Pharmacology for Immunity – Drug Classes That Target Cytokine Production & Signalling

week 1, pt. 2

Tumour Necrosis Factor (TNF) Inhibitors (e.g., Infliximab, Adalimumab, Etanercept) – Indications

• Rheumatoid, psoriatic arthritis

• Ankylosing spondylitis

• Inflammatory bowel disease (Crohn’s, ulcerative colitis)

Tumour Necrosis Factor (TNF) Inhibitors – Mechanism of Action:

• TNF = key pro-inflammatory cytokine

• Promotes immune activation & inflammation

• TNF inhibitors bind TNF → block receptor interaction

• → decreases inflammation & immune activation

Tumour Necrosis Factor (TNF) Inhibitors – Adverse Effects

• Reactivation of latent infections (TB, hep B)

• Increased infection risk

• Injection/infusion reactions

• Malignancy risk

Tumour Necrosis Factor (TNF) Inhibitors – Drug Interactions

• Additive immunosuppression with other biologic immunosuppressants

• Increased infection risk

• Decreased vaccine response

Tumour Necrosis Factor (TNF) Inhibitors – Contraindications

• Active serious infection

• Live vaccines

Interleukin Inhibitors (e.g., Toxilizumab, Secukinumab, Ustekinumab) – Indications

• Rheumatoid, psoriatic arthritis

• Ankylosing spondylitis

• Psoriasis

• Inflammatory Bowel Disease

Interleukin Inhibitors – Mechanism of Action

• Interleukins regulate immune activation & inflammation

• Specific interleukins (e.g., IL-6, IL17, IL-12/13) drive inflammatory pathways

• Interleukin inhibitors block specific cytokines or their receptors

→ decreases cytokine signalling & inflammation

Interleukin Inhibitors – Adverse Effects

• Increased infection risk

• Reactivation of latent infections

• Injection/infusion reactions

• Elevated liver enzymes

Interleukin Inhibitors – Drug Interactions

• Additive immunosuppression with other immunosuppressants

• Decrease vaccine response

Interleukin Inhibitors – Contraindications

• Active serious infections

• Live vaccines

Janus Kinase (JAK) Inhibitors (e.g., Tofacitinib, Baricitinib, Upadacitinib) – Indications

• Rheumatoid, psoriatic arthritis

• Ulcerative colitis

• Other inflammatory conditions

Janus Kinase (JAK) Inhibitors – Mechanism of Action

• Cytokines bind receptors → active intracellular signalling

• JAK enzymes transmit cytokine signals inside the cell

• JAK inhibitors block these intracellular pathways

• → decrease cytokine signalling & immune activation

Janus Kinase (JAK) Inhibitors – Adverse Effects

• Increase infection risk

• Herpes zoster reactivation

• Cytopenias (anemia, neutropenia)

• Elevated liver enzymes

• Increased thrombosis risk (DVT, PE)

Janus Kinase (JAK) Inhibitors – Drug Interactions

• Additive immunosuppression with other immunosuppressants

• CYP3A4 inhibitors → increase drug levels

• CYP3A4 inducers → decrease drug levels/efficacy

Janus Kinase (JAK) Inhibitors – Contraindications

• Active infection

• Live vaccines

Interferons (e.g., Interferon beta-1a, interferon beta-1b) – Indications

• Multiple sclerosis → reduces relapse rates

Interferons – Mechanism of Action

• Modulate immune response (not purely suppressive)

• Decrease pro-inflammatory cytokines

• Increase anti-inflammatory cytokines

• → reduced immune-mediated damage to myelin

Interferons – Adverse Effects

• Flu-like symptoms

• Injection site reactions

• Depression

• Elevated liver enzymes

Interferons – Drug Interactions

• Immunosuppressants - Increased risk of infections

• Hepatotoxic drugs - additive liver toxicity

Interferons – Contraindications

• Severe depression or suicidal ideation

• Significant liver disease