What are the side effects of Altebrel (etanercept) and how should they be monitored and managed?

Altebrel (Etanercept) Side Effects

Altebrel carries significant risks including serious infections (particularly tuberculosis reactivation), injection site reactions in up to 67.7% of patients, and rare but serious complications such as demyelinating disorders, with mandatory pre-treatment tuberculosis and hepatitis screening required before initiation. 1, 2

Most Common Side Effects

Injection Site Reactions

• Injection site reactions occur in 14-67.7% of patients and represent the most frequent adverse effect, typically presenting as mild to moderate reactions that diminish with ongoing therapy 3, 1, 4
• These reactions do not correlate with antibody development and rarely require treatment discontinuation 3, 1
• Rare recall site reactions can occur where all four rotated injection sites simultaneously develop hypersensitivity reactions, which respond to antihistamines without requiring drug cessation 5

Upper Respiratory and General Symptoms

• Upper respiratory tract infections, headache, rhinitis, and dizziness are commonly reported 3, 6, 4
• Allergic reactions occur but are generally manageable 3, 1

Serious Infectious Complications

Tuberculosis Reactivation

• Reactivation of latent tuberculosis is a critical concern, with approximately 50% of cases presenting as extrapulmonary disease 1, 2
• Etanercept carries lower tuberculosis reactivation risk compared to monoclonal TNF antagonists (infliximab and adalimumab), though postmarketing cases have been documented 3, 1, 2
• Tuberculin skin testing and chest radiograph are mandatory before initiating therapy, with induration of 5mm or greater considered positive even in BCG-vaccinated patients 3, 1, 2
• Tests for latent tuberculosis may be falsely negative while on etanercept therapy 2

Opportunistic Infections

• Serious infections include pneumonia, bronchitis, peritonitis, septicemia, pyelonephritis, cellulitis, and systemic fungal infections 3, 2
• Opportunistic pathogens include aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, and atypical mycobacteria 3, 1, 2
• For patients in endemic fungal regions, empiric anti-fungal therapy should be considered if serious systemic illness develops, as antigen and antibody testing may be falsely negative 2

Hepatitis B Reactivation

• Patients with chronic hepatitis B infection or positive surface antigen are at risk for viral reactivation, typically occurring with concomitant immunomodulatory agents 3, 1
• Hepatitis serology must be obtained prior to therapy initiation, and etanercept should be avoided if active viral hepatitis is present 3, 7
• Patients with chronic viral hepatitis or carrier states require monitoring for viral reactivation throughout therapy 3, 7

Autoimmune and Inflammatory Complications

Lupus-Like Syndrome

• A syndrome resembling lupus erythematosus has been reported, though rare 3, 1
• Antinuclear antibodies develop in up to 11% of patients but rarely lead to overt autoimmune disease during short- to medium-duration use 1
• Anti-double-stranded DNA antibodies can be measured if lupus-like symptoms develop during therapy 3

Vasculitis

• Leukocytoclastic vasculitis and cutaneous vasculitis have been reported, responding to treatment cessation and appropriate therapy 3, 5

Neurological Complications

• CNS demyelination including optic neuritis, transverse myelitis, and Guillain-Barré syndrome have been observed in postmarketing reports 3, 1
• Etanercept is contraindicated in patients with active demyelinating diseases such as multiple sclerosis 1, 7

Cardiovascular Effects

• Etanercept must be avoided in severe congestive heart failure (NYHA class III or IV) 1, 7
• Unlike infliximab, etanercept has not been convincingly linked to increased mortality in heart failure patients 1

Hematologic Toxicities

• Blood dyscrasias including anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and hemophagocytic syndrome have been reported 3, 1
• Drug-induced worsening of thrombocytopenia with purpuric rash at injection sites has been documented 5

Malignancy Concerns

Lymphoma

• Postmarketing surveillance reports of non-Hodgkin's lymphoma exist, including cases where lymphoma regressed after drug cessation 1
• The largest study in rheumatoid arthritis did not demonstrate statistically significant increased lymphoma incidence 1

Skin Cancer

• An increased risk of non-melanoma skin cancer (relative risk 1.7,95% CI 1.3-2.2) and melanoma (relative risk 2.6,95% CI 1.0-6.7) has been reported 3
• Regular comprehensive dermatological assessment for skin cancer is recommended before and at regular intervals during therapy, especially in patients at increased baseline risk 3

Other Adverse Effects

Gastrointestinal

• GI dysfunction including vomiting, abdominal pain, and cholecystitis have been reported 3

Metabolic and Endocrine

• Diabetic ketoacidosis, hyperthyroidism, and thyroiditis have been documented 3, 1

Respiratory

• Cough and viral pneumonia have been reported 3
• A very rare syndrome of granulomatous pulmonary inflammation resembling sarcoidosis has been observed 3

Hepatotoxicity

• Elevation in liver transaminases is well recognized, generally transient and asymptomatic 3
• Rare cases of severe hepatitis and acute liver failure resulting in transplantation or death have been reported 3

Critical Monitoring and Patient Education

Pre-Treatment Requirements

• Tuberculin skin testing and chest radiograph 3, 1, 7
• Hepatitis serology 3, 7
• Complete blood count and liver function tests 7, 8
• Assessment for risk factors including histoplasmosis, blastomycosis, or coccidioidomycosis in endemic areas 3

During Treatment Monitoring

• Patients must immediately report fever, cough, aches, chills, or any signs of infection including wound redness/discharge, burning with urination, or gastrointestinal symptoms 3, 1, 7
• Monitor temperature frequently 3
• Report shortness of breath or breathing changes 3

Drug Interactions

• Live vaccines must be avoided during etanercept therapy 3, 1, 7, 8
• Concomitant immunosuppressants (corticosteroids, methotrexate) may compound infection risks 7, 2

Special Populations

Pregnancy and Breastfeeding

• Etanercept is FDA pregnancy category B for all trimesters 3, 1
• Insufficient clinical data exist to confirm safety in breastfeeding 3, 1

High-Risk Patients

• Patients greater than 65 years, those with comorbid conditions, and those taking concomitant immunosuppressants are at greater risk of infection 2
• For HIV-positive patients, exercise particular caution given infection risks 7
• For patients undergoing surgery, discontinue etanercept 2 weeks prior (four half-lives) and restart only when there is no evidence of infection and wound healing is satisfactory 7