Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  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 354:899–910

    Article  PubMed  CAS  Google Scholar 

  2. Rudick RA, Stuart WH, Calabresi PA et al (2006) Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 354:911–923

    Article  PubMed  CAS  Google Scholar 

  3. Safety report from Biogen Idec, data on file. October 2010

  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]

  5. Killestein J, Vennegoor A, Strijbis EM et al (2010) Natalizumab drug holiday in multiple sclerosis: poorly tolerated. Ann Neurol 68:392–395

    Article  PubMed  Google Scholar 

  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):831–833

    Article  PubMed  CAS  Google Scholar 

  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 70:1150–1151

    Article  PubMed  CAS  Google Scholar 

  8. Hartung HP (2009) New cases of progressive multifocal leukoencephalopathy after treatment with natalizumab. Lancet Neurol 8:28–31

    Article  PubMed  Google Scholar 

  9. Miller DH, Khan OA, Sheremata WA et al (2003) A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 348:15–23

    Article  PubMed  CAS  Google Scholar 

  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 251:407–413

    Article  PubMed  CAS  Google Scholar 

  11. Stüve O, Cravens PD, Frohman EM et al (2009) Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy. Neurology 72:396–401

    Article  PubMed  Google Scholar 

  12. Giannuli E, Marousi S, Karkanis I, Graigos A, Kotsi V (2010) Natalizumab discontinuation after long-term administration: our own experience. Mult Scler 16:S138

    Google Scholar 

  13. West TW, Cree BA (2010) Natalizumab dosage suspension: are we helping or hurting? Ann Neurol 68:395–399

    Article  PubMed  Google Scholar 

  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 72:1458–1464

    Article  PubMed  CAS  Google Scholar 

  15. Shelburne SA, Montes M, Hamill RJ (2006) Immune reconstitution inflammatory syndrome: more answers, more questions. J Antimicrob Chemother 57:167–170

    Article  PubMed  CAS  Google Scholar 

  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 256:405–415

    Article  PubMed  CAS  Google Scholar 

  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:S240

    Google Scholar 

  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:S142

    Google Scholar 

  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:S128

    Google Scholar 

  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:S153

    Google Scholar 

  21. Baugmartner A, Stich O, Rauer S (2010) Clinical and radiological diseases reactivation after cessation of long-term therapy with natalizumab. Mult Scler 16:S145

    Google Scholar 

  22. Cocco E, Lorefice L, Frau J et al (2010) Natalizumab discontnuiation in multiple sclerosis: experience of a single center. Mult Scler 16:S299

    Google Scholar 

  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:S133

    Article  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Multiple Sclerosis Unit, Hospital Universitari I Politècnic La Fe, Valencia, Bulevar Sur s/n, 46026, Valencia, Spain

    María José Magraner, Isabel Boscá, María Simó, Matilde Escutia, Laura Navarro & Bonaventura Casanova

  2. Multiple Sclerosis Unit, Hospital Clínico Valencia, Valencia, Spain

    Francisco Coret, Arantxa Navarré & Ana Bernad

Authors
  1. María José Magraner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francisco Coret
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arantxa Navarré
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Isabel Boscá
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. María Simó
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Matilde Escutia
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ana Bernad
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Laura Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bonaventura Casanova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to María José Magraner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Magraner, M.J., 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 258, 1805–1811 (2011). https://doi.org/10.1007/s00415-011-6019-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-011-6019-8

Keywords

Search

Navigation