Natalizumab

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Dosage 4 Adverse-effects 5 Mechanism-of-action 6 Notes 7 More General Terms 8 References

Introduction

• Marketing suspended for evaluation of two cases of progressive multifocal leukoencephalopathy.

• Patients & prescribers must be enrolled in the Tysabri Outreach:Unified Commitment to Health (TOUCH) Prescribing program. Pharmacies must be authorized by the TOUCH Prescribing Program to dispense Tysabri. [7]

Indications

• investigational treatment of multiple sclerosis [6]
• treatment of Crohn's disease, FDA approved 2008

Dosage

• 300 mg by intravenous infusion monthly

Adverse-effects

• immunosuppression
• depression
• hypersensitivity, anaphylaxis
• progressive multifocal leukoencephalopathy [3,6,7,9]

• risk increases with number of infusions [8]
• risk linked to exposure to JC virus
• risk estimated at 1% with treatment > 2 years [9]

• hepatotoxicity [5]
  
• drug adverse effects of immunosuppressive agents

Mechanism-of-action

• recombinant humanized IgG4kappa monoclonal antibody produced in murine myeloma cells
• monoclonal antibody: binds to integrin alpha-4 subunit ( adhesion-molecule inhibitor)

• the glycoprotein alpha4 beta1-integrin a mediator of cell adhesion & transendothelial migration (blocks immune cells from entering CNS)

• regulates immune-cell activation within inflamed tissue
• may reduce replapses ( MS) 60%

Notes

• Cost = $24,000 yearly

More General Terms

• monoclonal antibody
• immunosuppressive agent

References

1. Journal Watch 23(4):34, 2003 Miller DH et al, N Engl J Med 348:15, 2003 Ghoush S et al, N Engl J Med 348:24, 2003 von Andrian UH & Engelhardt B, N Engl J Med 348:68, 2003
2. Prescriber's Letter 12(1): 2005 New Drug: Tysabri (Natalizumab) Detail-Document#: [1] (subscription needed) [2]
3. Prescriber's Letter 13(2): 2006 Detail-Document#: [3] (subscription needed) [4]
4. Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):899-910. PMID: [5]
   - Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue EW, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, Panzara MA, Sandrock AW; SENTINEL Investigators. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):911-23. PMID: [6]
   - Yousry TA, Major EO, Ryschkewitsch C, Fahle G, Fischer S, Hou J, Curfman B, Miszkiel K, Mueller-Lenke N, Sanchez E, Barkhof F, Radue EW, Jager HR, Clifford DB. Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med. 2006 Mar 2;354(9):924-33. PMID: [7]
5. FDA MedWatch [8]
6. FDA MedWatch [9]
7. FDA MedWatch Information on Natalizumab (marketed as Tysabri) Updated Information: [9/2009] [10]
8. FDA MedWatch Tysabri (Natalizumab): Update of Healthcare Professional Information [11]
9. FDA MedWatch Tysabri (natalizumab): Drug Safety Communication - New Risk Factor for Progressive Multifocal Leukoencephalopathy (PML) Posted 01/20/2012 [12]
10. Tysabri Outreach:Unified Commitment to Health (TOUCH) [13] (800) 456-2255
11. National Guideline Clearinghouse Natalizumab for the treatment of adults with highly active relapsing-remitting multiple sclerosis. National Institute for Health and Clinical Excellence ngc-guideline: [14]
    - Assessment: the use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review). Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. ngc-guideline: [15]

natalizumab (Tysabri)