Intro to Biologics - Magic Bullets Intro
- Engineered proteins (monoclonal antibodies, fusion proteins) acting as "magic bullets"; precisely target specific molecules in immune/inflammatory pathways.
- Advantages: High specificity & selectivity, often ↑efficacy in severe or refractory diseases.
- Considerations:
- Administration: Parenteral (IV/SC).
- Cost: Generally high.
- Immunogenicity: Risk of anti-drug antibodies (ADAs).
- Safety: ↑Infection risk (e.g., TB reactivation), potential for malignancy.
⭐ Biologics are large protein molecules, typically administered parenterally, targeting specific components of the immune system.
TNF-α Inhibitors - Tumour Necrosis Foes
📌 ACE-GI: Adalimumab, Certolizumab, Etanercept, Golimumab, Infliximab
| Drug | Structure | Key Derm Indications | Key AEs |
|---|---|---|---|
| Infliximab | Chimeric mAb | Psoriasis, Psoriatic Arthritis (PsA) | Infusion reactions, Infections (esp. TB reactivation), CHF worsening, Lupus-like syndrome |
| Adalimumab | Human mAb | Psoriasis, PsA, Hidradenitis Supp. | Injection site reactions, Infections (TB), Malignancy risk, Lupus-like syndrome |
| Etanercept | TNF receptor-IgG1 Fc fusion protein | Psoriasis, PsA | Injection site reactions, Infections (TB), Demyelinating disorders, CHF worsening |
- General Class AEs: ↑ Risk of serious infections (bacterial, fungal, viral; screen for latent TB & HBV prior to therapy), potential for malignancy (e.g., lymphoma), cytopenias, hepatotoxicity, new-onset or exacerbation of demyelinating diseases or CHF. Avoid live vaccines during therapy. Monitor CBC, LFTs regularly.
Interleukin Inhibitors - Cytokine Signal Jammers
Interleukins (ILs) are key signaling molecules (cytokines) in immune responses. Inhibiting specific ILs or their receptors can effectively treat various inflammatory skin diseases.
| Target | Drug(s) | Key Derm Indications | Specific Adverse Events (AEs) |
|---|---|---|---|
| IL-12/23 | Ustekinumab | Psoriasis, Psoriatic Arthritis (PsA) | ↑ Infections (URTI), MACE risk (caution), RPLS (rare) |
| IL-17 | Secukinumab, Ixekizumab (anti-IL-17A) | Psoriasis, PsA, Ankylosing Spondylitis (AS) | ↑ Candida infections (mucocutaneous), Neutropenia, IBD (new/exacerbation) |
| Brodalumab (anti-IL-17RA) | Psoriasis (refractory) | 📌 "Bro, don't be sad": Suicidal ideation/behavior (BBW), Candida, IBD | |
| IL-23 (p19) | Guselkumab, Risankizumab | Psoriasis, PsA | ↑ URTI, Arthralgia, Headache. Generally well-tolerated. |
| Tildrakizumab | Psoriasis | ↑ URTI, Arthralgia, Headache. Generally well-tolerated. | |
| IL-4/13 | Dupilumab (anti-IL-4Rα) | Atopic Dermatitis (mod-severe), Asthma, CRSwNP | Injection site reactions, Conjunctivitis, Eosinophilia, Facial redness |
Other Biologics & Screening - Special Ops Agents
- Omalizumab: Anti-IgE mAb.
- Indication: Chronic Spontaneous Urticaria (CSU) refractory to high-dose antihistamines.
⭐ Omalizumab, an anti-IgE antibody, is approved for chronic spontaneous urticaria refractory to antihistamines.
- Rituximab: Anti-CD20 mAb (B-cell depleter).
- Indication: Pemphigus vulgaris, other autoimmune blistering diseases (off-label).
- Pre-Biologic Screening: Mandatory before therapy.
- Screening Essentials:
- TB: Treat latent TB (LTBI) if positive before biologic initiation.
- Vaccinations: 📌 Administer non-live vaccines ideally 2-4 weeks pre-therapy. Live vaccines contraindicated.
High‑Yield Points - ⚡ Biggest Takeaways
- TNF-α inhibitors (e.g., Infliximab) treat psoriasis & psoriatic arthritis; screen for latent TB.
- Ustekinumab targets IL-12/23 for psoriasis and psoriatic arthritis.
- IL-17 inhibitors (Secukinumab, Ixekizumab) offer rapid efficacy in severe psoriasis.
- Dupilumab blocks IL-4/IL-13 pathways, a mainstay for atopic dermatitis.
- Rituximab (anti-CD20) is crucial for pemphigus vulgaris.
- Omalizumab (anti-IgE) treats refractory chronic spontaneous urticaria.
- Mandatory pre-biologic screening: latent TB, Hepatitis B & C.
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