ver no definitive conclusions can be made.
Infusion Reactions
Patients were not premedicated, however most patients were on concomitant corticosteroids as part of their background treatment for SJIA. Infusion related reactions were defined as all events occurring during or within 24 hours after an infusion. In the 12 week controlled phase, 4% of ACTEMRA and 0% of placebo treated patients experienced events occurring during infusion. One event (angioedema) was considered serious and life-threatening, and the patient was discontinued from study treatment.
Within 24 hours after infusion, 16% of patients in the ACTEMRA treatment group and 5% of patients in the placebo group experienced an event. In the ACTEMRA group the events included rash, urticaria, diarrhea, epigastric discomfort, arthralgia and headache. One of these events, urticaria, was considered serious.
Anaphylaxis
Anaphylaxis was reported in 1 out of 112 patients (less than 1%) treated with ACTEMRA during the controlled and open label extension study [see Warnings (5.5)].
Immunogenicity
All 112 patients were tested for anti-tocilizumab antibodies at baseline. Two patients developed positive anti-tocilizumab antibodies: one of these patients experienced serious adverse events of urticaria and angioedema consistent with an anaphylactic reaction which led to withdrawal; the other patient developed macrophage activation syndrome while on escape therapy and was discontinued from the study.
Laboratory Tests
Neutrophils
During routine monitoring in the 12 week controlled phase, a decrease in neutrophil below 1 × 109 per L occurred in 7% of patients in the ACTEMRA group, and in no patients in the placebo group. In the open label extension over an average duration of 73 weeks of treatment, a decreased neutrophil count occurred in 17% of the ACTEMRA group. There was no clear relationship between decrease in neutrophils below 1 × 109 per L and the occurrence of serious infections.
Platelets
During routine monitoring in the 12 week controlled phase, 1% of patients in the ACTEMRA group and 3% in the placebo group had a decrease in platelet count to no more than 100 × 103 per mcL.
In the open label extension over an average duration of 73 weeks of treatment, decreased platelet count occurred in 4% of patients in the ACTEMRA group, with no associated bleeding.
Liver Function Tests
During routine laboratory monitoring in the 12 week controlled phase, elevation in ALT or AST at or above 3x ULN occurred in 5% and 3% of patients, respectively in the ACTEMRA group and in 0% of placebo patients.
In the open label extension over an average duration of 73 weeks of treatment, the elevation in ALT or AST at or above 3x ULN occurred in 13% and 5% of ACTEMRA treated patients, respectively.
Lipids
During routine laboratory monitoring in the 12 week controlled phase, elevation in total cholesterol greater than 1.5x ULN – 2x ULN occurred in 1.5% of the ACTEMRA group and in 0% of placebo patients. Elevation in LDL greater than 1.5x ULN – 2x ULN occurred in 1.9% of patients in the ACTEMRA group and 0% of the placebo group.
In the open label extension study over an average duration of 73 weeks of treatment, the pattern and incidence of elevations in lipid parameters remained consistent with the 12 week controlled study data.
6.2Postmarketing Experience
The following adverse reactions have been identified during postapprov