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Journal of Neurology

, Volume 266, Issue 1, pp 165–173 | Cite as

Efficacy and safety of alemtuzumab versus fingolimod in RRMS after natalizumab cessation

  • Steffen Pfeuffer
  • Rene Schmidt
  • Frederike Anne Straeten
  • Refik Pul
  • Christoph Kleinschnitz
  • Marinus Wieshuber
  • De-Hyung Lee
  • Ralf A. Linker
  • Sebastian Doerck
  • Vera Straeten
  • Susanne Windhagen
  • Marc Pawlitzki
  • Christoph Aufenberg
  • Michael Lang
  • Christian Eienbroeker
  • Björn Tackenberg
  • Volker Limmroth
  • Brigitte Wildemann
  • Jürgen Haas
  • Luisa Klotz
  • Heinz Wiendl
  • Tobias Ruck
  • Sven G. MeuthEmail author
Original Communication

Abstract

Background

Natalizumab (NTZ) was the first approved monoclonal antibody for the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite proven and sustained efficacy, its use is limited by the risk of progressive multifocal leukoencephalopathy (PML). Moreover, some patients show ongoing disease activity under NTZ, requiring a switch to another disease-modifying treatment (DMT). However, evidence regarding the optimal DMT for treatment of active RRMS after NTZ-cessation is still scarce.

Objective

To evaluate efficacy and safety outcomes of ALEM vs FTY treatment after cessation of NTZ.

Methods

We retrospectively identified patients at 12 German neurology centers and analyzed risks for disease activity, adverse events, disability progression, and treatment discontinuation.

Results

195 patients were identified and 144 underwent final analysis (FTY: 101; ALEM: 42). The hazard ratio for clinical relapses was 2.24 favoring ALEM (95% CI 1.12–4.50; p = 0.015). The hazard ratio for adverse events was 7.78 (95% CI 1.04–57.95; p = 0.006) and 2.41 for MRI progression (95% CI 1.26–4.60; p = 0.004). The odds ratio for disability progression after 12 months was 4.84 (95% CI 1.74–13.47, p = 0.003). Differences remained after adjusting for possible confounders (e.g., age, sex, baseline disability, NTZ treatment duration, washout time).

Conclusion

Our findings indicated particular advantages of ALEM compared to FTY in patients stopping NTZ.

Keywords

Alemtuzumab Natalizumab Fingolimod Remitting-relapsing multiple sclerosis Progressive multifocal leukoencephalopathy Immunomodulatory therapy 

Notes

Acknowledgements

The study was financially supported by Sanofi Genzyme (ALAIN01 to Sven G. Meuth and Tobias Ruck) and the Competence Network Multiple Sclerosis (01GI1603D, PROGRAMMS to Sven G. Meuth and Heinz Wiendl).

Author contributions

SP: study concept and design, acquisition of data, analysis and interpretation of data, writing of the manuscript. RS: analysis and interpretation of data, writing of the manuscript. FAS: acquisition of data, analysis and interpretation of data. RP: acquisition of data, critical revision of manuscript for intellectual content. CK: acquisition of data, critical revision of manuscript for intellectual content. MW: acquisition of data. DL: acquisition of data, critical revision of manuscript for intellectual content. RL: acquisition of data, critical revision of manuscript for intellectual content. SD: acquisition of data, critical revision of manuscript for intellectual content. VS: acquisition of data, critical revision of manuscript for intellectual content. SW: acquisition of data, critical revision of manuscript for intellectual content. MP: acquisition of data, critical revision of manuscript for intellectual content. CA: acquisition of data, critical revision of manuscript for intellectual content. ML: acquisition of data, critical revision of manuscript for intellectual content. CE: acquisition of data, critical revision of manuscript for intellectual content. BT: acquisition of data, critical revision of manuscript for intellectual content. VL: acquisition of data, critical revision of manuscript for intellectual content. BW: acquisition of data, critical revision of manuscript for intellectual content. JH: acquisition of data, critical revision of manuscript for intellectual content. LK: acquisition of data, critical revision of manuscript for intellectual content. HW: critical revision of manuscript for intellectual content. TR: study concept and design, acquisition of data, analysis and interpretation of data, critical revision of manuscript for intellectual content. SGM: study concept and design, analysis and interpretation of data, critical revision of manuscript for intellectual content.

Funding

The study was financially supported by Sanofi Genzyme (ALAIN01 to Sven G. Meuth and Tobias Ruck) and the Competence Network Multiple Sclerosis (01GI1603D, PROGRAMMS to Sven G. Meuth and Heinz Wiendl).

Compliance with ethical standards

Conflicts of interest

Steffen Pfeuffer: received travel reimbursements from Sanofi-Genzyme and Merck and honoraria for lecturing from Sanofi Genzyme, Biogen and Mylan. Rene Schmidt: declares no conflicts of interest. Frederike Anne Straeten: declares no conflicts of interest. Refik Pul: received travel reimbursements from Merck, research support by Novartis, speaker honoraria from Merck Serono, Biogen, Novartis, Sanofi-Genzyme, Mylan and Roche. Christoph Kleinschnitz: received travel reimbursements, honoraria for lecturing and research support from Ablynx, Amgen, Bayer Vital, Bristol-Mayers Squibb, Biotronik, Boehringer Ingelheim, Biogen, CSL Behring, Daiichi-Sankyo, Desitin, Eisai, Ever Pharma, Sanofi Genzyme, Merck Serono, Mylan, Medday, Novartis, Pfizer, Roche, Siemens, Stago and Teva. Marinus Wieshuber: declares no conflict of interest. De-Hyung Lee: received compensation for activities with Biogen, Merck, Novartis, Roche, and Sanofi-Genzyme. Ralf A. Linker: received compensation for activities with Biogen, Merck, Novartis, Roche, and Sanofi-Genzyme. Sebastian Doerck: reports no conflicts of interest. Vera Straeten: received travel reimbursements from Novartis, Merck and Biogen and honoraria for lecturing from Sanofi Genzyme, Biogen and Novartis. Susanne Windhagen: declares no conflict of interest. Marc Pawlitzki: received honoraria for lecturing and travel reimbursements from Biogen, Sanofi Genzyme, Merck Serono, Roche and Novartis. Christoph Aufenberg: received travel reimbursements from Bayer. Michael Lang: received travel grants, honoraria for lecturing, financial research support and consultancy fees from Teva, Merck Serono, Sanofi Genzyme, Novartis, Bayer and Biogen. Christian Eienbroeker: received honoraria for lecturing from Bayer, Biogen, and CSL Behring. Björn Tackenberg: received personal speaker honoraria and consultancy fees as a speaker and advisor from Bayer Healthcare, Biogen, CSL Behring, GRIFOLS, Merck Serono, Novartis, Octapharma, Roche, Sanofi Genzyme, TEVA and UCB Pharma. Volker Limmroth: received honoraria as speaker, AD-Board member or research support from Antisense, Bayer, Biogen, Boehringer, Sanofi Genzyme, Novartis, Pfizer, Roche and Teva. Brigitte Wildemann: received grants and personal fees from Biogen, Merck Serono, Sanofi Genzyme, Novartis and Teva, and personal fees from Bayer Healthcare. Jürgen Haas: declares no conflict of interest. Luisa Klotz: received compensation for serving on scientific advisory boards from Sanofi Genzyme and Novartis, honoraria for lecturing and travel reimbursements from CSL Behring, Merck Serono, Biogen, Sanofi Genzyme, Novartis, and research support from Biogen and Novartis. Heinz Wiendl: received compensation for serving on Scientific Advisory Boards/Steering Committees from Bayer, Biogen, Sanofi Genzyme, Merck Serono and Novartis, honoraria for lecturing and travel reimbursements Bayer, Biogen, CSL Behring, EMD Serono, Fresenius Medical Care, Sanofi Genzyme, Merck Serono, Omniamed, Novartis and Sanofi Aventis. He received compensation as a consultant from Biogen, Merck Serono, Novartis, Roche and Sanofi Genzyme and research support from Bayer, Biogen, Merck Serono, Novartis, Sanofi Genzyme and Teva. Tobias Ruck: received travel reimbursements from Merck Serono and financial research support from Sanofi Genzyme and Novartis and honoraria for lecturing from Sanofi Genzyme, Roche, Biogen, Merck Serono and Teva. Sven G. Meuth: received honoraria for lecturing, travel reimbursements and financial research support from Bayer, Biogen, Sanofi Genzyme, Merck Serono, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi Aventis, UCB and Teva. The submitting author hereby declares that he takes responsibility for conduction and analysis of the data and that he had full access to all study data. The submitting author furthermore declares that there are no competing interests concerning these data and that the authors have all rights to publish the data. The submitted manuscript does not contain data that have been published in any other journal. The authors have no related articles under submission.

Ethical standards

The local institutional review board (IRB) has approved the conduction of this trial. Further details are listed in the “Methods” chapter.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Steffen Pfeuffer
    • 1
  • Rene Schmidt
    • 2
  • Frederike Anne Straeten
    • 1
  • Refik Pul
    • 3
  • Christoph Kleinschnitz
    • 3
  • Marinus Wieshuber
    • 4
  • De-Hyung Lee
    • 4
  • Ralf A. Linker
    • 4
  • Sebastian Doerck
    • 5
  • Vera Straeten
    • 6
  • Susanne Windhagen
    • 7
  • Marc Pawlitzki
    • 8
  • Christoph Aufenberg
    • 9
  • Michael Lang
    • 10
  • Christian Eienbroeker
    • 11
  • Björn Tackenberg
    • 11
  • Volker Limmroth
    • 12
  • Brigitte Wildemann
    • 13
  • Jürgen Haas
    • 13
  • Luisa Klotz
    • 1
  • Heinz Wiendl
    • 1
  • Tobias Ruck
    • 1
  • Sven G. Meuth
    • 1
    Email author
  1. 1.Department of Neurology and Institute for Translational Neurology, University Hospital MuensterUniversity of MuensterMuensterGermany
  2. 2.Institute of Biostatistics and Clinical ResearchUniversity of MuensterMuensterGermany
  3. 3.Department of NeurologyUniversity Duisburg-EssenDuisburgGermany
  4. 4.Department of NeurologyFriedrich-Alexander-UniversityErlangen-NurembergGermany
  5. 5.Department of NeurologyUniversity of WuerzburgWuerzburgGermany
  6. 6.Department of NeurologyJohannes-Wesling-Hospital MindenMindenGermany
  7. 7.Department of NeurologyClinics OsnabrueckOsnabrueckGermany
  8. 8.Department of NeurologyUniversity Medical Center MagdeburgMagdeburgGermany
  9. 9.Department of NeurologyHerz-Jesu-Hospital Muenster-HiltrupMuensterGermany
  10. 10.Center for NeurologyUlmGermany
  11. 11.Department of NeurologyUniversity of Giessen-MarburgMarburgGermany
  12. 12.Department of Neurology, Cologne General HospitalsUniversity of CologneCologneGermany
  13. 13.Department of NeurologyUniversity Hospital of HeidelbergHeidelbergGermany

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