ts [see ADVERSE REACTIONS (6.1 and 6.4)].
No clinically significant hypersensitivity reactions associated with tocilizumab and requiring treatment discontinuation were reported.
Immunogenicity
One patient, in the 10 mg/kg less than 30 kg group, developed positive anti-tocilizumab antibodies without developing a hypersensitivity reaction and subsequently withdrew from the study.
Laboratory Abnormalities
Neutropenia
During routine laboratory monitoring in the ACTEMRA-IV all exposure population, a decrease in neutrophil counts below 1 × 109 per L occurred in 3.7% of patients.
There was no clear relationship between decreases in neutrophils below 1 × 109 per L and the occurrence of serious infections.
Thrombocytopenia
During routine laboratory monitoring in the ACTEMRA-IV all exposure population, 1% of patients had a decrease in platelet count at or less than 50 × 103 per mcL without associated bleeding events.
Elevated Liver Enzymes
During routine laboratory monitoring in the ACTEMRA-IV all exposure population, elevation in ALT or AST at or greater than 3 × ULN occurred in 4% and less than 1% of patients, respectively.s
Lipids
During routine laboratory monitoring in the tocilizumab all exposure population, elevation in total cholesterol greater than 1.5-2 × ULN occurred in one patient (0.5%) and elevation in LDL greater than 1.5-2 × ULN occurred in one patient (0.5%).
6.4 Clinical Trials Experience in Systemic Juvenile Idiopathic Arthritis Patients Treated with Intravenous ACTEMRA (ACTEMRA-IV)
The data described below reflect exposure to ACTEMRA-IV in one randomized, double-blind, placebo-controlled trial of 112 pediatric patients with SJIA 2 to 17 years of age who had an inadequate clinical response to nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids due to toxicity or lack of efficacy. At baseline, approximately half of the patients were taking 0.3 mg/kg/day corticosteroids or more, and almost 70% were taking methotrexate. The trial included a 12 week controlled phase followed by an open-label extension. In the 12 week double-blind, controlled portion of the clinical study 75 patients received treatment with ACTEMRA-IV (8 or 12 mg per kg based upon body weight). After 12 weeks or at the time of escape, due to disease worsening, patients were treated with ACTEMRA-IV in the open-label extension phase.
The most common adverse events (at least 5%) seen in ACTEMRA-IV treated patients in the 12 week controlled portion of the study were: upper respiratory tract infection, headache, nasopharyngitis and diarrhea.
Infections
In the 12 week controlled phase, the rate of all infections in the ACTEMRA-IV group was 345 per 100 patient-years and 287 per 100 patient-years in the placebo group. In the open label extension over an average duration of 73 weeks of treatment, the overall rate of infections was 304 per 100 patient-years.
In the 12 week controlled phase, the rate of serious infections in the ACTEMRA-IV group was 11.5 per 100 patient years. In the open label extension over an average duration of 73 weeks of treatment, the overall rate of serious infections was 11.4 per 100 patient years. The most commonly reported serious infections included pneumonia, gastroenteritis, varicella, and otitis media.
Macrophage Activation Syndrome
In the 12 week controlled study, no patient in any treatment group experienced macrophage activation syndrome (MAS) whi |
