What are the side effects of adalimumab (Humira)?

Adalimumab Side Effects

Adalimumab causes injection site reactions in approximately 15% of patients, and while it increases the risk of serious infections including tuberculosis reactivation, the overall adverse event profile is generally well-tolerated with most events being mild to moderate. 1, 2

Common Side Effects

Injection Site Reactions

• Occur in 15% of adalimumab-treated patients compared to 9% receiving placebo 1
• Manifest as redness, rash, swelling, itching, or bruising at the injection site 2
• Generally do not require treatment discontinuation and typically resolve within the first 2 months of therapy 1
• Most reactions occur during the first month and subsequently decrease in frequency 3

Upper Respiratory and Systemic Effects

• Nasopharyngitis affects 19% of patients in controlled trials 1
• Headaches, dizziness, and vertigo are commonly reported 1
• Upper respiratory tract infections including sinusitis and rhinitis occur frequently 1
• Gastrointestinal upset including nausea and abdominal pain 1, 4
• Musculoskeletal pain, asthenia, and malaise 1
• Rash (non-injection site) 1
• Fatigue 2

Serious Infections

Tuberculosis Risk

• Tuberculosis screening with tuberculin skin testing and chest radiograph is mandatory before initiating therapy 5
• Reactivation of latent TB is the most notable infectious complication 6
• Anti-TNF therapy can cause false-negative M. tuberculosis-specific interferon-gamma testing 1
• Patients developing active TB may present with persistent cough, low-grade fever, weight loss, and wasting 2

Other Serious Infections

• Overall serious infection rate is 2.03 per 100 patient-years in long-term studies 1
• Legionella pneumophila pneumonia (cluster of cases reported) 1
• Pneumocystis jirovecii pneumonia 1
• Atypical mycobacteria 1
• Deep fungal infections including histoplasmosis, coccidioidomycosis, candidiasis, and aspergillosis (particularly in endemic areas) 1, 5
• Sepsis, cellulitis, pyelonephritis, and peritonitis 1
• Herpes zoster 1

Hepatic Effects

• Hepatitis B reactivation can occur in carriers of the virus 2
• Hepatitis B serology is required before treatment initiation 5
• Elevated liver transaminases may occur 1
• Symptoms of hepatitis B reactivation include muscle aches, extreme fatigue, dark urine, jaundice, clay-colored stools, fever, and abdominal discomfort 2

Malignancy Risk

• The risk for malignancy with anti-TNF agents remains unclear 1
• Standardized incidence ratio of 3.19 for lymphomas in some analyses, though similar increases are observed in severe rheumatoid arthritis without biologic interventions 1
• Increased risk of non-melanoma skin cancer: standardized incidence ratio 1.7 (95% CI 1.3-2.2) 1
• Melanoma risk: standardized incidence ratio 2.6 (95% CI 1.0-6.7) 1
• Rare postmarketing cases of hepatosplenic T-cell lymphoma in adolescent and young adult patients with Crohn's disease receiving concomitant azathioprine or 6-mercaptopurine 1

Autoimmune and Immunologic Reactions

Lupus-Like Syndrome

• Fifteen cases of lupus-like reactions reported with adalimumab in systematic analysis 1, 5
• Symptoms include chest discomfort or pain that does not resolve, shortness of breath, joint pain, or rash on cheeks or arms that worsens in sun exposure 2
• Symptoms may improve when adalimumab is stopped 2

Vasculitis

• Five cases of vasculitis reported with adalimumab in detailed analysis 1, 5

New or Worsening Psoriasis

• Some patients develop new psoriasis or worsening of existing psoriasis 2
• Presents as red scaly patches or raised bumps filled with pus 2

Hematologic Effects

• Cytopenias including pancytopenia can occur, though relatively uncommon 5, 4
• Aplastic anemia, isolated leukopenia, and thrombocytopenia have been reported 1
• Symptoms include persistent fever, easy bruising or bleeding, or pallor 1, 2
• Thromboembolic events have a hazard ratio of 7.6 in patients developing anti-adalimumab antibodies 5, 4
• The American Society of Clinical Oncology recommends hematology consultation for serious hematologic effects and potential treatment discontinuation 5, 4

Pulmonary Complications

• Pulmonary fibrosis can occur as new event or exacerbation of underlying fibrosis 1, 5
• Interstitial pneumonias reported in at least 18 patients receiving anti-TNF agents 1, 5
• Paradoxical sarcoidosis cases reported (mechanism unclear) 1, 5

Neurologic Effects

• CNS events including demyelination disorders sporadically reported 1
• Symptoms include numbness or tingling, vision problems, weakness in arms or legs, and dizziness 2
• Incidence rate of 0.08 per 100 patient-years for demyelinating disorders 1

Cardiovascular Effects

• New heart failure or worsening of existing heart failure 2
• Incidence rate of 0.28 per 100 patient-years for congestive cardiac failure 1
• Symptoms include shortness of breath, sudden weight gain, and swelling of ankles or feet 2

Pregnancy and Lactation

• FDA Category B for all trimesters 1, 5
• Increased rate of first trimester miscarriages reported 1, 5
• Insufficient data to establish safety in breastfeeding; antibodies are secreted in milk 5

Serious Adverse Events and Withdrawals

• Serious adverse events occurred in 8% of adalimumab patients versus 14% of placebo patients 7
• Withdrawal due to adverse events: 7% with adalimumab versus 13% with placebo 7
• Overall adverse event rate (87%) similar to placebo (85%) 7

Critical Monitoring Requirements

Before initiating therapy:

• Tuberculin skin testing and chest radiograph 5
• Hepatitis B serology 5

Patient education priorities:

• Report fever or signs of infection immediately 5
• Avoid live vaccines during therapy 5
• Seek immediate care for persistent injection site reactions beyond a few days 2