adalimumab
Summary
Adalimumab is a fully human monoclonal antibody that binds and neutralizes TNF-α, blocking its inflammatory effects. It is used to treat autoimmune conditions such as rheumatoid arthritis, ankylosing spondylitis, psoriasis/psoriatic arthritis, and inflammatory bowel disease (Crohn's disease, ulcerative colitis). Major risks include reactivation of latent infections (TB, hepatitis B) and increased susceptibility to infections.
Detail
Adalimumab is a TNF-α inhibitor (biologic DMARD) that works by binding soluble and membrane-bound TNF-α, preventing it from interacting with its receptors (TNFR1/TNFR2) on cell surfaces, thereby reducing downstream inflammatory signaling, leukocyte migration, and cytokine cascades that drive autoimmune tissue damage. Unlike infliximab (chimeric antibody) or etanercept (fusion protein), adalimumab is fully humanized, which reduces immunogenicity.
Clinical uses: rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease, ulcerative colitis, and hidradenitis suppurativa. It is often used when conventional DMARDs (e.g., methotrexate) fail or are contraindicated.
Mechanism-related adverse effects: Because TNF-α is critical for granuloma formation and immune surveillance against intracellular pathogens, TNF inhibitors increase risk of reactivation of latent tuberculosis and hepatitis B, as well as risk of serious bacterial and fungal infections (e.g., histoplasmosis). Screening for latent TB (PPD/IGRA) and hepatitis B is mandatory before starting therapy. Other risks include increased risk of lymphoma (rare), demyelinating disease (can unmask/worsen MS), heart failure exacerbation, and drug-induced lupus (anti-histone antibodies, unlike idiopathic lupus which shows anti-dsDNA).
High-yield associations: TNF-alpha inhibitors as a class = adalimumab, infliximab, etanercept, certolizumab, golimumab. Boards often test recognition of TNF-inhibitor use in IBD/RA/psoriasis with subsequent TB reactivation or infection as a complication. Also tested: pre-treatment screening requirements.
Sources
- First Aid for the USMLE Step 1
- Katzung's Basic and Clinical Pharmacology
- UpToDate: TNF-alpha inhibitors
- Robbins Basic Pathology
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