PReS-FINAL-2140: Neutropenia with Tocilizumab (TCZ) treatment is not associated with increased infection risk in patients with systemic juvenile idiopathic arthritis (SJIA)

Methods 112 children with active, persistent sJIA were randomised 2:1 to receive TCZ by body weight (12 mg/kg <30kg or 8 mg/kg ≥30kg) or placebo IV every 2 weeks for 12 weeks and continued in an ongoing, TCZ open-label extension. [1]. Worst common toxicity criteria (CTC) neutropenia grade (grade 1, ≥1.5 and <2.0 × 10/L; grade 2, ≥1.0 and <1.5 × 10/L; grade 3, ≥0.5 and <1.0 × 10/L; grade 4, <0.5 × 10/L) and lowest observed neutrophil count (10/L) were identified for each patient. Univariate linear regression analysis was performed to investigate association of patient characteristics with lowest observed neutrophil count. Rates of infections and serious infections (per 100 patient years [PY]) in periods ± 15 days around grade1-2 neutropenia (22.9 PY) and around grade 3-4 neutropenia (5.5 PY) were compared to corresponding rates in periods with normal neutrophil count (173.6 PY). Results Up to week 104, 64/112 patients (57.1%) had at least 1 episode of grade 1-4 neutropenia; worst grade: 1 (n = 2), 2 (n = 34), 3 (n = 26) and 4 (n = 2). Rates of infections and serious infections during period of normal neutrophil counts (276.5/100PY [95% CI 252.3, 302.3] and 11.5/ 100PY [95% CI 7.0, 17.8], respectively) were comparable to those observed ±15 days around grade 1-2 neutropenia (226.7/100PY [95% CI 169.3, 297.3]; 8.7/100PY [95% CI 1.1, 31.5]) and grade 3-4 neutropenia (292.5/100PY [95% CI 167.2, 475.0]; 0/100PY), with no trend towards increased risk with higher grade neutropenia. Methotrexate (MTX) use (Yes/No) was significantly associated with lowest observed neutrophil count (difference: -0.575 [95% CI: -1.02, -0.13], p = 0.012), with 62% of 77 patients receiving MTX vs 46% of 35 patients not receiving MTX having grade 1-4 neutropenia. Younger age was borderline associated with lowest observed neutrophil count (b = 0.04661, p = 0.047). Concurrent use of glucocorticoids (GC) and TCZ exposure were not associated with lowest observed neutrophil count (p>0.3).