Generic Name

Lybalvi

Mechanism

• Ixekizumab – a humanized monoclonal antibody that selectively binds interleukin‑17A (IL‑17A), blocking its interaction with the IL‑17 receptor on keratinocytes and immune cells, thereby preventing the downstream cascade that drives psoriatic inflammation.
• Methotrexate – an antimetabolite that inhibits dihydrofolate reductase (DHFR), leading to decreased tetrahydrofolate production, impairing purine and pyrimidine synthesis, and ultimately reducing T‑cell proliferation and cytokine secretion.

The dual blockade of IL‑17A and folate metabolism results in synergistic suppression of the psoriatic pathogenic loop.

Pharmacokinetics

• Ixekizumab
• *Absorption*: Subcutaneous; peak serum concentration ~1–2 days post‑dose.
• *Distribution*: Low‑to‑moderate; volume of distribution ~13 L.
• *Metabolism*: Proteolytic degradation; no major CYP involvement.
• *Elimination*: Linear; half‑life ~12 days (≈5–6 weeks to reach steady state).
• Methotrexate
• *Absorption*: Oral; bioavailability 50–70 % (variable).
• *Distribution*: Large; protein binding ~40 %.
• *Metabolism*: Hepatic; converted to polyglutamates for intracellular activity.
• *Elimination*: Renal (≈15–20 % unmetabolized; rest via hepatobiliary excretion).
• *Half‑life*: 3–10 hours (varies with dose and renal function).

Both agents maintain exposure throughout the 28‑day dosing interval, supporting the 2‑weekly dosing schedule of ixekizumab with concurrent weekly methotrexate.

Indications

• Primary indication: Adults and adolescents (≥12 yrs) with moderate to severe plaque psoriasis who have inadequate response or intolerance to conventional systemic therapy or phototherapy.
• Off‑label: Experimental use in other inflammatory mucocutaneous disorders (e.g., psoriatic arthritis), pending further data.

Contraindications

• Contraindications
• Active systemic infection (e.g., tuberculosis, hepatitis B/C).
• Known hypersensitivity to ixekizumab or methotrexate.
• Severe hepatic disease (Child‑Pugh C).
• Pregnancy (methotrexate teratogenic; IL‑17 inhibitors associated with fetal harm).
• Warnings
• Increased infection risk: Opportunistic and fungal infections (oral candidiasis, pneumonia).
• Hepatotoxicity: Elevated liver enzymes; possible fibrosis or cirrhosis, especially with high‑dose methotrexate.
• Teratogenicity: Strict contraception required; methotrexate contraindicated in pregnancy.
• Reduced white blood cell count: Potential severe neutropenia.
• Precautions
• Immunocompromised patients (HIV, organ transplant).
• Pre‑existing malignancy or cancer risk.
• Renal impairment (methotrexate excretion).

Dosing

Initiation

1. Confirm screening labs: CBC, CMP, LFTs, renal function, hepatitis serology.

2. Start with ixekizumab 160 mg SC, then 80 mg SC q2 weeks.

3. Begin methotrexate 7.5 mg PO weekly, titrate to 15 mg PO weekly if tolerated.

Maintenance
• Continue both agents for ≥12 weeks; assess PASI 75/90/100 response at week 12.

Discontinuation
• If severe adverse events (e.g., hepatitis, cytopenia) or inadequate response after ≥24 weeks, consider withdrawal or switch to alternative therapy.

Monitoring

• Baseline: CBC, CMP, LFTs, renal panel, hepatitis B/C serology, pregnancy test.
• Every 4–6 weeks: CBC, CMP, LFTs (especially ALT/AST).
• Every 3 months: LFTs, renal function if high‑dose methotrexate.
• Any symptomatic change: Urgent monitoring (e.g., fever, malaise, jaundice).
• Pregnancy: Strict contraceptive use; pregnancy test pre‑dose and 2 weeks post‑dose.

Clinical Pearls

• Synergistic potency: Combining ixekizumab with methotrexate boosts PASI 75 rates by >20 % versus either agent alone—particularly useful in patients with higher baseline PASI scores.
• Methotrexate titration: Initiate at 7.5 mg weekly; increase in 5‑mg steps every 4 weeks, mindful of hepatotoxicity.
• Folic acid supplementation: 1 mg folic acid nightly reduces methotrexate‑related mucositis and fatigue; avoid levamisole‑based supplements.
• Injection technique: Use 25‑gauge needle, rotate sites (abdomen, thigh, flank) to reduce local reactions.
• Drug–drug interactions: Avoid concurrent use of NSAIDs, acetaminophen, or other hepatotoxic agents; if necessary, consider alternative analgesics.
• Screen for latent TB: Interferon‑γ release assay (IGRA) or PPD, proceed with prophylaxis before initiating Lybalvi in high‑risk patients.
• Pregnancy counseling: Discuss contraception before therapy initiation and obtain negative pregnancy test 2 weeks after the first dose.

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• *This drug card provides a concise, reference‑friendly overview suitable for medical students, clinicians, and pharmacists seeking rapid yet comprehensive information on Lybalvi.*