STEPTRACKERIMMUNOLOGY + PHARMACOLOGY + ONCOLOGY | BIOLOGICS | HIGH-YIELD REVIEW

Therapeutic Antibodies & Biologics

Biologics name their target: learn each by what it blocks, where it is used, and the infection or toxicity that comes with it.

FOCUS ON
Naming: -ximab (chimeric), -zumab (humanized), -umab (human), -cept (receptor fusion protein). Cytokine blockers: TNF-α (infliximab, adalimumab, certolizumab, golimumab, etanercept = soluble receptor) → screen for latent TB and HBV, avoid in heart failure, demyelination; IL-6R (tocilizumab), IL-1 (anakinra), IL-17 (secukinumab), IL-12/23 (ustekinumab), IL-23 (guselkumab), IL-4Rα (dupilumab), IL-5 (mepolizumab), IgE (omalizumab). Cell targets: CD20 (rituximab → HBV reactivation, PML), CD52 (alemtuzumab), α4-integrin (natalizumab → PML; vedolizumab gut-selective), C5 (eculizumab → meningococcus). Checkpoint inhibitors: CTLA-4 (ipilimumab), PD-1 (nivolumab, pembrolizumab), PD-L1 (atezolizumab) → immune-related colitis, hepatitis, thyroiditis, hypophysitis. Cytokine therapy: IFN-α, IFN-β (MS), IFN-γ (CGD), IL-2 (aldesleukin), G-CSF, erythropoietin.
DRUG
TARGET
USES
KEY RISK
Infliximab · adalimumab · certolizumab · golimumab
TNF-α (antibodies)
RA, IBD, psoriasis, ankylosing spondylitis
TB reactivation, HBV, fungal infections, lymphoma, drug-induced lupus, demyelination, worsened HF
Etanercept
TNF-α (decoy receptor fused to IgG Fc)
RA, psoriasis, AS
Same class risks · not used in IBD
Tocilizumab · anakinra
IL-6 receptor · IL-1 receptor
RA, giant cell arteritis, cytokine release syndrome · periodic fevers, Still disease
Infections; tocilizumab ↑ lipids, GI perforation
Secukinumab · ixekizumab · ustekinumab · guselkumab
IL-17A · IL-17A · IL-12/23 p40 · IL-23 p19
Psoriasis, psoriatic arthritis, AS (IL-17); Crohn (IL-12/23, IL-23)
IL-17 blockers can worsen IBD; Candida
Dupilumab · mepolizumab · omalizumab
IL-4Rα · IL-5 · IgE
Atopic dermatitis, asthma · eosinophilic asthma, EGPA · allergic asthma, urticaria
Conjunctivitis (dupilumab); anaphylaxis rare
Rituximab · ocrelizumab
CD20 on B cells
B-cell lymphoma, CLL, RA, ANCA vasculitis, MS, pemphigus
HBV reactivation (screen), PML, infusion reactions, hypogammaglobulinemia
Natalizumab · vedolizumab
α4-integrin (VLA-4) · α4β7 (gut only)
MS, Crohn · IBD
PML (JC virus) with natalizumab — test JCV antibody
Alemtuzumab · daratumumab · brentuximab
CD52 · CD38 · CD30 (drug conjugate)
CLL, MS · multiple myeloma · Hodgkin, ALCL
Autoimmunity (alemtuzumab) · neuropathy (brentuximab)
Eculizumab · ravulizumab
C5
PNH, aHUS, myasthenia, NMO
Meningococcal infection — vaccinate first
Ipilimumab
CTLA-4
Melanoma, RCC (with nivolumab)
Colitis, hypophysitis, hepatitis, dermatitis
Nivolumab · pembrolizumab · atezolizumab
PD-1 · PD-1 · PD-L1
Melanoma, lung, kidney, MSI-high tumors, Hodgkin
Thyroiditis, pneumonitis, colitis, type 1 DM, myocarditis
Denosumab · abciximab · palivizumab
RANKL · GPIIb/IIIa · RSV F protein
Osteoporosis, bone metastases · PCI · RSV prevention in infants
Hypocalcemia, jaw osteonecrosis · bleeding · —
Recombinant cytokines
IFN-β · IFN-γ · IL-2 · G-CSF, GM-CSF · EPO · thrombopoietin agonists
MS · CGD · melanoma, RCC · neutropenia · anemia of CKD · ITP
IL-2: capillary leak · EPO: hypertension, thrombosis

Mechanism — how monoclonal antibodies act

Neutralize a ligandAnti-TNF, anti-IL-5, anti-IgE
Block a receptorTocilizumab, dupilumab, natalizumab
Deplete cellsRituximab (ADCC, complement)
Release brakesAnti-PD-1, anti-CTLA-4

Screen before you start

DRUG
SCREEN FOR
WHY
TNF-α inhibitors
Latent TB, HBV
Granulomas fail
Rituximab
HBV
Fulminant reactivation
Natalizumab
JC virus antibody
PML
Eculizumab
Meningococcal vaccination
No MAC
JAK inhibitors
Zoster vaccination, TB
Zoster risk

How it's tested

COMMON CONFUSIONEtanercept is a soluble TNF receptor (–cept), not an antibody, and it doesn't work in Crohn disease, unlike infliximab and adalimumab.
THE TRAPNew hypothyroidism, colitis or hypophysitis during cancer immunotherapy is an immune-related adverse event — steroids, not antibiotics.
YOUR APPROACHName → target → disease → mechanism of the side effect (infection from lost pathway, autoimmunity from lost brake) → screening test.

If you see… think…

Miliary TB after starting adalimumab for Crohn → TNF-α blockade
Fusion protein TNF decoy receptor → etanercept
Biologic for giant cell arteritis → tocilizumab (IL-6R)
Anti-CD20 causing HBV reactivation → rituximab
MS drug causing PML → natalizumab
Gut-selective integrin blocker → vedolizumab
Meningococcal sepsis in a PNH patient on treatment → eculizumab (C5)
Diarrhea and colitis on ipilimumab → immune-related adverse event
Anti-IgE for allergic asthma → omalizumab
IFN used for chronic granulomatous disease → IFN-γ