Stratyfikacja ryzyka postępującej wieloogniskowej leukoencefalopatii u chorych na stwardnienie rozsiane leczonych natalizumabem Artykuł przeglądowy
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Opublikowane:
cze 30, 2026
Słowa kluczowe:
natalizumab, postępująca wieloogniskowa leukoencefalopatia, wirus JC
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Abstrakt
Postępująca wieloogniskowa leukoencefalopatia (PML) to rzadkie, ale poważne powikłanie leczenia immunosupresyjnego i immunomodulującego. Najwyższy odsetek przypadków PML u chorych na stwardnienie rozsiane odnotowuje się wśród leczonych natalizumabem. Jednocześnie wysoka skuteczność tego leku w redukowaniu aktywności rzutowej, radiologicznej i progresji niepełnosprawności wskazuje na jego przydatność w terapii stwardnienia rozsianego, także w strategii wczesnego leczenia terapiami o wysokiej skuteczności. Z tego powodu niezbędne są narzędzia oceny i zarządzania ryzykiem PML u leczonych natalizumabem. Artykuł ten ma na celu scharakteryzowanie PML i omówienie sposobów ograniczenia ryzyka jej wystąpienia wraz z praktycznymi wskazówkami możliwymi do zastosowania w postępowaniu klinicznym.
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Bibliografia
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2. Markowitz RB, Thompson HC, Mueller JF et al. Incidence of BK virus and JC virus viruria in human immunodeficiency virus-infected and -uninfected subjects. J Infect Dis. 1993; 167(1): 13-20.
3. Astrom KE, Mancall EL, Richardson EP Jr. Progressive multifocal leuko-encephalopathy; a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin’s disease. Brain. 1958; 81(1): 93-111.
4. Grebenciucova E, Berger JR. Progressive Multifocal Leukoencephalopathy. Neurol Clin. 2018; 36(4): 739-50.
5. Bellizzi A, Anzivino E, Rodio DM et al. New insights on human polyomavirus JC and pathogenesis of progressive multifocal leukoencephalopathy. Clin Dev Immunol. 2013; 2013: 839719.
6. Berger JR, Aksamit AJ, Clifford DB et al. PML diagnostic criteria: consensus statement from the AAN Neuroinfectious Disease Section. Neurology. 2013; 80(15): 1430-8.
7. Brew B, Davies N, Cinque P et al. Progressive multifocal leukoencephalopathy and other forms of JC virus disease. Nat Rev Neurol. 2010; 6: 667-79.
8. Schweitzer F, Laurent S, Cortese I et al. Progressive Multifocal Leukoencephalopathy: Pathogenesis, Diagnostic Tools, and Potential Biomarkers of Response to Therapy. Neurology. 2023; 101(16): 700-13.
9. Sriwastava S, Kataria S, Srivastava S et al. Disease-modifying therapies and progressive multifocal leukoencephalopathy in multiple sclerosis: A systematic review and meta-analysis. J Neuroimmunol. 2021; 360: 577721.
10. Polman CH, O’Connor PW, Havrdova E et al.; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006; 354(9): 899-910.
11. Kappos L, O’Connor PW, Polman CH et al. Clinical effects of natalizumab on multiple sclerosis appear early in treatment course. J Neurol. 2013; 260(5): 1388-95.
12. Krysko KM, O’Connor PW. The Toronto observational study of natalizumab in multiple sclerosis. Can J Neurol Sci. 2011; 38(3): 422-8.
13. Outteryck O, Ongagna JC, Brochet B et al.; BIONAT Network; CFSEP. A prospective observational post-marketing study of natalizumab-treated multiple sclerosis patients: clinical, radiological and biological features and adverse events. The BIONAT cohort. Eur J Neurol. 2014; 21(1): 40-8.
14. Butzkueven H, Kappos L, Wiendl H et al.; Tysabri Observational Program (TOP) Investigators. Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP). J Neurol Neurosurg Psychiatry. 2020; 91(6): 660-8.
15. Singer BA, Feng J, Chiong-Rivero H. Early use of high-efficacy therapies in multiple sclerosis in the United States: benefits, barriers, and strategies for encouraging adoption. J Neurol. 2024; 271(6): 3116-30.
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17. Kleinschmidt-DeMasters BK, Tyler KL. Progressive Multifocal Leukoencephalopathy Complicating Treatment with Natalizumab and Interferon Beta-1a for Multiple Sclerosis. N Engl J Med. 2005; 353: 369-74.
18. Rindi LV, Zaçe D, Braccialarghe N et al. Drug-Induced Progressive Multifocal Leukoencephalopathy (PML): A Systematic Review and Meta-Analysis. Drug Saf. 2024; 47(4): 333-54.
19. Kartau M, Sipilä JO, Auvinen E et al. Progressive Multifocal Leukoencephalopathy: Current Insights. Degener Neurol Neuromuscul Dis. 2019; 9: 109-21.
20. Rae-Grant A, Day GS, Marrie RA et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018; 90(17): 777-88.
21. 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): e1452-62.
22. Toorop AA, van Lierop ZY, Gelissen LM et al. Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS). J Neurol Neurosurg Psychiatry. 2024; 95(5): 392-400.
23. Nakashima I, Ohashi T, Yokoyama K et al. A multicenter, retrospective study in patients with multiple sclerosis treated with natalizumab in a real-world setting in Japan: The REFIND study. Mult Scler Relat Disord. 2026; 107: 107007.
24. Yamout BI, Sahraian MA, Ayoubi NE et al. Efficacy and safety of natalizumab extended interval dosing. Mult Scler Relat Disord. 2018; 24: 113-6.
25. Chitnis T, Magliozzi R, Abdelhak A et al. Blood and CSF biomarkers for multiple sclerosis: emerging clinical applications. Lancet Neurol. 2025; 24(12): 1066-78.
2. Markowitz RB, Thompson HC, Mueller JF et al. Incidence of BK virus and JC virus viruria in human immunodeficiency virus-infected and -uninfected subjects. J Infect Dis. 1993; 167(1): 13-20.
3. Astrom KE, Mancall EL, Richardson EP Jr. Progressive multifocal leuko-encephalopathy; a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin’s disease. Brain. 1958; 81(1): 93-111.
4. Grebenciucova E, Berger JR. Progressive Multifocal Leukoencephalopathy. Neurol Clin. 2018; 36(4): 739-50.
5. Bellizzi A, Anzivino E, Rodio DM et al. New insights on human polyomavirus JC and pathogenesis of progressive multifocal leukoencephalopathy. Clin Dev Immunol. 2013; 2013: 839719.
6. Berger JR, Aksamit AJ, Clifford DB et al. PML diagnostic criteria: consensus statement from the AAN Neuroinfectious Disease Section. Neurology. 2013; 80(15): 1430-8.
7. Brew B, Davies N, Cinque P et al. Progressive multifocal leukoencephalopathy and other forms of JC virus disease. Nat Rev Neurol. 2010; 6: 667-79.
8. Schweitzer F, Laurent S, Cortese I et al. Progressive Multifocal Leukoencephalopathy: Pathogenesis, Diagnostic Tools, and Potential Biomarkers of Response to Therapy. Neurology. 2023; 101(16): 700-13.
9. Sriwastava S, Kataria S, Srivastava S et al. Disease-modifying therapies and progressive multifocal leukoencephalopathy in multiple sclerosis: A systematic review and meta-analysis. J Neuroimmunol. 2021; 360: 577721.
10. Polman CH, O’Connor PW, Havrdova E et al.; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006; 354(9): 899-910.
11. Kappos L, O’Connor PW, Polman CH et al. Clinical effects of natalizumab on multiple sclerosis appear early in treatment course. J Neurol. 2013; 260(5): 1388-95.
12. Krysko KM, O’Connor PW. The Toronto observational study of natalizumab in multiple sclerosis. Can J Neurol Sci. 2011; 38(3): 422-8.
13. Outteryck O, Ongagna JC, Brochet B et al.; BIONAT Network; CFSEP. A prospective observational post-marketing study of natalizumab-treated multiple sclerosis patients: clinical, radiological and biological features and adverse events. The BIONAT cohort. Eur J Neurol. 2014; 21(1): 40-8.
14. Butzkueven H, Kappos L, Wiendl H et al.; Tysabri Observational Program (TOP) Investigators. Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP). J Neurol Neurosurg Psychiatry. 2020; 91(6): 660-8.
15. Singer BA, Feng J, Chiong-Rivero H. Early use of high-efficacy therapies in multiple sclerosis in the United States: benefits, barriers, and strategies for encouraging adoption. J Neurol. 2024; 271(6): 3116-30.
16. Program Lekowy Leczenie Chorych Na Stwardnienie Rozsiane B.29.
17. Kleinschmidt-DeMasters BK, Tyler KL. Progressive Multifocal Leukoencephalopathy Complicating Treatment with Natalizumab and Interferon Beta-1a for Multiple Sclerosis. N Engl J Med. 2005; 353: 369-74.
18. Rindi LV, Zaçe D, Braccialarghe N et al. Drug-Induced Progressive Multifocal Leukoencephalopathy (PML): A Systematic Review and Meta-Analysis. Drug Saf. 2024; 47(4): 333-54.
19. Kartau M, Sipilä JO, Auvinen E et al. Progressive Multifocal Leukoencephalopathy: Current Insights. Degener Neurol Neuromuscul Dis. 2019; 9: 109-21.
20. Rae-Grant A, Day GS, Marrie RA et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018; 90(17): 777-88.
21. 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): e1452-62.
22. Toorop AA, van Lierop ZY, Gelissen LM et al. Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS). J Neurol Neurosurg Psychiatry. 2024; 95(5): 392-400.
23. Nakashima I, Ohashi T, Yokoyama K et al. A multicenter, retrospective study in patients with multiple sclerosis treated with natalizumab in a real-world setting in Japan: The REFIND study. Mult Scler Relat Disord. 2026; 107: 107007.
24. Yamout BI, Sahraian MA, Ayoubi NE et al. Efficacy and safety of natalizumab extended interval dosing. Mult Scler Relat Disord. 2018; 24: 113-6.
25. Chitnis T, Magliozzi R, Abdelhak A et al. Blood and CSF biomarkers for multiple sclerosis: emerging clinical applications. Lancet Neurol. 2025; 24(12): 1066-78.