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
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Definition (NCI) | A humanized recombinant IgG4 monoclonal antibody directed against the alpha4 subunit of the integrins alpha4beta1and alpha4beta7 with immunomodulating, anti-inflammatory, and potential antineoplastic activities. Natalizumab binds to the alpha4-subunit of alpha4beta1 and alpha4beta7 integrins expressed on the surface of all leukocytes except neutrophils, inhibiting the alpha4-mediated adhesion of leukocytes to counter-receptor(s) such as vascular cell adhesion molecule-1 (VCAM-1); natalizumab-mediated disruption of VCAM-1 binding by these integrins may prevent the transmigration of leukocytes across the endothelium into inflamed parenchymal tissue. Integrins are cellular adhesion molecules (CAMs) that are upregulated in various types of cancer and some autoimmune diseases; alpha4beta1 integrin (VLA4) has been implicated in the survival of myeloma cells, possibly by mediating their adhesion to stromal cells. |
Concepts | Amino Acid, Peptide, or Protein (T116) , Immunologic Factor (T129) , Pharmacologic Substance (T121) |
MSH | C469407 |
SnomedCT | 414804006, 414805007 |
LNC | LP64671-8 |
Spanish | Natalizumab, Natalizumab (producto), Natalizumab (sustancia) |
English | natalizumab (medication), Anti-VLA4, natalizumab [Chemical/Ingredient], natalizumab, Natalizumab, Natalizumab (product), Natalizumab (substance), NATALIZUMAB |