Long-term outcome of juvenile idiopathic arthritis following a placebo-controlled trial: sustained benefits of early sulfasalazine treatment.

OBJECTIVES: A previous 24-week randomised trial demonstrated that sulfasalazine (SSZ) treatment was superior to placebo (PLAC) in suppressing disease activity in patients with oligo- and polyarticular onset juvenile idiopathic arthritis (JIA). The current study determines the long-term outcome of the trial participants and evaluates whether the benefits of SSZ allocation are sustained over time. METHODS: Between 2001 and 2003, 32 SSZ and 29 PLAC patients (90% of all patients) were prospectively examined clinically and by chart review, median 9 years (range 7 to 10) after trial inclusion. In the follow-up assessment, variables of the American College of Rheumatology Pediatric 30 (ACR Pedi 30) criteria were collected. The assessor was blinded to trial treatment allocation. RESULTS: After the trial, patients had been routinely followed in rheumatology referral centres, and treated at the discretion of the attending physician. Almost all patients continued or started disease-modifying antirheumatic drugs (DMARDs) (SSZ 91%, PLAC 93%; SSZ treatment in about 80%). DMARD treatment appeared less intensive in the SSZ group as evidenced by a significantly shorter duration of SSZ use (median 2.5 vs 5.2 years; p = 0.02) and a trend towards less use of methotrexate and other DMARDs. More than one-third of the patients reported long periods of non-compliance with DMARD treatment in both groups. At follow-up, 74% of the patients had active joints, and 30% showed active polyarthritis. Almost all outcome scores were better for SSZ compared with PLAC patients. Differences (often exceeding 50%) were significant for the number of active joints, patients' overall well-being, number of patients with episodes of clinical remission off medication (CROM) and duration of these episodes, patients in CROM and ACR Pedi 30 response at follow-up. Additional exploratory analyses performed to detect potential confounders related to patient characteristics or follow-up treatment showed that DMARD treatment compliance was positively correlated with an ACR Pedi 30 response (odds ratio 3.8, 95% confidence interval (CI) 1.1 to 13.4; p = 0.03). Adjusted for compliance, an SSZ patient was 4.2 times as likely as a PLAC patient to be an ACR Pedi 30 responder at follow-up (95% CI 1.3 to 14.3; p = 0.02). CONCLUSIONS: This follow-up study shows that effective suppression of disease activity by SSZ treatment early in active disease in JIA patients has beneficial effects that persist for many years. Given these results, compliance with DMARD treatment deserves serious attention.

Development of a standardized method of assessment of radiographs and radiographic change in juvenile idiopathic arthritis: introduction of the Dijkstra composite score.

OBJECTIVE: To evaluate the sensitivity to change of a newly developed radiologic assessment tool, the Dijkstra score, and to develop a numeric composite score and progressor classification scheme to apply in juvenile idiopathic arthritis (JIA) trials. METHODS: A placebo-controlled trial of sulfasalazine (SSZ) in patients with oligoarticular- and polyarticular-onset JIA yielded the data for this study. Data were obtained from 418 sets of radiographs of the clinically involved and contralateral joints (at study entry and at 6 months' followup) from 66 JIA patients. The Dijkstra score assesses the presence or absence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment. These signs were combined in the Dijkstra composite score, to assess inflammation (DI), growth (DG), and damage (DD). Progression was defined as an increase in either the DG or the DD score. Scores were evaluated among all radiographs, a standard set of films (hand, foot, and knee), and per patient. All scores were used to explore differences between the 2 treatment groups. RESULTS: Over time, 58% of joints remained normal, 23% remained abnormal but stable, 14% showed an increase in signs, and 5% showed a decrease in signs. Of the 66 JIA patients, 12% had normal radiographic findings throughout followup, 27% showed abnormalities at some sites without change, and 61% showed change in at least 1 site. Changes in the DI, DG, and DD scores varied considerably per type of joint and occurred most frequently in joints of the standard set. DI and DG scores changed most often in the knees, while DD scores changed primarily in the hands and feet. The disease course in 8% of joints was classified as progressive. Films of SSZ-treated patients, versus the placebo group, showed less deterioration by the DD scores (P = 0.04), and the disease course was more often classified as nonprogressive in the SSZ group (P = 0.037). When progressors were defined as those who had at least one radiograph showing progression, significantly more placebo-treated patients were considered progressors (P = 0.046). CONCLUSION: In this trial data set, the Dijkstra composite score and the resulting progressor classification system are comprehensive and feasible tools that are sensitive to change and discriminate between clinical situations. They should now be tested by other investigators and in other data sets.

Radiologic features in juvenile idiopathic arthritis: a first step in the development of a standardized assessment method.

OBJECTIVE: To describe radiologic features of patients with juvenile idiopathic arthritis (JIA) in a standardized manner, to test the reliability and feasibility of this description, and to correlate these features with clinical signs as a first step in the development of a standardized assessment method. METHODS: The placebo-controlled study of sulfasalazine in patients with oligoarticular, extended oligoarticular, and polyarticular JIA performed by the Dutch Juvenile Idiopathic Arthritis Study Group yielded the data for this study. All trial entry radiographs (clinically involved joints and contralateral joints) were scored (in consensus by a skeletal radiologist and pediatric rheumatologist) for the presence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment. RESULTS: Data on 67 of 69 patients were analyzed. The mean age was 9.1 years (range 2.5-17.6 years), and the median disease duration was 24 months (range 5-176 months). Thirteen percent of the patients were IgM rheumatoid factor (IgM-RF) positive, and 16% were HLA-B27 positive. All 68 clinically evaluated joints were included in the maximum of 19 radiographed joints (or joint groups) per patient. The mean number of radiographed joints per patient was 7 (range 2-15); knees, hands, ankles, and feet were most frequently affected. Fifty-eight patients (87%) had radiologic abnormalities in at least one joint (soft-tissue swelling in 63% of patients, growth disturbances in 48%, joint space narrowing in 28%, and erosions in 15%). In total, half of the radiographs of the clinically involved joints showed radiologic abnormalities, including two-thirds of the radiographs of the clinically affected hands and knees. Univariate analysis revealed a good correlation between the overall articular (clinical) severity and the presence of radiologic abnormalities (odds ratio [OR] 1.38, P < 0.0001). Multivariate analysis showed increased ORs for the presence of radiologic abnormalities and IgM-RF positivity (OR 4.6, P = 0.005) or HLA-B27 positivity (OR 3.0, P = 0.004). In general, reproducibility of the radiologic scoring method was good (mean kappa coefficient of 0.74 [range 0.40-0.86]), although there were scoring discrepancies for swelling, osteopenia, and growth disturbances. The scoring took 10-20 minutes per patient. CONCLUSION: Our model of describing and scoring radiologic abnormalities of radiographed joints in JIA was feasible, mostly reproducible, correlated well with the overall articular severity score, and added substantial new information not available on clinical examination.