Juvenile idiopathic arthritis (JIA) (1) can lead to destructive lesions of joint cartilage and periarticular bone. Since the introduction of more potent treatment strategies, the evaluation of radiographic joint damage has become more prominent in the assessment of disease progression in JIA (2–4). Because one of the aims of JIA treatment is to prevent or retard joint damage, and radiographs are able to document this damage, a standardized tool for the radiologic evaluation of the lesions of the joints over time is needed. Several methods have been proposed to assess radiographs in JIA (5–8), but none have been tested for sensitivity to change or discrimination between treatment groups in a trial. Recently, we introduced the Dijkstra score as a standardized method to evaluate the radiographs of patients with oligoarticular- and polyarticular-onset JIA. Data were obtained from the data set of a placebo-controlled sulfasalazine (SSZ) trial performed in The Netherlands (9). All radiographs were assessed for the presence of a comprehensive spectrum of JIA radiologic features. We found the reliability, feasibility, and measurement properties of the Dijkstra score to be adequate for its purpose.
To decide whether a measure or instrument is applicable in a particular clinical setting, the OMERACT filter can be applied (10). This tool was developed for the Outcome Measures in Rheumatology Clinical Trials (OMERACT) initiative and summarizes applicability with 3 criteria: 1) truth (Does the instrument measure what it is supposed to?), 2) discrimination (Can the instrument discriminate between situations of interest?), and 3) feasibility (Can the instrument be feasibly applied in the intended setting?). We confirmed, to some degree, the truth and feasibility of the Dijkstra score in a clinical trial setting in our previous study (9). In the current study, we focus on the discrimination criterion as it applies to the Dijkstra score. More specifically, we studied whether the Dijkstra score could detect radiographic change in a 6-month period, and also whether differences in change between the treatment groups could be detected. For this purpose, we propose a composite score for inflammation, damage, and growth disturbances, and a classification scheme to distinguish between progressive and nonprogressive radiographic joint damage.
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- PATIENTS AND METHODS
This study demonstrates that the Dijkstra scoring method of assessing radiographs in oligoarticular- and polyarticular-onset JIA can detect change over a trial period of 6 months. Changes could be demonstrated at the level of 1) the presence of radiologically scored signs, 2) the number of scored signs per joint, and 3) the number of scored radiologic signs per patient. In addition, the differences between placebo and SSZ treatment groups, many of which were statistically significant, could be demonstrated at these 3 levels. Finally, a simple classification scheme to identify progressors and nonprogressors proved discriminative between the treatment groups.
Reduction in the number of radiographs to a standard set of images of the hands, feet, and knees appears feasible without losing essential information. Radiologically scored abnormalities changed most often in the knees, hands, and feet. We therefore propose that the radiologic assessment of all joints of this standard set be carried out in clinical trials, regardless of disease activity.
Most radiographs showed additional radiologic features at followup, but in some radiographs, abnormalities present at baseline were not present at followup. This feature of normalization occurred in several types of joints, but most often in the knees. We assume that an increase in the number of scored signs reflects disease progression, but a stable number or a decrease in the number of scored signs does not inevitably reflect disease improvement (e.g., JSN or erosions can replace growth abnormality). Only joints without remaining signs have unquestionably improved. In addition, one should be aware that in the Dijkstra scoring system, an increase in identical signs within joints is not reflected in an increase in the number of scored signs.
Changes were evident in all aspects of the score, comprising inflammation (swelling and osteopenia), pathologic changes in the cartilage (JSN and growth abnormalities), and those in the bone (growth abnormalities, bone cysts, and erosions). In our previous study, we demonstrated that scores for swelling and osteopenia were only moderately reliable (9). Despite detectable change, we still believe that both swelling and osteopenia are of limited value in a scoring system. Nevertheless, at this stage of scoring development, we consider it too early to reject these radiologic findings for further evaluation.
Changes in growth abnormalities were detected in several types of joints; in particular, in the hand and knee, growth abnormalities both regressed and appeared during the followup period. This sign is considered a key manifestation of JIA (8, 11, 12), but in our investigations, its reproducibility was moderate (9). Definitions of growth disturbance therefore need further refinement (e.g., an atlas of reference films) to improve the value in a scoring system.
JSN is also considered a key manifestation in JIA. JSN showed a reliable reproducibility in our previous study and in other studies (9,13). In the present study, changes in JSN were demonstrated in all joints of the standard set. Scores for bone cysts and erosions changed in several joints and appeared reliably reproducible in our previous study (9). Quantification and refinement of the erosion and JSN scores might further improve the performance of radiologic scoring in JIA, consistent with that achieved in rheumatoid arthritis (RA) (14). Future studies with a longer period of followup are needed to elaborate on this subject. Changes in malalignment were only rarely detected in the hands, and we therefore have too little data to evaluate the value of scoring of this sign in JIA.
To be applicable in trials, we developed a numeric score, the Dijkstra composite score, comprising separate values for inflammation, growth abnormalities, and damage. In our opinion, these 3 scores represent distinct radiologic information. The results of our study show that DI, DG, and DD scores changed significantly over time and elucidated specific changes in radiographs at the level of the joints and at the level of the patient. The study also demonstrates that the Dijkstra composite score adequately reflects the radiologic change in different patient groups.
For a further evaluation of change, we categorized the radiologic change into progressive or nonprogressive. In evaluations of radiologic outcome in adult RA trials, the progressor classification may provide a useful summary of the data per patient, although its significance for long-term prognosis remains to be determined (15–17). We posited that in JIA, clinically meaningful radiologic change would imply progression of either growth abnormalities or damage. Therefore, we defined progressive radiologic change as an increase in either the DG score or the DD score in a joint. In our study, application of this proposed definition for classification resulted in a distinct discrimination of radiographs originating from placebo-treated and SSZ-treated patient groups. Moreover, individual patient-based analysis showed a significant difference between progressor and nonprogressor patients to the advantage of SSZ-treated patients. These findings must be interpreted with caution, since the trial was not designed to evaluate differences in damage progression. Nevertheless, the radiologic findings are consistent with the clinical findings in the trial (3), and with the effects of SSZ in adult RA (18, 19). Thus, the findings appear to confer some additional construct validity to the composite scores and subsequent classifications.
In summary, this study completes the initial validation phase of the Dijkstra score. We suggest that it is the first radiologic measure in JIA to pass the OMERACT filter of truth, discrimination, and feasibility, at least in the setting of a placebo-controlled trial in oligoarticular- and polyarticular-onset JIA. Future studies by other investigators and in other data sets should put this measure to the test. For this purpose, we intend to produce training materials, and we will further validate the scoring method on the basis of a long-term followup of patients in the trial.