Introduction
Humira (adalimumab) is a biologic disease-modifying antirheumatic drug (DMARD) and tumor necrosis factor-alpha (TNF-α) inhibitor approved by the FDA in 2002. It represents a significant advancement in the treatment of various autoimmune and inflammatory conditions by specifically targeting and neutralizing TNF-α, a key cytokine in the inflammatory cascade.
Mechanism of Action
Humira is a recombinant human IgG1 monoclonal antibody that specifically binds to both soluble and membrane-bound TNF-α. By competitively inhibiting TNF-α from binding to its receptors (p55 and p75), adalimumab blocks the pro-inflammatory effects of TNF-α, including neutrophil activation, cytokine production (IL-1, IL-6), adhesion molecule expression, and acute phase reactant production. This results in decreased inflammation and tissue destruction in autoimmune conditions.
Indications
FDA-approved indications include:
- Rheumatoid arthritis (moderate to severe)
- Psoriatic arthritis
- Ankylosing spondylitis
- Crohn's disease (moderate to severe)
- Ulcerative colitis
- Plaque psoriasis
- Juvenile idiopathic arthritis (ages 2+)
- Hidradenitis suppurativa
- Uveitis
Dosage and Administration
Standard dosing:- Most indications: 40 mg subcutaneously every other week
- Some patients may require 40 mg weekly
- Loading dose: 160 mg initially, then 80 mg 2 weeks later (for Crohn's disease)
- Prefilled syringe or autoinjector
- Subcutaneous injection in thigh, abdomen, or upper arm
- Rotate injection sites
- Allow to reach room temperature (15-30 minutes) before injection
- Renal/hepatic impairment: No dose adjustment required
- Elderly: No specific dosing recommendations
- Pediatrics: Weight-based dosing (≥15 kg: 20 mg every other week; ≥30 kg: 40 mg every other week)
Pharmacokinetics
Absorption: Bioavailability approximately 64% following subcutaneous administration Distribution: Volume of distribution: 4.7-6.0 L; does not readily cross blood-brain barrier Metabolism: Cleared via proteolytic degradation throughout the body Elimination: Half-life: 10-20 days (mean 14 days); clearance: 12 mL/hr Steady-state: Achieved in 12-20 weeks with every-other-week dosingContraindications
- Active tuberculosis or other active infections
- History of hypersensitivity to adalimumab or any component
- Severe heart failure (NYHA Class III/IV)
- Active malignancy (except adequately treated non-melanoma skin cancer)
Warnings and Precautions
Black Box Warnings:- Serious infections (bacterial, viral, fungal, opportunistic)
- Increased risk of lymphoma and other malignancies
- Hepatitis B virus reactivation
- Neurologic events (demyelinating disorders)
- Hematologic events (pancytopenia, aplastic anemia)
- Congestive heart failure
- Autoimmunity (lupus-like syndrome)
- Hypersensitivity reactions
- Vaccinations: Avoid live vaccines during therapy
Drug Interactions
- Anakinra: Increased risk of serious infections (avoid combination)
- Abatacept: Increased risk of serious infections (avoid combination)
- Live vaccines: Theoretical risk of disseminated infection
- CYP450 substrates: TNF-α inhibition may affect CYP450 enzyme activity
Adverse Effects
Very common (>10%):- Injection site reactions (erythema, itching, pain, swelling)
- Upper respiratory infections
- Headache
- Rash
- Serious infections (pneumonia, cellulitis)
- Elevated liver enzymes
- Autoantibody formation
- Hypertension
- Sepsis
- Tuberculosis reactivation
- Opportunistic infections
- Demyelinating disorders
- Lymphoma
- Heart failure exacerbation
- Severe hypersensitivity reactions
- Hematologic disorders
Monitoring Parameters
Baseline:- TB screening (PPD or interferon-gamma release assay)
- Hepatitis B and C serology
- Complete blood count
- Comprehensive metabolic panel
- Pregnancy test if applicable
- Vaccination status review
- Signs/symptoms of infection at every visit
- CBC and LFTs every 3-6 months
- Clinical response assessment
- Injection site evaluation
- Annual TB screening in high-risk patients
- Dermatologic examination (psoriasis patients)
- Cardiovascular assessment
Patient Education
- Proper injection technique and site rotation
- Recognition of infection symptoms (fever, cough, unusual fatigue)
- Importance of not missing doses but contacting provider if ill
- Avoidance of live vaccines
- Need for regular monitoring appointments
- Storage requirements (refrigerate at 2-8°C; do not freeze)
- Travel considerations (maintain cold chain)
- Pregnancy planning discussion
- Reporting any new neurological symptoms
- Medication guide review with each prescription
References
1. Humira® (adalimumab) prescribing information. AbbVie Inc. 2021. 2. Singh JA, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res. 2016;68(1):1-25. 3. Lichtenstein GR, et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2018;113(4):481-517. 4. Menter A, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019;80(4):1029-1072. 5. Burmester GR, et al. Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn's disease. Ann Rheum Dis. 2013;72(4):517-524. 6. FDA-approved labeling and postmarketing surveillance data.