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Riluzole and other prognostic factors in ALS: a population-based registry study in Italy

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Abstract

Objective

In this prospective population-based registry study on ALS survival, we investigated the role of riluzole treatment, together with other clinical factors, on the prognosis in incident ALS cases in Emilia Romagna Region (ERR), Italy.

Methods

A registry for ALS has been collecting all incident cases in ERR since 2009. Detailed clinical data from all patients diagnosed with ALS between 1.1.2009 and 31.12.2014 have been analyzed for this study, with last follow up date set at 31.12.2015.

Results

During the 6 years of the study, there were 681 incident cases with a median tracheostomy-free survival of 40 months (95% CI 36–44) from onset and of 26 months (95% CI 24–30) from diagnosis; 573 patients (84.14%) were treated with riluzole, 207 (30.39%) patients underwent gastrostomy, 246 (36.12%) non invasive ventilation, and 103 (15.15%) invasive ventilation. Patients who took treatment for ≥ 75% of disease duration from diagnosis had a median survival of 29 months compared to 18 months in patients with < 75% treatment duration. In multivariable analysis, factors independently influencing survival were age at onset (HR 1.04, 95% CI 1.02–1.05, p < 0.001), dementia (HR 1.56, 95% CI 1.05–2.32, p = 0.027), degree of diagnostic certainty (HR 0.88, 95% CI 0.78–0.98, p = 0.021), gastrostomy (HR 1.46, 95% CI 1.14–1.88, p = 0.003), NIV (HR 1.43, 95% CI 1.12–1.82, p = 0.004), and weight loss at diagnosis (HR 1.05, 95% CI 1.03–1.07, p < 0.001), diagnostic delay (HR 0.98, 95% CI 0.97–0.99, p = 0.004), and % treatment duration (HR 0.98, 95% CI 0.98–0.99, p < 0.001).

Conclusions

Independently from other prognostic factors, patients who received riluzole for a longer period of time survived longer, but further population based studies are needed to verify if long-tem use of riluzole prolongs survival.

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Acknowledgements

The authors acknowledge ERRALS group: Project coordinator: J. Mandrioli. Collaborating centers: Department of Neuroscience, St. Agostino Estense Hospital, Azienda Ospedaliero Universitaria di Modena, Italy (J. Mandrioli, N. Fini, A. Fasano, E. Zucchi, A. Gessani, L. Ferri, S. Malerba, P. Nichelli). Department of Neurology, Bufalini Hospital, Cesena, Italy (Y. Handouk, S. Biguzzi, W. Neri). Department of Neurology, Forlì Hospital, Forlì, Italy (C. Guidi, W. Neri). Department of Neurosciences and Rehabilitation, St Anna Hospital, Ferrara (E. Sette, V. Tugnoli and M. R. Tola). Department of Neurology, G. Da Saliceto Hospital, Piacenza, Italy (E. Terlizzi, D. Guidetti). Department of Neurology, Infermi Hospital, Rimini, Italy (M. Currò Dossi, M. Pasquinelli, J. Andruccioli, A. Ravasio). Department of Neurology, Faenza and Ravenna Hospital, Ravenna, Italy (M. Casmiro,F. Rasi). Department of Neurology and IRCCS Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital, Bologna, Italy (F. Salvi, I. Bartolomei, R. Michelucci). Department of Biomedical and Neuromotor Science and IRCCS Istituto delle Scienze Neurologiche di Bologna, University of Bologna, Bologna, Italy (P. Avoni, S. De Pasqua, R. Liguori). Department of Neurology, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (R. Rizzi, E. Canali, L. Codeluppi, F. Valzania). Department of Neuroscience, University of Parma, Parma, Italy (A. Taga, V. Pietrini, M. C. Trapasso, and L. Zinno). Department of Clinical and Experimental Medicine, Respiratory Disease and Lung Function Unit, University of Parma, Parma, Italy (M. Aiello). Department of Neurology, Fidenza Hospital, Parma, Italy (D. Medici, E. Chierici, E. Montanari). Department of Neurology, Carpi Hospital, Modena, Italy (M. Santangelo, S. Amidei). Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy (I. Casetta, M. Pugliatti, E. Della Coletta, V. Govoni, E. Granieri). Department of Neurology, Imola Hospital, Bologna, Italy (P. De Massis, V. Mussuto). Department of Neurology and IRCCS Istituto delle Scienze Neurologiche di Bologna, Maggiore Hospital, Bologna, Italy (A. Borghi, A. Gabellini, R. Michelucci). Neurology Unit, St. Orsola-Malpighi University Hospital, AOU di Bologna, Italy (R. Rinaldi, F. Cirignotta). Department of Hospital Services, Emilia Romagna Regional Health Authority, Bologna, Italy (S. Ferro). Neuroepidemiology Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy (R. D’Alessandro). CREAGEN Research Center for Environmental, Genetic and Nutritional Epidemiology, University of Modena and Reggio Emilia, Modena, Italy.

Funding

Emilia Romagna Registry for ALS is supported by a Grant from the Emilia Romagna Regional Health Authority.

Author information

Authors and Affiliations

  1. Department of Neuroscience, St. Agostino-Estense Hospital, Azienda Ospedaliero Universitaria di Modena, University of Modena and Reggio Emilia, Via Pietro Giardini n. 1355, 41100, Modena, Italy

    Jessica Mandrioli, Sara Angela Malerba, Nicola Fini, Antonio Fasano & Elisabetta Zucchi

  2. Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy

    Ettore Beghi

  3. Department of Biomedical and Neuromotor Sciences, University of Bologna and IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

    Silvia De Pasqua & Rocco Liguori

  4. Department of Neurology, Forlì Hospital, Forlì, Italy

    Carlo Guidi

  5. Department of Neurology, G. Da Saliceto Hospital, Piacenza, Italy

    Emilio Terlizzi

  6. Department of Neurology, St. Anna Hospital, Ferrara, Italy

    Elisabetta Sette

  7. Department of Neurology, Infermi Hospital, Rimini, Italy

    Alessandro Ravasio

  8. Department of Neurology, Faenza and Ravenna Hospital, Ravenna, Italy

    Mario Casmiro

  9. Neurology Unit, Bellaria Hospital, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

    Fabrizio Salvi

  10. Department of Neuroscience, Neurology Unit, University of Parma, Parma, Italy

    Lucia Zinno

  11. Department of Neurology, Bufalini Hospital, Cesena, Italy

    Yasmin Handouk

  12. Department of Neurology, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy

    Romana Rizzi

  13. Neurology Unit, Maggiore Hospital, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

    Annamaria Borghi

  14. Department of Neuroscience, St. Orsola-Malpighi University Hospital, Bologna, Italy

    Rita Rinaldi

  15. Department of Neurology, Fidenza Hospital, Parma, Italy

    Doriana Medici

  16. Department of Neurology, Carpi Hospital, Modena, Italy

    Mario Santangelo

  17. Department of Neuroscience, University of Ferrara, Ferrara, Italy

    Enrico Granieri

  18. Department of Neurology, Imola Hospital, Bologna, Italy

    Vittoria Mussuto

  19. Department of Clinical and Experimental Medicine, Respiratory Disease and Lung Function Unit, University of Parma, Parma, Italy

    Marina Aiello

  20. Department of Hospital Services, Emilia Romagna Regional Health Authority, Bologna, Italy

    Salvatore Ferro

  21. Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), University of Modena and Reggio Emilia Medical School, Modena, Italy

    Marco Vinceti

Authors
  1. Jessica Mandrioli
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  2. Sara Angela Malerba
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  3. Ettore Beghi
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  4. Nicola Fini
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  5. Antonio Fasano
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  7. Silvia De Pasqua
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  8. Carlo Guidi
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  13. Fabrizio Salvi
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  14. Rocco Liguori
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  15. Lucia Zinno
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  16. Yasmin Handouk
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  17. Romana Rizzi
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  18. Annamaria Borghi
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  19. Rita Rinaldi
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  20. Doriana Medici
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  21. Mario Santangelo
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  24. Marina Aiello
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  26. Marco Vinceti
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Consortia

ERRALS Group

  • J. Mandrioli
  • , N. Fini
  • , A. Fasano
  • , E. Zucchi
  • , A. Gessani
  • , L. Ferri
  • , S. Malerba
  • , P. Nichelli
  • , Y. Handouk
  • , S. Biguzzi
  • , W. Neri
  • , C. Guidi
  • , W. Neri
  • , E. Sette
  • , V. Tugnoli
  • , M. R. Tola
  • , E. Terlizzi
  • , D. Guidetti
  • , M. Currò Dossi
  • , M. Pasquinelli
  • , J. Andruccioli
  • , A. Ravasio
  • , M. Casmiro
  • , F. Rasi
  • , F. Salvi
  • , I. Bartolomei
  • , R. Michelucci
  • , P. Avoni
  • , S. De Pasqua
  • , R. Liguori
  • , R. Rizzi
  • , E. Canali
  • , L. Codeluppi
  • , F. Valzania
  • , A. Taga
  • , V. Pietrini
  • , M. C. Trapasso
  • , L. Zinno
  • , M. Aiello
  • , D. Medici
  • , E. Chierici
  • , E. Montanari
  • , M. Santangelo
  • , S. Amidei
  • , I. Casetta
  • , M. Pugliatti
  • , E. Della Coletta
  • , V. Govoni
  • , E. Granieri
  • , P. De Massis
  • , V. Mussuto
  • , A. Borghi
  • , A. Gabellini
  • , R. Michelucci
  • , R. Rinaldi
  • , F. Cirignotta
  • , S. Ferro
  •  & R. D’Alessandro

Corresponding author

Correspondence to Jessica Mandrioli.

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Conflicts of interest

The authors declare no conflicts of interest.

Ethical standards

The study has been approved by the ethics committees of ERR and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

Additional information

Members of ERRALS Group are listed in the Acknowledgements.

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Mandrioli, J., Malerba, S.A., Beghi, E. et al. Riluzole and other prognostic factors in ALS: a population-based registry study in Italy. J Neurol 265, 817–827 (2018). https://doi.org/10.1007/s00415-018-8778-y

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  • DOI: https://doi.org/10.1007/s00415-018-8778-y

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