Background/Purpose: Systemic-onset juvenile idiopathic arthritis (s-JIA) is a subtype of chronic childhood arthritis characterized by spiking fever, rash, and arthritis. Tocilizumab (TCZ), an anti-IL-6 receptor monoclonal antibody, has dramatically improved patients’ inflammatory symptoms/signs as well as their prognosis. In the long-term treatment of s-JIA patients with TCZ, however, there found joint damages in some patients on X-ray examination although their clinical inflammatory symptoms/signs and laboratory findings were well-controlled. The objective of this study was to determine predictive markers of joint damages of s-JIA patients under the TCZ treatment.

Methods: Although 62 patients have been treated with TCZ, 33 patients were excluded from the study because 17 patients were effectively treated with TCZ to be drug-off, and the duration of TCZ treatment in 16 patients was shorter than 48 months and/or progression of radiographic joint damages were not detectable. Twenty-nine patients (16 boys and 13 girls) with s-JIA were eligible in this study who have been treated with TCZ over 48 months. The following blood tests were determined before and 6, 12, 24, 36, 48 months after the TCZ administration: CBC, CRP/ESR, D-dimer, liver function tests, creatinine, and MMP-3. The radiographs were serially examined before and after TCZ treatment.

Results: The mean age of disease onset was 5.2±2.9 years old. Of the 29 patients, 12 patients (41.3%) had radiographic progression of joint damages during the long-term TCZ treatment (JD (+)), and 17 patients (58.7%) had no joint damages on X-ray examinations (JD (-)) although there were no systemic inflammatory symptoms/signs demonstrable in both groups. Before TCZ treatment there were no significant differences of laboratory data between JD (+) and JD (-). By 12 months after TCZ treatment WBC counts were apparently more increased to normal range in JD (+) group than JD (-) group (p<0.05). By 24 months after TCZ treatment MMP-3 levels were still higher in JD (+) group than in JD (-) group (p<0.05). Taken together, although TCZ completely blocked clinically the inflammatory symptoms/signs as well as laboratory changes of inflammation such as CRP and ESR, there found a part of patients who had progressive joint damages even under the TCZ treatment, suggesting some biological mechanisms which were IL-6-independent will play an important role in damaging joints. For the patients who complained of something different on their joints, the tapering of prednisolone tended to be delayed. As the results, the mean doses of prednisolone at 12 months were significantly higher in JD (+) group than JD (-) group.

Conclusion: The long-lasting elevation of MMP-3 levels and higher WBC counts in patients with s-JIA treated with TCZ will be predictive of radiographic progression of joint damages.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/predictive-markers-of-joint-damages-of-children-with-systemic-onset-juvenile-idiopathic-arthritis-in-long-term-course-of-treatment-with-tocilizumab/