Contents

Search

natalizumab (Tysabri)

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: 1) investigational treatment of multiple sclerosis [6]* 2) treatment of Crohn's disease, FDA approved 2008 * on list of drugs to avoid for treatment of multiple sclerosis [11] - disproportionate adverse effects cited Contraindications: - pregnancy category: C Dosage: - 300 mg by intravenous infusion monthly - every 5-12 weeks may reduce incidence of PML Monitor: - per TOUCH Prescribing Program - JC virus antibody Adverse effects: 1) headache (common) 2) chest discomfort (common) 3) nausea 4) rash 5) immunosuppression, risk for infections 6) depression 7) infusion reactions, hypersensitivity, anaphylaxis 8) progressive multifocal leukoencephalopathy [3,6,7,9] a) risk increases with number of infusions [8] b) risk linked to exposure to JC virus c) risk estimated at 1% with treatment > 2 years [9] d) extending dosage interval from every 4 weeks to every 5-12 weeks every 5 to 12 weeks may reduced risk of PML in JC virus Ab+ patients [12] 9) hepatotoxicity (rare) [5] Laboratory: - natalizumab Ab in serum Mechanism of action: 1) recombinant humanized IgG4-kappa monoclonal antibody produced in murine myeloma cells 2) 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) 3) regulates immune-cell activation within inflamed tissue 4) may reduce replapses (MS) 60% Notes: Cost = $24,000 yearly

Interactions

drug adverse effects of immunosuppressive agents monitor with immunosuppressive agents

General

pharmaceutical 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#: 210109 (subscription needed) http://www.prescribersletter.com
  3. Prescriber's Letter 13(2): 2006 Detail-Document#: 220215 (subscription needed) http://www.prescribersletter.com
  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: 16510744 - 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: 16510745 - 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: 16510746
  5. FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Tysabri
  6. FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Tysabri2
  7. FDA MedWatch Information on Natalizumab (marketed as Tysabri) Updated Information: [9/2009] http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm107198.htm
  8. FDA MedWatch Tysabri (Natalizumab): Update of Healthcare Professional Information http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm199965.htm
  9. FDA MedWatch Tysabri (natalizumab): Drug Safety Communication - New Risk Factor for Progressive Multifocal Leukoencephalopathy (PML) Posted 01/20/2012 http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm288602.htm
  10. Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018.
  11. Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
  12. Campbell N et al Natalizumab Extended Interval Dosing Is Associated with a Reduction in Progressive Multifocal Leukoencephalopathy Risk in the Touch Registry. ACTRIMS Forum 2018, Feb 2 https://plan.core-apps.com/actrims2018/abstract/270ea0dccc6053d1219f9d4fc3570a3b
  13. Tysabri Outreach:Unified Commitment to Health (TOUCH) http://www.tysabri.com (800) 456-2255