Enbrel Adverse Reactions

Adult patients: The proportion of patients who discontinued treatment due to adverse reactions in controlled clinical studies in patients with rheumatoid arthritis was the same in both the Enbrel and placebo treatment groups.
Injection site reactions: Patients in controlled clinical studies treated with Enbrel had a significantly higher incidence of injection site reactions (erythema and/or itching, pain, or swelling) compared with placebo-treated patients. The frequency of injection site reactions was greatest in the first month and subsequently decreased in frequency. In clinical trials, these reactions were generally transient with a mean duration of 4 days. Some patients who experienced injection site reactions also experienced reactions at previous injection sites.
In post-marketing experience, injection site bleeding and bruising have also been observed in conjunction with Enbrel therapy.
Infections: Serious and fatal infections have been reported; reported pathogens include bacteria, mycobacteria (including tuberculosis), viruses, and fungi. Opportunistic infections have also been reported including invasive fungal, parasitic (including protozoal), viral (including herpes zoster), bacterial (including Listeria and Legionella, and atypical mycobacterial infections (see Precautions). The most commonly reported invasive fungal infections included Candida, Pneumocystis, Aspergillus, and Histoplasma.
In controlled trials in patients with rheumatoid arthritis, the rates of reported serious (fatal, life threatening, or required hospitalization or intravenous antibiotics) and non-serious infections were similar for Enbrel and placebo when adjusted for duration of exposure. Upper respiratory infections were the most commonly reported non-serious infections.
Data from a clinical trial in patients with established sepsis suggest that Enbrel treatment may increase mortality in these patients.
Malignancies and lymphoproliferative disorders: Reports of malignancies affecting various sites have been received in the post-marketing period.
There have been reports of malignancies in a clinical trial of patients being treated for Wegener's granulomatosis (see Precautions).
Interstitial lung disease: In controlled clinical trials of etanercept across all indications, the frequency (incidence proportion) of interstitial lung disease in patients receiving etanercept without concomitant methotrexate was 0.06% (frequency rare). In the controlled clinical trials that allowed concomitant treatment with etanercept and methotrexate, the frequency (incidence proportion) of interstitial lung disease was 0.47% (frequency uncommon). There have been post-marketing reports of interstitial lung disease (including pneumonitis and pulmonary fibrosis), some of which had fatal outcomes.
Elevated liver enzymes: In the double-blind periods of controlled clinical trials of etanercept across all indications, the frequency (incidence proportion) of adverse events of elevated liver enzymes in patients receiving etanercept without concomitant methotrexate was 0.54% (frequency uncommon). In the double-blind periods of controlled clinical trials that allowed concomitant treatment with etanercept and methotrexate, the frequency (incidence proportion) of adverse events of elevated liver enzymes was 4.18% (frequency common).
Autoimmune hepatitis: In controlled clinical trials of etanercept across all indications, the frequency (incidence proportion) of autoimmune hepatitis in patients receiving etanercept without concomitant methotrexate was 0.02% (frequency rare). In the controlled clinical trials that allowed concomitant treatment with etanercept and methotrexate, the frequency (incidence proportion) of autoimmune hepatitis was 0.24% (frequency uncommon).
Autoantibodies: In controlled trials, the percentage of patients who developed new positive antinuclear antibodies [ANA] (≥1:40), new positive anti-double-stranded DNA antibodies, and new anticardiolipin antibodies was increased compared to placebo-treated patients. The impact of long-term treatment with Enbrel on the development of autoimmune diseases is unknown.
Rare reports have been described in patients, including those with rheumatoid factor positive RA, who have developed additional autoantibodies in conjunction with a lupus-like syndrome or rashes compatible with subacute cutaneous lupus or discoid lupus by clinical presentation and biopsy (see table as follows, Other Adverse Reactions).
Other Adverse Reactions: The following table of suspected undesirable effects is based on clinical trials and/or spontaneous post-marketing reporting rates: (See Table 8.)

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Pediatric populations: In general, the adverse events in pediatric patients were similar in frequency and type to those seen in adult patients.
Undesirable effects in pediatric patients with juvenile idiopathic arthritis: Infection was the most common adverse event reported in pediatric patients taking Enbrel and occurred at an incidence similar to placebo. The types of infections reported in juvenile idiopathic arthritis patients were generally mild and consistent with those commonly seen in outpatient pediatric populations.
In clinical trials, two cases of varicella infection with signs and symptoms suggestive of aseptic meningitis have been reported among juvenile idiopathic arthritis patients treated with Enbrel.
There were 4 reports of macrophage activation syndrome in juvenile idiopathic arthritis clinical trials.
Undesirable effects in pediatric patients with plaque psoriasis: In a 48-week study of 211 children aged 4 to 17 years with pediatric plaque psoriasis, the adverse events reported were similar to those seen in previous studies in adults with plaque psoriasis.