SAN DIEGO, CA—There was no association between neutropenia and increased risk of infections with tocilizumab treatment in patients with systemic juvenile idiopathic arthritis (sJIA), according to results of the TENDER trial as presented at ACR/ARHP 2013.
In the Phase 3 TENDER trial that evaluated tocilizumab, decreases in neutrophils count were commonly observed. Fabrizio De Benedetti, MD, PhD, from IRCCS Ospedale Pediatrico Bambino Gesú, Rome, Italy, and colleagues performed an analysis to determine if neutropenia was associated with increased risk of infection, and to investigate the variable associated with development of neutropenia in patients treated with tocilizumab for up to 2 years.
A total of 112 children with active, persistent sJIA were randomized 2:1 to tocilizumab 12mg/kg (if <30kg), tocilizumab 8mg/kg (>30kg), or placebo IV every 2 weeks for 12 weeks. These patients continued in an ongoing tocilizumab open-label extension. Worst Common Toxicity Criteria (CTC) neutropenia grade (Grade 1, ≥1.5 and <2.0×109/L; Grade 2, ≥1.0 and <1.5×109/L; Grade 3, ≥0.5 and <1.0×109/L; Grade 4, <0.5×109/L) and lowest observed neutrophil count (109/L) were identified for each patient.
By Week 104, 57.1% (64/112) of patients had >1 episode of Grade 1–4 neutropenia: Grade 1 (n=2), Grade 2 (n=34), Grade 3 (n=26), and Grade 4 (n=2). Rates of infections and serious infections during period of normal neutrophil counts (276.5/100 [95% CI: 252.3, 302.3] and 11.5/100 [95% CI: 7.0, 17.8], respectively) were comparable to those observed ±15 days around Grade 1–2 neutropenia (226.7/100 [95% CI: 169.3, 297.3]; 8.7/100 [95% CI: 1.1, 31.5]) and Grade 3–4 neutropenia (292.5/100 [95% CI: 167.2, 475.0]; 0/100 PY), with no trend toward increased risk with higher grade neutropenia.
Also, methotrexate use was significantly associated with lowest observed neutrophil count (-0.575 [95% CI: -1.02, -0.13]; P=0.012) with 62% of 77 patients receiving methotrexate vs. 46% of 35 patients not receiving methotrexate having Grade 1–4 neutropenia.
Younger age was borderline associated with lowest observed neutrophil count (b=0.04661, P=0.047), however concomitant use of glucocorticoids with tocilizumab was not associated with lowest observed neutrophil count (P>0.3).
“Methotrexate use and younger age were associated with increased risk of neutropenia, while tocilizumab exposure and concurrent glucocorticoids were not,” concluded Dr. De Benedetti.