What are the potential side effects of Humira (adalimumab)?

Humira (Adalimumab) Side Effects

Humira carries significant risks including serious infections (particularly tuberculosis reactivation), injection site reactions, and rare but serious complications such as heart failure exacerbation, lupus-like syndrome, blood disorders, liver problems, and nervous system demyelination. 1

Common Side Effects

• Injection site reactions are the most frequent adverse effect, including redness, rash, swelling, itching, or bruising that typically resolve within a few days 1, 2
• Upper respiratory infections including sinus infections occur commonly 1
• Headaches are frequently reported 1
• Rash can develop during treatment 1
• Gastrointestinal symptoms including nausea and upset stomach are associated with adalimumab 3

Serious Infectious Complications

Tuberculosis reactivation is the most notable infectious complication requiring mandatory pre-treatment screening with tuberculin skin testing and chest radiograph 4, 3, 1. The TB reactivation risk is 171 per 100,000 patient-years, which is higher than with other TNF antagonists like etanercept 5.

• Serious infection rate is 2.03 per 100 patient-years in long-term studies 4, 3
• Atypical infections include Legionella pneumophila pneumonia, Pneumocystis jirovecii pneumonia, and atypical mycobacteria 3
• Deep fungal infections particularly in endemic areas (histoplasmosis, blastomycosis, coccidioidomycosis) 4, 2
• Hepatitis B reactivation can occur in carriers, requiring pre-treatment hepatitis serology and monitoring during and after therapy 4, 3, 1

Patients must report fever, cough that doesn't resolve, low-grade fever, weight loss, or any signs of infection immediately 1.

Autoimmune and Inflammatory Reactions

• Lupus-like syndrome has been reported in 15 patients treated with adalimumab, presenting with chest discomfort, shortness of breath, joint pain, or rash on cheeks/arms that worsens in sun 4, 3, 1
• Vasculitis documented in five cases with adalimumab 4, 3
• New or worsening psoriasis can paradoxically occur, presenting as red scaly patches or raised bumps filled with pus 1

Pulmonary Complications

• Pulmonary fibrosis can occur as a new event or exacerbation of underlying fibrosis 4, 3
• Interstitial pneumonias have been reported in at least 18 patients receiving anti-TNF agents 4, 3
• Sarcoidosis cases reported with unclear mechanism 4, 3

Hematologic Complications

• Cytopenias including pancytopenia can occur, though relatively uncommon 3, 2
• Blood cell production problems may manifest as persistent fever, easy bruising/bleeding, or pallor 1
• Thromboembolic events have a hazard ratio of 7.6 in patients developing anti-adalimumab antibodies 3

The American Society of Clinical Oncology recommends hematology consultation for serious hematologic effects and potential treatment discontinuation 3.

Cardiovascular Complications

• New heart failure or worsening of existing heart failure requires immediate reporting if shortness of breath, sudden weight gain, or ankle/feet swelling develops 1

Neurological Complications

• CNS demyelination is a rare but serious side effect, with cases of multiple sclerosis or demyelinating patterns reported 4, 6
• Nervous system problems include numbness, tingling, vision problems, weakness in arms/legs, and dizziness 1

Hepatic Complications

• Liver problems can lead to liver failure and death, requiring immediate reporting of fatigue, poor appetite, vomiting, jaundice, or right upper quadrant pain 1
• Elevated transaminases have been reported, suggesting intermittent monitoring of liver function is useful 2

Allergic Reactions

• Serious allergic reactions can occur with hives, trouble breathing, or swelling of face, eyes, lips, or mouth requiring immediate medical attention 1

Pregnancy and Lactation Considerations

• FDA Category B for all trimesters, but increased first trimester miscarriage rate has been reported 4, 3
• Safety in breastfeeding unknown with antibodies secreted in milk; caution recommended 3

Critical Monitoring Requirements

Pre-treatment screening must include: 4, 3

• Tuberculin skin testing and chest radiograph
• Hepatitis B serology
• Assessment for endemic fungal infection risk based on geographic location

During treatment: 4, 3

• Monitor for signs of infection continuously
• Avoid live vaccines
• Check temperature frequently
• Hepatitis B carriers require ongoing viral monitoring

Important Clinical Pitfalls

The two-fold risk of serious infections should not be minimized—adalimumab should never be used during active infection 2. Patients must understand the importance of immediately reporting any signs of infection, as immunosuppressed individuals require prompt, aggressive treatment 7. The higher tuberculosis reactivation risk compared to other TNF antagonists necessitates more vigilant screening 5.