ed patients (5%). The percentage of patients who developed new positive anti-double-stranded DNA antibodies was also higher by radioimmunoassay (15% of patients treated with ENBREL® compared to 4% of placebo-treated patients) and by Crithidia luciliae assay (3% of patients treated with ENBREL® compared to none of placebo-treated patients). The proportion of patients treated with ENBREL® who developed anticardiolipin antibodies was similarly increased compared to placebo-treated patients. In Study III, no pattern of increased autoantibody development was seen in ENBREL® patients compared to MTX patients.
The impact of long-term treatment with ENBREL® on the development of autoimmune diseases is unknown. Rare adverse event reports have described patients with rheumatoid factor positive and/or erosive RA who have developed additional autoantibodies in conjunction with rash and other features suggesting a lupus-like syndrome.
Other Adverse Reactions
Table 10 summarizes events reported in at least 3% of all patients with higher incidence in patients treated with ENBREL® compared to controls in placebo-controlled RA trials (including the combination methotrexate trial) and relevant events from Study III. In placebo-controlled plaque psoriasis trials, the percentages of patients reporting injection site reactions were lower in the placebo dose group (6.4%) than in the ENBREL® dose groups (15.5%) in Studies I and II. Otherwise, the percentages of patients reporting adverse events in the 50 mg twice a week dose group were similar to those observed in the 25 mg twice a week dose group or placebo group. In psoriasis Study I, there were no serious adverse events of worsening psoriasis following withdrawal of study drug. However, adverse events of worsening psoriasis including three serious adverse events were observed during the course of the clinical trials. Urticaria and non-infectious hepatitis were observed in a small number of patients and angioedema was observed in one patient in clinical studies. Urticaria and angioedema have also been reported in spontaneous post-marketing reports. Adverse events in psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis trials were similar to those reported in RA clinical trials.
Table 10: Percent of RA Patients Reporting Adverse Events in Controlled Clinical Trials * *
Includes data from the 6-month study in which patients received concurrent MTX therapy.
†
The duration of exposure for patients receiving placebo was less than the ENBREL ®-treated patients.
‡
Infection (total) includes data from all three placebo-controlled trials. Non-URI and URI include data only from the two placebo-controlled trials where infections were collected separately from adverse events (placebo N = 110, ENBREL ® N = 213).
Event
Placebo Controlled Active Controlled
(Study III)
Percent of patients Percent of patients
Placebo†
(N = 152) ENBREL®
(N = 349) MTX
(N = 217) ENBREL®
(N = 415)
Injection site reaction 10 37 7 34
Infection (total)‡ 32 35 72 64
Non-upper respiratory infection (non-URI)‡ 32 38 60 51
Upper respiratory infection (URI)‡ 16 29 39 31
Headache 13 17 27 24
Nausea 10 9 29 15
Rhinitis 8 12 14 16
Dizziness 5 7 11 8
Pharyngitis 5 7 9 6
Cough 3 6 6 5
Asthenia 3 5 12 11
Abdominal pain 3 5 10 10
Rash 3 5 23 14
Peripheral edema 3 2 4 8
Respiratory disorder 1 5 NA NA
Dys |
