, which occurred at a rate of approximately 20% among both ENBREL®- and placebo-treated patients in RA, psoriatic arthritis, and AS trials, and at a rate of approximately 12% among both ENBREL®- and placebo-treated patients in plaque psoriasis trials in the first 3 months of treatment.
In placebo-controlled trials in RA, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis no increase in the incidence of serious infections was observed (approximately 1% in both placebo- and ENBREL®-treated groups). In all clinical trials in RA, serious infections experienced by patients have included: pyelonephritis, bronchitis, septic arthritis, abdominal abscess, cellulitis, osteomyelitis, wound infection, pneumonia, foot abscess, leg ulcer, diarrhea, sinusitis, and sepsis. The rate of serious infections has not increased in open-label extension trials and is similar to that observed in ENBREL®- and placebo-treated patients from controlled trials. Serious infections, including sepsis and death, have also been reported during post-marketing use of ENBREL®. Some have occurred within a few weeks after initiating treatment with ENBREL®. Many of the patients had underlying conditions (e.g., diabetes, congestive heart failure, history of active or chronic infections) in addition to their rheumatoid arthritis (see WARNINGS). Data from a sepsis clinical trial not specifically in patients with RA suggest that ENBREL® treatment may increase mortality in patients with established sepsis.9
In patients who received both ENBREL® and anakinra for up to 24 weeks, the incidence of serious infections was 7%. The most common infections consisted of bacterial pneumonia (4 cases) and cellulitis (4 cases). One patient with pulmonary fibrosis and pneumonia died due to respiratory failure.
In post-marketing experience in rheumatologic indications, infections have been observed with various pathogens including viral, bacterial, fungal, and protozoal organisms. Infections have been noted in all organ systems and have been reported in patients receiving ENBREL® alone or in combination with immunosuppressive agents.
In clinical trials in plaque psoriasis, serious infections experienced by ENBREL®-treated patients have included: cellulitis, gastroenteritis, pneumonia, abscess, and osteomyelitis.
In global clinical studies of 20,070 patients (28,308 patient-years of therapy), tuberculosis was observed in approximately 0.01% of patients. In 15,438 patients (23,524 patient-years of therapy) from clinical studies in the US and Canada, tuberculosis was observed in approximately 0.007% of patients. These studies include reports of pulmonary and extra-pulmonary tuberculosis (see WARNINGS).
Malignancies
Patients have been observed in clinical trials with ENBREL® for over five years. Among 4462 rheumatoid arthritis patients treated with ENBREL® in clinical trials for a mean of 27 months (approximately 10000 patient-years of therapy), 9 lymphomas were observed for a rate of 0.09 cases per 100 patient-years. This is 3-fold higher than the rate of lymphomas expected in the general population based on the Surveillance, Epidemiology, and End Results Database.10 An increased rate of lymphoma up to several fold has been reported in the rheumatoid arthritis patient population, and may be further increased in patients with more severe disease activity11, 12 (see WARNINGS: Malignancies). Sixty-seven malig |
