Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis

Pietro Iaffaldano, Giuseppe Lucisano, Carlo Pozzilli, Vincenzo Brescia Morra, Angelo Ghezzi, Enrico Millefiorini, Francesco Patti, Alessandra Lugaresi, Giovanni Bosco Zimatore, Maria Giovanna Marrosu, Maria Pia Amato, Antonio Bertolotto, Roberto Bergamaschi, Franco Granella, Gabriella Coniglio, Gioacchino Tedeschi, Patrizia Sola, Giacomo Lus, Maria Teresa Ferrò, Gerardo IulianoFrancesco Corea, Alessandra Protti, Paola Cavalla, Angelica Guareschi, Mariaemma Rodegher, Damiano Paolicelli, Carla Tortorella, Vito Lepore, Luca Prosperini, Francesco Saccà, Damiano Baroncini, Giancarlo Comi, Maria Trojano

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in separated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence rate ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence rate ratio = 2.33, P = 0.0288), patient's choice (incidence rate ratio = 2.18, P = 0.0064) and adverse events (incidence rate ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duration longer than 3 months (incidence rate ratio = 1.78, P <0.0001), the number of relapses experienced during and before natalizumab treatment (incidence rate ratio = 1.61, P <0.0001; incidence rate ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence rate ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence rate ratio = 0.36, P <0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence rate ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate (P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out durations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard ratio = 0.58; P = 0.1931). Our results indicate a superiority of fingolimod in comparison to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in the real life setting.

Original languageEnglish
Pages (from-to)3275-3286
Number of pages12
JournalBrain
Volume138
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

Fingerprint

Interferon-beta
Multiple Sclerosis
Suspensions
Incidence
Recurrence
Propensity Score
Natalizumab
Glatiramer Acetate
Fingolimod Hydrochloride
Therapeutics
Risk Reduction Behavior
Registries
Comorbidity
Cohort Studies
Regression Analysis

Keywords

  • fingolimod
  • glatiramer acetate
  • interferon beta
  • multiple sclerosis
  • natalizumab discontinuation

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)

Cite this

Iaffaldano, P., Lucisano, G., Pozzilli, C., Brescia Morra, V., Ghezzi, A., Millefiorini, E., ... Trojano, M. (2015). Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis. Brain, 138(11), 3275-3286. https://doi.org/10.1093/brain/awv260

Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis. / Iaffaldano, Pietro; Lucisano, Giuseppe; Pozzilli, Carlo; Brescia Morra, Vincenzo; Ghezzi, Angelo; Millefiorini, Enrico; Patti, Francesco; Lugaresi, Alessandra; Zimatore, Giovanni Bosco; Marrosu, Maria Giovanna; Amato, Maria Pia; Bertolotto, Antonio; Bergamaschi, Roberto; Granella, Franco; Coniglio, Gabriella; Tedeschi, Gioacchino; Sola, Patrizia; Lus, Giacomo; Ferrò, Maria Teresa; Iuliano, Gerardo; Corea, Francesco; Protti, Alessandra; Cavalla, Paola; Guareschi, Angelica; Rodegher, Mariaemma; Paolicelli, Damiano; Tortorella, Carla; Lepore, Vito; Prosperini, Luca; Saccà, Francesco; Baroncini, Damiano; Comi, Giancarlo; Trojano, Maria.

In: Brain, Vol. 138, No. 11, 01.11.2015, p. 3275-3286.

Research output: Contribution to journalArticle

Iaffaldano, P, Lucisano, G, Pozzilli, C, Brescia Morra, V, Ghezzi, A, Millefiorini, E, Patti, F, Lugaresi, A, Zimatore, GB, Marrosu, MG, Amato, MP, Bertolotto, A, Bergamaschi, R, Granella, F, Coniglio, G, Tedeschi, G, Sola, P, Lus, G, Ferrò, MT, Iuliano, G, Corea, F, Protti, A, Cavalla, P, Guareschi, A, Rodegher, M, Paolicelli, D, Tortorella, C, Lepore, V, Prosperini, L, Saccà, F, Baroncini, D, Comi, G & Trojano, M 2015, 'Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis', Brain, vol. 138, no. 11, pp. 3275-3286. https://doi.org/10.1093/brain/awv260
Iaffaldano P, Lucisano G, Pozzilli C, Brescia Morra V, Ghezzi A, Millefiorini E et al. Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis. Brain. 2015 Nov 1;138(11):3275-3286. https://doi.org/10.1093/brain/awv260
Iaffaldano, Pietro ; Lucisano, Giuseppe ; Pozzilli, Carlo ; Brescia Morra, Vincenzo ; Ghezzi, Angelo ; Millefiorini, Enrico ; Patti, Francesco ; Lugaresi, Alessandra ; Zimatore, Giovanni Bosco ; Marrosu, Maria Giovanna ; Amato, Maria Pia ; Bertolotto, Antonio ; Bergamaschi, Roberto ; Granella, Franco ; Coniglio, Gabriella ; Tedeschi, Gioacchino ; Sola, Patrizia ; Lus, Giacomo ; Ferrò, Maria Teresa ; Iuliano, Gerardo ; Corea, Francesco ; Protti, Alessandra ; Cavalla, Paola ; Guareschi, Angelica ; Rodegher, Mariaemma ; Paolicelli, Damiano ; Tortorella, Carla ; Lepore, Vito ; Prosperini, Luca ; Saccà, Francesco ; Baroncini, Damiano ; Comi, Giancarlo ; Trojano, Maria. / Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis. In: Brain. 2015 ; Vol. 138, No. 11. pp. 3275-3286.
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AU - Marrosu, Maria Giovanna

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AU - Prosperini, Luca

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AU - Trojano, Maria

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N2 - The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in separated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence rate ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence rate ratio = 2.33, P = 0.0288), patient's choice (incidence rate ratio = 2.18, P = 0.0064) and adverse events (incidence rate ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duration longer than 3 months (incidence rate ratio = 1.78, P <0.0001), the number of relapses experienced during and before natalizumab treatment (incidence rate ratio = 1.61, P <0.0001; incidence rate ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence rate ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence rate ratio = 0.36, P <0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence rate ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate (P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out durations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard ratio = 0.58; P = 0.1931). Our results indicate a superiority of fingolimod in comparison to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in the real life setting.

AB - The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in separated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence rate ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence rate ratio = 2.33, P = 0.0288), patient's choice (incidence rate ratio = 2.18, P = 0.0064) and adverse events (incidence rate ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duration longer than 3 months (incidence rate ratio = 1.78, P <0.0001), the number of relapses experienced during and before natalizumab treatment (incidence rate ratio = 1.61, P <0.0001; incidence rate ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence rate ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence rate ratio = 0.36, P <0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence rate ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate (P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out durations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard ratio = 0.58; P = 0.1931). Our results indicate a superiority of fingolimod in comparison to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in the real life setting.

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