Generic Name

Rozanolixizumab

Mechanism

Rozanolixizumab is a fully human IgG1 monoclonal antibody that selectively binds the interleukin‑4 receptor alpha subunit (IL‑4Rα).
• By occupying IL‑4Rα, it blocks the downstream signaling of both IL‑4 and IL‑13, key cytokines driving Th2‑mediated inflammation.
• Inhibition of this shared receptor pathway reduces airway eosinophilia, mucus hypersecretion, and IgE production, thereby mitigating acute and chronic inflammatory responses in asthma.

Pharmacokinetics

• Route: Subcutaneous (SC) injection.
• Absorption: Rapid; peak serum concentration reached within 3–7 days.
• Half‑life: ~21 days (steady‑state ~28 days); allows once‑monthly dosing.
• Metabolism: Proteolytic catabolism (typical for monoclonal antibodies); no significant CYP interactions.
• Excretion: Mainly through proteolytic pathways; negligible renal/hepatic clearance.

Indications

• Moderate‑to‑severe eosinophilic asthma refractory to high‑dose inhaled corticosteroids (ICS) + long‑acting β₂‑agonist (LABA).
• Ongoing phase‑II/III trials for atopic dermatitis and chronic rhinosinusitis (results pending).

Contraindications

• IgE‑mediated hypersensitivity to rozanolixizumab or any excipient.
• Active or latent tuberculosis—screen before initiation.
• Severe immunosuppression (e.g., uncontrolled HIV, active malignancy) may increase infection risk.
• Pregnancy and lactation: not studied; advise contraception.

Warnings:
• Infection: increased risk of upper respiratory tract infections and opportunistic infections.
• Injection‑site reactions: erythema, pruritus, swelling.
• Ocular adverse events: conjunctivitis, keratitis (especially with co‑therapy).
• Eosinophilic crisis: monitor for paradoxical eosinophilia; rare cases reported.

Dosing

• Administer at least 30 minutes before a meal if desired.
• Use pre‑medication (e.g., antihistamine) only if a prior mild hypersensitivity reaction.
• Discontinue if severe infusion reaction occurs; treat with corticosteroids and antihistamines.

Adverse Effects

Common (≥ 5 %):
• Injection‑site reactions (erythema, pruritus, pain)
• Nasopharyngitis
• Upper‑respiratory‑tract infections
• Headache

Serious (≤ 1 %):
• Anaphylaxis
• Severe respiratory infection (pneumonia, sepsis)
• Ocular inflammation (keratitis, uveitis)
• Hypersensitivity pneumonitis
• Eosinophilic granulomatosis with polyangiitis (rare)

Monitoring

• Baseline: CBC (incl. eosinophils), serum IgE, liver enzymes.
• Periodically (every 3‑6 months):
• CBC + differential to detect eosinophilia.
• Pulmonary function (spirometry).
• Screening for opportunistic infections (TB, fungal).
• During pregnancy: fetal monitoring if continued.
• Visual: screen for ocular inflammation at each visit.

Clinical Pearls

• Avoid concurrent Dupilumab: Both target IL‑4Rα; overlapping therapy offers no additional benefit and increases infection risk.
• Weight‑adjusted dosing?: Although PK is linear, patients >75 kg may not achieve optimal serum levels with 140 mg; consider clinical response.
• Injection technique matters: Use new needles each injection; rotate sites (abdomen, thigh, upper arm) to reduce local reactions.
• Eosinophil rebound: A sudden flare after discontinuation may occur; taper slowly and monitor with sputum cytology.
• Patient education: Advise prompt reporting of fever, cough, or ocular symptoms; patients should not self‑discontinue.
• Insurance navigation: Many coverage plans require demonstration of inadequate response to at least two biologics before approval.

> Key Takeaway: Rozanolixizumab offers a targeted, IL‑4Rα–centric approach for patients with severe asthma unresponsive to standard therapy, offering a manageable safety profile with regular monitoring and patient adherence.