28 score of 3.2 (range 0.37–6.91), the matched patients with RA (RA1) had a mean DAS28 score of 3.21 (range 0.65–6.73), and the consecutive patients with RA (RA2) had a mean score of 3.79 (range 0.28–7.18) (Table 2).

In 33 (38.8%) patients with PsA, some arthritic manifestations were not covered by the DAS28, namely, spondylitis in 16 (18.8%) patients; feet involvement, including Achilles tendon enthesopathy, in 26 (30.6%); and distal interphalangeal joint involvement in 5 (5.9%). DAS28 values of the PsA and RA1 patients were statistically not significantly different, nor were the single components of the score (Table 2). As expected, a statistically significant difference between PsA and RA2 patients was found for the DAS28 values (P = 0.006), SJC (P = 0.004), and VAS GH (P < 0.002), but not for the TJC or ESR (Table 1). Likewise, DAS28 values of both RA patient groups appeared to be statistically significantly different (P = 0.01), as were the SJC (P = 0.028) and VAS GH (P = 0.011), but not ESR or TJC.

The most striking difference in DAS28 scores between PsA and RA patients, however, was found by performing factor analysis. As shown in the component matrices, the DAS28 proved to be a bidimensional instrument in patients with PsA in contrast to both RA cohorts, where it appeared to be monodimensional, apart from their statistically significant differences with respect to disease activity (Tables 3 and 4). Item loading was considerably different between the 2 groups of patients with RA, predominantly with respect to ESR. However, this difference may constitute an issue of sample size and sampling error.

Internal consistency testing was performed by calculating Cronbach's alpha. The consecutively included RA2 patients had the highest alpha value (α = 0.604). In both other groups the alpha value was considerably lower: 0.392 in the RA1 patient cohort and 0.437 in the PsA patient group. Therefore in all 3 patient groups, alpha did not reach 0.7, the threshold expressing reasonably high internal consistency.

DISCUSSION

The most important finding of this investigation was the substantial difference concerning the contribution of the single items to the total DAS28 in patients with RA and PsA. Whereas in patients with PsA the joint counts and the VAS GH express different aspects of disease activity, with the ESR contributing to both dimensions, in patients with RA each single item contributes to the total score in the same direction, as we reported previously in larger patient cohorts (19), indicating that the sample size is of less importance for this finding. This result was not completely unexpected, as PsA in contrast to RA commonly affects 2 organ systems, namely, the joints and the skin. Indeed, all of our patients with PsA experienced skin manifestations. The component analysis put the focus on global health assessment. Clearly, patients with PsA have skin disease and asking for their global health assessment will also strongly incorporate skin changes, in contrast to patients with RA. This is a methodologic problem of the DAS that may have been spotted by the component analysis, similar to ESR, which may be influenced by skin changes as well (20). This finding does not necessarily refute the DAS, because it may not be bad to capture all of these aspects of the disease in one score. However, it just shows that the components measure different underlying attributes and can be regarded as a major reason for a formal validation procedure of the score in PsA.

RA1 patients had a mean DAS28 score of 3.2, which was in fact very low for patients with RA and was also heavily weighted towards seronegative disease (∼40% rheumatoid factor). The RA2 cohort was likewise not the best representation of active RA, with a mean DAS28 score of 3.8 (∼20% of the patients were in low disease activity and only ∼15% fell into the high activity range), but it mirrored an average RA outpatient population. A DAS28 value of 3.2 constitutes the limit of low disease activity for patients with RA. Does this mean that patients with PsA on average are in low disease activity? The reliability of the DAS28 proved to be higher in the RA patient group (RA2) at higher disease activity. Therefore, differences between the PsA population and a highly active RA patient group can be assumed to be substantially greater. Because the RA patient groups were highly significantly different with respect to sex and age, one also may speculate about sex and/or age dependency of either the disease course or the score itself (21, 22).

The considerable differences of the DAS28 in patients with RA and those with PsA did not come up unexpectedly because, as it turned out, the DAS28 constitutes a bidimensional instrument in PsA. It is obviously more difficult to achieve the same level of reliability for a tool targeting disease activity as a whole in a disorder affecting 2 organ systems.

The DAS28 was developed for a general sample of patients with RA. It is obvious that taking any subsample of this disease influences the reliability coefficients. However, PsA corresponds to such an atypical RA subsample, which is another indication not to apply the DAS28 without validation in this disease.

Given the differences in dimensionality, single-item loading, and internal consistency of the DAS28 in patients with RA and PsA, it seems to be much more likely that DAS28 calculation in a patient with PsA indeed gives a number with little meaningfulness, as is the case when applying the DAS28 in patients with fibromyalgia (12). Although Ujfalussy and Koo (10) previously described the DAS28 as valid for assessing PsA disease activity and as sensitive for disease activity changes, this statement cannot remain unopposed in light of the results obtained here. Ujfalussy and Koo had correlated DAS28 changes with changes of patients' global assessment, which is indeed part of the index (10). To validate a composite score by relating it to one of its components may obviously flaw the results.

When considering a disease-specific activity score for PsA, the inclusion of other parameters, such as dactylitis or enthesitis and the degree of skin involvement, must be discussed intensively. In any case, considering all the trials dealing with the application of new therapies in PsA (11-13), there is of course a need for a PsA-specific activity score. Moreover, in light of internal consistency testing and factor analysis, one would not recommend the 4 items of the DAS28 to be the elements of a composite index to describe PsA activity, because the DAS28 excludes ankle and foot joints and PsA often exclusively involves joints of the lower extremities. Primarily, the original DAS, including a 44-joint count and thereby ankle and foot joints, appears to constitute the better choice and should be assessed for this purpose (23). In summary, there are good reasons not to recommend the use of the DAS28 to assess disease activity in patients with PsA in the same manner as in patients with RA.

AUTHOR CONTRIBUTIONS

Dr. Leeb had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study design. Leeb, Sautner, Rintelen.

Acquisition of data. Leeb, Andel, Fassl, Nothnagl.

Analysis and interpretation of data. Leeb, Andel, Sautner, Fassl, Nothnagl, Rintelen.

Manuscript preparation. Leeb, Andel, Fassl, Nothnagl.

Statistical analysis. Leeb, Sautner, Rintelen.