What are the indications, dosing regimens, contraindications, adverse effects, monitoring requirements, and alternative therapies for Humira (adalimumab)?

Humira (Adalimumab): Clinical Overview

Humira (adalimumab) is a fully human anti-TNF monoclonal antibody with FDA approval for multiple autoimmune conditions, requiring mandatory pre-treatment screening for tuberculosis and hepatitis B, with the most critical safety concern being serious infections including opportunistic pathogens. 1

FDA-Approved Indications

Adalimumab is approved for the following conditions 1:

• Rheumatoid arthritis (moderate to severe, active disease)
• Psoriatic arthritis
• Ankylosing spondylitis
• Juvenile idiopathic arthritis (ages 2 and older)
• Crohn's disease (adults and pediatric patients ≥6 years)
• Ulcerative colitis (adults and pediatric patients ≥5 years)
• Plaque psoriasis (moderate to severe chronic disease in candidates for systemic therapy)
• Hidradenitis suppurativa (moderate to severe, ages ≥12 years)
• Non-infectious uveitis (intermediate, posterior, and panuveitis in adults and pediatric patients ≥2 years)

Standard Dosing Regimens

Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis

• 40 mg subcutaneously every other week 2, 1
• For RA patients not receiving methotrexate who have inadequate response: may increase to 40 mg weekly or 80 mg every other week 1

Plaque Psoriasis

• Loading dose: 80 mg at week 0
• Maintenance: 40 mg at week 1, then every other week thereafter 2, 1
• Achieves PASI-75 in 80% of patients at 12 weeks, with 68% maintaining response at 60 weeks 2

Crohn's Disease (Adults)

• Day 1: 160 mg (single dose or split over two consecutive days)
• Day 15: 80 mg
• Day 29 and beyond: 40 mg every other week 1

Hidradenitis Suppurativa (Adults)

• Day 1: 160 mg (single dose or split over two consecutive days)
• Day 15: 80 mg
• Day 29 and beyond: 40 mg weekly or 80 mg every other week 1

Dose Escalation Considerations

• Consider escalation from every-other-week to weekly dosing in obese patients or those experiencing disease relapse during treatment cycles 2
• Note increased infection risk with dose escalation 2

Contraindications

There are no absolute contraindications listed in the FDA label 1, however:

• Active serious infections are a critical contraindication in clinical practice 3, 1
• Active viral hepatitis should preclude use 4
• NYHA class III/IV congestive heart failure represents a strong contraindication 3
• Multiple sclerosis or demyelinating diseases should avoid adalimumab 3

Mandatory Pre-Treatment Screening

Tuberculosis Assessment

• Tuberculin skin testing (PPD) and chest radiograph must be obtained before initiating therapy 4, 3
• Consider risk for histoplasmosis, blastomycosis, or coccidioidomycosis in patients living in or visiting endemic areas 4

Hepatitis B Screening

• Hepatitis B serology is mandatory prior to treatment initiation 4, 3
• Reactivation of hepatitis B can occur, particularly with concomitant immunosuppression 4

Cardiac Evaluation

• Echocardiogram for patients with class I/II CHF; avoid if ejection fraction <50% 3
• Evaluate for any history of congestive heart failure 3

Additional Baseline Testing

• Complete blood count (CBC) 3
• Liver function tests (LFTs) 3
• Evaluation for demyelinating diseases 3

Ongoing Monitoring Requirements

Infection Surveillance

• Yearly tuberculosis testing throughout treatment 3
• Periodic history and physical examination focusing on infection symptoms 3
• Patients with viral hepatitis history or chronic carrier states require monitoring for viral reactivation 4

Laboratory Monitoring

• Regular CBC and liver function tests 3
• Anti-double-stranded DNA antibodies if lupus-like symptoms develop 4

Patient Education on Infection Warning Signs

Patients must report immediately 4:

• Fever, cough, aches, chills
• Wound infections with redness, pain, discharge, or pus
• Burning with urination
• Nausea, vomiting, diarrhea
• Shortness of breath or breathing changes

Major Adverse Effects

Serious Infections (Most Critical Safety Concern)

• Rate of serious infections: 2.03 per 100 patient-years in long-term studies 4
• Opportunistic infections include Legionella pneumophila, Pneumocystis jirovecii, and atypical mycobacteria 4
• TB reactivation is a well-documented risk requiring pre-treatment screening 4, 3
• Concomitant prednisone use increases infection risk more than adalimumab itself 4

Autoimmune Phenomena

• Lupus-like reactions: 15 cases reported with adalimumab in comprehensive analysis 4
• Vasculitis: 5 cases reported with adalimumab 4
• Drug-induced lupus is rare but recognized 3

Pulmonary Complications

• Pulmonary fibrosis or exacerbation of underlying fibrosis has been reported 4
• Interstitial pneumonias: at least 18 cases across anti-TNF agents 4
• Paradoxical sarcoidosis can develop during anti-TNF therapy 4

Neurological Events

• CNS demyelination disorders have been sporadically reported 4
• One case of demyelinating disease in 262 patients treated for 3.4 years 4

Cardiovascular

• Worsening or new-onset heart failure can occur 3, 1
• One case of CHF exacerbation in 262 patients over 3.4 years 4

Hematologic

• Cytopenias and pancytopenia: patients should seek immediate medical attention if symptoms develop 3, 1

Malignancy Risk

• Incidence of malignancies greater in adalimumab-treated patients than controls per FDA label 1
• Overall malignancy risk remains unclear and requires ongoing surveillance 4

Common Adverse Effects (>10%)

• Injection site reactions (12% in trials) 4, 3, 1
• Upper respiratory infections and sinusitis 1
• Nasopharyngitis (19% in trials) 4
• Headache 1
• Rash 1

Important Drug Interactions

Contraindicated Combinations

• Live vaccines must be avoided during adalimumab therapy 4, 1

Use with Caution

• Abatacept: increased risk of serious infection 1
• Anakinra: increased risk of serious infection 1

Beneficial Combinations

• Methotrexate or other DMARDs can be combined with adalimumab to increase efficacy, particularly in psoriatic arthritis 2

Pregnancy and Breastfeeding

• FDA Pregnancy Category B for all trimesters 4
• Increased rate of first-trimester miscarriages noted, though some successful pregnancies reported 4
• Insufficient data for breastfeeding safety 4

Alternative Therapies

Other Anti-TNF Agents

• Etanercept: approved for rheumatoid arthritis, psoriasis, juvenile rheumatoid arthritis, and ankylosing spondylitis 4
• Infliximab: similar efficacy profile to adalimumab 5

Conventional DMARDs

• Methotrexate remains first-line for many conditions and can be combined with adalimumab 2, 6
• Other conventional DMARDs should be tried before anti-TNF therapy per clinical guidelines 5

Critical Clinical Pitfalls

Infection Screening Failures

The most dangerous pitfall is initiating adalimumab without proper TB and hepatitis B screening, as reactivation can be life-threatening 4, 3. Always obtain tuberculin skin testing, chest radiograph, and hepatitis serology before the first dose.

Missed Active Infections

Never start adalimumab during active infection 3, 1. If infection develops during treatment, monitor carefully and discontinue if it becomes serious 1.

Inadequate Patient Education

Patients must understand infection warning signs and report fever immediately 4. Temperature monitoring should be routine.

Endemic Fungal Exposure

For patients with systemic illness on adalimumab who reside in or travel to endemic mycosis regions, consider empiric antifungal therapy 1. Don't wait for definitive diagnosis if clinical suspicion is high.