Skip to main content
SpringerLink
Log in

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

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

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.

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

Similar content being viewed by others

References

  1. Freedman MS, Selchen D, Prat A, Giacomini PS (2018) Managing multiple sclerosis: treatment initiation, modification, and sequencing. Can J Neurol Sci 45(5):489–503

    Article  Google Scholar 

  2. Oh J, Vidal-Jordana A, Montalban X (2018) Multiple sclerosis: clinical aspects. Curr Opin Neurol 31(6):752–759

    Article  Google Scholar 

  3. Gross RH, Corboy JR (2019) Monitoring, switching, and stopping multiple sclerosis disease-modifying therapies. Continuum (Minneap Minn) 25(3):715–735

    Google Scholar 

  4. Sormani MP, Bruzzi P (2015) Can we measure long-term treatment effects in multiple sclerosis? Nat Rev Neurol 11(3):176–182

    Article  Google Scholar 

  5. Signori A, Gallo F, Bovis F et al (2016) Long-term impact of interferon or Glatiramer acetate in multiple sclerosis: a systematic review and meta-analysis. Mult Scler Relat Disord 6:57–63

    Article  Google Scholar 

  6. Kappos L, Kuhle J, Multanen J et al (2015) Factors influencing long-term outcomes in relapsing-remitting multiple sclerosis: PRISMS-15. J Neurol Neurosurg Psychiatry 86:1202–1207

    Article  Google Scholar 

  7. Mendes D, Alves C, Batel-Marques F (2016) Benefit-risk of therapies for relapsing–remitting multiple sclerosis: testing the number needed to treat to benefit (NNTB), number needed to treat to harm (NNTH) and the likelihood to be helped or harmed (LHH): a systematic review and meta-analysis. CNS Drugs 30:909–929

    Article  Google Scholar 

  8. Cohen JA, Barkhof F, Comi G et al (2010) Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 362:402–415

    Article  CAS  Google Scholar 

  9. 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 362:387–401

    Article  CAS  Google Scholar 

  10. Kappos L, O'Connor P, Radue EW et al (2015) Long-term effects of fingolimod in multiple sclerosis: the randomized FREEDOMS extension trial. Neurology 84:1582–1591

    Article  CAS  Google Scholar 

  11. Cohen JA, Khatri B, Barkhof F et al (2016) Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study. J Neurol Neurosurg Psychiatry 87:468–475

    Article  Google Scholar 

  12. Trojano M, Bergamaschi R, Amato MP et al (2019) The Italian multiple sclerosis register. Neurol Sci 40:155–165

    Article  Google Scholar 

  13. Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302

    Article  Google Scholar 

  14. Pardo G, Jones DE (2017) The sequence of disease-modifying therapies in relapsing multiple sclerosis: safety and immunologic considerations. J Neurol 264:2351–2374

    Article  Google Scholar 

  15. Montalban X, Gold R, Thompson AJ et al (2018) ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler 24:96–120

    Article  Google Scholar 

  16. Rae-Grant A, Day GS, Marrie RA et al (2018) Practice guideline recommendations summary: disease- modifying therapies for adults with multiple sclerosis: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 90:777–788

    Article  Google Scholar 

  17. Comi G, Radaelli M, Soelberg Sørensen P (2017) Evolving concepts in the treatment of relapsing multiple sclerosis. Lancet 389:1347–1356

    Article  Google Scholar 

  18. Corboy JR, Weinshenker BG, Wingerchuk DM (2018) Comment on 2018 American Academy of Neurology guidelines on disease- modifying therapies in MS. Neurology 90:1106–1112

    Article  Google Scholar 

  19. Rio J, Castilló J, Rovira A et al (2009) Measures in the first year of therapy predict the response to interferon beta in MS. Mult Scler 15:848–853

    Article  CAS  Google Scholar 

  20. Sormani MP, Rio J, Tintorè M et al (2013) Scoring treatment response in patients with relapsing multiple sclerosis. Mult Scler 19:605–612

    Article  CAS  Google Scholar 

  21. Lee S, Baxter DC, Limone B et al (2012) Cost-effectiveness of fingolimod versus interferon beta-1a for relapsing remitting multiple sclerosis in the United States. J Med Econ 15:1088–1096

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Basic Medical Sciences, Neurosciences, and Sense Organs, Multiple Sclerosis Center, University of Bari “Aldo Moro”, Bari, Italy

    Damiano Paolicelli, Alessia Manni, Antonio Iaffaldano, Pietro Iaffaldano & Maria Trojano

  2. Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy

    Giuseppe Lucisano

  3. Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy

    Carlo Avolio

  4. Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Napoli, Italy

    Simona Bonavita & Giacomo Lus

  5. Department of Neurosciences, Reproductive and Odontostomatological Sciences, “Federico II” University of Naples, Naples, Italy

    Vincenzo Brescia Morra

  6. Department of Neurology and Regional Multiple Sclerosis Centre, University Hospital San Luigi, Orbassano, TO, Italy

    Marco Capobianco

  7. Department of Medical Science and Public Health, University of Cagliari and Multiple Sclerosis Center, Cagliari, Italy

    Eleonora Cocco

  8. Department of Human Neurosciences, Sapienza, University of Rome, Rome, Italy

    Antonella Conte

  9. IRCCS Neuromed, Pozzilli, IS, Italy

    Antonella Conte

  10. Neurology Clinic, Multiple Sclerosis Centre, SS Annunziata Hospital, Chieti, Italy

    Giovanna De Luca

  11. Department of Neurology, Vito Fazzi Hospital, ASL, Lecce, Italy

    Francesca De Robertis

  12. Department of Neuroscience, San Camillo Hospital, Rome, Italy

    Claudio Gasperini

  13. Neurology Unit, “F. Miulli” Hospital, Acquaviva delle Fonti BA, Italy

    Maurizia Gatto

  14. Departemental Center for the Diagnosis and Treatment of Demyelinating Diseases, Sestri Ponente, Genoa, Italy

    Paola Gazzola

  15. Multiple Sclerosis Center, Garibaldi Hospital, Catania, Italy

    Davide Maimone

  16. Multiple Sclerosis Center of IRCCS Mondino Foundation, Pavia, Italy

    Giulia Mallucci

  17. Multiple Sclerosis Regional Center, A. Cardarelli Hospital, Naples, Italy

    Giorgia T. Maniscalco

  18. Department of Systems Medicine, Multiple Sclerosis Clinical and Research Center, University of Rome Tor Vergata, Rome, Italy

    Girolama A. Marfia

  19. Department “G.F. Ingrassia”, Multiple Sclerosis Center, University of Catania, Catania, Italy

    Francesco Patti

  20. Multiple Sclerosis Center, Ospedale di Vaio (I.P.), Fidenza, PR, Italy

    Ilaria Pesci

  21. Multiple Sclerosis Center, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy

    Carlo Pozzilli

  22. Department of Neurology, University La Sapienza, Rome, Italy

    Carlo Pozzilli

  23. Multiple Sclerosis Center, IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy

    Marco Rovaris

  24. Department of Biomedicine, Neuroscience and Advanced Diagnostics, Palermo University, Palermo, Italy

    Giuseppe Salemi

  25. Department of Neuroscience, Mental Health and Sensory Organs, Sapienza University, Rome, Italy

    Marco Salvetti

  26. Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Isernia, Italy

    Marco Salvetti

  27. UOC Neurology, AORN San G. Moscati, Avellino, Italy

    Daniele Spitaleri

  28. Department of Neurology, Demyelinating Disease Center, San Salvatore Hospital, L’Aquila, Italy

    Rocco Totaro

  29. Multiple Sclerosis Center, Hospital of Gallarate, Gallarate, Italy

    Mauro Zaffaroni

  30. Department of Neurology, San Raffaele Hospital, Milan, Italy

    Giancarlo Comi

  31. Department NEUROFARBA, University of Florence, Florence, Italy

    Maria Pia Amato

  32. IRCCS and Fondazione Don Carlo Gnocchi, Florence, Italy

    Maria Pia Amato

Authors
  1. Damiano Paolicelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giuseppe Lucisano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessia Manni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carlo Avolio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Simona Bonavita
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vincenzo Brescia Morra
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marco Capobianco
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eleonora Cocco
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Antonella Conte
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Giovanna De Luca
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Francesca De Robertis
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Claudio Gasperini
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Maurizia Gatto
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Paola Gazzola
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Giacomo Lus
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Antonio Iaffaldano
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Pietro Iaffaldano
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Davide Maimone
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Giulia Mallucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Giorgia T. Maniscalco
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Girolama A. Marfia
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Francesco Patti
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Ilaria Pesci
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Carlo Pozzilli
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Marco Rovaris
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Giuseppe Salemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Marco Salvetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Daniele Spitaleri
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Rocco Totaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Mauro Zaffaroni
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. Giancarlo Comi
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Maria Pia Amato
    View author publications

    You can also search for this author in PubMed Google Scholar

  33. Maria Trojano
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the Italian MS Register

Corresponding author

Correspondence to Damiano Paolicelli.

Ethics declarations

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.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 13 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Paolicelli, D., Lucisano, G., Manni, A. et al. 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. J Neurol 266, 3098–3107 (2019). https://doi.org/10.1007/s00415-019-09531-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-019-09531-6

Keywords

Search

Navigation