Biological Agents in Dermatology

Biologics Basics - Tiny Titans Tussle

• Definition: Engineered proteins (e.g., mAbs) targeting specific immune pathways.
• Nomenclature (Suffixes):
  • mAbs: -omab (murine), -ximab (chimeric), -zumab (humanized), -umab (human). 📌 'O'rigin: mUrIne, xImeric, ZUmanized, hUman.
  • Fusion Proteins: -cept.
• MOA: Highly specific; target cytokines (TNF-α, ILs) or receptors.
• Advantages: ↑ Specificity, ↓ off-target effects.
• Disadvantages: High cost, immunosuppression risk, parenteral route.

⭐ The '-umab' suffix in monoclonal antibodies indicates a fully human antibody, generally associated with lower immunogenicity.

TNF-α Blockers - Inflammation Assassins

• MOA: Neutralize TNF-α, reducing inflammation.
• Drugs: 📌 'ACE In Good Psoriasis Care'

  Drug	Type
  Adalimumab	Fully human mAb
  Certolizumab pegol	Humanized Fab' fragment
  Etanercept	Fusion protein
  Infliximab	Chimeric mAb
  Golimumab	Fully human mAb

• Key Derm Indications: Psoriasis, Psoriatic Arthritis, Hidradenitis Suppurativa.
• Major SEs:
  • ↑ Infection risk (esp. TB reactivation, fungal)
  • Demyelinating disorders
  • Worsening CHF
  • Drug-induced lupus
  • Injection site/infusion reactions
• Screening (Pre-therapy): TB (QFT/TST, CXR), HBV, HCV, HIV.

⭐ All patients must be screened for latent TB before starting TNF-α inhibitor therapy due to risk of reactivation.

IL Inhibitors (12/23 & 17) - Cytokine Crushers

These agents selectively target interleukin pathways.

• IL-12/23 Inhibitor:
  • Ustekinumab: Targets the p40 subunit common to IL-12 and IL-23.
• IL-17 Inhibitors:
  • Secukinumab, Ixekizumab: Target IL-17A.
  • Brodalumab: Targets IL-17 Receptor A (IL-17RA).

Key Uses & Side Effects

Newer ILs & Other Key Players - Precision Powerhouses

• IL-23p19 Inhibitors: Specifically target the IL-23 p19 subunit. Effective for Psoriasis.
  • Guselkumab
  • Risankizumab
  • Tildrakizumab
• Dupilumab: An IL-4Rα antagonist, blocking both IL-4 and IL-13 signaling. Used for Atopic Dermatitis and Asthma.
  • Key Side Effect: Conjunctivitis.

  ⭐ Dupilumab, an IL-4Rα antagonist, is a key biologic for moderate-to-severe Atopic Dermatitis.

• Rituximab: Targets CD20 on B-cells. Indicated for Pemphigus Vulgaris.
  • Side Effects: Infusion reactions, risk of Progressive Multifocal Leukoencephalopathy (PML).
• Omalizumab: An anti-IgE antibody. Used for Chronic Spontaneous Urticaria (CSU).
  • Side Effect: Risk of anaphylaxis.

Biologics Workup & Watch - Safety Net Spells

Pre-Treatment Screening:

• Detailed history & physical.
• TB: QFT gold or Mantoux, CXR.
• Viral serology: HBV, HCV, HIV, VZV.
• Baseline labs: CBC, LFT, RFT.
• Age-appropriate cancer screening.

Vaccinations:

• Update all inactivated vaccines prior to therapy.
• ⚠️ Live vaccines contraindicated during therapy and for a period after discontinuation.

Monitoring:

• Regular clinical F/U for efficacy & AEs.
• Periodic labs based on drug.

⭐ Live vaccines are strictly contraindicated in patients receiving biologic therapy due to the risk of disseminated infection.

High‑Yield Points - ⚡ Biggest Takeaways

• TNF-α inhibitors (e.g., Infliximab) treat psoriasis & psoriatic arthritis; screen for latent TB.
• Ustekinumab targets IL-12/23, effective for psoriasis.
• IL-17 inhibitors (Secukinumab, Ixekizumab) show rapid efficacy in psoriasis.
• Dupilumab blocks IL-4/IL-13 (via IL-4Rα), used for atopic dermatitis.
• Rituximab (anti-CD20) is a choice for pemphigus vulgaris.
• Omalizumab (anti-IgE) is beneficial for chronic spontaneous urticaria.
• Pre-treatment screening: latent TB, Hepatitis B & C are crucial.