Results

A total of 110 patients eligible for the study were identified. Sixteen of them were excluded for the following reasons: apparent radiographic closure of the second metacarpal growth plate within the first 2 years of followup (9 patients), lack of clinical data (4 patients), lost radiographs (2 patients), and advanced bone changes making the RM and M2 measurements unreliable within the first 2 years of followup (1 patient). These 16 patients were comparable to the remaining 94 patients with regard to sex ratio, JIA subtype distribution, disease duration at first observation, and time lag between disease onset and start of second-line drug treatment. However, the excluded group had a significantly older age at disease onset, partly reflecting the fact that more than half of them (9 of 16) had already developed radiographic closure of the second metacarpal growth plate during the early phase of the study (data not shown). The 110 potentially eligible patients were part of a group of ∼ 350 JIA patients who were seen during the study period. The ineligible patients did not have bilateral wrist involvement or lacked the necessary radiographs.

The baseline demographic and clinical characteristics of the 94 patients who were available for radiologic analysis are shown in Table 1. Thirty-five patients had systemic arthritis, 30 had polyarthritis, 24 had extended oligoarthritis, 2 had enthesitis-related arthritis, and 3 had psoriatic arthritis. All disease status measures varied widely along their ranges, but the individual mean values indicated that, on average, the entire patient group had rather active disease at the start of the study. The median duration of followup from baseline to the final radiographic assessment was 4.5 years (range 2–13.5 years). During the study period, all but 5 patients had received 1 or more second-line medications: 87 patients took methotrexate, 24 took cyclosporin A, 13 took sulfasalazine, 3 took etanercept, 3 took cyclophosphamide, 2 took azathioprine, and 2 took hydroxychloroquine.

In the whole cohort, the amount of radiographic damage increased significantly over time (Figure 2). The mean ± SD Poznanski score was − 1.2 ± 1.3 at baseline, − 1.7 ± 1.8 at the 1-year visit, and − 1.9 ± 2.2 at the final visit (P < 0.0001). The mean radiographic progression during the first year (− 0.5 ± 1.1) was greater than the mean radiographic progression during the remaining followup period (− 0.2 ± 1.3). The mean yearly radiographic progression during the entire followup period was − 0.1 ± 0.4. The mean Z scores for M2 length and for height were − 0.3 ± 1.5 and − 0.2 ± 1.6, respectively, at baseline, and − 0.7 ± 1.9 and − 1.0 ± 1.8, respectively, at the final visit. The Z scores for M2 length and for height were strongly correlated, both at the baseline visit (r = 0.84, P < 0.0001) and at the final visit (r = 0.82, P < 0.0001), indicating that there was no disproportionate retardation of growth of M2 in comparison with the impairment of height throughout the disease course. The Z score for M2 length correlated with male sex and with disease duration, but not with age at disease onset (data not shown).

Figure 2. Poznanski scores over the study period. The amount of radiographic damage increased significantly over time (P < 0.0001).

The results obtained by univariate analyses of the relationship between the baseline variables and the yearly radiographic progression, the final Poznanski score, and the final C-HAQ score are presented in Table 2. Radiographic progression in the first year was consistently the strongest correlate for all 3 outcomes. Male sex was the only other variable that was related to all 3 outcomes, whereas the systemic subtype of JIA was related to the yearly radiographic progression and the final Poznanski score, but not the final C-HAQ score. Other significant relationships were those between the baseline and final Poznanski scores, between the baseline and final C-HAQ scores, and between the number of joints with active disease at baseline and the final Poznanski score. Notably, the baseline M2 length Z score was not related to any of the 3 outcomes. The baseline M2 length Z score was not related to the baseline Poznanski score, whereas its final level was related to both the yearly radiographic progression and the final Poznanski score, suggesting that patients with greater radiographic progression developed a more severe retardation of growth of the M2 bone (data not shown).

Table 3 shows the baseline parameters identified by multivariate logistic regression models that had as dependent variables the yearly radiographic progression, the final Poznanski score, and the final C-HAQ score, as well as the sensitivity and specificity of each model in predicting the study outcome and the percentage of patients correctly classified. Radiographic progression in the first year entered the regression in all 3 models, with odds ratios (ORs) of 14.32 for the yearly radiographic progression, 6.49 for the final Poznanski score, and 8.42 for the final C-HAQ score. Female sex was protective against yearly radiographic progression, with an OR of 0.14, and the baseline Poznanski score affected the final Poznanski score, with an OR of 9.28. Other baseline variables, such as JIA subtype, age at disease onset, disease duration, and measures of disease activity and physical disability, had no significant predictive power, nor was the Z score for the M2 length related to radiographic outcome. With regard to disease duration, the distribution was similar in the systemic (median 0.9 years), polyarticular (median 0.8 years), and extended oligoarticular (median 1.6 years) subtypes (P = 0.19), suggesting that the apparent predictive power of early radiographic progression could apply to all JIA subtypes.

The results of the logistic regression analyses (which implied dichotomization of study outcomes into binary outcomes) were comparable to those obtained with multiple regression analyses (i.e., handling the outcomes as continuous variables) (data not shown). Notably, the yearly radiographic progression was strongly correlated with the degree of joint damage at the final visit, as measured by the Poznanski score (P < 0.0001), and with the level of physical disability at the final visit, as measured by the C-HAQ score (P = 0.0004) and the number of joints with limited range of motion (P = 0.0003). Among the clinical indicators of disease activity at the final assessment, the yearly radiographic progression was correlated with the number of joints with active disease (P < 0.0001), but not with the physician's or the parent's global assessments, the ESR, or the CRP (Table 4).

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