Enbrel - Side Effects & Drug Interactions

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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 0.09cases 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 (seeWARNINGS: Malignancies).

Sixty-seven malignancies, 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 22patients 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) 1patient was diagnosed with 2 squamous cell cancers. The size of the placebo group and limitedduration of the controlled portions of studies precludes the ability to draw firm conclusions.

Immunogenicity

Patients with RA, psoriatic arthritis, ankylosing spondylitis, or plaque psoriasis were tested atmultiple time points for antibodies to ENBREL®. Antibodies to the TNF receptor portion or otherprotein 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. No apparent correlation of antibody development to clinical response or adverse events was observed. Results from JRA patients were similar to those seen in adult RA patients treated with ENBREL®. The long-term immunogenicityof ENBREL® is unknown.