Efficacy and Safety of Tocilizumab for Polyarticular‐Course Juvenile Idiopathic Arthritis in the Open‐Label Two‐Year Extension of a Phase III Trial

Abstract

Objective. To report the 2-year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular-course juvenile idiopathic arthritis (JIA). Methods. Patients ages 2-17 years with active polyarticular-course JIA, in whom treatment with methotrexate was unsuccessful, received 16 weeks of open-label intravenous TCZ in part 1 (once every 4 weeks: 8 mg/kg or 10 mg/kg for body weight [BW] <30 kg; 8 mg/kg for BW ≥30 kg). Assessments were based on the JIA-American College of Rheumatology (ACR) response (defined as percentage of improvement in ≥3 of the 6 JIA core response variables [CRVs]). Patients with at least a JIA-ACR30 response (defined as ≥30% improvement in ≥3 of the 6 JIA CRVs without worsening in >1 of the remaining JIA CRVs by >30%) at week 16 were randomly assigned (1:1) to receive TCZ or placebo in part 2. Patients remained in part 2 until either week 40 or the occurrence of JIA flare. Upon starting part 3, all patients received open-label TCZ. At week 104 of the study, efficacy was assessed using JIA-ACR50/70/90 response rates (defined as 50%, 70%, or 90% improvement, respectively), achievement of inactive disease, and the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71). Safety was assessed in the all-exposure population per 100 patient-years of exposure. Results. Overall, 188 patients entered part 1, 166 patients entered part 2, and 160 patients entered part 3. By week 104, among the 188 patients in the modified intent-to-treat group who received TCZ, JIA-ACR50/70/90 response rates were 80.3%/77.1%/59.6%, respectively, the median JADAS-71 score decreased from 3.6 at week 40 to 0.7 at week 104, 51.1% of patients had achieved inactive disease, and 31 of 66 patients who had been receiving glucocorticoids discontinued them. Adverse event (AE) and serious AE rates were 406.5 per 100 patient-years and 11.1 per 100 patient-years, respectively. The infection rate was 151.4 per 100 patient-years, and the serious infection rate was 5.2 per 100 patient-years. Conclusion. Patients treated with TCZ for polyarticular-course JIA showed high-level disease control for up to 2 years. The TCZ safety profile was consistent with that previously reported.

Tocilizumab in management of refractory juvenile idiopathic arthritis, 10 years of experience at tertiary university hospital

“…As mentioned in several studies, infection is the most frequently revealed side effect of TCZ use [13,23,25]. Contrary to expectations, none of our patients developed TCZ possibly related significant infections.…”

“…Neutropenia is one of the most frequently reported AE in previous reports [8,11,23,25,28] who have reported neutropenia in both sJIA and pJIA in variable frequencies (18%, 50%, 10%, 17%, 37.2%), respectively. In line with the results from previous studies, we reported neutropenia in 3 (5 events) (2 sJIA and one pJIA) (21.4%) patients during the TCZ course.…”

“…At about 24 months of TCZ use, JIA ACR 50, 70, and 90 responses were achieved by 80.3, 77.1, and 59.6%, respectively. Additionally, the median JADAS-71 score decreased from 3.6 at week 40 to 0.7 at the 24 months [25].…”

Signals and Mechanisms Regulating Monocyte and Macrophage Activation in the Pathogenesis of Juvenile Idiopathic Arthritis

“…Patients with dominant IL-6 cytokines have more severe joint disease, and those with dominant IL-18 cytokines are more likely to develop MAS [ 114 ]. As the severity of experimental inflammatory arthritis is greatly suppressed in IL-6 -/- transgenic mice [ 115 ], a promising result was also noted by applying tocilizumab, an IL-6 receptor targeting agent, for the treatment of polyarticular JIA and sJIA [ 116 , 117 ].…”

Laparoscopic transabdominal preperitoneal repair for inguinal hernia in a patient with an adult Still’s disease receiving anti-interleukin-6 receptor monoclonal antibody therapy

“…Therefore, there are increasing opportunities for surgery in patients using molecularly targeted drugs. Tocilizumab, a monoclonal antibody drug against interleukin (IL)-6 receptor, is used for rheumatoid arthritis [ 1 ], Castleman disease, adult Still’s disease [ 2 ] and juvenile idiopathic arthritis [ 3 ]. In addition to these diseases, anti-IL-6 receptor antibodies are anticipated to expand their application as a means of controlling organ damage secondary to cytokine storms generated by the induction of inflammatory responses, and have recently been used for coronavirus disease pneumonia [ 4 ].…”