Generic Name

Tremfya

Mechanism

Tremfya (guselkumab) is a human monoclonal IgG1κ antibody that selectively binds the p19 subunit of interleukin‑23 (IL‑23).
• Inhibits IL‑23 signaling to T‑helper 17 cells, reducing pro‑inflammatory cytokine release.
• Blocks downstream activation pathways that drive epidermal proliferation in psoriasis.
• Minimal off‑target effects due to high specificity for IL‑23R.

Pharmacokinetics

• Absorption: Subcutaneous injection; bioavailability ~90 %.
• Distribution: Predominantly confined to the extracellular fluid; serum concentrations peak 24‑48 h post‑dose.
• Metabolism: Proteolytic catabolism via Fc‑Rn recycling; no significant CYP enzyme involvement.
• Elimination: Half‑life ≈ 21 days; steady state attained after 2–3 modes of dosing.
• Population PK: No major influence from age, weight, or mild renal/hepatic impairment.

Indications

• Moderate‑to‑severe plaque psoriasis in adults:
• Over‑40 kg patients: 100 mg SC at day 0, week 4, then every 8 weeks.
• Adolescent psoriasis (≥12 yrs, ≥40 kg) pending regulatory approval.

Contraindications

• Hypersensitivity to guselkumab or any excipient.
• Concurrent uncontrolled infections (TB, fungal, viral).
• Pregnancy/Lactation: Category B; limited data—use only if benefit outweighs risk.
• Immunocompromised patients: caution; may increase infection risk.
• Autoimmune comorbidities (e.g., Crohn’s disease): evaluate carefully before initiation.

Dosing

• Initial dose: 100 mg SC (single 3 mL prefilled syringe).
• Maintenance: 100 mg SC every 8 weeks (via 6 mL syringe).
• Route: Subcutaneous injection in the abdomen, thigh, or upper arm.
• Pre‑injection: No special pre‑medication required; monitor for allergic reactions.

Adverse Effects

• Common (≥5 %): Injection‑site reactions, upper‑respiratory infections, headache, fatigue.
• Serious (≤1 %): Serious infections (severe bacterial, opportunistic), hypersensitivity/anaphylaxis, malignancies (rare).
• Rare (≤0.1 %): Cytopenias, elevated liver enzymes, neurologic manifestations.

Monitoring

• Baseline: CBC, CMP, TB test (IGRA or TST).
• Follow‑up visits: CBC and CMP at 12 weeks; repeat TB screening if immunocompromised.
• Infections: Advise patients to report signs of infection promptly.
• Adverse drug reactions: Document injection‑site signs; consider dose adjustment if significant reactions.

Clinical Pearls

• Rapid Onset of Efficacy: Significant improvement seen within 4 weeks; optimal for patients needing early control.
• Long‑Term Safety Profile: Compared to other biologics, lower reports of systemic infections, making it a favorable option for patients with comorbidities.
• Dosing Flexibility: The 8‑week interval reduces clinic visits, improving adherence and patient convenience.
• Drug‑Drug Interactions: None identified—safe to co‑administer with most immunosuppressants.
• Immunogenicity: Low rates of anti‑drug antibodies (<1 %) due to humanized antibody design.

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• Tremfya is a valuable addition to the biologic arsenal for plaque psoriasis, offering targeted IL‑23 inhibition with a robust safety profile and manageable dosing regimen.