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Recurrence or rebound of clinical relapses after discontinuation of natalizumab therapy in highly active MS patients

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Abstract

A number of studies have reported flare-up of multiple sclerosis (MS) disease activity after cessation of natalizumab, increasing to a level beyond the pre-natalizumab treatment level. Our aim was to describe the development in clinical disease activity following cessation of natalizumab therapy in a large unselected cohort of highly active patients. We studied 375 highly active patients who had suffered at least two significant relapses within 1 year or three relapses within 2 years, or had been treated with mitoxantrone for highly active disease. All patients had discontinued therapy with natalizumab after at least 24 weeks on therapy, and had been followed 3–12 months (mean 8.9 months) after cessation of natalizumab therapy. The annualised relapse rate before start of natalizumab therapy was 0.94 (95 % confidence interval [CI] 0.88–1.00), 0.47 (95 % CI 0.43–0.52) during natalizumab therapy, 0.63 (95 % CI 0.51–0.76) 1–6 months after natalizumab and 0.55 (95 % CI 0.42–0.70) 7–12 months after natalizumab. However, 83 (22 %) of the patients could be classified as showing rebound of relapses, defined as a higher individual relapse rate after cessation of natalizumab than before natalizumab. These patients had a higher annualised relapse rate during natalizumab therapy. For the whole patient group, the relapse rate after discontinuation did not exceed the pre-natalizumab relapse rate at any time, but 22 % of the patients showed rebound of relapses after discontinuation of natalizumab.

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Conflicts of interest

Per Soelberg Sorensen received personal compensation from Biogen Idec, Merck Serono, Novartis, Genmab, TEVA, GSK, and Sanofi-aventis, Genzyme as member of scientific advisory boards, steering committees or independent data monitoring boards in clinical trials, or as a speaker at meetings. His research unit has received research support from Biogen Idec, Bayer Schering, Merck Serono, TEVA, Sanofi-aventis, Novartis, RoFAR, Roche, and Genzyme, the Danish Multiple Sclerosis Society, the Danish Medical Research Council, and the European Union Sixth Framework Programme: Life sciences, Genomics and Biotechnology for health. Nils Koch-Henriksen has received honoraria for lecturing and participation in advisory councils, travel expenses for attending congresses and meetings, and financial support for monitoring the Danish MS Treatment Register from Bayer, Merck-Serono, BiogenIdec, Sanofi-Avensis, Novartis, and TEVA. Thor Petersen has received funding or speaker honoraria from Biogen Idec, Merck Serono, Novartis, Bayer Schering, Sanofi-Aventis, Roche, and Genzyme. Mads Ravnborg has received travel grants and consultant honoraries from Bayer Health, Biogen-Idec, Sanofi Aventis, TEVA, Merck Serono, Genzyme and Novartis. Annette Oturai has served on scientific advisory boards for Novartis, and served as consultant for Biogen Idec; has received support for congress participation from Biogen Idec, Novartis, Sanofi Aventis and Teva; and has received speaker honoraria from Biogen Idec, Novartis, and Sanofi-Aventis. Her laboratory has received research support from Biogen Idec and Novartis. Finn Sellebjerg has served on scientific advisory boards, been on the steering committees of clinical trials, served as a consultant, received support for congress participation, received speaker honoraria, or received research support for his laboratory from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novo Nordisk, Novartis, Sanofi-Aventis, Schering Plough and Teva.

Ethical standard

The study was approved by the Central Ethical Committee. All patients treated with disease-modifying drug are registered in the Danish Multiple Sclerosis Treatment Register as decided by the Danish National Board of Health. The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Authors and Affiliations

  1. Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark

    Per Soelberg Sorensen, Annette Oturai & Finn Sellebjerg

  2. Department of Clinical Epidemiology, Clinical Institute, University of Aarhus, Århus, Denmark

    Nils Koch-Henriksen

  3. The Danish Multiple Sclerosis Registry, Neuroscience Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Nils Koch-Henriksen

  4. Department of Neurology, Aarhus University Hospital, Århus, Denmark

    Thor Petersen

  5. Department of Neurology, University Hospital of Odense, Odense, Denmark

    Mads Ravnborg

  6. The Multiple Sclerosis Registry, Rigshospitalet, Copenhagen, Denmark

    Nils Koch-Henriksen

Authors
  1. Per Soelberg Sorensen
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  2. Nils Koch-Henriksen
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  3. Thor Petersen
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  4. Mads Ravnborg
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  5. Annette Oturai
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  6. Finn Sellebjerg
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Correspondence to Per Soelberg Sorensen.

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Sorensen, P.S., Koch-Henriksen, N., Petersen, T. et al. Recurrence or rebound of clinical relapses after discontinuation of natalizumab therapy in highly active MS patients. J Neurol 261, 1170–1177 (2014). https://doi.org/10.1007/s00415-014-7325-8

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  • DOI: https://doi.org/10.1007/s00415-014-7325-8

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