nts receiving ACTEMRA. Because IL-6 inhibition may interfere with the normal immune response to new antigens, patients should be brought up to date on all recommended vaccinations, except for live vaccines, prior to initiation of therapy with ACTEMRA.
6 ADVERSE REACTIONS
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice.
The ACTEMRA data described below includes 5 double-blind, controlled, multicenter studies. In these studies, patients received doses of ACTEMRA 8 mg/kg monotherapy (288 patients), ACTEMRA 8 mg/kg in combination with DMARDs (including methotrexate) (1582 patients), or ACTEMRA 4 mg/kg in combination with methotrexate (774 patients).
The all exposure population includes all patients in registration studies who received at least one dose of ACTEMRA. Of the 4009 patients in this population, 3577 received treatment for at least 6 months, 3296 for at least one year; 2806 received treatment for at least 2 years and 1222 for 3 years.
All patients in these studies had moderately to severely active rheumatoid arthritis. The study population had a mean age of 52 years, 82% were female and 74% were Caucasian.
6.1 Clinical Trials Experience
The most common serious adverse reactions were serious infections [see Warnings and Precautions (5.1)]. The most commonly reported adverse reactions in controlled studies up to 6 months (occurring in ≥ 5% of patients treated with ACTEMRA monotherapy or in combination with DMARDs) were upper respiratory tract infections, nasopharyngitis, headache, hypertension and increased ALT.
The proportion of patients who discontinued treatment due to any adverse reactions during the double-blind, placebo-controlled studies was 5% for patients taking ACTEMRA and 3% for placebo-treated patients. The most common adverse reactions that required discontinuation of ACTEMRA were increased hepatic transaminase values (per protocol requirement) and serious infections.
Overall Infections
In the 6-month, controlled clinical studies, the rate of infections in the ACTEMRA monotherapy group was 119 events per 100 patient-years and was similar in the methotrexate monotherapy group. The rate of infections in the 4 mg/kg and 8 mg/kg ACTEMRA plus DMARD group was 133 and 127 events per 100 patient-years, respectively, compared to 112 events per 100 patient-years in the placebo plus DMARD group. The most commonly reported infections (5% to 8% of patients) were upper respiratory tract infections and nasopharyngitis.
The overall rate of infections with ACTEMRA in the all exposure population was 108 events per 100 patient-years.
Serious Infections
In the 6-month, controlled clinical studies, the rate of serious infections in the ACTEMRA monotherapy group was 3.6 per 100 patient-years compared to 1.5 per 100 patient-years in the methotrexate group. The rate of serious infections in the 4 mg/kg and 8 mg/kg ACTEMRA plus DMARD group was 4.4 and 5.3 events per 100 patient-years, respectively, compared to 3.9 events per 100 patient-years in the placebo plus DMARD group.
In the all-exposure population, the overall rate of serious infections was 4.7 events per 100 patient-years. The most common serious infections included pneumonia, urinary tract infection, celluli |
