First-line disease-modifying drugs in relapsing–remitting multiple sclerosis: an Italian real-life multicenter study on persistence

Abstract

Objective: The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for relapsing–remitting multiple sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. The aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months. Secondary aims were to compare the time to discontinuation and the reasons for discontinuation between the two groups and to explore the demographic and clinical factors associated with DMD discontinuation.

Methods: In this prospective, multi-center, real-life observational study, patients commencing any first-line DMD between 1 January 2015 and 31 July 2016 were enrolled and followed up for at least 12 months or until the drug was discontinued.

Results: Of the 520 included patients, 262 (49.6%) started an injectable and 258 (50.4%) an oral DMD. There was no difference in the proportion of patients on oral (n = 62, 24%) or on injectable (n = 60, 23%) DMDs discontinuing treatment, the most frequent reason being adverse events/side-effects. Higher baseline Expanded Disability Status Scale (EDSS) scores and younger age increased the odds of treatment withdrawal. Time to treatment discontinuation was not different between the two groups and was not influenced by the initiated DMD (oral versus injectable), even after adjustment for baseline differences.

Conclusion: The route of administration alone (i.e. oral versus injectable) was not a significant predictor of persistence with first-line DMDs in RRMS.

Keywords:

• Multiple sclerosis
• disease-modifying drugs
• persistence
• oral
• injectable

Transparency

Declaration of funding

This study was not funded.

Author contributions: D.F., E.B., P.I., F.G. and P.S. were involved in the conception and design of the study. V.C., E.B., V.V., M.F., E.C., A.G., S.Ma., S.Mo., S.S. and M.S. were involved in data collection. D.F. analyzed data and drafted the paper. All authors critically revised the paper for intellectual content and approved the final version to be published. All authors agree to be accountable for all aspects of the work.

Declaration of financial/other relationships

D.F. has disclosed that she has received travel grants and/or speaker honoraria from Merck Serono, Biogen, Novartis, TEVA and Sanofi-Genzyme. E.C. has disclosed that she has served on scientific advisory boards for Merck Serono; and has received funding for travel from Biogen, Merck Serono, Novartis and Sanofi Genzyme. S.Ma. has disclosed that she has served on advisory boards and/or received travel grants from Bayer, Biogen and Sanofi-Genzyme. A.L. has disclosed that she has served as a Bayer, Biogen, Sanofi/Genzyme, Merck Serono, Novartis and Teva Advisory Board Member; she received travel grants and honoraria from Bayer, Biogen, Genzyme, Merck Serono, Novartis, Sanofi and Teva; and her institution received research grants from Almirall, Bayer, Biogen, Merck Serono, Novartis, Sanofi and Teva; she has also received travel and research grants from the Associazione Italiana Sclerosi Multipla. F.G. has disclosed that he has received research grants for his institution from Biogen; has served on scientific advisory boards for Biogen, Novartis, Sanofi Genzyme and Merck Serono; and has received funding for travel from Biogen, Merck Serono and Sanofi Genzyme. I.P. has disclosed that she has served on scientific advisory boards for Merck Serono; and has received travel grants from Teva, Biogen, Merck Serono and Novartis. E.M. has disclosed that he has received funds and/or travel grants from Teva, Biogen, Merck Serono and Novartis. A.M.S. has disclosed that she has received travel grants and/or speaker honoraria from Merck Serono, Biogen, Novartis, Teva and Sanofi-Genzyme. P.S. has disclosed that she has received travel grants and/or speaker honoraria from Merck Serono, Biogen, Novartis, TEVA and Sanofi-Genzyme. V.C., E.B., V.V., A.G., S.Mo., S.S., M.S., L.C., M.F., L.M., W.N., P.I. and F.V. have nothing to disclose.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

We would like to thank the following investigators: Cinzia Scandellari, Carmelina Trocino, Francesca Falzone, Federica Pinardi (IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy), Luca Mancinelli (Department of Biomedical and Neuromotor Sciences, University of Bologna), Elena Tsantes, Ernesto Siena (Neurology Unit, Department of Medicine and Surgery, University of Parma, Italy), Michele Laudisi (Neurology Unit, Department of Neuroscience/Rehabilitation, Azienda Ospedaliera–Universitaria S. Anna, Ferrara, Italy) and Francesca Sireci (Arcispedale Santa Maria Nuova–IRCCS, Reggio Emilia, Italy).