Generic Name

Kevzara

Mechanism

Kevzara (sarilumab) is a monoclonal antibody that selectively targets the interleukin‑6 receptor (IL‑6R).
• Binds both soluble and membrane IL‑6R, inhibiting IL‑6 from activating the downstream JAK/STAT signaling cascade.
• Reduces pro‑inflammatory cytokine production (e.g., TNF‑α, IL‑1β) and suppresses acute‑phase reactants such as C‑reactive protein (CRP).
• Interrupts the feedback loop that sustains synovial inflammation, cartilage degradation, and bone erosion in rheumatoid arthritis (RA).

Pharmacokinetics

• Route: Subcutaneous injection; administered in clinic or at home.
• Absorption: ~65‑75 % bioavailability; maximal serum concentration 24‑48 h post‑dose.
• Distribution: Volume of distribution ~22 L; plasma protein binding ≈ 70 %.
• Metabolism: Largely by proteolytic catabolism; not a substrate for CYP enzymes.
• Elimination: Half‑life 14‑18 days; excreted via reticulo‑endothelial system.
• Drug interactions: Minimal; no clinically significant interactions with common concomitant DMARDs.

Indications

• Adult moderate‑to‑severe RA: 150 mg SC every 3 weeks, or 200 mg SC every 2 weeks.
• Juvenile idiopathic arthritis (JIA) (polyarticular course): 150 mg SC every 3 weeks (≥ 12 kg).
• Can be used as first‑line biologic or after inadequate response to methotrexate or TNF inhibitors.

Contraindications

• Hypersensitivity to sarilumab or murine protein products.
• Severe active infections (TB, hepatitis, HIV, etc.).
• Active malignancy or history of malignancy within 5 years (except treated basal cell carcinoma).
• Pregnancy: No evidence of benefit; potential fetal risk.
• Breastfeeding: Not recommended.

Warnings
• Serious infections: Bacterial, viral, fungal, opportunistic (e.g., Pneumocystis jirovecii).
• TB reactivation: Required baseline and periodic screening.
• Neutropenia: Monitor CBC; risk of secondary infections.
• Hepatotoxicity: Transaminases may rise; severe liver injury uncommon but possible.
• Gastrointestinal perforation: Rare but serious, especially in patients with diverticulitis.

Dosing

• Injection technique: Use 18‑20 G needle, rotate sites, avoid lips, face, and genitalia.
• Storage: 2‑8 °C; freeze‑thaw cycle cautions; 2 years shelf‑life at controlled room temperature.

Adverse Effects

Common (≥ 10 %)
• Injection‑site reactions (pain, erythema, pruritus)
• Upper respiratory tract infections (nasopharyngitis)
• Headache
• Elevated liver enzymes (15–30 % mild)

Serious (≤ 5 %)
• Bacterial sepsis, including MRSA
• Viral reactivation (HBV, CMV, HSV)
• Opportunistic infections (Pneumocystis, fungal)
• Severe hepatotoxicity (ALT/AST > 5× ULN)
• Neutropenia (ANC < 1.0 × 10^9/L)
• Gastrointestinal perforation (especially in diverticulitis)

Monitoring

• Baseline: CBC, CMP (LFTs, bilirubin), CRP, ESR, hepatitis B/C serology, TB skin/IGRA test, pregnancy test for females of childbearing potential.
• During therapy:
• CBC & CMP every 3 months; sooner if clinical suspicion.
• TB screening annually if risk factors present.
• ALT/AST, bilirubin, and alkaline phosphatase at each visit.
• Lymphocyte subset counts not routinely required.
• Patient education: Sign and report signs of infection, jaundice, fever, or GI bleeding promptly.

Clinical Pearls

• Dual DMARD strategy: Combining Kevzara with methotrexate exerts synergistic effects; patients on monotherapy often need dose escalation.
• Weight‑based dosing nuance: Even though the drug is weight‑independent, a 10‑% adjustment for patients in the middle weight band can improve tolerability without compromising efficacy.
• TB reactivation vigilance: A negative baseline IGRA does not preclude latent TB; maintain asymptomatic raise suspicion especially in endemic areas or immunocompromised patients.
• Injection‑site linespecific technique: Use a 40 mm syringe and wrap the arm; motility restrictions may improve compliance.
• Rapid-onset arthritis flare: If fever and sudden swelling occur, suspect infection or vasculitis; treat early, stop drug if necessary.
• Pregnancy: If pregnancy occurs, discontinue promptly; cross‑blood‑barrier data minimal.
• Patient monitoring file: Keep a structured log of lipids, LFTs, CBC, and notes on injection site reactions to identify trends before serious AEs.

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• Key Takeaway: Kevzara offers a targeted IL‑6 blockade with a favorable safety profile when patients are carefully screened for infections and monitored for hematologic and hepatic parameters. Reminder: always corroborate with up‑to‑date prescribing information and local guidelines.