Background Systemic-onset juvenile idiopathic arthritis (SoJIA) is one of the most striking forms of juvenile arthritis, which can lead to severe joint disability, organ involvement and potentially could be life-threatening.
Objectives The aim of our study was to evaluate clinical response to IL-6 blockade, according to different tocilizumab (TCZ) treatment, outcomes and possibility to achieve drug-free remission.
Methods Our retrospective study was included 37 active SJIA children who fall corticosteroids (CS) and DMARDs and their combination and in whom TCZ was initiated in standard dosage. We used TCZ in 2 branches: every 2 weeks (Q2W) and every 4 weeks (Q4W), depended on the severity of disease, steroid-dependence, presence of MAS and organ involvement. Patients with milder SJIA course (CS≤0.2-0.3 mg/kg, no signs of MAS and no organ involvement) were considered as suitable for Q4W treatment. Only patients who had no signs of flare, exacerbation, side effects and signs of TCZ inefficacy during 4 weeks and received TCZ Q4W (n=26). Patients who successfully treated with TCZ Q4W were recognized as group of low disease activity (LDA). If any signs of inefficacy during first 4 weeks were occurred the patient was treated with TCZ Q2W (n=11). Also if patient later had any signs of insufficient efficacy of TCZ Q4W this patient was re-assessed as HDA patient and referred to appropriate group.
Results From 37 children included in the trial 33 (89.1%) successfully completed it. TCZ was discontinued in 10 patients during the trial: 6 children achieved inactive disease, allowed to stop TCZ, 4 had severe adverse events. Currently 6 patients have TCZ-free remission (3/6 remission off-medication, 3/6 still on MTX) with median duration 661 days. Patients who treated Q4W had milder SJIA course: higher hemoglobin, total protein, albumin, lower WBC, granulocytes, CRP, ESR, ferritin, LDH, no new cases of macrophage activation syndrome (MAS), lower frequency of organ involvement and relapses during TCZ treatment. No patients, who required TCZ every 2 weeks, experienced TCZ-free remission by now. All cases of MAS relapses during TCZ course were only in Q2W group. Q4W patients decreased the granulocytes number intensively than Q2W. Hb>10.3 g/dl, granulocytes≤9792 cells in 1 μl, granulocytes in 1 week≤8142 cells in 1 μl, WBC in 2 weeks≤7.5*109/l, granulocytes in 2 weeks≤3975 cells in 1 μl, platelets>208*109/l, ESR≤26 mm/h, ferritin≤605 mg/ml, LDH≤571 U/l, total protein>7.2 g/dl, albumin>2.8 g/dl, absence of hepatosplenomegaly, coagulopathy, cardiorespiratory, CNS and kidney involvement, no MAS during TCZ were factors increased possibility to use TCZ Q4W and referred the patient to LDA group. Fever before and MAS after TCZ initiation, lymphadenopathy, coagulopathy, CNS dysfunction and treatment Q2W decreased possibility to achieve TCZ-off remission.
Conclusions Different response to IL-6 blockade distinguishes two different subsets of SJIA. We offer the provisional criteria distinguish patients with LDA and HDA and provisional criteria probability to rich TCZ-free remission.
Disclosure of Interest None declared