II. Indications
- Multiple Sclerosis (relapsing)
- Moderate to severe Inflammatory Bowel Disease (refractory to TNF Inhibitors)
III. Contraindications
- Severe Infection
IV. Mechanism
- See Integrin Receptor Antagonist
-
Integrin Receptor Antagonist (alpha-4)
- Humanized recombinant IgG4 Monoclonal Antibody
- Targets Integrin's alpha4 subunit (beta1 and beta7)
-
Integrins
- Cell surface Glycoproteins that act as cellular adhesion molecules (CAMs)
- Integrins are upregulated in autoimmune and neoplastic conditions
- Integrins beta 1 and beta 7 are specifically expressed on the surface of all Leukocytes (except Neutrophils)
- Natalizumab has immunomodulating and antiinflammatory effects
- Blocks Integrin activity on the Leukocyte surface
- Blocks Leukocyte migration into inflamed tissue (e.g. bowel wall, Myelin Sheath)
V. Precautions
- See Monoclonal Antibody for preparation before first dose
VI. Medications
- Natalizumab injection solution: 300 mg/15 ml (intended for further dilution)
VII. Dosing: Adults
- Dosing is the same for Multiple Sclerosis and Inflammatory Bowel Disease
- Infuse 300 mg IV over 1 hour every 4 weeks
- Discontinue if insignificant clinical response at 12 weeks or unable to taper off chronic Corticosteroids at 6 months
VIII. Safety
- Unknown safety in pregnancy
- Unknown safety in Lactation
IX. Adverse Effects
- Hypersensitivity (including Anaphylaxis)
- Infusion reaction
- Headache Fatigue
- Hepatotoxicity
- Elevated Liver Function Tests (Transaminitis, Hyperbilirubinemia)
-
Progressive Multifocal Leukoencephalopathy (PML)
- Obtain John Cunningham Virus (JCV) Antibody every 6 months
- Discontinue Natalizumab if positive Antibody (increased PML risk)
- Discontinue (and MRI) if motor weakness, Incoordination or personality changes
X. Efficacy
-
Multiple Sclerosis
- May be superior to Interferon Beta-1 agents at preventing relapse
- May reduce relapse rate by >60%
-
Inflammatory Bowel Disease
- Slower effects than with TNF Inhibitors
XI. Resources
XII. References
- (2023) Biologics for Crohn's Disease, Presc Lett, #390826
- (2023) Drugs for Inflammatory Bowel Disease, Med Lett Drug Ther 65: 105-12