tis, herpes zoster, gastroenteritis, diverticulitis, sepsis and bacterial arthritis. The overall rate of fatal serious infections was 0.13 per 100 patient-years. Cases of opportunistic infections have been reported [see Warnings and Precautions (5.1)].
Gastrointestinal Perforations
During the 6-month, controlled clinical trials, the overall rate of gastrointestinal perforation was 0.26 events per 100 patient-years with ACTEMRA therapy.
In the all-exposure population, the overall rate of gastrointestinal perforation was 0.28 events per 100 patient-years. Reports of gastrointestinal perforation were primarily reported as complications of diverticulitis including generalized purulent peritonitis, lower GI perforation, fistula and abscess. Most patients who developed gastrointestinal perforations were taking concomitant nonsteroidal anti-inflammatory medications (NSAIDs), corticosteroids, or methotrexate [see Warnings and Precautions (5.2)]. The relative contribution of these concomitant medications versus ACTEMRA to the development of GI perforations is not known.
Infusion Reactions
In the 6-month, controlled clinical studies, adverse events associated with the infusion (occurring during or within 24 hours of the start of infusion) were reported in 8% and 7% of patients in the 4 mg/kg and 8 mg/kg ACTEMRA plus DMARD group, respectively, compared to 5% of patients in the placebo plus DMARD group. The most frequently reported event on the 4 mg/kg and 8 mg/kg dose during the infusion was hypertension (1% for both doses), while the most frequently reported event occurring within 24 hours of finishing an infusion were headache (1% for both doses) and skin reactions (1% for both doses), including rash, pruritus and urticaria. These events were not treatment limiting.
Clinically significant hypersensitivity reactions (e.g., anaphylactoid and anaphylactic reactions) associated with ACTEMRA and requiring treatment discontinuation were reported 0.1% (3/2644) in the 6-month, controlled trials and in 0.2% (9/4009) in the all-exposure population. These reactions were generally observed during the second to fourth infusion of ACTEMRA. Appropriate medical treatment should be available for immediate use in the event of a serious hypersensitivity reaction [see Warnings and Precautions (5.5)].
Laboratory Tests
Neutrophils
In the 6-month, controlled clinical studies, decreases in neutrophil counts below 1000/mm3 occurred in 1.8% and 3.4% of patients in the 4 mg/kg and 8 mg/kg ACTEMRA plus DMARD group, respectively, compared to 0.1% of patients in the placebo plus DMARD group. Approximately half of the instances of ANC below 1000/mm3 occurred within 8 weeks of starting therapy. Decreases in neutrophil counts below 500/mm3 occurred in 0.4% and 0.3% of patients in the 4 mg/kg and 8 mg/kg ACTEMRA plus DMARD, respectively, compared to 0.1% of patients in the placebo plus DMARD group. There was no clear relationship between decreases in neutrophils below 1000/mm3 and the occurrence of serious infections.
In the all-exposure population, the pattern and incidence of decreases in neutrophil counts remained consistent with what was seen in the 6-month controlled clinical studies [see Warnings and Precautions (5.3)].
Platelets
In the 6-month, controlled clinical studies, decreases in platelet counts below 100,000/mm3 occurred in 1.3% and 1.7% of patients on 4 mg/kg and 8 mg/kg ACTEMRA plus DMARD, respectively, compared to 0.5 |
