నైరూప్య

Severe infusion reactions to tocilizumab in young children with systemic juvenile idiopathic arthritis

Tomo Nozawa, Kenichi Nishimura, Takashi Ohya, Asami Oohara, Ryoki Hara & Shuichi Ito

Objective: Tocilizumab (TCZ) is the first-line agent against systemic juvenile idiopathic arthritis (sJIA) refractory to glucocorticoids. However, some patients discontinue TCZ because of severe infusion reactions (IRs). This study aimed to demonstrate the characteristics of patients with sJIA who develop severe IRs to TCZ, and investigate its risk factors.

Method: Thirty-one patients with newly diagnosed sJIA (boys-16; girls-15) who received at least one infusion of TCZ were enrolled.

Results: Four patients presented with TCZ-induced severe IRs. IRs appeared in the early phase of treatment, especially within the 10th infusion of TCZ. All of these patients were girls (IR group vs. non-IR group, p=0.043) and younger than 3 years old. The median age at initiation of TCZ in the IR group was significantly younger than that in the non-IR group (p=0.001). At disease onset, more patients in the IR group (75%) were complicated by macrophage activation syndrome than those in the non-IR group (11%, p=0.016). The dose of TCZ per kg was not different between the groups. However, the dose per m2 was less in the IR group than in the non-IR group (212 vs. 252 mg/m2 , p=0.052). In the IR group, except for one patient, anti-TCZ IgG and/or anti-TCZ IgE antibodies were detected.

Conclusions: Risk factors of TCZ-induced severe IRs are female sex, age younger than 3 years old, and onset with macrophage activation syndrome. An optimal regimen of induction of remission with TCZ in such patients should be established.