gns and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on ENBREL®. Discontinuation of ENBREL® therapy should be considered in patients with confirmed significant hematologic abnormalities.
Two percent of patients treated concurrently with ENBREL® and anakinra developed neutropenia (ANC < 1 x 109/L). While neutropenic, one patient developed cellulitis which recovered with antibiotic therapy.
Malignancies
In the controlled portions of clinical trials of all the TNF-blocking agents, more cases of lymphoma have been observed among patients receiving the TNF blocker compared to control patients. During the controlled portions of ENBREL® trials, 3 lymphomas were observed among 4509 ENBREL®-treated patients versus 0 among 2040 control patients (duration of controlled treatment ranged from 3 to 24 months). In the controlled and open-label portions of clinical trials of ENBREL®, 9 lymphomas were observed in 5723 patients over approximately 11,201 patient-years of therapy. This is 3-fold higher than that expected in the general population. While patients with rheumatoid arthritis or psoriasis, particularly those with highly active disease, may be at a higher risk (up to several fold) for the development of lymphoma, the potential role of TNF-blocking therapy in the development of malignancies is not known (see ADVERSE REACTIONS: Malignancies).11, 12
Cases of acute and chronic leukemia have been reported in association with postmarketing TNF-blocker use in rheumatoid arthritis and other indications. Even in the absence of TNF-blocker therapy, patients with rheumatoid arthritis may be at higher risk (approximately 2-fold) than the general population for the development of leukemia.
During the controlled portions of ENBREL® trials, 2 cases of leukemia were observed among 5445 (0.06 cases per 100 patient years) ENBREL®-treated patients versus 0 among 2890 (0%) control patients (duration of controlled treatment ranged from 3 to 48 months).
Among 15,401 patients treated with ENBREL® in controlled and open portions of clinical trials representing approximately 23,325 patient-years of therapy, the observed rate of leukemia was 0.03 cases per 100 patient years.
Pediatric Patients
Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy at ≤ 18 years of age), including ENBREL® . Approximately half the cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months of therapy (range 1 to 84 months). Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources including registries and spontaneous postmarketing reports.
In clinical trials of 696 patients, representing 1282 patient-years of therapy, no malignancies, including lymphoma or NMSC, have been reported.
Wegener’s Granulomatosis Patients
In a randomized, placebo-controlled study of 180 patients with Wegener's granulomatosis where ENBREL® was added to standard trea |
