Immunology / Multiple Specialties · Medicine Class
Targeted binding and neutralization or activation of specific proteins — cytokines, receptors, cell surface antigens, growth factors
Biologics are medicines derived from living cells or biological systems — in contrast to small-molecule drugs synthesized by chemical processes. Monoclonal antibodies (mAbs) are the largest class: engineered proteins that bind to a single specific antigen with high affinity. mAb names encode origin: -ximab (chimeric: mouse variable/human constant), -zumab (humanized), -umab (fully human), -mab (various origins). Biologics also include recombinant proteins (erythropoietin, insulin, filgrastim), fusion proteins (etanercept: TNF receptor fused to IgG Fc), and newer modalities (bispecific antibodies, antibody-drug conjugates, CAR-T cells). Target selection determines indication: anti-TNF-α agents suppress inflammation in autoimmune disease; anti-IL-17, anti-IL-23 agents treat psoriasis and IBD; anti-VEGF agents inhibit tumor angiogenesis; anti-CD20 depletes B cells in lymphoma and autoimmune conditions.
Adalimumab (Humira)
Fully human anti-TNF-α mAb. World's best-selling drug for over a decade. Used in RA, psoriasis, IBD, AS, PsA, juvenile idiopathic arthritis, uveitis. 2023: major biosimilars entered US market (Hadlima, Hyrimoz, etc.), dramatically reducing costs.
Infliximab (Remicade)
Chimeric anti-TNF-α mAb (IV infusion). First biologic approved for Crohn's disease. Also RA, UC, psoriasis, PsA, AS. Multiple biosimilars available (Inflectra, Renflexis).
Pembrolizumab (Keytruda)
Anti-PD-1 checkpoint inhibitor. Approved in 30+ cancer indications. First tumor-agnostic approval (MSI-H tumors). Immune-related adverse events require careful monitoring.
Trastuzumab (Herceptin)
Anti-HER2 mAb. Transformed HER2+ breast and gastric cancer outcomes. Cardiotoxicity requires LVEF monitoring. Many biosimilars now available.
Rituximab (Rituxan)
Anti-CD20 mAb depleting B cells. Used in lymphoma, CLL, RA, vasculitis, multiple sclerosis (ocrelizumab successor in MS). HBV reactivation risk — screen before treatment.
Dupilumab (Dupixent)
Anti-IL-4Rα mAb blocking IL-4 and IL-13 signaling. Approved for atopic dermatitis, asthma, CRS with nasal polyps, eosinophilic esophagitis. Very favorable safety profile — conjunctivitis most notable side effect.
Secukinumab (Cosentyx)
Anti-IL-17A mAb. Effective for plaque psoriasis, psoriatic arthritis, ankylosing spondylitis. Watch for worsening IBD (IL-17 inhibitors may exacerbate IBD).
Evolocumab (Repatha)
Anti-PCSK9 mAb. Reduces LDL by 50-60% on top of maximally-tolerated statin. FOURIER trial: CV event reduction. Very high cost (though falling with competition from alirocumab, inclisiran).
Live vaccines — contraindicated with most immunosuppressive biologics; complete vaccination before starting
Other immunosuppressants (methotrexate, azathioprine) — commonly co-prescribed to reduce immunogenicity; increases overall immunosuppression
CYP3A4 drug metabolism — IL-6 inhibitors (tocilizumab, sarilumab) normalize CYP3A4 activity suppressed by inflammation; may reduce plasma levels of CYP3A4-metabolized drugs (warfarin, cyclosporine) — monitor and adjust
Other biologics — combining biologic classes generally avoided due to markedly increased infection risk
A biosimilar is a biologic medicine that is highly similar to an already-approved biologic (the reference product), with no clinically meaningful differences in safety, purity, or potency. Biosimilars are not 'generic' biologics — because biologics are complex proteins produced by living cells, exact replication is not possible. Instead, biosimilars must demonstrate structural and functional similarity and clinical equivalence in comparative trials. The FDA approval standard for biosimilars is rigorous. Major biosimilars in the US include multiple adalimumab (Humira) biosimilars (Hadlima, Hyrimoz, Cyltezo, etc.) and infliximab biosimilars. Biosimilars significantly reduce costs — adalimumab biosimilars entered the US market in 2023 at 5-85% discounts to Humira's list price.
Biologics that suppress immune function — particularly anti-TNF agents, B-cell depleting agents, and JAK inhibitors — require comprehensive screening because they reduce the immune system's ability to control latent infections and malignancies that are normally held in check. Latent tuberculosis, which is suppressed but not eradicated by the immune system in approximately 1-2 billion people worldwide, can reactivate rapidly when anti-TNF therapy blunts the granulomatous immune response. Hepatitis B can reactivate similarly. HIV status, complete blood counts, and sometimes liver function tests are also evaluated. These screenings prevent life-threatening complications and make biologic therapy far safer when properly conducted.