What are the secondary effects of Brenzys (etanercept)?

Secondary Effects of Brenzys (Etanercept)

The most common adverse effects of Brenzys (etanercept) are injection site reactions occurring in up to 37% of patients, though most are mild to moderate and self-limiting, while the most serious risks include opportunistic infections (particularly tuberculosis reactivation), hepatitis B reactivation, and rare but significant neurological complications such as demyelinating disorders. 1

Most Common Adverse Effects

Injection Site Reactions

• Injection site reactions occur in 14-67.7% of patients and represent the most frequent adverse effect 1, 2
• These reactions are typically mild to moderate, diminish with ongoing therapy, and do not correlate with antibody development 1
• Serious injection site reactions can rarely occur, including necrotizing fasciitis, though this is extremely uncommon 1

General Systemic Effects

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

Serious Infectious Complications

Tuberculosis Reactivation

• Reactivation of latent TB is a significant concern, with extrapulmonary involvement occurring in approximately 50% of cases 1
• Etanercept appears to carry lower TB reactivation risk compared to monoclonal TNF antagonists (infliximab and adalimumab) 1
• Tuberculin skin testing and chest radiograph are mandatory before initiating therapy 1, 4

Other Opportunistic Infections

• Documented infections include endemic fungi, atypical mycobacteria, candidiasis, aspergillosis, cytomegalovirus, herpes zoster, Pneumocystis, and Listeria monocytogenes 1
• Serious infections reported include pneumonia, bronchitis, peritonitis, septicemia, pyelonephritis, cellulitis, and systemic fungal infections 1
• Infection risk increases substantially when etanercept is combined with other immunosuppressants 1

Hepatitis B Reactivation

• Patients with chronic HBV infection or positive surface antigen are at risk for viral reactivation 1
• Reactivation typically occurs with concomitant immunomodulatory agents and responds to drug withdrawal and/or antiviral therapy 1

Autoimmune and Inflammatory Complications

Lupus-Like Syndrome

• A syndrome resembling lupus erythematosus has been reported 1
• Antinuclear antibodies develop in up to 11% of patients, though they rarely lead to overt autoimmune disease during short- to medium-duration use 1

Vasculitis

• Leukocytoclastic vasculitis has been associated with etanercept therapy 1

Rare Pulmonary Inflammation

• A very rare syndrome of granulomatous pulmonary inflammation resembling sarcoidosis has been reported 1

Neurological Complications

Demyelinating Disorders

• CNS demyelination, including optic neuritis, transverse myelitis, and Guillain-Barré syndrome, have been observed in postmarketing reports 1
• While de novo demyelination rates do not exceed baseline population rates, well-described cases exist in patients with preexisting multiple sclerosis 1
• Etanercept is contraindicated in patients with active demyelinating diseases 4

Cardiovascular Effects

Congestive Heart Failure

• Etanercept has not been convincingly linked to the increased mortality seen with infliximab in heart failure patients 1
• Two large trials showed no benefit and no clear indication of increased mortality in established heart failure 1
• However, case reports of de novo cardiac failure or worsening preexisting cardiac dysfunction exist 1
• Etanercept must be avoided in severe congestive heart failure (NYHA class III or IV) 4

Hematologic Toxicities

• Blood dyscrasias including anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and hemophagocytic syndrome have been reported 1
• These associations are primarily based on case reports with weak strength of association 1

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
• Baseline lymphoma incidence is already elevated in chronic inflammatory diseases treated with etanercept 1

Skin Cancer

• Increased risk of non-melanoma skin cancer has been reported with TNF inhibitors as a class 1
• Regular comprehensive dermatological assessment is recommended, especially in high-risk patients 1

Other Malignancies

• Other malignancies do not appear more frequent in etanercept-treated individuals 1

Metabolic and Endocrine Effects

• Diabetic ketoacidosis, hyperthyroidism, and thyroiditis have been reported 1
• The strength of association for these effects is extremely weak, based primarily on case reports 1

Gastrointestinal Effects

• GI dysfunction including vomiting, abdominal pain, and cholecystitis has been reported 1

Other Rare Complications

• Septic arthritis and optic neuritis have been documented 1
• Cough and viral pneumonia are possible adverse effects 1

Critical Monitoring Requirements

Pre-Treatment Screening

• Tuberculin skin testing and chest radiograph are mandatory 1, 4
• Hepatitis B serology, complete blood count, and liver function tests required 4
• Consider endemic fungal infection risk (histoplasmosis, blastomycosis, coccidioidomycosis) in relevant geographic areas 1, 4

During Treatment

• Patients must immediately report fever, cough, aches, chills, or any signs of infection 1, 4
• Monitor for viral reactivation in patients with chronic viral hepatitis 4
• Live vaccines must be avoided during therapy 1, 4

Pregnancy and Breastfeeding

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

Important Clinical Caveats

• Most reported toxicities are associations based on case reports or FDA Adverse Event Reporting System reports, with extremely weak strength of association for many 1
• The therapeutic advantages of etanercept generally outweigh side effects when appropriately monitored 5
• Withdrawal rates due to adverse events are lower with etanercept compared to other biologics 6