PDF herunterladen
Semin Neurol 2013; 33(01): 026-036
DOI: 10.1055/s-0033-1343793
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Natalizumab Therapy for Multiple Sclerosis

Tobias Derfuss
1   Department of Neurology, University Hospital Basel, Basel, Switzerland
2   Division of Clinical Neuroimmunology, Department of Biomedicine, Basel, Switzerland
,
Jens Kuhle
1   Department of Neurology, University Hospital Basel, Basel, Switzerland
2   Division of Clinical Neuroimmunology, Department of Biomedicine, Basel, Switzerland
3   Queen Mary University of London, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK
,
Raija Lindberg
2   Division of Clinical Neuroimmunology, Department of Biomedicine, Basel, Switzerland
,
Ludwig Kappos
1   Department of Neurology, University Hospital Basel, Basel, Switzerland
2   Division of Clinical Neuroimmunology, Department of Biomedicine, Basel, Switzerland
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
25. Mai 2013 (online)

    Lizenzen und Reprints

Abstract

Natalizumab is a monoclonal therapeutic antibody that inhibits migration of lymphocytes into the central nervous system (CNS) by blocking integrins. Several clinical trials have shown an excellent efficacy in the treatment of relapsing remitting multiple sclerosis. This efficacy is also underlined by postmarketing data of patients with a more aggressive disease compared with the clinical trials. Certain patients might even improve during natalizumab treatment. These positive effects have to be balanced against potential adverse events. In this respect, allergic reactions, hematologic abnormalities, melanoma, lymphoma, infections, and most importantly, progressive multifocal leukoencephalopathy (PML) are discussed. A special emphasis is put on the risk stratification algorithm for PML and approaches for PML treatment. Further, patient and disease characteristics are discussed that might prompt the start or cessation of natalizumab. Finally, data on how to continue after stopping natalizumab are summarized.

Keywords

natalizumab - multiple sclerosis - progressive multifocal leukoencephalopathy
 

  • References

  • 1 Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N. Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 1992; 356 (6364) 63-66
    CrossrefPubMedGoogle Scholar
  • 2 Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell 2002; 110 (6) 673-687
    CrossrefPubMedGoogle Scholar
  • 3 Miller DH, Khan OA, Sheremata WA , et al; International Natalizumab Multiple Sclerosis Trial Group. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2003; 348 (1) 15-23
    CrossrefPubMedGoogle Scholar
  • 4 Tubridy N, Behan PO, Capildeo R , et al; The UK Antegren Study Group. The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. Neurology 1999; 53 (3) 466-472
    CrossrefPubMedGoogle Scholar
  • 5 Dalton CM, Miszkiel KA, Barker GJ , et al. Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis. J Neurol 2004; 251 (4) 407-413
    CrossrefPubMedGoogle Scholar
  • 6 O'Connor PW, Goodman A, Willmer-Hulme AJ , et al; Natalizumab Multiple Sclerosis Trial Group. Randomized multicenter trial of natalizumab in acute MS relapses: clinical and MRI effects. Neurology 2004; 62 (11) 2038-2043
    CrossrefPubMedGoogle Scholar
  • 7 Rudick RA, Stuart WH, Calabresi PA , et al; SENTINEL Investigators. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006; 354 (9) 911-923
    CrossrefPubMedGoogle Scholar
  • 8 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
    CrossrefPubMedGoogle Scholar
  • 9 Miller DH, Soon D, Fernando KT , et al; AFFIRM Investigators. MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurology 2007; 68 (17) 1390-1401
    CrossrefPubMedGoogle Scholar
  • 10 Havrdova E, Galetta S, Hutchinson M , et al. Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study. Lancet Neurol 2009; 8 (3) 254-260
    CrossrefPubMedGoogle Scholar
  • 11 Radue EW, Stuart WH, Calabresi PA , et al; SENTINEL Investigators. Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis. J Neurol Sci 2010; 292 (1-2) 28-35
    CrossrefPubMedGoogle Scholar
  • 12 Cree BA, Stuart WH, Tornatore CS, Jeffery DR, Pace AL, Cha CH. Efficacy of natalizumab therapy in patients of African descent with relapsing multiple sclerosis: analysis of AFFIRM and SENTINEL data. Arch Neurol 2011; 68 (4) 464-468
    CrossrefPubMedGoogle Scholar
  • 13 Cree BA, Al-Sabbagh A, Bennett R, Goodin D. Response to interferon beta-1a treatment in African American multiple sclerosis patients. Arch Neurol 2005; 62 (11) 1681-1683
    CrossrefPubMedGoogle Scholar
  • 14 Hutchinson M, Kappos L, Calabresi PA , et al; AFFIRM and SENTINEL Investigators. The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL. J Neurol 2009; 256 (3) 405-415
    CrossrefPubMedGoogle Scholar
  • 15 Weinstock-Guttman B, Galetta SL, Giovannoni G , et al. Additional efficacy endpoints from pivotal natalizumab trials in relapsing-remitting MS. J Neurol 2012; 259 (5) 898-905
    CrossrefPubMedGoogle Scholar
  • 16 Rudick RA, Miller D, Hass S , et al; AFFIRM and SENTINEL Investigators. Health-related quality of life in multiple sclerosis: effects of natalizumab. Ann Neurol 2007; 62 (4) 335-346
    CrossrefPubMedGoogle Scholar
  • 17 Goodman AD, Rossman H, Bar-Or A , et al; GLANCE Investigators. GLANCE: results of a phase 2, randomized, double-blind, placebo-controlled study. Neurology 2009; 72 (9) 806-812
    CrossrefPubMedGoogle Scholar
  • 18 O'Connor P, Polman C, Goodman A , et al. Efficacy and safety of natalizumab in the STRATA study. Paper presented at: 61st Annual Meeting of the American Academy of Neurology. ; April 25–May 2, 2009; Seattle, WA
    PubMedGoogle Scholar
  • 19 O'Connor PW, Goodman A, Kappos L , et al. Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis. Neurology 2011; 76 (22) 1858-1865
    CrossrefPubMedGoogle Scholar
  • 20 Lanzillo R, Bonavita S, Quarantelli M , et al. Natalizumab is effective in multiple sclerosis patients switching from other disease modifying therapies in clinical practice. Neurol Sci 2012;
    PubMedGoogle Scholar
  • 21 Prosperini L, Giannì C, Leonardi L , et al. Escalation to natalizumab or switching among immunomodulators in relapsing multiple sclerosis. Mult Scler 2012; 18 (1) 64-71
    CrossrefPubMedGoogle Scholar
  • 22 Putzki N, Yaldizli O, Bühler R, Schwegler G, Curtius D, Tettenborn B. Natalizumab reduces clinical and MRI activity in multiple sclerosis patients with high disease activity: results from a multicenter study in Switzerland. Eur Neurol 2010; 63 (2) 101-106
    CrossrefPubMedGoogle Scholar
  • 23 Oturai AB, Koch-Henriksen N, Petersen T, Jensen PE, Sellebjerg F, Sorensen PS. Efficacy of natalizumab in multiple sclerosis patients with high disease activity: a Danish nationwide study. Eur J Neurol 2009; 16 (3) 420-423
    CrossrefPubMedGoogle Scholar
  • 24 Holmén C, Piehl F, Hillert J , et al. A Swedish national post-marketing surveillance study of natalizumab treatment in multiple sclerosis. Mult Scler 2011; 17 (6) 708-719
    CrossrefPubMedGoogle Scholar
  • 25 Prosperini L, Fortuna D, Gianni C, Leonardi L, Pozzilli C. The diagnostic accuracy of static posturography in predicting accidental falls in people with multiple sclerosis. Neurorehabil Neural Repair 2013; 27 (1) 45-52
    PubMedGoogle Scholar
  • 26 Ghezzi A, Pozzilli C, Grimaldi LM , et al. Safety and efficacy of natalizumab in children with multiple sclerosis. Neurology 2010; 75 (10) 912-917
    CrossrefPubMedGoogle Scholar
  • 27 Papeix C, Vidal JS, de Seze J , et al. Immunosuppressive therapy is more effective than interferon in neuromyelitis optica. Mult Scler 2007; 13 (2) 256-259
    CrossrefPubMedGoogle Scholar
  • 28 Warabi Y, Matsumoto Y, Hayashi H. Interferon beta-1b exacerbates multiple sclerosis with severe optic nerve and spinal cord demyelination. J Neurol Sci 2007; 252 (1) 57-61
    CrossrefPubMedGoogle Scholar
  • 29 Kleiter I, Hellwig K, Berthele A , et al; Neuromyelitis Optica Study Group. Failure of natalizumab to prevent relapses in neuromyelitis optica. Arch Neurol 2012; 69 (2) 239-245
    CrossrefPubMedGoogle Scholar
  • 30 Barnett MH, Prineas JW, Buckland ME, Parratt JD, Pollard JD. Massive astrocyte destruction in neuromyelitis optica despite natalizumab therapy. Mult Scler 2012; 18 (1) 108-112
    CrossrefPubMedGoogle Scholar
  • 31 Jacob A, Weinshenker BG, Violich I , et al. Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients. Arch Neurol 2008; 65 (11) 1443-1448
    CrossrefPubMedGoogle Scholar
  • 32 Leussink VI, Lehmann HC, Meyer zu Hörste G, Hartung HP, Stüve O, Kieseier BC. Rituximab induces clinical stabilization in a patient with fulminant multiple sclerosis not responding to natalizumab. Evidence for disease heterogeneity. J Neurol 2008; 255 (9) 1436-1438
    CrossrefPubMedGoogle Scholar
  • 33 Fisher E, Lee JC, Nakamura K, Rudick RA. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol 2008; 64 (3) 255-265
    CrossrefPubMedGoogle Scholar
  • 34 Rinaldi F, Calabrese M, Seppi D, Puthenparampil M, Perini P, Gallo P. Natalizumab strongly suppresses cortical pathology in relapsing-remitting multiple sclerosis. Mult Scler 2012; 18 (12) 1760-1767
    CrossrefPubMedGoogle Scholar
  • 35 Gunnarsson M, Malmestrom C, Axelsson M , et al. Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab. Ann Neurol 2011; 69 (1) 83-89
    CrossrefPubMedGoogle Scholar
  • 36 Phillips JT, Giovannoni G, Lublin FD , et al. Sustained improvement in Expanded Disability Status Scale as a new efficacy measure of neurological change in multiple sclerosis: treatment effects with natalizumab in patients with relapsing multiple sclerosis. Mult Scler 2011; 17 (8) 970-979
    CrossrefPubMedGoogle Scholar
  • 37 Belachew S, Phan-Ba R, Bartholomé E , et al. Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis. Eur J Neurol 2011; 18 (2) 240-245
    CrossrefPubMedGoogle Scholar
  • 38 Balcer LJ, Galetta SL, Calabresi PA , et al. Natalizumab reduces visual loss in patients with relapsing multiple sclerosis. Neurology 2007; 68 (16) 1299-1304
    CrossrefPubMedGoogle Scholar
  • 39 Meuth SG, Bittner S, Seiler C, Göbel K, Wiendl H. Natalizumab restores evoked potential abnormalities in patients with relapsing-remitting multiple sclerosis. Mult Scler 2011; 17 (2) 198-203
    CrossrefPubMedGoogle Scholar
  • 40 Mattioli F, Stampatori C, Bellomi F, Capra R. Natalizumab efficacy on cognitive impairment in MS. Neurol Sci 2011; 31 (Suppl. 03) 321-323
    CrossrefPubMedGoogle Scholar
  • 41 Lang C, Reiss C, Mäurer M. Natalizumab may improve cognition and mood in multiple sclerosis. Eur Neurol 2012; 67 (3) 162-166
    CrossrefPubMedGoogle Scholar
  • 42 Iaffaldano P, Viterbo RG, Paolicelli D , et al. Impact of natalizumab on cognitive performances and fatigue in relapsing multiple sclerosis: a prospective, open-label, two years observational study. PLoS ONE 2012; 7 (4) e35843
    CrossrefPubMedGoogle Scholar
  • 43 Phillips JT, O'Connor PW, Havrdova E , et al; AFFIRM Investigators. Infusion-related hypersensitivity reactions during natalizumab treatment. Neurology 2006; 67 (9) 1717-1718
    CrossrefPubMedGoogle Scholar
  • 44 Hellwig K, Schimrigk S, Fischer M , et al. Allergic and nonallergic delayed infusion reactions during natalizumab therapy. Arch Neurol 2008; 65 (5) 656-658
    CrossrefPubMedGoogle Scholar
  • 45 Krumbholz M, Pellkofer H, Gold R, Hoffmann LA, Hohlfeld R, Kümpfel T. Delayed allergic reaction to natalizumab associated with early formation of neutralizing antibodies. Arch Neurol 2007; 64 (9) 1331-1333
    CrossrefPubMedGoogle Scholar
  • 46 Calabresi PA, Giovannoni G, Confavreux C , et al; AFFIRM and SENTINEL Investigators. The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL. Neurology 2007; 69 (14) 1391-1403
    CrossrefPubMedGoogle Scholar
  • 47 Sørensen PS, Jensen PE, Haghikia A , et al. Occurrence of antibodies against natalizumab in relapsing multiple sclerosis patients treated with natalizumab. Mult Scler 2011; 17 (9) 1074-1078
    CrossrefPubMedGoogle Scholar
  • 48 Oliver B, Fernández O, Orpez T , et al. Kinetics and incidence of anti-natalizumab antibodies in multiple sclerosis patients on treatment for 18 months. Mult Scler 2011; 17 (3) 368-371
    CrossrefPubMedGoogle Scholar
  • 49 Jensen PE, Koch-Henriksen N, Sellebjerg F, Sørensen PS. Prediction of antibody persistency from antibody titres to natalizumab. Mult Scler 2012; 18 (10) 1493-1499
    CrossrefPubMedGoogle Scholar
  • 50 Sørensen PS, Koch-Henriksen N, Jensen PE. Neutralizing antibodies against interferon-β do not predispose antibodies against natalizumab. Neurology 2011; 76 (8) 759-760
    CrossrefPubMedGoogle Scholar
  • 51 Zohren F, Toutzaris D, Klärner V, Hartung HP, Kieseier B, Haas R. The monoclonal anti-VLA-4 antibody natalizumab mobilizes CD34+ hematopoietic progenitor cells in humans. Blood 2008; 111 (7) 3893-3895
    CrossrefPubMedGoogle Scholar
  • 52 Bonig H, Wundes A, Chang KH, Lucas S, Papayannopoulou T. Increased numbers of circulating hematopoietic stem/progenitor cells are chronically maintained in patients treated with the CD49d blocking antibody natalizumab. Blood 2008; 111 (7) 3439-3441
    CrossrefPubMedGoogle Scholar
  • 53 Abbas M, Lalive PH, Chofflon M, Simon HU, Chizzolini C, Ribi C. Hypereosinophilia in patients with multiple sclerosis treated with natalizumab. Neurology 2011; 77 (16) 1561-1564
    CrossrefPubMedGoogle Scholar
  • 54 Midaglia L, Rodriguez Ruiz M, Muñoz-García D. Severe haematological complications during treatment with natalizumab. Mult Scler 2012; 18 (11) 1644-1646
    CrossrefPubMedGoogle Scholar
  • 55 Stosic M, De Jesus P, McCarthy J, Hutton G, Rivera V. Immune thrombocytopenic purpura in a patient with multiple sclerosis treated with natalizumab. Neurology 2011; 77 (5) 505-507
    CrossrefPubMedGoogle Scholar
  • 56 Mullen JT, Vartanian TK, Atkins MB. Melanoma complicating treatment with natalizumab for multiple sclerosis. N Engl J Med 2008; 358 (6) 647-648
    PubMedGoogle Scholar
  • 57 Bergamaschi R, Montomoli C. Melanoma in multiple sclerosis treated with natalizumab: causal association or coincidence?. Mult Scler 2009; 15 (12) 1532-1533
    CrossrefPubMedGoogle Scholar
  • 58 Vavricka BM, Baumberger P, Russmann S, Kullak-Ublick GA. Diagnosis of melanoma under concomitant natalizumab therapy. Mult Scler 2011; 17 (2) 255-256
    CrossrefPubMedGoogle Scholar
  • 59 Laroni A, Bedognetti M, Uccelli A, Capello E, Mancardi GL. Association of melanoma and natalizumab therapy in the Italian MS population: a second case report. Neurol Sci 2011; 32 (1) 181-182
    PubMedGoogle Scholar
  • 60 Ismail A, Kemp J, Sharrack B. Melanoma complicating treatment with natalizumab (Tysabri) for multiple sclerosis. J Neurol 2009; 256 (10) 1771-1772
    CrossrefPubMedGoogle Scholar
  • 61 Castela E, Lebrun-Frenay C, Laffon M , et al. Evolution of nevi during treatment with natalizumab: a prospective follow-up of patients treated with natalizumab for multiple sclerosis. Arch Dermatol 2011; 147 (1) 72-76
    PubMedGoogle Scholar
  • 62 Panzara MA, Bozic C, Sandrock AW. More on melanoma with transdifferentiation. N Engl J Med 2008; 359 (1) 99-100 , author reply 99–100
    CrossrefPubMedGoogle Scholar
  • 63 Schweikert A, Kremer M, Ringel F , et al. Primary central nervous system lymphoma in a patient treated with natalizumab. Ann Neurol 2009; 66 (3) 403-406
    CrossrefPubMedGoogle Scholar
  • 64 Bozic C, LaGuette J, Panzara MA, Sandrock AW. Natalizumab and central nervous system lymphoma: no clear association. Ann Neurol 2009; 66 (3) 261-262
    CrossrefPubMedGoogle Scholar
  • 65 Kappos L, Bates D, Edan G , et al. Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring. Lancet Neurol 2011; 10 (8) 745-758
    CrossrefPubMedGoogle Scholar
  • 66 DeAngelis LM. Primary central nervous system lymphoma imitates multiple sclerosis. J Neurooncol 1990; 9 (2) 177-181
    CrossrefPubMedGoogle Scholar
  • 67 Ng S, Butzkueven H, Kalnins R, Rowe C. Prolonged interval between sentinel pseudotumoral demyelination and development of primary CNS lymphoma. J Clin Neurosci 2007; 14 (11) 1126-1129
    CrossrefPubMedGoogle Scholar
  • 68 Ransohoff RM. Natalizumab, multiple sclerosis, and primary central nervous system lymphoma: enigma, wrapped in mystery, enclosed in conundrum. Ann Neurol 2009; 66 (3) 259-261
    CrossrefPubMedGoogle Scholar
  • 69 Schowinsky J, Corboy J, Vollmer T, Kleinschmidt-DeMasters BK. Natalizumab-associated complication? First case of peripheral T cell lymphoma. Acta Neuropathol 2012; 123 (5) 751-752
    CrossrefPubMedGoogle Scholar
  • 70 Zecca C, Nessi F, Bernasconi E, Gobbi C. Ocular toxoplasmosis during natalizumab treatment. Neurology 2009; 73 (17) 1418-1419
    CrossrefPubMedGoogle Scholar
  • 71 Shenoy ES, Mylonakis E, Hurtado RM, Venna N. Natalizumab and HSV meningitis. J Neurovirol 2011; 17 (3) 288-290
    CrossrefPubMedGoogle Scholar
  • 72 Scheiss N, Zong J, Hayward G, Calabresi P. Reactivation of herpes virus in multiple sclerosis patients on natalizumab. Ther Clin Risk Manag 2009; 5: 585-594
    PubMedGoogle Scholar
  • 73 Mulero P, Caminero AB, Neri Crespo MJ, Fernández-Herranz R, Téllez Lara N. Latent tuberculosis seems not to reactivate in multiple sclerosis patients on natalizumab. J Neuroimmunol 2012; 243 (1-2) 103-105
    CrossrefPubMedGoogle Scholar
  • 74 Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet 1971; 1 (7712) 1257-1260
    PubMedGoogle Scholar
  • 75 Tan CS, Koralnik IJ. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol 2010; 9 (4) 425-437
    CrossrefPubMedGoogle Scholar
  • 76 Jensen PN, Major EO. A classification scheme for human polyomavirus JCV variants based on the nucleotide sequence of the noncoding regulatory region. J Neurovirol 2001; 7 (4) 280-287
    CrossrefPubMedGoogle Scholar
  • 77 Calabrese LH, Molloy ES, Huang D, Ransohoff RM. Progressive multifocal leukoencephalopathy in rheumatic diseases: evolving clinical and pathologic patterns of disease. Arthritis Rheum 2007; 56 (7) 2116-2128
    CrossrefPubMedGoogle Scholar
  • 78 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 (4) 369-374
    CrossrefPubMedGoogle Scholar
  • 79 Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 2005; 353 (4) 375-381
    CrossrefPubMedGoogle Scholar
  • 80 Van Assche G, Van Ranst M, Sciot R , et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease. N Engl J Med 2005; 353 (4) 362-368
    CrossrefPubMedGoogle Scholar
  • 81 Yousry TA, Major EO, Ryschkewitsch C , et al. Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med 2006; 354 (9) 924-933
    CrossrefPubMedGoogle Scholar
  • 82 Lindå H, von Heijne A, Major EO , et al. Progressive multifocal leukoencephalopathy after natalizumab monotherapy. N Engl J Med 2009; 361 (11) 1081-1087
    CrossrefPubMedGoogle Scholar
  • 83 Bloomgren G, Richman S, Hotermans C , et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 2012; 366 (20) 1870-1880
    CrossrefPubMedGoogle Scholar
  • 84 Chen Y, Bord E, Tompkins T , et al. Asymptomatic reactivation of JC virus in patients treated with natalizumab. N Engl J Med 2009; 361 (11) 1067-1074
    CrossrefPubMedGoogle Scholar
  • 85 Jilek S, Jaquiéry E, Hirsch HH , et al. Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study. Lancet Neurol 2010; 9 (3) 264-272
    CrossrefPubMedGoogle Scholar
  • 86 Rudick RA, O'Connor PW, Polman CH , et al. Assessment of JC virus DNA in blood and urine from natalizumab-treated patients. Ann Neurol 2010; 68 (3) 304-310
    CrossrefPubMedGoogle Scholar
  • 87 Du Pasquier RA, Stein MC, Lima MA , et al. JC virus induces a vigorous CD8. + cytotoxic T cell response in multiple sclerosis patients. J Neuroimmunol 2006; 176 (1-2) 181-186
    CrossrefPubMedGoogle Scholar
  • 88 Warnke C, Smolianov V, Dehmel T , et al. CD34+ progenitor cells mobilized by natalizumab are not a relevant reservoir for JC virus. Mult Scler 2011; 17 (2) 151-156
    CrossrefPubMedGoogle Scholar
  • 89 Wenning W, Haghikia A, Laubenberger J , et al. Treatment of progressive multifocal leukoencephalopathy associated with natalizumab. N Engl J Med 2009; 361 (11) 1075-1080
    CrossrefPubMedGoogle Scholar
  • 90 Boster A, Hreha S, Berger JR , et al. Progressive multifocal leukoencephalopathy and relapsing-remitting multiple sclerosis: a comparative study. Arch Neurol 2009; 66 (5) 593-599
    CrossrefPubMedGoogle Scholar
  • 91 Kappos L, Bates D, Edan G , et al. Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring. Lancet Neurol 2011; 10 (8) 745-758
    CrossrefPubMedGoogle Scholar
  • 92 Decard BF, Haghikia A, Tonnes C , et al. Natalizumab-associated reversible encephalopathy syndrome mimicking progressive multifocal leukoencephalopathy. Mult Scler 2013; 19 (2) 249-251
    CrossrefPubMedGoogle Scholar
  • 93 Kuhle J, Gosert R, Bühler R , et al. Management and outcome of CSF-JC virus PCR-negative PML in a natalizumab-treated patient with MS. Neurology 2011; 77 (23) 2010-2016
    CrossrefPubMedGoogle Scholar
  • 94 Blair NF, Brew BJ, Halpern JP. Natalizumab-associated PML identified in the presymptomatic phase using MRI surveillance. Neurology 2012; 78 (7) 507-508
    CrossrefPubMedGoogle Scholar
  • 95 Schröder A, Lee DH, Hellwig K, Lukas C, Linker RA, Gold R. Successful management of natalizumab-associated progressive multifocal leukoencephalopathy and immune reconstitution syndrome in a patient with multiple sclerosis. Arch Neurol 2010; 67 (11) 1391-1394
    CrossrefPubMedGoogle Scholar
  • 96 Khatri BO, Man S, Giovannoni G , et al. Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function. Neurology 2009; 72 (5) 402-409
    CrossrefPubMedGoogle Scholar
  • 97 Stüve O, Marra CM, Bar-Or A , et al. Altered CD. 4 + /CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis. Arch Neurol 2006; 63 (10) 1383-1387
    CrossrefPubMedGoogle Scholar
  • 98 Hall CD, Dafni U, Simpson D , et al. Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. AIDS Clinical Trials Group 243 Team. N Engl J Med 1998; 338 (19) 1345-1351
    CrossrefPubMedGoogle Scholar
  • 99 De Luca A, Ammassari A, Pezzotti P , et al; Gesida 9/99, IRINA, ACTG 363 Study Groups. Cidofovir in addition to antiretroviral treatment is not effective for AIDS-associated progressive multifocal leukoencephalopathy: a multicohort analysis. AIDS 2008; 22 (14) 1759-1767
    CrossrefPubMedGoogle Scholar
  • 100 Brickelmaier M, Lugovskoy A, Kartikeyan R , et al. Identification and characterization of mefloquine efficacy against JC virus in vitro. Antimicrob Agents Chemother 2009; 53 (5) 1840-1849
    CrossrefPubMedGoogle Scholar
  • 101 Cettomai D, McArthur JC. Mirtazapine use in human immunodeficiency virus-infected patients with progressive multifocal leukoencephalopathy. Arch Neurol 2009; 66 (2) 255-258
    CrossrefPubMedGoogle Scholar
  • 102 Tan IL, McArthur JC, Clifford DB, Major EO, Nath A. Immune reconstitution inflammatory syndrome in natalizumab-associated PML. Neurology 2011; 77 (11) 1061-1067
    CrossrefPubMedGoogle Scholar
  • 103 Metz I, Radue EW, Oterino A , et al. Pathology of immune reconstitution inflammatory syndrome in multiple sclerosis with natalizumab-associated progressive multifocal leukoencephalopathy. Acta Neuropathol 2012; 123 (2) 235-245
    CrossrefPubMedGoogle Scholar
  • 104 Aly L, Yousef S, Schippling S , et al. Central role of JC virus-specific CD4+ lymphocytes in progressive multi-focal leucoencephalopathy-immune reconstitution inflammatory syndrome. Brain 2011; 134 (Pt 9) 2687-2702
    CrossrefPubMedGoogle Scholar
  • 105 Ryschkewitsch CF, Jensen PN, Monaco MC, Major EO. JC virus persistence following progressive multifocal leukoencephalopathy in multiple sclerosis patients treated with natalizumab. Ann Neurol 2010; 68 (3) 384-391
    CrossrefPubMedGoogle Scholar
  • 106 Vermersch P, Kappos L, Gold R , et al. Clinical outcomes of natalizumab-associated progressive multifocal leukoencephalopathy. Neurology 2011; 76 (20) 1697-1704
    CrossrefPubMedGoogle Scholar
  • 107 Clifford DB, De Luca A, Simpson DM, Arendt G, Giovannoni G, Nath A. Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases. Lancet Neurol 2010; 9 (4) 438-446
    CrossrefPubMedGoogle Scholar
  • 108 Bozic C, Belcher G, Kroojimans M , et al. The safety of natalizumab in patients with relapsing multiple sclerosis: an update from TOUCH™ and TYGRIS. Paper presented at: 59th Annual Meeting of the American Academy of Neurology. ; April 28–May 5, 2007; Boston, MA
    PubMedGoogle Scholar
  • 109 Gorelik L, Goelz S, Sandrock AW. Asymptomatic reactivation of JC virus in patients treated with natalizumab. N Engl J Med 2009; 361 (25) 2487-2488 , author reply 2489–2490
    CrossrefPubMedGoogle Scholar
  • 110 Jilek S, Jaquiéry E, Hirsch HH , et al. Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study. Lancet Neurol 2010; 9 (3) 264-272
    CrossrefPubMedGoogle Scholar
  • 111 Gorelik L, Lerner M, Bixler S , et al. Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol 2010; 68 (3) 295-303
    CrossrefPubMedGoogle Scholar
  • 112 Bozic C, Richman S, Plavina T , et al. Anti-John Cunnigham virus antibody prevalence in multiple sclerosis patients: baseline results of STRATIFY-1. Ann Neurol 2011; 70 (5) 742-750
    CrossrefPubMedGoogle Scholar
  • 113 Trampe AK, Hemmelmann C, Stroet A , et al. Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort. Neurology 2012; 78 (22) 1736-1742
    CrossrefPubMedGoogle Scholar
  • 114 Sørensen PS, Bertolotto A, Edan G , et al. Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab. Mult Scler 2012; 18 (2) 143-152
    CrossrefPubMedGoogle Scholar
  • 115 Heesen C, Kleiter I, Nguyen F , et al. Risk perception in natalizumab-treated multiple sclerosis patients and their neurologists. Mult Scler 2010; 16 (12) 1507-1512
    CrossrefPubMedGoogle Scholar
  • 116 Tur C, Tintoré M, Vidal-Jordana A , et al. Natalizumab discontinuation after PML risk stratification: outcome from a shared and informed decision. Mult Scler 2012; 18 (8) 1193-1196
    CrossrefPubMedGoogle Scholar
  • 117 Goodin DS, Cohen BA, O'Connor P, Kappos L, Stevens JC. Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. 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. Neurology 2008; 71 (10) 766-773
    CrossrefPubMedGoogle Scholar
  • 118 Kappos L, Bates D, Hartung HP , et al. Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring. Lancet Neurol 2007; 6 (5) 431-441
    CrossrefPubMedGoogle Scholar
  • 119 Leussink VI, Lehmann HC, Meyer zu Hörste G, Hartung HP, Stüve O, Kieseier BC. Rituximab induces clinical stabilization in a patient with fulminant multiple sclerosis not responding to natalizumab. Evidence for disease heterogeneity. J Neurol 2008; 255 (9) 1436-1438
    CrossrefPubMedGoogle Scholar
  • 120 Hellwig K, Haghikia A, Gold R. Pregnancy and natalizumab: results of an observational study in 35 accidental pregnancies during natalizumab treatment. Mult Scler 2011; 17 (8) 958-963
    CrossrefPubMedGoogle Scholar
  • 121 Hoevenaren IA, de Vries LC, Rijnders RJ, Lotgering FK. Delivery of healthy babies after natalizumab use for multiple sclerosis: a report of two cases. Acta Neurol Scand 2011; 123 (6) 430-433
    CrossrefPubMedGoogle Scholar
  • 122 Stüve O, Cravens PD, Frohman EM , et al. Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy. Neurology 2009; 72 (5) 396-401
    CrossrefPubMedGoogle Scholar
  • 123 Rispens T, Vennegoor A, Wolbink GJ, Polman CH, Killestein J. Natalizumab remains detectable in patients with multiple sclerosis long after treatment is stopped. Mult Scler 2012; 18 (6) 899-901
    CrossrefPubMedGoogle Scholar
  • 124 Vellinga MM, Castelijns JA, Barkhof F, Uitdehaag BM, Polman CH. Postwithdrawal rebound increase in T2 lesional activity in natalizumab-treated MS patients. Neurology 2008; 70 (13 Pt 2) 1150-1151
    CrossrefPubMedGoogle Scholar
  • 125 Papeix C, Depaz R, Tourbah A, Stankoff B, Lubetzki C. Dramatic worsening following plasma exchange in severe post-natalizumab withdrawal multiple sclerosis relapse. Mult Scler 2011; 17 (12) 1520-1522
    CrossrefPubMedGoogle Scholar
  • 126 Lenhard T, Biller A, Mueller W, Metz I, Schönberger J, Wildemann B. Immune reconstitution inflammatory syndrome after withdrawal of natalizumab?. Neurology 2010; 75 (9) 831-833
    CrossrefPubMedGoogle Scholar
  • 127 Kerbrat A, Le Page E, Leray E , et al. Natalizumab and drug holiday in clinical practice: an observational study in very active relapsing remitting multiple sclerosis patients. J Neurol Sci 2011; 308 (1-2) 98-102
    CrossrefPubMedGoogle Scholar
  • 128 Killestein J, Vennegoor A, Strijbis EM , et al. Natalizumab drug holiday in multiple sclerosis: poorly tolerated. Ann Neurol 2010; 68 (3) 392-395
    CrossrefPubMedGoogle Scholar
  • 129 O'Connor PW, Goodman A, Kappos L , et al. Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis. Neurology 2011; 76 (22) 1858-1865
    CrossrefPubMedGoogle Scholar
  • 130 Havla J, Gerdes LA, Meinl I , et al. De-escalation from natalizumab in multiple sclerosis: recurrence of disease activity despite switching to glatiramer acetate. J Neurol 2011; 258 (9) 1665-1669
    CrossrefPubMedGoogle Scholar
  • 131 Magraner MJ, Coret F, Navarré A , et al. Pulsed steroids followed by glatiramer acetate to prevent inflammatory activity after cessation of natalizumab therapy: a prospective, 6-month observational study. J Neurol 2011; 258 (10) 1805-1811
    CrossrefPubMedGoogle Scholar
  • 132 Fox R, Kappos L, Cree B , et al. Effects of a 24-week natalizumab treatment interruption on clinical and radiologic parameters of multiple sclerosis disease activity: the RESTORE study. Abstract presented at: 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis; October 19–22, 2011; Amsterdam, The Netherlands
    Google Scholar
  • 133 Rossi S, Motta C, Studer V , et al. A genetic variant of the anti-apoptotic protein Akt predicts natalizumab-induced lymphocytosis and post-natalizumab multiple sclerosis reactivation. Mult Scler 2013; 19 (1) 59-68
    CrossrefPubMedGoogle Scholar