Safety of the first dose of fingolimod for multiple sclerosis

Results of an open-label clinical trial

Alice Laroni, Davide Brogi, Vincenzo B. Morra, Leonello Guidi, Carlo Pozzilli, Giancarlo Comi, Alessandra Lugaresi, Renato Turrini, Debora Raimondi, Antonio Uccelli, Giovanni L. Mancardi, M. P. Amato, L. Appendino, B. Ardito, C. Avolio, F. Bandini, A. P. Batocchi, P. Bellantonio, M. D. Benedetti, R. Bergamaschi & 62 others F. Bortolon, A. Bosco, M. Buccafusca, D. Cargnelutti, P. Cavalla, R. Cavallo, D. Centonze, M. G. Coniglio, G. Costantino, S. Cottone, M. C. Danni, F. De Robertis, L. Deotto, M. Dotta, G. Di Battista, M. M. Filippi, C. Florio, A. Francia, S. Galgani, P. Gallo, A. Ghezzi, B. Giometto, G. Giuliani, L. M E Grimaldi, M. Guidotti, A. Iudice, G. L. Lenzi, L. Lorusso, G. Lus, D. Maimone, G. M. Malentacchi, R. E. Mantegazza, L. Massacesi, M. Melato, E. Millefiorini, E. Montanari, F. Patti, P. S M Perrone, A. Protti, P. Provera, A. Quattrone, F. Rasi, G. Rosati, M. Rovaris, F. Saccà, G. Salemi, P. Sarchielli, E. A. Scarpini, R. Schoenhuber, C. Serrati, L. Sinisi, P. Sola, D. L A Spitaleri, G. Tedeschi, F. Tezzon, M. C. Tinebra Asti, M. R. Tola, R. Totaro, M. Trojano, M. Ulivelli, M. M. Vecchio, G. B. Zimatore

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background: In patients with relapsing-remitting MS (RRMS) fingolimod prevents disease relapses and delays disability progression. First dose administration of fingolimod is associated with a transient, dose-dependent decrease in heart rate (HR) in the 6 hours after drug intake. The aim of the study is to to assess safety and tolerability of the first dose of fingolimod in a cohort of Italian patients with RRMS without alternative therapeutic options. Methods: Open-label, single arm, multicentre study. After the first dose of fingolimod, patients were observed for 6 hours and had their vital signs monitored hourly. Extended on-site monitoring was provided when required. Results: Of the 906 patients enrolled in the study, most (95.2%) did not experience any adverse event (AE) following fingolimod administration. Cardiovascular AEs occurred in 18 patients and included bradycardia (1.3%), first-and second-degree atrioventricular block (0.1% and 0.2%), palpitations (0.1%), sinus arrhythmia (0.1%) and ventricular premature beats (0.1%). All events were self-limiting and did not require any intervention. Extended monitoring was required in 34 patients. Conclusions: These results, in a population who better resembled real-world clinical practice in terms of concomitant diseases and medications, are consistent with previous clinical trials and confirmed that the first dose administration of fingolimod is generally safe and well tolerated.

Original languageEnglish
Article number65
JournalBMC Neurology
Volume14
Issue number1
DOIs
Publication statusPublished - Apr 1 2014

Fingerprint

Multiple Sclerosis
Clinical Trials
Safety
Sinus Arrhythmia
Ventricular Premature Complexes
Vital Signs
Atrioventricular Block
Bradycardia
Multicenter Studies
Fingolimod Hydrochloride
Heart Rate
Recurrence
Pharmaceutical Preparations
Population

Keywords

  • Atrioventricular block
  • Bradycardia
  • Fingolimod
  • Multiple sclerosis
  • Safety
  • Tolerability

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)

Cite this

Safety of the first dose of fingolimod for multiple sclerosis : Results of an open-label clinical trial. / Laroni, Alice; Brogi, Davide; Morra, Vincenzo B.; Guidi, Leonello; Pozzilli, Carlo; Comi, Giancarlo; Lugaresi, Alessandra; Turrini, Renato; Raimondi, Debora; Uccelli, Antonio; Mancardi, Giovanni L.; Amato, M. P.; Appendino, L.; Ardito, B.; Avolio, C.; Bandini, F.; Batocchi, A. P.; Bellantonio, P.; Benedetti, M. D.; Bergamaschi, R.; Bortolon, F.; Bosco, A.; Buccafusca, M.; Cargnelutti, D.; Cavalla, P.; Cavallo, R.; Centonze, D.; Coniglio, M. G.; Costantino, G.; Cottone, S.; Danni, M. C.; De Robertis, F.; Deotto, L.; Dotta, M.; Di Battista, G.; Filippi, M. M.; Florio, C.; Francia, A.; Galgani, S.; Gallo, P.; Ghezzi, A.; Giometto, B.; Giuliani, G.; Grimaldi, L. M E; Guidotti, M.; Iudice, A.; Lenzi, G. L.; Lorusso, L.; Lus, G.; Maimone, D.; Malentacchi, G. M.; Mantegazza, R. E.; Massacesi, L.; Melato, M.; Millefiorini, E.; Montanari, E.; Patti, F.; Perrone, P. S M; Protti, A.; Provera, P.; Quattrone, A.; Rasi, F.; Rosati, G.; Rovaris, M.; Saccà, F.; Salemi, G.; Sarchielli, P.; Scarpini, E. A.; Schoenhuber, R.; Serrati, C.; Sinisi, L.; Sola, P.; Spitaleri, D. L A; Tedeschi, G.; Tezzon, F.; Tinebra Asti, M. C.; Tola, M. R.; Totaro, R.; Trojano, M.; Ulivelli, M.; Vecchio, M. M.; Zimatore, G. B.

In: BMC Neurology, Vol. 14, No. 1, 65, 01.04.2014.

Research output: Contribution to journalArticle

Laroni, A, Brogi, D, Morra, VB, Guidi, L, Pozzilli, C, Comi, G, Lugaresi, A, Turrini, R, Raimondi, D, Uccelli, A, Mancardi, GL, Amato, MP, Appendino, L, Ardito, B, Avolio, C, Bandini, F, Batocchi, AP, Bellantonio, P, Benedetti, MD, Bergamaschi, R, Bortolon, F, Bosco, A, Buccafusca, M, Cargnelutti, D, Cavalla, P, Cavallo, R, Centonze, D, Coniglio, MG, Costantino, G, Cottone, S, Danni, MC, De Robertis, F, Deotto, L, Dotta, M, Di Battista, G, Filippi, MM, Florio, C, Francia, A, Galgani, S, Gallo, P, Ghezzi, A, Giometto, B, Giuliani, G, Grimaldi, LME, Guidotti, M, Iudice, A, Lenzi, GL, Lorusso, L, Lus, G, Maimone, D, Malentacchi, GM, Mantegazza, RE, Massacesi, L, Melato, M, Millefiorini, E, Montanari, E, Patti, F, Perrone, PSM, Protti, A, Provera, P, Quattrone, A, Rasi, F, Rosati, G, Rovaris, M, Saccà, F, Salemi, G, Sarchielli, P, Scarpini, EA, Schoenhuber, R, Serrati, C, Sinisi, L, Sola, P, Spitaleri, DLA, Tedeschi, G, Tezzon, F, Tinebra Asti, MC, Tola, MR, Totaro, R, Trojano, M, Ulivelli, M, Vecchio, MM & Zimatore, GB 2014, 'Safety of the first dose of fingolimod for multiple sclerosis: Results of an open-label clinical trial', BMC Neurology, vol. 14, no. 1, 65. https://doi.org/10.1186/1471-2377-14-65
Laroni, Alice ; Brogi, Davide ; Morra, Vincenzo B. ; Guidi, Leonello ; Pozzilli, Carlo ; Comi, Giancarlo ; Lugaresi, Alessandra ; Turrini, Renato ; Raimondi, Debora ; Uccelli, Antonio ; Mancardi, Giovanni L. ; Amato, M. P. ; Appendino, L. ; Ardito, B. ; Avolio, C. ; Bandini, F. ; Batocchi, A. P. ; Bellantonio, P. ; Benedetti, M. D. ; Bergamaschi, R. ; Bortolon, F. ; Bosco, A. ; Buccafusca, M. ; Cargnelutti, D. ; Cavalla, P. ; Cavallo, R. ; Centonze, D. ; Coniglio, M. G. ; Costantino, G. ; Cottone, S. ; Danni, M. C. ; De Robertis, F. ; Deotto, L. ; Dotta, M. ; Di Battista, G. ; Filippi, M. M. ; Florio, C. ; Francia, A. ; Galgani, S. ; Gallo, P. ; Ghezzi, A. ; Giometto, B. ; Giuliani, G. ; Grimaldi, L. M E ; Guidotti, M. ; Iudice, A. ; Lenzi, G. L. ; Lorusso, L. ; Lus, G. ; Maimone, D. ; Malentacchi, G. M. ; Mantegazza, R. E. ; Massacesi, L. ; Melato, M. ; Millefiorini, E. ; Montanari, E. ; Patti, F. ; Perrone, P. S M ; Protti, A. ; Provera, P. ; Quattrone, A. ; Rasi, F. ; Rosati, G. ; Rovaris, M. ; Saccà, F. ; Salemi, G. ; Sarchielli, P. ; Scarpini, E. A. ; Schoenhuber, R. ; Serrati, C. ; Sinisi, L. ; Sola, P. ; Spitaleri, D. L A ; Tedeschi, G. ; Tezzon, F. ; Tinebra Asti, M. C. ; Tola, M. R. ; Totaro, R. ; Trojano, M. ; Ulivelli, M. ; Vecchio, M. M. ; Zimatore, G. B. / Safety of the first dose of fingolimod for multiple sclerosis : Results of an open-label clinical trial. In: BMC Neurology. 2014 ; Vol. 14, No. 1.
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abstract = "Background: In patients with relapsing-remitting MS (RRMS) fingolimod prevents disease relapses and delays disability progression. First dose administration of fingolimod is associated with a transient, dose-dependent decrease in heart rate (HR) in the 6 hours after drug intake. The aim of the study is to to assess safety and tolerability of the first dose of fingolimod in a cohort of Italian patients with RRMS without alternative therapeutic options. Methods: Open-label, single arm, multicentre study. After the first dose of fingolimod, patients were observed for 6 hours and had their vital signs monitored hourly. Extended on-site monitoring was provided when required. Results: Of the 906 patients enrolled in the study, most (95.2{\%}) did not experience any adverse event (AE) following fingolimod administration. Cardiovascular AEs occurred in 18 patients and included bradycardia (1.3{\%}), first-and second-degree atrioventricular block (0.1{\%} and 0.2{\%}), palpitations (0.1{\%}), sinus arrhythmia (0.1{\%}) and ventricular premature beats (0.1{\%}). All events were self-limiting and did not require any intervention. Extended monitoring was required in 34 patients. Conclusions: These results, in a population who better resembled real-world clinical practice in terms of concomitant diseases and medications, are consistent with previous clinical trials and confirmed that the first dose administration of fingolimod is generally safe and well tolerated.",
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author = "Alice Laroni and Davide Brogi and Morra, {Vincenzo B.} and Leonello Guidi and Carlo Pozzilli and Giancarlo Comi and Alessandra Lugaresi and Renato Turrini and Debora Raimondi and Antonio Uccelli and Mancardi, {Giovanni L.} and Amato, {M. P.} and L. Appendino and B. Ardito and C. Avolio and F. Bandini and Batocchi, {A. P.} and P. Bellantonio and Benedetti, {M. D.} and R. Bergamaschi and F. Bortolon and A. Bosco and M. Buccafusca and D. Cargnelutti and P. Cavalla and R. Cavallo and D. Centonze and Coniglio, {M. G.} and G. Costantino and S. Cottone and Danni, {M. C.} and {De Robertis}, F. and L. Deotto and M. Dotta and {Di Battista}, G. and Filippi, {M. M.} and C. Florio and A. Francia and S. Galgani and P. Gallo and A. Ghezzi and B. Giometto and G. Giuliani and Grimaldi, {L. M E} and M. Guidotti and A. Iudice and Lenzi, {G. L.} and L. Lorusso and G. Lus and D. Maimone and Malentacchi, {G. M.} and Mantegazza, {R. E.} and L. Massacesi and M. Melato and E. Millefiorini and E. Montanari and F. Patti and Perrone, {P. S M} and A. Protti and P. Provera and A. Quattrone and F. Rasi and G. Rosati and M. Rovaris and F. Sacc{\`a} and G. Salemi and P. Sarchielli and Scarpini, {E. A.} and R. Schoenhuber and C. Serrati and L. Sinisi and P. Sola and Spitaleri, {D. L A} and G. Tedeschi and F. Tezzon and {Tinebra Asti}, {M. C.} and Tola, {M. R.} and R. Totaro and M. Trojano and M. Ulivelli and Vecchio, {M. M.} and Zimatore, {G. B.}",
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TY - JOUR

T1 - Safety of the first dose of fingolimod for multiple sclerosis

T2 - Results of an open-label clinical trial

AU - Laroni, Alice

AU - Brogi, Davide

AU - Morra, Vincenzo B.

AU - Guidi, Leonello

AU - Pozzilli, Carlo

AU - Comi, Giancarlo

AU - Lugaresi, Alessandra

AU - Turrini, Renato

AU - Raimondi, Debora

AU - Uccelli, Antonio

AU - Mancardi, Giovanni L.

AU - Amato, M. P.

AU - Appendino, L.

AU - Ardito, B.

AU - Avolio, C.

AU - Bandini, F.

AU - Batocchi, A. P.

AU - Bellantonio, P.

AU - Benedetti, M. D.

AU - Bergamaschi, R.

AU - Bortolon, F.

AU - Bosco, A.

AU - Buccafusca, M.

AU - Cargnelutti, D.

AU - Cavalla, P.

AU - Cavallo, R.

AU - Centonze, D.

AU - Coniglio, M. G.

AU - Costantino, G.

AU - Cottone, S.

AU - Danni, M. C.

AU - De Robertis, F.

AU - Deotto, L.

AU - Dotta, M.

AU - Di Battista, G.

AU - Filippi, M. M.

AU - Florio, C.

AU - Francia, A.

AU - Galgani, S.

AU - Gallo, P.

AU - Ghezzi, A.

AU - Giometto, B.

AU - Giuliani, G.

AU - Grimaldi, L. M E

AU - Guidotti, M.

AU - Iudice, A.

AU - Lenzi, G. L.

AU - Lorusso, L.

AU - Lus, G.

AU - Maimone, D.

AU - Malentacchi, G. M.

AU - Mantegazza, R. E.

AU - Massacesi, L.

AU - Melato, M.

AU - Millefiorini, E.

AU - Montanari, E.

AU - Patti, F.

AU - Perrone, P. S M

AU - Protti, A.

AU - Provera, P.

AU - Quattrone, A.

AU - Rasi, F.

AU - Rosati, G.

AU - Rovaris, M.

AU - Saccà, F.

AU - Salemi, G.

AU - Sarchielli, P.

AU - Scarpini, E. A.

AU - Schoenhuber, R.

AU - Serrati, C.

AU - Sinisi, L.

AU - Sola, P.

AU - Spitaleri, D. L A

AU - Tedeschi, G.

AU - Tezzon, F.

AU - Tinebra Asti, M. C.

AU - Tola, M. R.

AU - Totaro, R.

AU - Trojano, M.

AU - Ulivelli, M.

AU - Vecchio, M. M.

AU - Zimatore, G. B.

PY - 2014/4/1

Y1 - 2014/4/1

N2 - Background: In patients with relapsing-remitting MS (RRMS) fingolimod prevents disease relapses and delays disability progression. First dose administration of fingolimod is associated with a transient, dose-dependent decrease in heart rate (HR) in the 6 hours after drug intake. The aim of the study is to to assess safety and tolerability of the first dose of fingolimod in a cohort of Italian patients with RRMS without alternative therapeutic options. Methods: Open-label, single arm, multicentre study. After the first dose of fingolimod, patients were observed for 6 hours and had their vital signs monitored hourly. Extended on-site monitoring was provided when required. Results: Of the 906 patients enrolled in the study, most (95.2%) did not experience any adverse event (AE) following fingolimod administration. Cardiovascular AEs occurred in 18 patients and included bradycardia (1.3%), first-and second-degree atrioventricular block (0.1% and 0.2%), palpitations (0.1%), sinus arrhythmia (0.1%) and ventricular premature beats (0.1%). All events were self-limiting and did not require any intervention. Extended monitoring was required in 34 patients. Conclusions: These results, in a population who better resembled real-world clinical practice in terms of concomitant diseases and medications, are consistent with previous clinical trials and confirmed that the first dose administration of fingolimod is generally safe and well tolerated.

AB - Background: In patients with relapsing-remitting MS (RRMS) fingolimod prevents disease relapses and delays disability progression. First dose administration of fingolimod is associated with a transient, dose-dependent decrease in heart rate (HR) in the 6 hours after drug intake. The aim of the study is to to assess safety and tolerability of the first dose of fingolimod in a cohort of Italian patients with RRMS without alternative therapeutic options. Methods: Open-label, single arm, multicentre study. After the first dose of fingolimod, patients were observed for 6 hours and had their vital signs monitored hourly. Extended on-site monitoring was provided when required. Results: Of the 906 patients enrolled in the study, most (95.2%) did not experience any adverse event (AE) following fingolimod administration. Cardiovascular AEs occurred in 18 patients and included bradycardia (1.3%), first-and second-degree atrioventricular block (0.1% and 0.2%), palpitations (0.1%), sinus arrhythmia (0.1%) and ventricular premature beats (0.1%). All events were self-limiting and did not require any intervention. Extended monitoring was required in 34 patients. Conclusions: These results, in a population who better resembled real-world clinical practice in terms of concomitant diseases and medications, are consistent with previous clinical trials and confirmed that the first dose administration of fingolimod is generally safe and well tolerated.

KW - Atrioventricular block

KW - Bradycardia

KW - Fingolimod

KW - Multiple sclerosis

KW - Safety

KW - Tolerability

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U2 - 10.1186/1471-2377-14-65

DO - 10.1186/1471-2377-14-65

M3 - Article

VL - 14

JO - BMC Neurology

JF - BMC Neurology

SN - 1471-2377

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ER -