Risk Monitoring of Biologicals Derived from Adverse Reaction Management of Natalizumab: A Systematic Review Based on Serious Adverse Reaction Reports and Related Regulatory Documents_Chinese Journal of Evidence-Based Medicine

Authors：

LI Yuanyuan ,  LI Youping , SUN Xin , WANG Li

Division of Evidence-Based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

LI Youping, Email: yzmylab@hotmail.com

Keywords：

Natalizumab; Adverse reaction management; Biologicals; Risk monitoring; System review

DOI：

10.7507/1672-2531.20090214

Video：

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Objective 　To analyze the withdrawal reason of natalizumab in depth based on the serious adverse reaction reports and approval channel, and to provide decision references for more safe and effective report method of other biologicals.
Methods 　We searched MEDLINE, EMbase, and the official websites of Food and Drug Administration (FDA) for case reports, approval channel, and the relevant information of drug marketing or withdrawal.
Results 　Four case reports and fourteen official reports were included. Three cases of progressive multifocal leukoencephalopathy (PML) were reported in the clinical trials after natalizumab’s initially approval with two dead and one disabled, which could be retrieved by hemodialysis (2 cases hitherto). Consequently, multiple sclerosis (MS) patients were willing to bear the risk. Two cases of natalizumab-related PML (0.06‰) were confirmed in 32 000 patients without death report after two years of its remarketing, in July 2008. Another PML patient was reported in October 2008. Because of its non-substitutability for treating MS and Crohn disease (CD), FDA announced that patients could still use natalizumab under the close monitoring.
Conclusion 　(1) The most serious adverse reaction of treating MS and CD with natalizumab is PML, but it can be preventable and curable now. The monitoring findings of efficacy and adverse reaction during the postmarketing indicate that the review system is perfect and practicable relatively, and can give references for other high-risk drugs on the fast or standard approval channel, for example, Chinese medicine injection can draw lessons from it. (2) The remarketing of natalizumab not only provide significant risk management precedent for other drug-development firms, but also brings hope to the remarketing or relaunching clinical trials for the suspected sideeffect drugs. (3) Because of the fast-track reviewing of natalizumab and the overlap between the research of Good Clinical Practice (GCP) and the post-marketing evaluation, we should continue to track the information and provide new evidence.

Citation： LI Yuanyuan,LI Youping,SUN Xin,WANG Li. Risk Monitoring of Biologicals Derived from Adverse Reaction Management of Natalizumab: A Systematic Review Based on Serious Adverse Reaction Reports and Related Regulatory Documents. Chinese Journal of Evidence-Based Medicine, 2009, 09(11): 1185-1192. doi: 10.7507/1672-2531.20090214 Copy

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2.	Demasters BK , Tyler KL. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med, 2005, 353: 369-374.
3.	Gould A, Atlas S, Green AJ, et al. Pelletier D. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med, 2005, 353: 375-381.
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28.	Tysabri Relaunch Solid, As Efficacy Trumps Risk. [cited 2009, Aug, 15]. Available from: URL: (http://blogs.wsj.com/health/2008/02/29/ tysabri-relaunch-solid-as-efficacy-trumps-risk/).
29.	Walsh G. Biopharmaceutical benchmarks 2006. Nat Biotechnol, 2006, 24(7): 769-776.
30.	Aggarwal S. What’s fueling the biotech engine? Nat Biotechnol, 2007, 25(10): 1097-2011.

1. Assche GV, Ranst PD, RafSciot PD, et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med, 2005, 353: 1-7.
2. Demasters BK , Tyler KL. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med, 2005, 353: 369-374.
3. Gould A, Atlas S, Green AJ, et al. Pelletier D. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med, 2005, 353: 375-381.
4. Hartung HP . New cases of progressive multifocal leukoencephalopathy after treatment with natalizumab. Lancet Neurol, 2009, 8: 28-31.
5. U.S. Department of Health and Human Services. Center for Drug Evaluation and Research 2002 Report to the Nation Improving Public Health Through Human Drugs [cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/downloads/AboutFDA/ CentersOffices/CDER/WhatWeDo/UCM078985.pdf.
6. U.S. Department of Health and Human Services. Center for Drug Evaluation and Research 2003 Report to the NationReport to the Nation Improving Public Health Through Human Drugs[cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/downloads/ AboutFDA/CentersOffices/CDER/WhatWeDo/UCM078975.pdf. U.S. Department of Health and Human Services.
7. U.S. Department of Health and Human Services.Center for Drug Evaluation and Research 2004 Report to the NationReport to the Nation Improving Public Health Through Human Drugs[cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/downloads/ AboutFDA/CentersOffices/CDER/WhatWeDo/UCM078941.pdf..
8. U.S. Department of Health and Human Services.Center for Drug Evaluation and Research 2005 Report to the NationReport to the Nation Improving Public Health Through Human Drugs[cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/downloads/ AboutFDA/CentersOffices/CDER/WhatWeDo/UCM078935.pdf.
9. U.S. Department of Health and Human Services.Center for Drug Evaluation and Research UPDAE[cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/downloads/AboutFDA/ CentersOffices/CDER/WhatWeDo/UCM121704.pdf.
10. NME Drug and New Biologic Approvals in 2002[cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/Drugs/Developmen tApprovalProcess/HowDrugsareDevelopedandApproved/Drugan dBiologicApprovalReports/NMEDrugandNewBiologicApprovals/ ucm081683.htm.
11. NME Drug and New Biologic Approvals in 2003[cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/Drugs/Developmen tApprovalProcess/HowDrugsareDevelopedandApproved/Drugan dBiologicApprovalReports/NMEDrugandNewBiologicApprovals/ ucm081680.htm.
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13. NME Drug and New Biologic Approvals in 2005[cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/Drugs/Developmen tApprovalProcess/HowDrugsareDevelopedandApproved/Drugan dBiologicApprovalReports/NMEDrugandNewBiologicApprovals/ ucm081676.htm.
14. NME Drug and New Biologic Approvals in 2006[cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/Drugs/Developmen tApprovalProcess/HowDrugsareDevelopedandApproved/Drugan dBiologicApprovalReports/NMEDrugandNewBiologicApprovals/ ucm081673.htm.
15. NME Drug and New Biologic Approvals in [cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/Drugs/DevelopmentA pprovalProcess/HowDrugsareDevelopedandApproved/Drugand BiologicApprovalReports/NMEDrugandNewBiologicApprovals/ ucm081690.htm 2007.
16. CDER New Molecular Entity (NME) Drug and New Biologic Approvals for Calendar Year 2008 Updated through November 30, 2008[cited 2009, Aug, 15]. Available from: URL: http://www.fda. gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsare DevelopedandApproved/DrugandBiologicApprovalReports/NMEDr ugandNewBiologicApprovals/UCM081805.pdf.
17. CDER Approval Times for Priority and Standard NMEs and New BLAs CY 1993 – 2008[cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProces s/HowDrugsareDevelopedandApproved/DrugandBiologicApproval Reports/UCM123959.pdf.
18. Fast Track, Accelerated Approval and Priority Review[cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/ForConsumers/ ByAudience/ForPatientAdvocates/SpeedingAccesstoImportantNew Therapies/ucm128291.htm.
19. 杜蕾. 新药的快速审批及风险. 上海食品药品监管情报研究, 2007, (87): 1-4, 47.
20. Shankar G, Pendley C, Stein KE. A risk—based bioanalytical strategy for the assessment of antibody immune responses against biological drugs. Nat Biotechnol, 2007, 25(5):555-561.
21. Baumann A. Early development of therapeutic biologics– pharmacokinetics. Curr DrugMetab, 2006, 7(1): 15-21.
22. Schneeweiss S. Developments in post-marketing comparative effectiveness research. Clin Pharmacol Ther, 2007, 82(2): 143-156.
23. Stricker BH, Psaty BM. Detection, verification, and quantification of adverse drug reactions. BMJ, 2004, 329(7456): 44-47.
24. Giezen TJ, Mantel-Teeuwisse AK, Straus SM, et al. Safety-Related Regulatory Actions for Biologicals Approved in the United States and the European Union. JAMA, 2008, 300(16): 1887-1896.
25. FDA Issues Final Risk Minimization Guiances[EB/OL]. [cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/bbs/topics/ news/2005/NEW01169.html.
26. Yousry TA, Habil M, Major EO, et al. Evaluation of Patients Treated with Natalizumab for Progressive Multifocal Leukoencephalopathy. N Engl J Med, 2006, 354: 924-933.
27. Information on Natalizumab (marketed as Tysabri). [cited 2009, Aug, 15]. Available from: URL: http://www.fda.gov/Drugs/ DrugSafety/PostmarketDrugSafetyInformationforPatientsandProvid ers/ucm107198.htm.
28. Tysabri Relaunch Solid, As Efficacy Trumps Risk. [cited 2009, Aug, 15]. Available from: URL: (http://blogs.wsj.com/health/2008/02/29/ tysabri-relaunch-solid-as-efficacy-trumps-risk/).
29. Walsh G. Biopharmaceutical benchmarks 2006. Nat Biotechnol, 2006, 24(7): 769-776.
30. Aggarwal S. What’s fueling the biotech engine? Nat Biotechnol, 2007, 25(10): 1097-2011.

Chinese Journal of Evidence-Based Medicine

Risk Monitoring of Biologicals Derived from Adverse Reaction Management of Natalizumab: A Systematic Review Based on Serious Adverse Reaction Reports and Related Regulatory Documents

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