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Journal of Neurology

, Volume 266, Issue 12, pp 3098–3107 | Cite as

Retrospectively acquired cohort study to evaluate the long-term impact of two different treatment strategies on disability outcomes in patients with relapsing multiple sclerosis (RE.LO.DI.MS): data from the Italian MS Register

  • Damiano PaolicelliEmail author
  • Giuseppe Lucisano
  • Alessia Manni
  • Carlo Avolio
  • Simona Bonavita
  • Vincenzo Brescia Morra
  • Marco Capobianco
  • Eleonora Cocco
  • Antonella Conte
  • Giovanna De Luca
  • Francesca De Robertis
  • Claudio Gasperini
  • Maurizia Gatto
  • Paola Gazzola
  • Giacomo Lus
  • Antonio Iaffaldano
  • Pietro Iaffaldano
  • Davide Maimone
  • Giulia Mallucci
  • Giorgia T. Maniscalco
  • Girolama A. Marfia
  • Francesco Patti
  • Ilaria Pesci
  • Carlo Pozzilli
  • Marco Rovaris
  • Giuseppe Salemi
  • Marco Salvetti
  • Daniele Spitaleri
  • Rocco Totaro
  • Mauro Zaffaroni
  • Giancarlo Comi
  • Maria Pia Amato
  • Maria Trojano
  • the Italian MS Register
Original Communication

Abstract

Background

The increase in disease-modifying drugs (DMDs) allows individualization of treatment in relapsing multiple sclerosis (RMS); however, the long-term impact of different treatment sequences is not well established. This is particularly relevant for MS patients who may need to postpone more aggressive DMD strategies.

Objective

To evaluate different therapeutic strategies and their long-term outcomes, measured as relapses and confirmed disability progression (CDP), in MS ‘real-world’ settings.

Methods

Multicentre, observational, retrospectively acquired cohort study evaluating the long-term impact of different treatment strategies on disability outcomes in patients with RMS in the Italian MS Register.

Results

We evaluated 1152 RMS-naïve patients after propensity-score adjustment. Patients included were receiving: interferon beta-1a (IFN-β1a) 44 µg switching to fingolimod (FTY; IFN-switchers; n = 97); FTY only (FTY-stayers; n = 157); IFN-β1a only (IFN-stayers; n = 849). CDP and relapses did not differ between FTY-stayers and IFN-switchers [HR (95% CI) 0.99 (0.48–2.04), p = 0.98 and 0.81 (0.42–1.58), p = 0.55, respectively]. However, IFN-stayers showed increased risk of relapses compared with FTY-stayers [HR (95% CI) 1.46 (1.00–2.12), p = 0.05].

Conclusion

The ideal treatment option for MS is becoming increasingly complex, with the need to balance benefit and risks. Our results suggest that starting with FTY affects the long-term disease outcome similarly to escalating from IFN-β1a to FTY.

Keywords

Multiple sclerosis Interferons Long-term outcomes Real-world setting Treatment sequences EDSS score 

Notes

Compliance with ethical standards

Conflicts of interest

G. Lucisano, A. Manni, S. Bonavita, V. Brescia Morra, A. Conte, F. De Robertis, P. Gazzola, A. Iaffaldano, C. Gasperini, M. Gatto, G.T. Maniscalco, I. Pesci report no disclosures relevant to the manuscript. D. Paolicelli received advisory board membership, speakers honoraria, travel support, research grants, consulting fees, or clinical trial support from Almirall, Bayer Schering, Biogen, Celgene, Excemed, Genzyme, Merck, Mylan, Novartis, Sanofi, Roche, Teva. M.P. Amato has received research grants and honoraria as a speaker and member of advisory boards by Biogen, Merck, Sanofi Genzyme, Teva, Novartis, Roche. C. Avolio served on scientific advisory boards for Merck, Sanofi-Genzyme and Roche, and has received travel and/or speaker honoraria from Merck, Roche, Teva, Biogen, Novartis and Sanofi-Genzyme. M. Capobianco received personal compensation for speaking at meeting or participating in advisory board from Almirall, Biogen, Merck, Novartis, Sanofi, Roche. E. Cocco has served on scientific Advisory Boards for Bayer, Biogen, Merck, Novartis, Roche, Sanofi Genzyme and TEVA; she also received speaker honoraria and research grants for her department by the same companies. G. Comi received personal compensation for consulting services and/or speaking activities from Novartis, Teva, Sanofi, Sanofi-Genzyme, Merck, Biogen, Excemed, Serono Symposia International Foundation, Roche, Almirall, Receptos, Celgene, and Forward Pharma. G. De Luca served on scientific advisory boards for Merck, Sanofi-Genzyme and Roche, and has received travel and/or speaker honoraria from Merck, Roche, Teva, Biogen, Novartis and Sanofi-Genzyme. G. Lus receveid travel fundings, research support, speaker honoraria from: Biogen, Novartis, Sanofi Genzyme, Bayer, Teva, Almirall, Allergan, Ipsen, Merck, Merz Pharma Italia. P. Iaffaldano received advisory board membership, speaker honoraria, travel support, research grants, consulting fees, or clinical trial support from Almirall, Bayer Schering, Biogen, Celgene, Excemed, Genzyme, Merck, Mylan, Novartis, Sanofi, Roche, Teva. D. Maimone receveid travel funds and speaker honoraria from Biogen, Novartis, Sanofi Genzyme, Teva, Almirall, Merck, Roche. G. Mallucci received support to travel to scientific meetings from Bayer Schering, Biogen, Genzyme, Merck Serono, Novartis, Roche, Sanofi-Aventis, Teva; received research grants for the MS Center at IRCCS Mondino, Pavia, Italy from Biogen and served on the scientific advisory board for Biogen, Genzyme and Merck Serono. G.A. Marfia is an Advisory Board member of Biogen Idec, Genzyme, Merck-Serono, Novartis, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, Teva. She is the principal investigator in clinical trials for Actelion, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, Teva. F. Patti has received honoraria for speaking activities by Bayer Schering, Biogen, Merck, Novartis, Roche, TEVA and Sanofi Aventis; he also served as advisory board member the following companies: Bayer Schering, Roche, Biogen, Merck, Novartis; he was also funded by Pfizer and FISM for epidemiological studies; finally he received grant for congress participation from Bayer Schering, Roche, Biogen, Merck, Novartis, Sanofi Aventis, and TEVA. C. Pozzilli has received consultant fees from Actelion, Biogen, Genzyme, Merck-Serono, Novartis, Teva Neurosciences and grant or research support from Biogen, Merck-serono, Novartis and Teva neuroscinces. M. Rovaris received fees for consulting or scientific speaking from Almirall, Biogen, Genzyme-Sanofi, Merck Serono and TEVA. G. Salemi received grants and honoraria by Almirall, Biogen-Dompè, Merck-Serono, Novartis, Roche, Sanofi-Aventis, and TEVA. M. Salvetti received research support and consulting fees from Biogen, Merck, Novartis, Roche, Sanofi, Teva. D. Spitaleri received fees for consulting or congress participation from Novartis, TEVA, Sanofi and Biogen. R. Totaro has served on advisory boards and/or received honoraria for speaking or consultation fees from Biogen, CSL behring, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, Shire, Teva. M. Zaffaroni received personal financial support for attending scientific meetings from Merck and financial support for his Department from Novartis. M. Trojano received advisory board membership, speaker honoraria, travel support, research grants, consulting fees, or clinical trial support from Actelion, Allergan, Almirall, Bayer Schering, Biogen, Celgene, Excemed, Genzyme, Merck, Mylan, Novartis, Sanofi, Roche, Teva.

Ethic approval

The study was conducted in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975. The study was approved by the Ethic Committee of AOU Policlinico, Bari on 17 July 2018; ID number 0060669.

Supplementary material

415_2019_9531_MOESM1_ESM.docx (14 kb)
Supplementary file1 (DOCX 13 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Damiano Paolicelli
    • 1
    Email author
  • Giuseppe Lucisano
    • 2
  • Alessia Manni
    • 1
  • Carlo Avolio
    • 3
  • Simona Bonavita
    • 4
  • Vincenzo Brescia Morra
    • 5
  • Marco Capobianco
    • 6
  • Eleonora Cocco
    • 7
  • Antonella Conte
    • 8
    • 9
  • Giovanna De Luca
    • 10
  • Francesca De Robertis
    • 11
  • Claudio Gasperini
    • 12
  • Maurizia Gatto
    • 13
  • Paola Gazzola
    • 14
  • Giacomo Lus
    • 4
  • Antonio Iaffaldano
    • 1
  • Pietro Iaffaldano
    • 1
  • Davide Maimone
    • 15
  • Giulia Mallucci
    • 16
  • Giorgia T. Maniscalco
    • 17
  • Girolama A. Marfia
    • 18
  • Francesco Patti
    • 19
  • Ilaria Pesci
    • 20
  • Carlo Pozzilli
    • 21
    • 22
  • Marco Rovaris
    • 23
  • Giuseppe Salemi
    • 24
  • Marco Salvetti
    • 25
    • 26
  • Daniele Spitaleri
    • 27
  • Rocco Totaro
    • 28
  • Mauro Zaffaroni
    • 29
  • Giancarlo Comi
    • 30
  • Maria Pia Amato
    • 31
    • 32
  • Maria Trojano
    • 1
  • the Italian MS Register
  1. 1.Department of Basic Medical Sciences, Neurosciences, and Sense Organs, Multiple Sclerosis CenterUniversity of Bari “Aldo Moro”BariItaly
  2. 2.Center for Outcomes Research and Clinical EpidemiologyPescaraItaly
  3. 3.Department of Medical and Surgical SciencesUniversity of FoggiaFoggiaItaly
  4. 4.Department of Advanced Medical and Surgical SciencesUniversity of Campania “Luigi Vanvitelli”NapoliItaly
  5. 5.Department of Neurosciences, Reproductive and Odontostomatological Sciences“Federico II” University of NaplesNaplesItaly
  6. 6.Department of Neurology and Regional Multiple Sclerosis CentreUniversity Hospital San LuigiOrbassanoItaly
  7. 7.Department of Medical Science and Public HealthUniversity of Cagliari and Multiple Sclerosis CenterCagliariItaly
  8. 8.Department of Human NeurosciencesSapienza, University of RomeRomeItaly
  9. 9.IRCCS NeuromedPozzilliItaly
  10. 10.Neurology Clinic, Multiple Sclerosis CentreSS Annunziata HospitalChietiItaly
  11. 11.Department of NeurologyVito Fazzi Hospital, ASLLecceItaly
  12. 12.Department of NeuroscienceSan Camillo HospitalRomeItaly
  13. 13.Neurology Unit“F. Miulli” HospitalAcquaviva delle Fonti BAItaly
  14. 14.Departemental Center for the Diagnosis and Treatment of Demyelinating DiseasesSestri PonenteGenoaItaly
  15. 15.Multiple Sclerosis CenterGaribaldi HospitalCataniaItaly
  16. 16.Multiple Sclerosis Center of IRCCS Mondino FoundationPaviaItaly
  17. 17.Multiple Sclerosis Regional CenterA. Cardarelli HospitalNaplesItaly
  18. 18.Department of Systems Medicine, Multiple Sclerosis Clinical and Research CenterUniversity of Rome Tor VergataRomeItaly
  19. 19.Department “G.F. Ingrassia”, Multiple Sclerosis CenterUniversity of CataniaCataniaItaly
  20. 20.Multiple Sclerosis CenterOspedale di Vaio (I.P.)FidenzaItaly
  21. 21.Multiple Sclerosis Center, Sant’Andrea HospitalSapienza University of RomeRomeItaly
  22. 22.Department of NeurologyUniversity La SapienzaRomeItaly
  23. 23.Multiple Sclerosis CenterIRCCS Fondazione Don Carlo GnocchiMilanItaly
  24. 24.Department of Biomedicine, Neuroscience and Advanced DiagnosticsPalermo UniversityPalermoItaly
  25. 25.Department of Neuroscience, Mental Health and Sensory OrgansSapienza UniversityRomeItaly
  26. 26.Istituto Neurologico Mediterraneo (INM) NeuromedPozzilliItaly
  27. 27.UOC NeurologyAORN San G. MoscatiAvellinoItaly
  28. 28.Department of Neurology, Demyelinating Disease CenterSan Salvatore HospitalL’AquilaItaly
  29. 29.Multiple Sclerosis CenterHospital of GallarateGallarateItaly
  30. 30.Department of NeurologySan Raffaele HospitalMilanItaly
  31. 31.Department NEUROFARBAUniversity of FlorenceFlorenceItaly
  32. 32.IRCCS and Fondazione Don Carlo GnocchiFlorenceItaly

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