Journal of Neurology

, 258:1805 | Cite as

Pulsed steroids followed by glatiramer acetate to prevent inflammatory activity after cessation of natalizumab therapy: a prospective, 6-month observational study

  • María José Magraner
  • Francisco Coret
  • Arantxa Navarré
  • Isabel Boscá
  • María Simó
  • Matilde Escutia
  • Ana Bernad
  • Laura Navarro
  • Bonaventura Casanova
Original Communication

Abstract

In this study, the tolerability and safety of treatment with pulsed steroids and glatiramer acetate and the occurrence of clinical and radiological activity after natalizumab (NTZ) cessation in multiple sclerosis (MS) patients were assessed. MS patients with NTZ were discontinued after 2 years of treatment, or if adverse events or disease progressed during NTZ. They were offered as alternative treatment 1 g methylprednisolone per month during 3 months followed by daily 20 mcg glatiramer acetate and were prospectively studied. Adverse events, occurrence of immune reconstitution inflammatory syndrome, clinical exacerbations, and gadolinium-enhancing lesions in MRI performed at 3 and 6 months after NTZ cessation were recorded. EDSS change during follow-up was also recorded. A total of 18 MS patients entered the study and were followed up for a mean of 10 months (range 6–18 months). There were no significant adverse events. At month 3, no patient had clinical or radiological disease activity. At month 6, 16.6% of patients had had a relapse and 55.5% of patients showed gadolinium-enhancing lesions in the MRI. After 6 months, 33.3% of patients had a further relapse. There was no IRIS, severe relapses, or significant difference between EDSS at NTZ discontinuation and after follow-up. The alternative treatment with monthly prednisolone followed by GA prevents the development of IRIS, but not the return to previous inflammatory activity, which occurs between 5 and 6 months after NTZ withdrawal.

Keywords

Natalizumab Drug holidays Pulses of steroids 

Notes

Acknowledgments

This work has been performed with the financial support from the following national projects (FIS PI060822 and FIS PS09/00551 from the Carlos III Institute from Spain). The authors also thank nurses of the MS units (Matilde Escutia and Ana Bernal).

Conflict of interest

None.

References

  1. 1.
    Polman CH, O’Connor PW, Havrdova E et al (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899–910PubMedCrossRefGoogle Scholar
  2. 2.
    Rudick RA, Stuart WH, Calabresi PA et al (2006) Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 354:911–923PubMedCrossRefGoogle Scholar
  3. 3.
    Safety report from Biogen Idec, data on file. October 2010Google Scholar
  4. 4.
    Miravalle A, Jensen R, Kinkel RP et al (2010) Immune reconstitution inflammatory syndrome in patients with multiple sclerosis following cessation of natalizumab therapy. Arch Neurol. [Epub ahead of print]Google Scholar
  5. 5.
    Killestein J, Vennegoor A, Strijbis EM et al (2010) Natalizumab drug holiday in multiple sclerosis: poorly tolerated. Ann Neurol 68:392–395PubMedCrossRefGoogle Scholar
  6. 6.
    Lenhard T, Biller A, Mueller W, Metz I, Schönberger J, Wildemann B (2010) Immune reconstitution inflammatory syndrome after withdrawal of natalizumab? Neurology 75(9):831–833PubMedCrossRefGoogle Scholar
  7. 7.
    Vellinga MM, Castelijns JA, Barkhof F, Uitdehaag BM, Polman CH (2008) Postwithdrawal rebound increase in T2 lesional activity in natalizumab-treated MS patients. Neurology 70:1150–1151PubMedCrossRefGoogle Scholar
  8. 8.
    Hartung HP (2009) New cases of progressive multifocal leukoencephalopathy after treatment with natalizumab. Lancet Neurol 8:28–31PubMedCrossRefGoogle Scholar
  9. 9.
    Miller DH, Khan OA, Sheremata WA et al (2003) A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 348:15–23PubMedCrossRefGoogle Scholar
  10. 10.
    Dalton CM, Miszkiel KA, Barker GJ et al (2004) Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis. J Neurol 251:407–413PubMedCrossRefGoogle Scholar
  11. 11.
    Stüve O, Cravens PD, Frohman EM et al (2009) Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy. Neurology 72:396–401PubMedCrossRefGoogle Scholar
  12. 12.
    Giannuli E, Marousi S, Karkanis I, Graigos A, Kotsi V (2010) Natalizumab discontinuation after long-term administration: our own experience. Mult Scler 16:S138Google Scholar
  13. 13.
    West TW, Cree BA (2010) Natalizumab dosage suspension: are we helping or hurting? Ann Neurol 68:395–399PubMedCrossRefGoogle Scholar
  14. 14.
    Tan K, Roda R, Ostrow L, McArthur J, Nath A (2009) PML-IRIS in patients with HIV infection: clinical manifestations and treatment with steroids. Neurology 72:1458–1464PubMedCrossRefGoogle Scholar
  15. 15.
    Shelburne SA, Montes M, Hamill RJ (2006) Immune reconstitution inflammatory syndrome: more answers, more questions. J Antimicrob Chemother 57:167–170PubMedCrossRefGoogle Scholar
  16. 16.
    Hutchinson M, Kappos L, Calabresi PA et al (2009) The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL. J Neurol 256:405–415PubMedCrossRefGoogle Scholar
  17. 17.
    O’Connor PW, Goodman AD, Kappos L et al (2009) Return of disease activity after cessation of natalizumab therapy in patients with multiple sclerosis. Mult Scler 15:S240Google Scholar
  18. 18.
    Sangalli F, Moiola L, Radaelli M, Barcella V, Martinelli V, Comi G (2010) Starting immunomodulatand shortly after natalizumab discontinuation: initial impressions. Mult Scler 16:S142Google Scholar
  19. 19.
    Kebrat A, Le Page E, Leray E et al (2010) Assessment of disease activity within 6 months after natalizumab discontinuation: and observational study of 28 consecutive relapsing-remitting multiple sclerosis patients. Mult Scler 16:S128Google Scholar
  20. 20.
    Pesci I, Magnani S, Carini D et al (2010) Stopping natalizumab therapy: experience of follow-up in a MS center, FIdrenza, Italy. Mult Scler 16:S153Google Scholar
  21. 21.
    Baugmartner A, Stich O, Rauer S (2010) Clinical and radiological diseases reactivation after cessation of long-term therapy with natalizumab. Mult Scler 16:S145Google Scholar
  22. 22.
    Cocco E, Lorefice L, Frau J et al (2010) Natalizumab discontnuiation in multiple sclerosis: experience of a single center. Mult Scler 16:S299Google Scholar
  23. 23.
    Rossi S, Ristori G, Studer V et al (2010) An open-label, nonrandomized, prospective, multicenter study to evaluate the safety and tolerability of glatiramer acetate 20 mg sc once daily in patients with severe relapsing-remitting multiple sclerosis that have discontinued natalizumab after 12 to 18 months therapy. Preliminary results. Mult Scler 16:S133CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • María José Magraner
    • 1
  • Francisco Coret
    • 2
  • Arantxa Navarré
    • 2
  • Isabel Boscá
    • 1
  • María Simó
    • 1
  • Matilde Escutia
    • 1
  • Ana Bernad
    • 2
  • Laura Navarro
    • 1
  • Bonaventura Casanova
    • 1
  1. 1.Multiple Sclerosis UnitHospital Universitari I Politècnic La Fe, ValenciaValenciaSpain
  2. 2.Multiple Sclerosis UnitHospital Clínico ValenciaValenciaSpain

Personalised recommendations