Trends in Immunotherapy

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The first study of real-world efficacy and safety of Natalizumab (Tysabri®) in Iran

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https://doi.org/10.24294/ti.v8.i1.3920
Amin Shahrbaf, M., Samimi, M., Karimi, S., Salari, M., Ghaffari, M., Yazdanbakhsh, S., Najafian, A., Vosough, M., & Massood Nabavi, S. (2024). The first study of real-world efficacy and safety of Natalizumab (Tysabri®) in Iran. Trends in Immunotherapy, 8(1). https://doi.org/10.24294/ti.v8.i1.3920
Volume 8 Issue 1 (2024)
Copyright (c) 2024 Mohammad Amin Shahrbaf, Monireh Samimi, Shahedeh Karimi, Mehri Salari, Mehran Ghaffari, Sepideh Yazdanbakhsh, Abbas Najafian, Massoud Vosough, Seyed Massood Nabavi
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Authors

  • Mohammad Amin Shahrbaf Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Tehran 16635-148, Iran; Arya Group for Treatment and Research in Multiple Sclerosis, Tehran 16635-148, Iran
  • Monireh Samimi Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Tehran 16635-148, Iran; Arya Group for Treatment and Research in Multiple Sclerosis, Tehran 16635-148, Iran
  • Shahedeh Karimi Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Tehran 16635-148, Iran; Arya Group for Treatment and Research in Multiple Sclerosis, Tehran 16635-148, Iran
  • Mehri Salari Neuro Functional Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
  • Mehran Ghaffari Neurology Department, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
  • Sepideh Yazdanbakhsh Arya Group for Treatment and Research in Multiple Sclerosis, Tehran 16635-148, Iran
  • Abbas Najafian Arya Group for Treatment and Research in Multiple Sclerosis, Tehran 16635-148, Iran
  • Massoud Vosough Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Tehran 16635-148, Iran; Arya Group for Treatment and Research in Multiple Sclerosis, Tehran 16635-148, Iran
  • Seyed Massood Nabavi
    Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Tehran 16635-148, Iran; Arya Group for Treatment and Research in Multiple Sclerosis, Tehran 16635-148, Iran

Objectives: Natalizumab is an injectable DMT (disease-modifying therapy) which used for RRMS (relapsing-remitting multiple sclerosis) since 2006. The drug has been available in Iran since 2014. Introduction: This study was aimed to evaluate the real-world effectiveness of Natalizumab in a referral center in Tehran, Iran. This study is the first real world analysis of efficacy and safety of Natalizumab in our country. Methods: In this retrospective study, patients with RRMS were investigated in a high-volume center in Tehran from 2019 to 2021. MS (Multiple Sclerosis) patients under treatment with Natalizumab who have received at least 3 infusions of the drug and had completed follow-up data, have been evaluated for safety and efficacy of Natalizumab. Results: 100 patients were included in the final analysis. The mean follow-up time was 20 months (6–33 months). The median EDSS (Expanded Disability Status Scale) score of patients reached to 2 from 2.5 after the treatment course (P < 0.0001). The annualized relapse rate (ARR) decreased from 0.81 (95% CI: 0.73–0.87) to 0.023 (95% CI 0.009–0.061). The median JCV (John Cunningham virus) index remained unchanged before treatment 0.85 (IQR: 0.21–2.41) compare to after the treatment 0.85 (IQR: 0.21–2.31). The number of patients with active brain and cervical MRI (Magnetic Resonance Imaging) lesions decreased significantly (P = 0.001). NEDA-3 (No evidence of disease activity) was improved from 9% to 87% after the treatment with Natalizumab. No serious adverse events except than one progressive multifocal encephalopathy (PML) case have been found. The main reasons of switching from Natalizumab to the other DMDs (Disease Modifying Drugs) were positive JC index, starting phase, noncompliance, pregnancy, MRI activity and seroconversion after starting the drug. Conclusion: Natalizumab is a safe and effective choice in RRMS patients for reducing relapse rate, disability score, active MRI lesion, and improving the NEDA (No evidence of disease activity).

Keywords:

multiple sclerosis disease modifying therapy Natalizumab

References

  1. Ezabadi SG, Sahraian MA, Maroufi H, et al. Global assessment of characteristics of multiple sclerosis registries; A systematic review. Multiple Sclerosis and Related Disorders. 2022; 63: 103928. doi: 10.1016/j.msard.2022.103928
  2. Killestein J, Wattjes MP. Low JC virus antibody index during natalizumab treatment less safe than assumed? Multiple Sclerosis Journal. 2015; 21(14): 1753-1754. doi: 10.1177/1352458515611499
  3. Kheradmand M, Afshari M, Nasehi MM, et al. Prevalence of subtypes of multiple sclerosis and the most common clinical symptoms in Iranian patients: A meta‐analysis. Clinical and Experimental Neuroimmunology. 2018; 10(1): 33-40. doi: 10.1111/cen3.12489
  4. Cohan SL, Hendin BA, Reder AT, et al. Interferons and Multiple Sclerosis: Lessons from 25 Years of Clinical and Real-World Experience with Intramuscular Interferon Beta-1a (Avonex). CNS Drugs. 2021; 35(7): 743-767. doi: 10.1007/s40263-021-00822-z
  5. Tsivgoulis G, Katsanos AH, Grigoriadis N, et al. The Effect of Disease Modifying Therapies on Disease Progression in Patients with Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis. Linker RA, ed. PLOS ONE. 2015; 10(12): e0144538. doi: 10.1371/journal.pone.0144538
  6. Ysrraelit MC, Caride A, Sinay V, et al. Real-world effectiveness of natalizumab treatment in patients with relapsing multiple sclerosis in Argentina and Chile. Arquivos de Neuro-Psiquiatria. 2021; 79(5): 407-414. doi: 10.1590/0004-282x-anp-2020-0303
  7. Brandstadter R, Katz Sand I. The use of natalizumab for multiple sclerosis. Neuropsychiatric Disease and Treatment. 2017; Volume 13: 1691-1702. doi: 10.2147/ndt.s114636
  8. Krysko KM, O’Connor PW. The Toronto Observational Study of Natalizumab in Multiple Sclerosis. Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques. 2011; 38(3): 422-428. doi: 10.1017/s0317167100011811
  9. Auer M, Zinganell A, Hegen H, et al. Experiences in treatment of multiple sclerosis with natalizumab from a real-life cohort over 15 years. Scientific Reports. 2021; 11(1). doi: 10.1038/s41598-021-02665-6
  10. Mathew T, Kamath V, John SK, et al. A real world multi center study on efficacy and safety of natalizumab in Indian patients with multiple sclerosis. Multiple Sclerosis and Related Disorders. 2022; 66: 104059. doi: 10.1016/j.msard.2022.104059
  11. Saida T, Yokoyama K, Sato R, et al. Safety and Effectiveness of Natalizumab: First Report of Interim Results of Post-Marketing Surveillance in Japan. Neurology and Therapy. 2017; 6(2): 197-211. doi: 10.1007/s40120-017-0084-6
  12. Lublin FD, Cutter G, Giovannoni G, et al. Natalizumab reduces relapse clinical severity and improves relapse recovery in MS. Multiple Sclerosis and Related Disorders. 2014; 3(6): 705-711. doi: 10.1016/j.msard.2014.08.005
  13. Cohan S, Chen C, Baraban E, et al. MRI utility in the detection of disease activity in clinically stable patients with multiple sclerosis: a retrospective analysis of a community based cohort. BMC Neurology. 2016; 16(1). doi: 10.1186/s12883-016-0699-8
  14. Horakova D, Uher T, Krasensky J, et al. Long-term effectiveness of natalizumab on MRI outcomes and no evidence of disease activity in relapsing-remitting multiple sclerosis patients treated in a Czech Republic real-world setting: A longitudinal, retrospective study. Multiple Sclerosis and Related Disorders. 2020; 46: 102543. doi: 10.1016/j.msard.2020.102543
  15. Boziki M, Bakirtzis C, Giantzi V, et al. Long-Term Efficacy Outcomes of Natalizumab vs. Fingolimod in Patients With Highly Active Relapsing-Remitting Multiple Sclerosis: Real-World Data From a Multiple Sclerosis Reference Center. Frontiers in Neurology. 2021; 12. doi: 10.3389/fneur.2021.699844
  16. Hersh CM, Harris H, Conway D, et al. Effect of switching from natalizumab to moderate- vs high-efficacy DMT in clinical practice. Neurology Clinical Practice. 2020; 10(6). doi: 10.1212/cpj.0000000000000809
  17. Sá MJ, Nunes CC, da Silva AM, et al. JC virus antibodies in Portuguese multiple sclerosis patients: JUSTIFY study results. Journal of the Neurological Sciences. 2019; 406: 116426. doi: 10.1016/j.jns.2019.116426
  18. Bozic C, Subramanyam M, Richman S, et al. Anti‐JC virus (JCV) antibody prevalence in the JCV Epidemiology in MS (JEMS) trial. European Journal of Neurology. 2013; 21(2): 299-304. doi: 10.1111/ene.12304
  19. Clerico M, Artusi C, Liberto A, et al. Natalizumab in Multiple Sclerosis: Long-Term Management. International Journal of Molecular Sciences. 2017; 18(5): 940. doi: 10.3390/ijms18050940
  20. McGuigan C, Craner M, Guadagno J, et al. Stratification and monitoring of natalizumab-associated progressive multifocal leukoencephalopathy risk: recommendations from an expert group. Journal of Neurology, Neurosurgery and Psychiatry. 2016; 87(2): 117-125.
  21. Peters J, Williamson E. Natalizumab therapy is associated with changes in serum JC virus antibody indices over time. Journal of Neurology. 2017; 264(12): 2409-2412. doi: 10.1007/s00415-017-8643-4
  22. Schwab N, Schneider-Hohendorf T, Pignolet B, et al. Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values. Neurology Neuroimmunology & Neuroinflammation. 2016; 3(1). doi: 10.1212/nxi.0000000000000195
  23. Plavina T, Subramanyam M, Bloomgren G, et al. Anti–JC virus antibody levels in serum or plasma further define risk of natalizumab‐associated progressive multifocal leukoencephalopathy. Annals of Neurology. 2014; 76(6): 802-812. doi: 10.1002/ana.24286
  24. Warnke C, Ramanujam R, Plavina T, et al. Changes to anti-JCV antibody levels in a Swedish national MS cohort. Journal of Neurology, Neurosurgery & Psychiatry. 2013; 84(11): 1199-1205. doi: 10.1136/jnnp-2012-304332
  25. Chalkley JJ, Berger JR. Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis. Current Neurology and Neuroscience Reports. 2013; 13(12). doi: 10.1007/s11910-013-0408-6
  26. Ryerson LZ, Foley J, Chang I, et al. Risk of natalizumab-associated PML in patients with MS is reduced with extended interval dosing. Neurology. 2019; 93(15). doi: 10.1212/wnl.0000000000008243
  27. Borriello G, Ianniello A. COVID-19 occurring during Natalizumab treatment: a case report in a patient with extended interval dosing approach. Multiple Sclerosis and Related Disorders. 2020; 41: 102165. doi: 10.1016/j.msard.2020.102165
  28. Khalagi K, Gharibzadeh S, Khalili D, et al. Prevalence of COVID-19 in Iran: results of the first survey of the Iranian COVID-19 Serological Surveillance programme. Clinical Microbiology and Infection. 2021; 27(11): 1666-1671. doi: 10.1016/j.cmi.2021.06.002
  29. Morrow SA, Clift F, Devonshire V, et al. Use of natalizumab in persons with multiple sclerosis: 2022 update. Multiple Sclerosis and Related Disorders. 2022; 65: 103995. doi: 10.1016/j.msard.2022.103995
  30. Jaklin AK, Benjaminsen E, Alstadhaug KB. Effectiveness of Natalizumab in Achieving No Evidence of Disease Activity (NEDA-3)—Data From a Local Norwegian Cohort. Frontiers in Neurology. 2021; 12. doi: 10.3389/fneur.2021.765837
  31. Prosperini L, Saccà F, Cordioli C, et al. Real-world effectiveness of natalizumab and fingolimod compared with self-injectable drugs in non-responders and in treatment-naïve patients with multiple sclerosis. Journal of Neurology. 2016; 264(2): 284-294. doi: 10.1007/s00415-016-8343-5
  32. Perumal J, Fox RJ, Balabanov R, et al. Outcomes of natalizumab treatment within 3 years of relapsing-remitting multiple sclerosis diagnosis: a prespecified 2-year interim analysis of STRIVE. BMC Neurology. 2019; 19(1). doi: 10.1186/s12883-019-1337-z
  33. Hartung HP, Mares J, Meuth SG, et al. Multiple Sclerosis: Switching from Natalizumab to Other High-Efficacy Treatments to Mitigate Progressive Multifocal Leukoencephalopathy Risk. Neurotherapeutics. 2021; 18(3): 1654-1656. doi: 10.1007/s13311-021-01102-w
  34. van Lierop Z, Toorop A, Coerver E, et al. Ocrelizumab after natalizumab in JC-virus positive relapsing remitting multiple sclerosis patients. Multiple Sclerosis Journal - Experimental, Translational and Clinical. 2021; 7(2): 205521732110138. doi: 10.1177/20552173211013831
  35. Alping P, Frisell T, Novakova L, et al. Rituximab versus fingolimod after natalizumab in multiple sclerosis patients. Annals of Neurology. 2016; 79(6): 950-958. doi: 10.1002/ana.24651
  36. Butzkueven H, Kappos L, Wiendl H, et al. Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP). Journal of Neurology, Neurosurgery & Psychiatry. 2020; 91(6): 660-668. doi: 10.1136/jnnp-2019-322326