nancies, other than lymphoma, were observed. Of these, the most common malignancies were colon, breast, lung, and prostate, which were similar in type and number to what would be expected in the general population.10 Analysis of the cancer rates at 6 month intervals suggest constant rates over five years of observation.
In the placebo-controlled portions of the psoriasis studies, 8 of 933 patients who received ENBREL® at any dose were diagnosed with a malignancy compared to 1 of 414 patients who received placebo. Among the 1261 patients with psoriasis who received ENBREL® at any dose in the controlled and uncontrolled portions of the psoriasis studies (1062 patient-years), a total of 22 patients were diagnosed with 23 malignancies; 9 patients with non-cutaneous solid tumors, 12 patients with 13 non-melanoma skin cancers (8 basal, 5 squamous), and 1 patient with non-Hodgkin’s lymphoma. Among the placebo-treated patients (90 patient-years of observation) 1 patient was diagnosed with 2 squamous cell cancers. The size of the placebo group and limited duration of the controlled portions of studies precludes the ability to draw firm conclusions.
Among 89 patients with Wegener’s granulomatosis receiving ENBREL® in a randomized, placebo-controlled trial, 5 experienced a variety of non-cutaneous solid malignancies compared with none receiving placebo (see WARNINGS: Malignancies).
Immunogenicity
Patients with RA, psoriatic arthritis, ankylosing spondylitis, or plaque psoriasis were tested at multiple timepoints for antibodies to ENBREL®. Antibodies to the TNF receptor portion or other protein components of the ENBREL® drug product were detected at least once in sera of approximately 6% of adult patients with RA, psoriatic arthritis, ankylosing spondylitis, or plaque psoriasis. These antibodies were all non-neutralizing. Results from JIA patients were similar to those seen in adult RA patients treated with ENBREL®.
In PsO studies that eva luated the exposure of etanercept for up to 120 weeks, the percentage of patients testing positive at the assessed time points of 24, 48, 72, and 96 weeks ranged from 3.6%- 8.7% and were all non-neutralizing. The percentage of patients testing positive increased with an increase in the duration of study, however, the clinical significance of this finding is unknown. No apparent correlation of antibody development to clinical response or adverse events was observed. The immunogenicity data of ENBREL® beyond 120 weeks of exposure is unknown.
The data reflect the percentage of patients whose test results were considered positive for antibodies to ENBREL® in an ELISA assay, and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of any antibody positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to ENBREL® with the incidence of antibodies to other products may be misleading.
Autoantibodies
Patients with RA had serum samples tested for autoantibodies at multiple timepoints. In RA Studies I and II, the percentage of patients eva luated for antinuclear antibodies (ANA) who developed new positive ANA (titer ≥ 1:40) was higher in patients treated with ENBREL® (11%) than in placebo-treat |
