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Dimethyl fumarate vs Teriflunomide: an Italian time-to-event data analysis

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Abstract

Background

The introduction of oral disease-modifying therapies (DMTs) for relapsing–remitting multiple sclerosis (RRMS) changed algorithms of RRMS treatment.

Objectives

To compare the effectiveness of treatment with dimethyl fumarate (DMF) and teriflunomide (TRF) in a large multicentre Italian cohort of RRMS patients.

Materials and Methods

Patients with RRMS who received treatment with DMF and TRF between January 1st, 2012 and December 31st, 2018 from twelve MS centers were identified. The events investigated were “time-to-first-relapse”, “time-to-Magnetic-Resonance-Imaging (MRI)-activity” and “time-to-disability-progression”.

Results

1445 patients were enrolled (1039 on DMF, 406 on TRF) and followed for a median of 34 months. Patients on TRF were older (43.5 ± 8.6 vs 38.8 ± 9.2 years), with a predominance of men and higher level of disability (p < 0.001 for all). Patients on DMF had a higher number of relapses and radiological activity (p < .05) at baseline.

Time-varying Cox-model for the event “time-to-first relapse” revealed that no differences were found between the two groups in the first 38 months of treatment (HRt < 38DMF = 0.73, CI = 0.52 to 1.03, p = 0.079). When the time-on-therapy exceeds 38 months patients on DMF had an approximately 0.3 times lower relapse hazard risk than those who took TRF (HRt>38DMF = 3.83, CI = 1.11 to 13.23, p = 0.033). Both DMTs controlled similarly MRI activity and disability progression.

Conclusions

Patients on DMF had higher relapse-free survival time than TRF group after the first 38 months on therapy.

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Data availability

Anonymised data will be shared upon request from any qualified investigator for the sole purpose of replicating procedures and results presented in the report provided that data transfer is in agreement with EU legislation on the general data protection regulation.

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Funding

The researchers were independent of funders and sponsors. All researchers could access all the data.

Author information

Authors and Affiliations

  1. Department “G.F. Ingrassia”, MS Center University of Catania, Policlinico G. Rodolico, V. Santa Sofia 78, 95123, Catania, Italy

    Emanuele D’Amico, Aurora Zanghì & Francesco Patti

  2. Department of Economics, Business and Statistics”, University of Palermo, Palermo, Italy

    Mariangela Sciandra

  3. Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy

    Roberta Lanzillo & Vincenzo Bresciamorra

  4. Institute Foundation “G. Giglio”, Cefalù, Italy

    Graziella Callari & Luigi Maria Edoardo Grimaldi

  5. San Filippo Neri Hospital - ASL, Roma 1, Rome, Italy

    Antonio Cortese

  6. Multiple Sclerosis Center, II Division of Neurology, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy

    Giacomo Lus & Elisabetta Signoriello

  7. Fondazione Policlinico Universitario “Gemelli”, Catholic University of Sacred Heart, Rome, Italy

    Matteo Lucchini & Massimiliano Mirabella

  8. Azienda Ospedaliera Universitaria “G. Martino”, Messina, Italy

    Maria Buccafusca

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

    Simona Bonavita & Maddalena Sparaco

  10. University of Campania Luigi Vanvitelli, 1st Clinic of Neurology, Naples, Italy

    Antonio Gallo & Alvino Bisecco

  11. AOU Maggiore, Parma, Italy

    Erica Curti & Franco Granella

  12. Policlinico G.B. Rossi, Verona, Italy

    Alberto Gajofatto & Francesca Gobbin

  13. Neuroimmunology, Center for Multiple Sclerosis, ASST, Crema, Italy

    Maria Teresa Ferrò

  14. University La Sapienza, Rome, Italy

    Gina Ferrazzano

  15. Azienda Ospedaliera Universitaria “Mater Domini”, Catanzaro, Italy

    Paola Valentino

Authors
  1. Emanuele D’Amico
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  2. Aurora Zanghì
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  3. Mariangela Sciandra
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  4. Roberta Lanzillo
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  5. Graziella Callari
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  6. Antonio Cortese
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  7. Giacomo Lus
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  8. Matteo Lucchini
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  9. Maria Buccafusca
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  10. Simona Bonavita
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  11. Antonio Gallo
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  12. Erica Curti
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  13. Alberto Gajofatto
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  14. Elisabetta Signoriello
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  15. Alvino Bisecco
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  16. Francesca Gobbin
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  17. Maria Teresa Ferrò
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  18. Gina Ferrazzano
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  19. Maddalena Sparaco
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  20. Paola Valentino
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  21. Massimiliano Mirabella
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  22. Franco Granella
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  23. Vincenzo Bresciamorra
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  24. Luigi Maria Edoardo Grimaldi
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  25. Francesco Patti
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Consortia

ITALIAN-DIME-TERI group

  • Giovanna Borriello
  • , Paola Grossi
  • , Antonio Carotenuto
  • , Ernesto Siena
  • , Elena Tsantes
  • , Alessia Giugno
  • , Gian Marco Abbadessa
  •  & Clara Grazia Chisari

Contributions

Acquisition of data–Giovanna Borriello: Co-investigator, Sant Andrea Hospital; Paola Grossi: Co-investigator, Neuroimmunology, Center for Multiple Sclerosis, ASST Crema; Antonio Carotenuto: Co-investigator, University of Naples; Ernesto Siena: Co-investigator, University of Parma, Maggiore Hospital; Elena Tsantes: Co-investigator, University of Parma, Maggiore Hospital; Alessia Giugno: Co-investigator, University of Catanzaro Magna Grecia; Gian Marco Abbadessa: Co-investigator, University Luigi Van Vitelli, Naples; Clara Grazia Chisari: Co-investigator, University of Catania, MS center.

Corresponding author

Correspondence to Emanuele D’Amico.

Ethics declarations

Conflicts of interest

Dr Emanuele D’Amico has received personal fees from Biogen and Sanofi. He also received travel funding from Bayer Biogen and Merck. Dr Aurora Zanghì received travel funding from Bayer-Schering and Sanofi Genzyme outside of the described work. Dr Mariangela Sciandra has nothing to disclose. Dr Roberta Lanzillo has received personal fees for public speaking or consultancy from Merck, Novartis, Biogen, Genzyme, Teva, Roche and Almirall. Dr Graziella Callari has received personal fees from Biogen and Sanofi. She also received travel funding from Bayer Biogen and Merck. Dr Antonio Cortese has received speaker honoraria from Biogen, Sanofi Genzyme, and Teva, and travel grants from Biogen, Merck, Sanofi Genzyme, and Teva. He also received advisory board member honoraria from Biogen, Merck, Novartis, and Teva. Dr Giacomo Lus has nothing to disclose related to this manuscript. Dr Matteo Lucchini has received travel grants from Almirall, Biogen, Sanofi-Genzyme and Roche, speaker honoraria from Biogen and consulting fees from Merck Serono, Almirall and Novartis. Dr Maria Buccafusca has nothing to disclose related to this manuscript. Dr Simona Bonavita has nothing to disclose related to this manuscript. Dr Antonio Gallo has nothing to disclose related to this manuscript. Dr Erica Curti has nothing to disclose related to this manuscript. Dr Alberto Gajofatto has nothing to disclose related to this manuscript. Dr Elisabetta Signoriello has nothing to disclose related to this manuscript. Dr Alvino Bisecco has nothing to disclose related to this manuscript. Dr Francesca Gobbin has nothing to disclose related to this manuscript. Dr Maria Teresa Ferrò has nothing to disclose related to this manuscript. De Gina Ferrazzano has nothing to disclose related to this manuscript. Dr Maddalena Sparaco has nothing to disclose related to this manuscript. Dr Paola Valentino has nothing to disclose related to this manuscript. Dr Massimiliano Mirabella has received honoraria for speaking, serving on the advisory board and consulting for Biogen, Novartis, Merck Serono, Roche, Almirall and Sanofi Genzyme. He has received reimbursement for congress attendance and travel costs from Biogen, Novartis, Sanofi Genzyme, Roche, Merck Serono and Teva. He was also a principal investigator for clinical trials for Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva and Ultragenix. Dr Franco Granella has nothing to disclose related to this manuscript. Dr Vincenzo Brescia Morra has nothing to disclose related to this manuscript. Dr Luigi Maria Edoardo Grimaldi has served on the advisory boards of Bayer, Biogen Celgene, Merck, Novartis, Roche, Sanofi and Teva. He has also received personal fees for speaking activities at congresses or sponsored symposia. Dr Francesco Patti has served on the advisory boards of Bayer, Biogen Celgene, Merck, Novartis, Roche, Sanofi, Teva and Almirall. He has also received personal fees for speaking activities at congresses or sponsored symposia.

Ethical approval

The study protocol was approved by the local ethics committee (Comitato Etico Catania 1, n.177/2017/PO) of the coordinating centre (Policlinico Vittorio Emanuele, Catania, Italy) and transmitted to the participating centres. Patients provided written informed consent. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and with the appropriate national regulations.

Electronic supplementary material

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415_2020_9959_MOESM1_ESM.jpg

Supplementary Appendix 1. Patients’ selection flow chart DMF, dimethyl fumarate; PPMS, Primary Progressive Multiple Sclerosis; RRMS, Relapsing Remitting Multiple Sclerosis; SPMS, Secondary Progressive Multiple Sclerosis; TRF, teriflunomide (JPG 76 kb)

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D’Amico, E., Zanghì, A., Sciandra, M. et al. Dimethyl fumarate vs Teriflunomide: an Italian time-to-event data analysis. J Neurol 267, 3008–3020 (2020). https://doi.org/10.1007/s00415-020-09959-1

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  • DOI: https://doi.org/10.1007/s00415-020-09959-1

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