Allergic reactions associated with etanercept administration have been reported commonly. Allergic reactions have included angioedema and urticaria; serious reactions have occurred. If any serious allergic or anaphylactic reaction occurs, Erelzi therapy should be discontinued immediately and appropriate therapy initiated. Immunosuppression The possibility exists for TNF-antagonists, including Erelzi, to affect host defences against infections and malignancies since TNF mediates inflammation and modulates cellular immune responses.
In a study of 49 adult patients with rheumatoid arthritis treated with etanercept, there was no evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in enumeration of effector cell populations. Two juvenile idiopathic arthritis patients developed varicella infection and signs and symptoms of aseptic meningitis, which resolved without sequelae. Patients with a significant exposure to varicella virus should temporarily discontinue Erelzi therapy and be considered for prophylactic treatment with Varicella Zoster Immune Globulin. The safety and efficacy of etanercept in patients with immunosuppression have not been evaluated.
Malignancies and lymphoproliferative disorders Solid and haematopoietic malignancies (excluding skin cancers) Reports of various malignancies (including breast and lung carcinoma and lymphoma) have been received in the post-marketing period (see section 4.8). In the controlled portions of clinical trials of TNF-antagonists, more cases of lymphoma have been observed among patients receiving a TNF-antagonist compared with control patients. However, the occurrence was rare, and the follow-up period of placebo patients was shorter than for patients receiving TNF-antagonist therapy. In the post-marketing setting, cases of leukaemia have been reported in patients treated with TNF-antagonists.
There is an increased background risk for lymphoma and leukaemia in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, which complicates risk estimation. Based on current knowledge, a possible risk for the development of lymphomas, leukaemia or other haematopoietic or solid malignancies in patients treated with a TNF-antagonist cannot be excluded. Caution should be exercised when considering TNF-antagonist therapy for patients with a history of malignancy or when considering continuing treatment in patients who develop a malignancy.
Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 22 years of age) treated with TNF-antagonists (initiation of therapy ≤ 18 years of age), including etanercept, in the post-marketing setting. Approximately half the cases were lymphomas. The other cases represented a variety of different malignancies and included rare malignancies typically associated with immunosuppression. A risk for the development of malignancies in children and adolescents treated with TNF-antagonists cannot be excluded. Skin cancers Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated with TNF-antagonists, including etanercept.
Post-marketing cases of Merkel cell carcinoma have been reported very infrequently in patients treated with etanercept. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Combining the results of controlled clinical trials, more cases of NMSC were observed in patients receiving etanercept compared with control patients, particularly in patients with psoriasis. Vaccinations 7