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Erschienen in: Journal of Neurology 11/2019

16.07.2019 | Original Communication

Switching from natalizumab to fingolimod treatment in multiple sclerosis: real life data from the Austrian MS Treatment Registry

verfasst von: Michael Guger, Christian Enzinger, Fritz Leutmezer, Jörg Kraus, Stefan Kalcher, Erich Kvas, Thomas Berger, on behalf of the Austrian MS Treatment Registry (AMSTR)

Erschienen in: Journal of Neurology | Ausgabe 11/2019

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Abstract

Objectives

To compare the efficacy of natalizumab (NTZ) and fingolimod (FTY) in the treatment of relapsing–remitting multiple sclerosis (MS) in sequential use in common and as a function of transition periods in a nationwide observational cohort using prospectively collected data from a real-life setting.

Materials and methods

We included 195 patients from the Austrian MS Treatment Registry, who had started treatment with NTZ at any time since 2006 and stayed on NTZ for at least 24 months, switched afterwards within 1 year to FTY and stayed on FTY for at least another 12 months. Transition periods between NTZ and FTY were grouped into three different intervals: < 3 months (135 patients), 3–6 months (44 patients), and 6–12 months (16 patients).

Results

Estimated mean annualized relapse rates (ARR) over a mean treatment period of 44 months were 0.26 for NTZ and 0.32 for FTY (p = 0.381) over 46 months. In the treatment gap, differences were found concerning the relapse probability, seven (5.2%) patients in the < 3 months group, six (13.6%) in thef 3–6 months group, and seven (43.8%) in the 6–12 months group (p < 0.001). After this treatment gap, no significant differences concerning ARR, EDSS change, EDSS progression, and regression were observed regardless the proceeding transition periods. Significantly higher efficacy of NTZ compared to FTY in sequential use was found regarding EDSS change, EDSS progression, and EDSS regression sustained for 12 and 24 weeks.

Conclusions

First, we here show an increased short-time risk for relapses during the treatment gap between NTZ and FTY therapy, dependent on the length of transition time. Second, the disease course after switching to FTY remained stable in the long-term evaluation. Therefore, switching from NTZ to FTY in a real-world setting appears efficacious and safe, but this data advocate for a short switching gap of 3 months or less.
Literatur
1.
Zurück zum Zitat 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 354:899–910CrossRef 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 354:899–910CrossRef
2.
Zurück zum Zitat Kappos L, Radue EW, O’Connor P et al (2010) A placebo- controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 362:387–401CrossRef Kappos L, Radue EW, O’Connor P et al (2010) A placebo- controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 362:387–401CrossRef
3.
Zurück zum Zitat Calabresi PA, Radue EW, Goodin D et al (2014) Safety and efficacy of fingolimod in patients with relapsing- remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol 13:545–556CrossRef Calabresi PA, Radue EW, Goodin D et al (2014) Safety and efficacy of fingolimod in patients with relapsing- remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol 13:545–556CrossRef
4.
Zurück zum Zitat Cohen JA, Barkhof F, Comi G et al (2010) Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 362:402–415CrossRef Cohen JA, Barkhof F, Comi G et al (2010) Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 362:402–415CrossRef
5.
Zurück zum Zitat Plavina T, Subramanyam M, Bloomgren G et al (2014) Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol. 76(6):802–812CrossRef Plavina T, Subramanyam M, Bloomgren G et al (2014) Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol. 76(6):802–812CrossRef
6.
Zurück zum Zitat O’Connor PW, Goodman A, Kappos L et al (2011) Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis. Neurology 76:1858–1865CrossRef O’Connor PW, Goodman A, Kappos L et al (2011) Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis. Neurology 76:1858–1865CrossRef
7.
Zurück zum Zitat Salhofer-Polanyi S, Baumgartner A, Kraus J et al (2014) What to expect after natalizumab cessation in a real-life setting. Acta Neurol Scand 130:97–102CrossRef Salhofer-Polanyi S, Baumgartner A, Kraus J et al (2014) What to expect after natalizumab cessation in a real-life setting. Acta Neurol Scand 130:97–102CrossRef
8.
Zurück zum Zitat Cohen M, Maillart E, Tourbah A et al (2014) Switching from natalizumab to fingolimod in multiple sclerosis: a French prospective study. JAMA Neurol 71:436–441CrossRef Cohen M, Maillart E, Tourbah A et al (2014) Switching from natalizumab to fingolimod in multiple sclerosis: a French prospective study. JAMA Neurol 71:436–441CrossRef
9.
Zurück zum Zitat Diem L, Nedeltchev K, Kahles T et al (2018) Long-term evaluation of NEDA-3 status in relapsing-remitting multiple sclerosis patients after switching from natalizumab to fingolimod. Ther Adv Neurol Disord. 9(11):1756286418791103 Diem L, Nedeltchev K, Kahles T et al (2018) Long-term evaluation of NEDA-3 status in relapsing-remitting multiple sclerosis patients after switching from natalizumab to fingolimod. Ther Adv Neurol Disord. 9(11):1756286418791103
10.
Zurück zum Zitat Comi G, Gold R, Dahlke F et al (2015) Relapses in patients treated with fingolimod after previous exposure to natalizumab. Mult Scler 21:786–790CrossRef Comi G, Gold R, Dahlke F et al (2015) Relapses in patients treated with fingolimod after previous exposure to natalizumab. Mult Scler 21:786–790CrossRef
11.
Zurück zum Zitat Sempere AP, Martin-Medina P, Berenguer- Ruiz L et al (2013) Switching from natalizumab to fingolimod: an observational study. Acta Neurol Scand 128:e6–e10CrossRef Sempere AP, Martin-Medina P, Berenguer- Ruiz L et al (2013) Switching from natalizumab to fingolimod: an observational study. Acta Neurol Scand 128:e6–e10CrossRef
12.
Zurück zum Zitat Havla J, Tackenberg B, Hellwig K et al (2013) Fingolimod reduces recurrence of disease activity after natalizumab withdrawal in multiple sclerosis. J Neurol 260:1382–1387CrossRef Havla J, Tackenberg B, Hellwig K et al (2013) Fingolimod reduces recurrence of disease activity after natalizumab withdrawal in multiple sclerosis. J Neurol 260:1382–1387CrossRef
13.
Zurück zum Zitat Jokubaitis VG, Li V, Kalincik T, Izquierdo G (2014) Fingolimod after natalizumab and the risk of short-term relapse. Neurology. 82(14):1204–1211CrossRef Jokubaitis VG, Li V, Kalincik T, Izquierdo G (2014) Fingolimod after natalizumab and the risk of short-term relapse. Neurology. 82(14):1204–1211CrossRef
14.
Zurück zum Zitat Villaverde-Gonzalez R, Gracia Gil J, Perez Sempere A et al (2017) Observational study of switching from natalizumab to immunomodulatory drugs. Eur Neurol 77:130–136CrossRef Villaverde-Gonzalez R, Gracia Gil J, Perez Sempere A et al (2017) Observational study of switching from natalizumab to immunomodulatory drugs. Eur Neurol 77:130–136CrossRef
15.
Zurück zum Zitat Vollmer B, Honce JM, Sillau S et al (2018) The impact of very short transition times on switching from Natalizumab to Fingolimod on imaging and clinical effectiveness outcomes in multiple sclerosis. J Neurol Sci. 15(390):89–93CrossRef Vollmer B, Honce JM, Sillau S et al (2018) The impact of very short transition times on switching from Natalizumab to Fingolimod on imaging and clinical effectiveness outcomes in multiple sclerosis. J Neurol Sci. 15(390):89–93CrossRef
16.
Zurück zum Zitat Leurs CE, van Kempen ZL, Dekker I et al (2018) Switching natalizumab to fingolimod within 6 weeks reduces recurrence of disease activity in MS patients. Mult Scler. 24(11):1453–1460CrossRef Leurs CE, van Kempen ZL, Dekker I et al (2018) Switching natalizumab to fingolimod within 6 weeks reduces recurrence of disease activity in MS patients. Mult Scler. 24(11):1453–1460CrossRef
17.
Zurück zum Zitat Guger M, Enzinger C, Leutmezer F et al (2018) Real-life clinical use of natalizumab and fingolimod in Austria. Acta Neurol Scand. 137(2):181–187CrossRef Guger M, Enzinger C, Leutmezer F et al (2018) Real-life clinical use of natalizumab and fingolimod in Austria. Acta Neurol Scand. 137(2):181–187CrossRef
18.
Zurück zum Zitat Kerbrat A, Le Page E, Leray E et al (2011) Natalizumab and drug holiday in clinical practice: an observational study in very active relapsing remitting multiple sclerosis patients. J. Neurol. Sci. 308(1):98–102CrossRef Kerbrat A, Le Page E, Leray E et al (2011) Natalizumab and drug holiday in clinical practice: an observational study in very active relapsing remitting multiple sclerosis patients. J. Neurol. Sci. 308(1):98–102CrossRef
19.
Zurück zum Zitat Giovannoni G, Marta M, Davis A et al (2016) Switching patients at high risk of PML from natalizumab to another disease-modifying therapy. Pract. Neurol. 16(5):389CrossRef Giovannoni G, Marta M, Davis A et al (2016) Switching patients at high risk of PML from natalizumab to another disease-modifying therapy. Pract. Neurol. 16(5):389CrossRef
Metadaten
Titel
Switching from natalizumab to fingolimod treatment in multiple sclerosis: real life data from the Austrian MS Treatment Registry
verfasst von
Michael Guger
Christian Enzinger
Fritz Leutmezer
Jörg Kraus
Stefan Kalcher
Erich Kvas
Thomas Berger
on behalf of the Austrian MS Treatment Registry (AMSTR)
Publikationsdatum
16.07.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 11/2019
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-019-09464-0

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