Humira (Adalimumab) Side Effects and Monitoring
Humira carries significant risks of serious infections (particularly tuberculosis reactivation), injection site reactions, and rare but serious complications including malignancies, hematologic disorders, and autoimmune phenomena that require mandatory pre-treatment screening and ongoing vigilance. 1, 2, 3
Most Common Side Effects
Injection site reactions are the most frequent adverse effect, occurring in 15% of patients compared to 9% receiving placebo. 2, 4 These typically manifest as:
- Redness, rash, swelling, itching, or bruising at injection sites 2, 3
- Most reactions occur during the first month and diminish with continued therapy 4
- Generally do not require discontinuation and resolve within the first 2 months 2, 4
Infectious complications include:
- Nasopharyngitis (19% of patients) 2
- Upper respiratory infections including sinusitis and rhinitis 2, 3
- Headaches, dizziness, and vertigo 2
- Gastrointestinal upset including nausea and abdominal pain 2
Serious Infections (Critical Safety Concern)
The overall serious infection rate is 2.03 per 100 patient-years. 1, 2 Life-threatening infections include:
- Tuberculosis reactivation - the most notable infectious complication requiring mandatory screening 1, 5
- Legionella pneumophila pneumonia 2
- Pneumocystis jirovecii pneumonia 2
- Atypical mycobacteria 2
- Deep fungal infections (histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis) particularly in endemic areas 2
- Sepsis, cellulitis, pyelonephritis, peritonitis 2
- Herpes zoster 2
Malignancy Risk
The malignancy risk with anti-TNF agents remains unclear but appears elevated for certain cancers. 1, 2
- Lymphoma: standardized incidence ratio of 3.19 in some analyses 2
- Non-melanoma skin cancer: standardized incidence ratio 1.7 (95% CI 1.3-2.2) 2
- Melanoma: standardized incidence ratio 2.6 (95% CI 1.0-6.7) 2, 6
- Rare hepatosplenic T-cell lymphoma in adolescents/young adults with Crohn's disease receiving concomitant azathioprine or 6-mercaptopurine 2, 3
Hematologic Complications
Cytopenias can occur and may be life-threatening. 2, 7
- Pancytopenia, aplastic anemia, isolated leukopenia, and thrombocytopenia 2, 8
- Thromboembolic events have a hazard ratio of 7.6 in patients developing anti-adalimumab antibodies 2, 7
- The American Society of Clinical Oncology recommends hematology consultation for serious hematologic effects and potential treatment discontinuation 2, 7
Autoimmune Reactions
Adalimumab can paradoxically induce autoimmune phenomena: 1, 2
- Lupus-like syndrome (15 cases reported with adalimumab) 1, 2
- Vasculitis (5 cases reported with adalimumab) 1, 2
- Anti-double-stranded DNA antibodies should be measured if lupus-like symptoms develop 1
Pulmonary Complications
Paradoxical pulmonary disease can occur: 1, 2
- Pulmonary fibrosis as new event or exacerbation of underlying fibrosis 1, 2
- Interstitial pneumonias (at least 18 cases with anti-TNF agents) 1, 2
- Paradoxical sarcoidosis (mechanism unclear) 1, 2
Neurologic Effects
CNS demyelination disorders have been sporadically reported with an incidence rate of 0.08 per 100 patient-years. 1, 2 Symptoms include numbness, tingling, vision problems, weakness in extremities, and dizziness. 3
Cardiovascular Effects
New or worsening congestive heart failure occurs at 0.28 per 100 patient-years. 2 Patients should report shortness of breath, sudden weight gain, or ankle/feet swelling immediately. 3
Hepatic Effects
Hepatitis B reactivation is a critical risk. 1, 2
- Patients with chronic HBV infection or carriers are at risk for reactivation 1
- Elevated liver transaminases may occur 2, 5
- Liver problems can lead to liver failure and death 3
Pregnancy and Lactation
FDA Category B for all trimesters, but increased first trimester miscarriage rate reported. 1, 2 Insufficient data exist to establish safety in breastfeeding. 1, 2
Mandatory Pre-Treatment Screening
Before initiating adalimumab, the following must be completed: 1, 2
- Tuberculosis screening: Tuberculin skin testing and chest radiograph 1, 2
- Consider risk for histoplasmosis, blastomycosis, or coccidioidomycosis in endemic areas 1
- Hepatitis B serology 1, 2
Ongoing Monitoring Requirements
Patients with viral hepatitis history or chronic carrier states require monitoring for viral reactivation throughout therapy. 1
Live vaccines must be avoided during adalimumab therapy. 1, 2
Critical Patient Education
Patients must immediately report: 1, 3
- Fever or temperature elevation 1
- Signs of infection: cough, aches, fever, chills, wound redness/discharge, burning with urination, nausea, vomiting, diarrhea 1
- Shortness of breath or breathing changes 1
- Injection site reactions that worsen or persist beyond a few days 3
Common Pitfalls to Avoid
Do not minimize the two-fold risk of serious infections - this is a clinically significant increase requiring careful patient selection and monitoring. 5
Do not use adalimumab during active infections. 5
Consider intermittent laboratory monitoring of blood counts and liver function despite lack of formal requirements, given reports of pancytopenia and elevated transaminases. 5