Natalizumab

Aka: Natalizumab, Tysabri, Antegren

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II. Indications

  1. Multiple Sclerosis (relapsing)
  2. Moderate to severe Inflammatory Bowel Disease (refractory to TNF Inhibitors)
    1. Ulcerative Colitis
    2. Crohns Disease

III. Contraindications

  1. Severe Infection

IV. Mechanism

  1. See Integrin Receptor Antagonist
  2. Integrin Receptor Antagonist (alpha-4)
    1. Humanized recombinant IgG4 Monoclonal Antibody
    2. Targets Integrin's alpha4 subunit (beta1 and beta7)
  3. Integrins
    1. Cell surface Glycoproteins that act as cellular adhesion molecules (CAMs)
    2. Integrins are upregulated in autoimmune and neoplastic conditions
    3. Integrins beta 1 and beta 7 are specifically expressed on the surface of all Leukocytes (except Neutrophils)
  4. Natalizumab has immunomodulating and antiinflammatory effects
    1. Blocks Integrin activity on the Leukocyte surface
    2. Blocks Leukocyte migration into inflamed tissue (e.g. bowel wall, Myelin Sheath)

V. Precautions

  1. See Monoclonal Antibody for preparation before first dose

VI. Medications

  1. Natalizumab injection solution: 300 mg/15 ml (intended for further dilution)

VII. Dosing: Adults

  1. Dosing is the same for Multiple Sclerosis and Inflammatory Bowel Disease
  2. Infuse 300 mg IV over 1 hour every 4 weeks
  3. Discontinue if insignificant clinical response at 12 weeks or unable to taper off chronic Corticosteroids at 6 months

VIII. Safety

  1. Unknown safety in pregnancy
  2. Unknown safety in Lactation

IX. Adverse Effects

  1. Hypersensitivity (including Anaphylaxis)
  2. Infusion reaction
  3. Headache Fatigue
  4. Hepatotoxicity
    1. Elevated Liver Function Tests (Transaminitis, Hyperbilirubinemia)
  5. Progressive Multifocal Leukoencephalopathy (PML)
    1. Obtain John Cunningham Virus (JCV) Antibody every 6 months
    2. Discontinue Natalizumab if positive Antibody (increased PML risk)
    3. Discontinue (and MRI) if motor weakness, Incoordination or personality changes

X. Efficacy

  1. Multiple Sclerosis
    1. May be superior to Interferon Beta-1 agents at preventing relapse
    2. May reduce relapse rate by >60%
      1. (2004) Neurology 62:2038 [PubMed]
  2. Inflammatory Bowel Disease
    1. Slower effects than with TNF Inhibitors

XI. Resources

  1. Natalizumab (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c5fdde91-1989-4dd2-9129-4f3323ea2962

XII. References

  1. (2023) Biologics for Crohn's Disease, Presc Lett, #390826
  2. (2023) Drugs for Inflammatory Bowel Disease, Med Lett Drug Ther 65: 105-12

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