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- PATIENTS AND METHODS
Disease activity and damage in systemic lupus erythematosus (SLE) cannot be measured directly by using any individual laboratory value or clinical sign. Thus, disease activity and damage measures have been developed for adult SLE (1–5). Because the clinical and laboratory features associated with childhood-onset SLE (cSLE; defined as SLE with disease onset prior to age 18 years) are different from adult SLE (6–14), all disease indices that have been developed and tested for adult SLE require reevaluation prior to use in children (14). The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) were developed to measure, respectively, disease activity and irreversible damage in adult SLE (5, 14–16). Both the SLEDAI and SDI have been validated for use in cSLE, and it has been shown that cumulative disease activity over time as measured by the SLEDAI is one of the single best predictors of disease damage in cSLE (14, 17).
The European Consensus Lupus Activity Measurement (ECLAM) is a disease activity scale developed for adult SLE (17–19) whose usefulness for cSLE has not yet been examined. It has been suggested that the ECLAM may be preferable to the SLEDAI for measuring disease activity because of its superior quantitative properties; the ECLAM has a higher correlation with changes in the physician global assessment of disease activity compared with the SLEDAI (18). If this was truly the case, then changes of ECLAM rather than SLEDAI scores could guide clinical decision making in children with cSLE because ECLAM scores would correlate better with expert assessment of changes in disease activity and, presumably, with decisions regarding patient therapies.
Our study objectives were 1) to assess the responsiveness of the ECLAM in cSLE when compared with the SLEDAI and 2) to test the hypothesis that the ECLAM has better quantitative properties compared with the SLEDAI by comparing the ability of the 2 measures to predict disease damage and patient medication requirements over time.
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- PATIENTS AND METHODS
The ECLAM is a useful measure of disease activity for children with lupus. Compared with the SLEDAI, the ECLAM appears marginally more sensitive to changes in disease activity over time. However, the SLEDAI and the ECLAM are very similar in predicting disease damage and the need for steroids of patients with cSLE.
There is no universally accepted best measure of disease activity for adults or children with lupus (14). Such a measure would be desirable to make studies that include measurements of disease activity better comparable to each other. We recently validated the BILAG (British Isles Lupus Assessment Group Index) (2), the SLAM (Systemic Lupus Activity Measure) (3) and the SLEDAI for use in cSLE (14). The present study supports that the ECLAM can also be used for measuring disease activity in children with cSLE. As previously suggested for adults (33), the ECLAM appeared to be slightly more sensitive to changes in disease activity than the SLEDAI when used in cSLE. However, the responsiveness of the ECLAM compared with the SLEDAI was only significantly better when using the REI, but not when using the SRM (overlapping confidence intervals). Thus the superiority of the ECLAM over the SLEDAI for cSLE cannot be concluded on the basis of the results of this study. Another approach to evaluate whether the ECLAM may be preferable to the SLEDAI for use in cSLE is to assess whether there are significant differences between the 2 measures when predicting a clinically relevant surrogate of disease activity, such as the steroid dose chosen by the treating physicians. The ECLAM scores, however, were no different from those of the SLEDAI in estimating the daily weight-corrected dose of oral steroids of a patient. We further examined whether the ECLAM and the SLEDAI differed in the ability to predict damage (17). Again, the ECLAM and the SLEDAI were similarly suitable to predict disease damage in children with cSLE. Thus, the current data do not support that the ECLAM has better quantitative properties compared with the SLEDAI, as was previously suggested (18).
Taken together, the statistical evidence that the ECLAM is superior to the SLEDAI is weak and inconsistent. We previously suggested (14) that the SLEDAI may be the preferable disease activity measure in cSLE. Using statistical criteria, the results of this study do not support that the ECLAM is clearly superior to the SLEDAI for use in cSLE.
Five methodologic criteria are required for a successful disease activity measure: the measure has to have credibility (face validity), accuracy, and sensitivity to change; it should make biological sense; and it must be simple for daily use (34). The results of this and previous studies (14, 17) support that both the ECLAM and the SLEDAI are suitable for measuring disease activity in cSLE. However, the face validity of the ECLAM may be inferior to that of the SLEDAI. This is because, unlike for the SLEDAI, the items of the ECLAM are not exactly defined. For example, there is not an exact definition for the severity of fatigue that should be scored in the ECLAM. Also, the time frame during which symptoms are regarded as “evolving” is unclear and the decrease of complement levels necessary to be scored as “significantly reduced compared to the last observation” (attribute 12b) is not well defined. As opposed to some other lupus disease activity measures (2, 3, 5), the ECLAM lacks a clearly defined time frame during which symptoms have to occur to be included in a certain measurement of disease activity. Although previous studies suggest that both the ECLAM and the SLEDAI are highly reliable when used in prospective and retrospective studies (2, 34–36), the lack in exact definitions may lead to decreased inter- and intrarater reliability of the ECLAM. However, if exact definitions for all items of the ECLAM were generated, then the credibility of the ECLAM could likely be enhanced.
The acceptance of a disease measure in research and clinical practice is also influenced by its ease of use. Because the ECLAM has 34 items but the SLEDAI only has 24 items, completion of the ECLAM requires more time. Opposed to the SLEDAI disease activity score, the final disease activity score of the ECLAM is not equal to the simple sum of the domain scores. Instead, a more complicated scoring scheme is suggested for the calculation of the final ECLAM disease activity score, which is not consistently applied in the literature (37, 38). Thus the scoring scheme for the final ECLAM disease activity score not only increases the time requirements to measure disease activity, but it is also a potential source of error and may not even be necessary. In an exploratory analysis, we evaluated the measurement properties of the ECLAM in our cohort without using the suggested scoring scheme to calculate the final ECLAM disease activity score. There were no important differences in the responsiveness of the ECLAM or its ability to predict the weight-adjusted oral steroid dose or disease damage, irrespective of whether the simple sum of the domain scores or the final ECLAM disease activity score (using the differential scoring scheme) was used (data not shown).
Our study supports the idea that the ECLAM is a useful and responsive measure of disease activity in cSLE. However, the ECLAM does not offer a clear and consistent advantage over the SLEDAI in measuring disease activity in cSLE. We feel that given its ease of use, its wide acceptance in adult SLE, and its excellent measurement properties, the SLEDAI remains the preferred measure of disease activity in cSLE.