Neutropenia During Tocilizumab Treatment Is Not Associated with Infection Risk in Systemic or Polyarticular-course Juvenile Idiopathic Arthritis

Abstract

Objective. To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ). Methods. Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112; ClinicalTrials.gov, NCT00642460) and pcJIA (n = 188; ClinicalTrials.gov, NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts. Results. ANC decreased to grade ≥ 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8-16.5) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3-8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial. Conclusion. Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number

Translating IL-6 biology into effective treatments

“…Consistent with expectations for a biologic DMARD for RA, serious infections, including serious bacterial infections, are among the most common serious adverse events reported in clinical trials, post-marketing surveillance studies, short-term studies and open-label extension studies. The overall rate of serious infections in patients with long-term exposure to IL-6 pathway inhibitors is in line with rates seen in studies with a short duration of exposure 58,145,159,161,[164][165][166][167][168][169] .…”

Efficacy and safety of tocilizumab in a real-life observational cohort of patients with polyarticular juvenile idiopathic arthritis

“…We detected a higher rate of grade 3 neutropenia (⩽1.0×109/l) in 18% of our patients compared with 5.9% reported in the CHERISH study patients during 2 years of follow-up [35]. Pardeo and colleagues found no association between development of neutropenia and tocilizumab trough levels or concomitant MTX use, and neutropenia was not associated with the development of infections [35]. The difference in the rate of neutropenia might be explained by the fact that many of our patients used concomitant sDMARDs other than MTX as well as combinations of sDMARDs, while only MTX and glucocorticoids were allowed in the CHERISH study [25].…”

“…However, one typical AE for tocilizumab is neutropenia [35]. We detected a higher rate of grade 3 neutropenia (⩽1.0×109/l) in 18% of our patients compared with 5.9% reported in the CHERISH study patients during 2 years of follow-up [35]. Pardeo and colleagues found no association between development of neutropenia and tocilizumab trough levels or concomitant MTX use, and neutropenia was not associated with the development of infections [35].…”

“…systemic JIA or pJIA) [25,30,35]. However, one typical AE for tocilizumab is neutropenia [35]. We detected a higher rate of grade 3 neutropenia (⩽1.0×109/l) in 18% of our patients compared with 5.9% reported in the CHERISH study patients during 2 years of follow-up [35].…”

“…Furthermore, the rates of AEs associated with tocilizumab differ depending on the indication (i.e. systemic JIA or pJIA) [25,30,35]. However, one typical AE for tocilizumab is neutropenia [35].…”