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Safety and tolerability of fingolimod in patients with relapsing-remitting multiple sclerosis: results of an open-label clinical trial in Italy

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Abstract

The safety profile of fingolimod is well established in clinical trials and post-marketing studies. This study aimed to evaluate the safety and tolerability of fingolimod in a cohort of Italian patients with relapsing-remitting multiple sclerosis (RRMS). This is a non-comparative, open-label, multicentre, interventional study conducted in patients with RRMS with no suitable alternative treatment option. Safety and tolerability of fingolimod 0.5 mg were assessed by recording adverse events (AEs) and serious AEs (SAEs). Of the 906 patients enrolled in the study, 91 % of the patients completed the study. AEs and SAEs were reported in 35.4 and 2.9 % of the patients, respectively. Most common AEs reported were headache (4.1 %), influenza (2.1 %), lymphopenia (1.8 %), asthenia (1.8 %) and pyrexia (1.8 %). Increased alanine aminotransferase levels and hypertension were reported as AE in 1.0 and 1.4 % of the patients, respectively. Macular oedema was reported in three patients. These results emphasize the safety of fingolimod in patients representing the real-world clinical practice in the Italian population. Fingolimod was safe and well tolerated in this population, which, compared to those enrolled in pivotal trials in terms of concomitant diseases and used medications, is broader.

Trial registration: EudraCT 2011-000770-60.

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Acknowledgements

Authors thank all the patients who participated in the study. The authors would like to thank Sreelatha Komatireddy (Medical communications, Novartis Healthcare Pvt. Ltd.) for medical writing assistance in developing the first draft of the manuscript, formatting, referencing, preparing tables and incorporating the authors’ revisions, all under the direction of the authors. All authors edited the manuscript for intellectual content, provided guidance during manuscript development and approved the final version submitted for publication.

In addition, authors would like to thank all investigators from participating sites: MP Amato, Firenze, Italy; L Appendino, Torino, Italy; B Ardito, Acquaviva delle Fonti, Bari, Italy; C Avolio, Foggia, Italy; F Bandini, Savona, Italy; AP Batocchi, Roma, Italy; P Bellantonio, Pozzilli, Isernia, Italy; MD Benedetti, Verona, Italy; R Bergamaschi, Pavia, Italy; F Bortolon, Vicenza, Italy; A Bosco, Trieste, Italy; V Brescia Morra, Naples, Italy; M Buccafusca, Messina, Italy; D Cargnelutti, Udine, Italy; P Cavalla, Torino, Italy; R Cavallo, Torino, Italy; D Centonze, Roma, Italy; G Comi, Milano, Italy; MG Coniglio, Matera, Italy; G Costantino, Foggia, Italy; S Cottone, Palermo, Italy; MC Danni, Ancona, Italy; F De Robertis, Lecce, Italy; L Deotto, Verona, Italy; M Dotta, Alba (CN), Italy; G Di Battista, Roma, Italy; MM Filippi, Roma, Italy; C Florio, Napoli, Italy; A Francia, Roma, Italy; S Galgani, Roma, Italy; P Gallo, Padova, Italy; A Ghezzi, Gallarate (Varese), Italy; B Giometto, Treviso, Italy; G Giuliani, Macerata, Italy; LME Grimaldi, Cefalù (Palermo), Italy; L Guidi, Empoli, Italy; M Guidotti, Como, Italy; A Iudice, Pisa, Italy; GL Lenzi, Roma, Italy; L Lorusso, Chiari (Brescia), Italy; A Lugaresi, Chieti, Italy; G Lus, Napoli, Italy; D Maimone, Catania, Italy; GM Malentacchi, Potenza, Italy; GL Mancardi, Genova, Italy; RE Mantegazza, Milano, Italy; L Massacesi, Firenze, Italy; M Melato, Alessandria, Italy; E Millefiorini, Roma, Italy; E Montanari, Fidenza, Italy; F Patti, Catania, Italy; PSM Perrone, Legnano (Milano), Italy; C Pozzilli, Roma, Italy; A Protti, Milano, Italy; P Provera, Tortona (Alessandria), Italy; A Quattrone, Catanzaro, Italy; F Rasi, Ravenna, Italy; G Rosati, Sassari, Italy; M Rovaris, Milano, Italy; F Saccà, Napoli, Italy; G Salemi, Palermo, Italy; P Sarchielli, Perugia, Italy; EA Scarpini, Milano, Italy; R Schoenhuber, Bolzano, Italy; C Serrati, Genova, Italy; L Sinisi, Napoli, Italy; P Sola, Modena, Italy; DLA Spitaleri, Avellino, Italy; G Tedeschi, Napoli, Italy; F Tezzon, Merano (Bolzano), Italy; MC Tinebra Asti, Italy; MR Tola, Cona (Ferrara), Italy; R Totaro, L’Aquila, Italy; M Trojano, Bari, Italy; M Ulivelli, Siena, Italy; MM Vecchio, Caltanissetta, Italy; GB Zimatore, Barletta, Italy.

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Authors and Affiliations

  1. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Largo Daneo 3, 16132, Genoa, Italy

    Alice Laroni, Davide Brogi, Antonio Uccelli & Giovanni Luigi Mancardi

  2. Department of Neurological Sciences, University Federico II, Naples, Italy

    Vincenzo Brescia Morra

  3. Neurology Unit, S. Giuseppe Hospital, Empoli, Italy

    Leonello Guidi

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

    Carlo Pozzilli

  5. Department of Neurology, Scientific Institute, INSPE, Vita-Salute San Raffaele University, Scientific Institute San Raffaele, Milan, Italy

    Giancarlo Comi

  6. Department of Neuroscience, Imaging and Clinical Sciences, University G. d’Annunzio, Chieti, Italy

    Alessandra Lugaresi

  7. Novartis Farma, Origgio, Varese, Italy

    Renato Turrini & Debora Raimondi

  8. IRCCS San Martino-IST, Genova, Italy

    Alice Laroni, Antonio Uccelli & Giovanni Luigi Mancardi

  9. Center of Excellence for Biomedical Research, Genova, Italy

    Alice Laroni & Antonio Uccelli

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  1. Alice Laroni
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  2. Davide Brogi
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  3. Vincenzo Brescia Morra
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  4. Leonello Guidi
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  5. Carlo Pozzilli
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  6. Giancarlo Comi
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  7. Alessandra Lugaresi
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  8. Renato Turrini
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  9. Debora Raimondi
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  10. Antonio Uccelli
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  11. Giovanni Luigi Mancardi
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Corresponding author

Correspondence to Giovanni Luigi Mancardi.

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Funding

This study was sponsored by Novartis Farma SpA, Origgio, Italy.

Conflict of interest

A. Laroni has received honoraria for speaking from Biogen and Novartis, received consulting honoraria from Merck Serono, Sanofi Genzyme, Novartis and Teva, and travel grants from Teva, Merck Serono, Biogen and Novartis. D. Brogi has received travel grants from Biogen, Novartis, Merck Serono, Almirall. V. Brescia Morra has received funding for travel, speaker honoraria, and research support from Sanofi-Aventis, Bayer Schering Pharma, Merck Serono, and Biogen Idec. C. Pozzilli has received compensation for participating in scientific advisory board/consulting honoraria/travel grants from Genzyme, Actelion, Novartis, Roche, Serono, Teva, Biogen, Chughai. He received speaking fees from Biogen, Novartis and Teva and his institution has received research grants from Novartis, Biogen, and Genzyme. G. Comi has received personal fees from Novartis, Teva, Sanofi, Genzyme, Merck Serono, Biogen, Bayer Schering, Serono Symposia International Foundation, Excemed, Roche, Almirall, Chugai, Receptos, Forward Pharma, outside the submitted work. A. Lugaresi has received compensation for participating in scientific advisory board/speaking fees/travel grants from Bayer Schering, Biogen Idec, Sanofi, Merck Serono, Novartisand Teva. Her institution received research grants from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi and Teva. Prof. Lugaresi has also received travel and research grants from the Associazione Italiana Sclerosi Multipla and was a Consultant of “Fondazione Cesare Serono”. A. Uccelli has received consulting/speaking fees from Merck Serono, Biogen-Idec, Novartis, Teva, Roche and Genzyme. His institution has received research grants from Biogen-Idec, Merck Serono, and Novartis. G. Mancardi/his institution has received honoraria/speaking fees/research grants from Bayer Schering, Biogen-Idec, Sanofi Aventis, Teva, Merck Serono, and Novartis. L. Guidi declares no conflicts of interest. Dr. Turrini and Dr. Raimondi are employees of Novartis Farma, Italy.

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Laroni, A., Brogi, D., Brescia Morra, V. et al. Safety and tolerability of fingolimod in patients with relapsing-remitting multiple sclerosis: results of an open-label clinical trial in Italy. Neurol Sci 38, 53–59 (2017). https://doi.org/10.1007/s10072-016-2701-z

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