Chapter 40 · Module 3
Biologic Immunosuppressants
TNF inhibitors, interleukin antagonists, and B-cell therapies
ADCC = antibody-dependent cellular cytotoxicity  ·  ADA = anti-drug antibody  ·  BAFF = B-cell activating factor  ·  BCG = Bacille Calmette-Guerin  ·  BLyS = B lymphocyte stimulator  ·  CRP = C-reactive protein  ·  CRS = cytokine release syndrome  ·  FKBP-12 = FK-binding protein 12  ·  IBD = inflammatory bowel disease  ·  IFNAR1 = type I interferon receptor subunit 1  ·  IGRA = interferon-gamma release assay  ·  IL = interleukin  ·  PML = progressive multifocal leukoencephalopathy  ·  RA = rheumatoid arthritis  ·  SLE = systemic lupus erythematosus  ·  TNF = tumor necrosis factor  ·  TST = tuberculin skin test  ·  TSLP = thymic stromal lymphopoietin
TNF Inhibitors — Five Agents, Three Structural Classes
Feature Infliximab Adalimumab Certolizumab Etanercept
Structure Chimeric mAb (25% murine) Fully human mAb Pegylated Fab — no Fc TNFR2-Fc fusion protein
Fc region Yes Yes No → safe in pregnancy Yes
Targets TNF-alpha TNF-alpha TNF-alpha TNF-alpha + lymphotoxin-alpha
Crohn's / UC Yes Yes Crohn's only Not approved — ineffective in IBD
Interleukin Axis Targeted Biologics
IL-6 receptor
Tocilizumab / Sarilumab
  • Block IL-6R alpha chain
  • RA, giant cell arteritis, CRS (CAR-T)
  • CRP suppressed to zero — cannot monitor infection with CRP
  • Use procalcitonin for infection detection
IL-23 / IL-12 p40
Ustekinumab
  • Blocks shared p40 subunit (IL-12 + IL-23)
  • Psoriasis, PsA, Crohn's, UC
  • q12wk maintenance — least frequent of any biologic
IL-23 p19 (selective)
Guselkumab / Risankizumab
  • Block IL-23 p19 only — spares IL-12
  • Psoriasis, PsA; risankizumab also for IBD
  • Safe in IBD — preferred over IL-17 inhibitors when IBD coexists
IL-17A inhibitors
Secukinumab / Ixekizumab / Bimekizumab
  • Block IL-17A (bimekizumab also IL-17F)
  • Psoriasis, PsA, ankylosing spondylitis
  • Highest efficacy in plaque psoriasis (PASI 90: 60-90%)
  • Contraindicated in active IBD — risk of worsening
  • Mucocutaneous candidiasis: 3-4% (treat topically)
Type 2 inflammation
Dupilumab / Anti-IL-5 / Omalizumab
  • Dupilumab: anti-IL-4Ralpha (blocks IL-4 + IL-13) — AD, asthma, CRSwNP, EoE
  • Mepolizumab / benralizumab: anti-IL-5 axis — eosinophilic asthma
  • Tezepelumab: anti-TSLP — all severe asthma phenotypes
  • Omalizumab: anti-IgE — allergic asthma, urticaria
  • No significant immunosuppression with dupilumab
B-Cell and Plasma Cell Targeted Biologics
Anti-CD20
Rituximab
  • Depletes pre-B through memory B cells
  • Plasma cells (CD20-negative) are spared
  • RA (after TNF failure), GPA, MPA, pemphigus
  • PML risk (JC virus reactivation)
  • HBV reactivation screening mandatory
Anti-BAFF/BLyS
Belimumab
  • Blocks B-cell survival factor BLyS
  • Active, autoantibody-positive SLE
  • Also approved for lupus nephritis
Anti-IFNAR1
Anifrolumab
  • Blocks type I interferon receptor (IFNAR1)
  • Moderate-to-severe SLE with positive IFN gene signature
  • Increased herpes zoster risk
Universal Pre-Treatment Screening — All Biologics

TST or IGRA (latent TB)  ·  HBsAg + anti-HBc (hepatitis B)  ·  CBC + metabolic panel  ·  Complete all live vaccines at least 2-4 weeks before starting  ·  Never combine two biologic agents.