What is the recommended use and dosage of Adalimumab (adalimumab) for treating inflammatory conditions?

Adalimumab: Recommended Use and Dosing for Inflammatory Conditions

Standard Dosing Regimens

For most inflammatory conditions, adalimumab is administered as 40 mg subcutaneously every other week, with specific loading doses required for certain indications. 1, 2

Psoriatic Arthritis

• 40 mg subcutaneously every other week is the standard maintenance dose 3, 1
• No loading dose required for psoriatic arthritis 3
• Can be combined with methotrexate, though prospective trials comparing combination versus monotherapy have not been adequately powered in psoriatic arthritis 3
• ACR20 response achieved in 57% of patients at 24 weeks (compared to 15% with placebo) 3
• ACR50 and ACR70 responses were 39% and 23% respectively at 24 weeks 3

Plaque Psoriasis

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

Rheumatoid Arthritis

• 40 mg subcutaneously every other week 2, 4
• Combination with methotrexate (12.5-25 mg) is considered standard of care and increases efficacy 3, 4
• Mean steady-state trough concentrations are 5 mcg/mL as monotherapy and 8-9 mcg/mL with concomitant methotrexate 2
• Rapid onset: ACR20 response achieved in 25% at week 1,52% at week 4, and 67% at week 24 4

Inflammatory Bowel Disease

• Crohn's Disease: Loading dose of 160 mg at week 0, followed by 80 mg at week 2 2, 5

• Maintenance: 40 mg every other week 2, 5

• Mean trough concentrations approximately 12 mcg/mL at weeks 2 and 4, with steady-state of 7 mcg/mL at weeks 24 and 56 2

• Ulcerative Colitis: Same loading regimen (160 mg/80 mg) 2

• Maintenance: 40 mg every other week or weekly for more severe disease 2

• Mean steady-state concentrations are 8 mcg/mL with every-other-week dosing and 15 mcg/mL with weekly dosing 2

Hidradenitis Suppurativa

• Loading: 160 mg at week 0, followed by 80 mg at week 2 2
• Maintenance: 40 mg weekly (note: more frequent than other indications) 1, 2
• Mean steady-state trough concentrations 7-11 mcg/mL during weekly treatment 2

Dose Escalation Strategies

Consider escalating from 40 mg every other week to 40 mg weekly in patients with inadequate response, particularly in obese patients or those experiencing disease relapse during the treatment cycle. 1

• This escalation strategy carries a potentially increased risk of infection 1
• For juvenile idiopathic arthritis-associated uveitis, dose escalation can occur 8 weeks after initiation if uveitis remains uncontrolled 1

Mandatory Baseline Monitoring

Before initiating adalimumab, the following screening is required: 1, 6

• Tuberculosis testing (PPD or interferon-gamma release assay) - critical due to reactivation risk 6, 7
• Complete blood count (CBC) 6
• Liver function tests (LFT) 6
• Hepatitis B screening in appropriate clinical settings 6
• Evaluation for demyelinating diseases (history of multiple sclerosis or similar conditions) 6
• Congestive heart failure assessment - echocardiogram if class I/II CHF present; avoid if ejection fraction <50% 6

Ongoing Monitoring Requirements

During treatment, perform the following: 1, 6

• Periodic history and physical examination focusing on signs of infection 1, 6
• Yearly tuberculosis testing 1, 6
• Regular CBC and liver function tests (frequency not strictly defined but intermittent monitoring recommended) 6, 7

Critical Safety Considerations and Contraindications

Absolute contraindications: 6

• Active, serious infections 6
• NYHA class III/IV congestive heart failure 6

Relative contraindications and cautions: 6, 7

• Multiple sclerosis or other demyelinating diseases 6
• History of lymphoma 7
• Concurrent live vaccines (avoid) 6

Two-fold increased risk of serious infections compared to placebo, including tuberculosis reactivation, deep fungal infections, and atypical infections 7

Common and Serious Adverse Events

Most common: 6, 7

• Injection site reactions (generally mild to moderate) 6, 7
• Rash 6
• Back pain 6

Rare but serious: 6, 7

• Drug-induced lupus 6, 7
• Cytopenias (including pancytopenia) 6, 7
• Exacerbation of congestive heart failure 6, 7
• Lymphoma promotion 7
• Worsening of neurological disease 7

Pharmacokinetic Considerations

Terminal half-life is approximately 2 weeks (10-20 days), with time to maximum concentration of 5.5 days after subcutaneous administration. 2

• Absolute bioavailability is 64% following subcutaneous injection 2
• Anti-adalimumab antibodies reduce serum concentrations and efficacy 2
• Methotrexate reduces adalimumab clearance by 29-44%, explaining improved efficacy with combination therapy 2

Clinical Efficacy Benchmarks

If inadequate efficacy is observed after 3 months, discontinue adalimumab as continued treatment is unlikely to provide benefit. 8

• Sustained ACR responses maintained up to 30 months with methotrexate combination and up to 5 years as monotherapy 4
• Radiographic progression of joint damage significantly inhibited (mean Sharp score change -0.2 with adalimumab versus 1.0 with placebo) 3
• Significant improvements in quality of life measures (HAQ improvement -0.4 versus -0.1 with placebo) 3