What is the difference between Enbrel (etanercept) and Humira (adalimumab) in terms of treatment?

Enbrel vs Humira: Key Differences

Both Enbrel (etanercept) and Humira (adalimumab) are effective TNF antagonists with similar indications, but Enbrel has a more favorable tolerability profile with lower withdrawal rates (0.4% vs 0.3% monthly) and fewer serious adverse events (0.6% vs 0.5% monthly), while Humira demonstrates slightly faster onset of action and comparable long-term efficacy. 1

Mechanism of Action Differences

Enbrel is a soluble TNF receptor fusion protein, while Humira is a fully human monoclonal antibody, resulting in distinct pharmacologic properties:

• Etanercept (Enbrel) is a genetically engineered fusion protein composed of the extracellular portions of human TNFR2 (p75) fused to the Fc domain of human IgG1 1
• Adalimumab (Humira) is a fully human monoclonal antibody (100% human protein) that directly binds TNF-alpha 2, 3
• Both agents bind soluble and transmembrane forms of TNF, but etanercept additionally binds lymphotoxin family members (LTα3 and LTα2β1), though the clinical significance remains unclear 1
• These structural differences likely account for observed variations in efficacy, adverse event profiles, and immunogenicity 1

Administration and Dosing

Enbrel offers more flexible dosing options with subcutaneous administration, while Humira follows a standardized every-other-week schedule:

• Enbrel: 25 mg twice weekly OR 50 mg once weekly (up to 24 weeks), OR 50 mg twice weekly up to 12 weeks then reduced to once weekly 1
• Humira: 80 mg at week 0, then 40 mg at week 1, followed by 40 mg every other week 1
• Both are administered subcutaneously, eliminating the need for infusion center visits required with infliximab 1

Efficacy Comparison

Enbrel demonstrates slower onset but sustained efficacy, while Humira shows comparable long-term response rates:

• Etanercept achieves PASI 75 in 34% (25 mg biweekly) and 48% (50 mg biweekly) at 12 weeks, improving to 43% and 57% respectively at 6 months 1
• Clinically significant improvement with etanercept becomes evident between 4-8 weeks after initiation 1
• Direct comparison data suggest comparable efficacy between the two agents for chronic plaque psoriasis 1
• Continuous therapy with etanercept provides better disease control than interrupted therapy, with median time to relapse of 85-91 days after discontinuation 1

Safety and Tolerability Profile

Enbrel demonstrates superior tolerability with lower withdrawal rates and fewer injection site reactions:

• Monthly withdrawal rates: Etanercept 0.4% (range 0.3-1.4) vs Adalimumab 0.3% 1
• Serious adverse events: Etanercept 0.6% monthly vs Adalimumab 0.5% monthly 1
• Injection site reactions: Etanercept has standard rates vs Adalimumab 1.5% (uncommon due to less frequent dosing) 1
• Relative risk of adverse events compared to placebo: Etanercept 1.05 vs Adalimumab data not included in meta-analysis 1

Infection Risk Differences

Adalimumab carries higher tuberculosis reactivation risk compared to etanercept, requiring more vigilant screening:

• TB incidence in RA patients: Etanercept 39 per 100,000 patient-years vs Adalimumab 171 per 100,000 patient-years 1
• Median time to TB diagnosis: Etanercept 11.5 months vs Adalimumab 4-6 months 1
• Adalimumab serious infection rate: 2.03 per 100 patient-years in long-term studies 4
• Both require mandatory TB screening with tuberculin skin testing and chest radiograph before initiation 1, 4
• Risk of atypical infections including Legionella, Pneumocystis jirovecii, and deep fungal infections exists with both agents 4

Immunogenicity

Adalimumab demonstrates lower antibody formation rates, potentially due to its fully human structure:

• Adalimumab: Neutralizing antibodies develop in approximately 5% of patients, associated with poorer therapeutic response 1
• Thromboembolic events have a hazard ratio of 7.6 in patients developing anti-adalimumab antibodies 4
• Etanercept immunogenicity data less extensively reported in available guidelines 1

Clinical Selection Criteria

For stable chronic plaque psoriasis, both etanercept and adalimumab are recommended as first-choice TNF antagonists based on favorable risk/benefit profiles:

• Both agents are appropriate first-line biologic therapy for patients meeting treatment criteria (PASI ≥10, DLQI >10, failed/contraindicated conventional systemic therapy) 1
• Choice should be based on clinical need with careful assessment of individual patient risks and benefits 1
• Consider etanercept in patients at higher TB risk given lower reactivation rates 1
• Consider adalimumab when less frequent dosing is preferred for adherence 1

Monitoring Requirements

Both agents require similar pre-treatment screening and ongoing surveillance:

• Pre-treatment: TB screening (tuberculin skin test and chest X-ray), hepatitis B serology 1, 4
• Adalimumab specifically requires intermittent monitoring of blood counts and liver function due to reported pancytopenia and elevated transaminases 3
• Patient education priorities include reporting fever, infection signs, and avoiding live vaccines during therapy 4

Special Populations

Adalimumab is FDA Category B for pregnancy, while safety data for etanercept in pregnancy requires similar caution:

• Adalimumab: FDA Category B for all trimesters, with increased first trimester miscarriage rate reported 4
• Safety in breastfeeding unknown for both agents, with antibodies secreted in milk 4
• Etanercept approved for children >8 years at 0.8 mg/kg up to maximum 50 mg weekly 1