Adalimumab

Tumor necrosis factor (TNF) inhibitor Monoclonal antibody Disease-modifying antirheumatic drug (DMARD) Biologic response modifier

Adalimumab is a fully human monoclonal antibody that binds specifically to TNF-α: • Neutralizes TNF-α by blocking its interaction with p55 and p75 cell surface receptors • Modulates biological responses induced by TNF-α including leukocyte migration • Reduces serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) • Decreases endothelial adhesion molecule expression • Inhibits matrix metalloproteinases involved in tissue destruction

Absorption: Bioavailability ~64% following subcutaneous administration; peak serum concentration occurs 5 days post-dose Distribution: Volume of distribution 4.7-6.0 L; limited extravascular distribution Metabolism: Proteolytically degraded throughout the body; no specific organ clearance Excretion: Primarily via the reticuloendothelial system Half-life: 10-20 days (mean 14 days)

• Rapid reduction in inflammatory markers (CRP, ESR) • Decreases serum IL-6 levels by 50-60% • Reduces circulating lymphocyte counts • Improves endothelial function within 4 weeks • Clinical response typically seen within 2-12 weeks

• Rheumatoid Arthritis: Reduces signs/symptoms and inhibits structural damage in moderate to severe cases • Psoriatic Arthritis: Treatment of active arthritis and inhibition of structural damage • Ankylosing Spondylitis: Reduces signs/symptoms in active disease • Crohn's Disease: Treatment of moderate to severe disease in patients with inadequate response to conventional therapy • Ulcerative Colitis: Treatment of moderately to severely active disease • Plaque Psoriasis: Treatment of chronic severe cases • Hidradenitis Suppurativa: Treatment of moderate to severe disease • Uveitis: Treatment of non-infectious intermediate, posterior, and panuveitis • Juvenile Idiopathic Arthritis: Treatment of moderate to severe polyarticular disease in patients ≥2 years

Absolute: • Active tuberculosis or other serious infections • Hypersensitivity to adalimumab or any component Relative: • Moderate to severe heart failure (NYHA class III/IV) • Demyelinating disorders • History of lymphoma or other malignancies • Chronic or recurrent infections

Rheumatoid Arthritis/Psoriatic Arthritis/Ankylosing Spondylitis: 40 mg SC every other week Crohn's Disease: Initial 160 mg at day 1, 80 mg at day 15, then 40 mg every other week Ulcerative Colitis: Initial 160 mg at day 1, 80 mg at day 15, then 40 mg every other week Plaque Psoriasis: Initial 80 mg, then 40 mg every other week starting one week after initial dose Hidradenitis Suppurativa: Initial 160 mg, then 80 mg at week 2, then 40 mg weekly Uveitis: Initial 80 mg, then 40 mg every other week Juvenile Idiopathic Arthritis (≥30 kg): 40 mg every other week

Pediatric: Approved for JIA ≥2 years; weight-based dosing for children <30 kg Geriatric: Increased risk of serious infections; monitor closely Renal impairment: No dose adjustment required Hepatic impairment: No dose adjustment required

Common (>10%): • Injection site reactions (erythema, itching, pain) • Upper respiratory infections • Headache • Rash Serious (<1%): • Tuberculosis reactivation • Invasive fungal infections • Lymphoma and other malignancies • Heart failure exacerbation • Demyelinating disorders • Lupus-like syndrome • Severe allergic reactions

• Methotrexate: Reduces adalimumab clearance by 29-44% • Anakinra: Increased risk of serious infections • Abatacept: Increased risk of adverse reactions • Live vaccines: Contraindicated due to immunosuppression • Other TNF blockers: Increased toxicity without added benefit

• Black Box Warning: Serious infections leading to hospitalization or death • Black Box Warning: Lymphoma and other malignancies reported • Increased risk of HBV reactivation • May worsen heart failure • Autoantibody formation with potential for lupus-like syndrome • Hematologic reactions including pancytopenia

Pregnancy: FDA Category B - No adequate human studies; use only if clearly needed Lactation: Human IgG excreted in milk; potential for absorption in infant unknown

• Baseline TB test (PPD or IGRA) and chest X-ray • Periodic CBC with differential • Liver function tests • Signs of infection • Clinical response assessment • Autoantibody development in prolonged therapy • Lipid profile changes

• Proper injection technique and site rotation • Recognition of infection symptoms • Importance of adherence to dosing schedule • Avoidance of live vaccines • Reporting of persistent fever or unusual symptoms • Storage requirements (refrigeration) • Pregnancy planning considerations

• Refrigerate at 2-8°C (36-46°F) • Protect from light • Do not freeze • May be stored at room temperature (up to 25°C/77°F) for maximum 14 days • Do not use if liquid is discolored or contains particles

• Always screen for latent TB before initiation • Consider concomitant methotrexate to reduce immunogenicity • Monitor for paradoxical psoriasis in treated patients • Higher trough levels correlate with better clinical response • Loss of response may require dose intensification • Consider checking drug/antibody levels in non-responders

• Adalimumab (Humira) Package Insert. AbbVie Inc. Revised 2023 • Singh JA, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res. 2016 • Hanauer SB, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002 • FDA Drug Safety Communication: TNF blockers - updated safety warnings. FDA.gov 2021