Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis

Tomas Kalincik, Eva Kubala Havrdova, Dana Horakova, Guillermo Izquierdo, Alexandre Prat, Marc Girard, Pierre Duquette, Pierre Grammond, Marco Onofrj, Alessandra Lugaresi, Serkan Ozakbas, Ludwig Kappos, Jens Kuhle, Murat Terzi, Jeannette Lechner-Scott, Cavit Boz, Francois Grand'Maison, Julie Prevost, Patrizia Sola, Diana Ferraro & 24 others Franco Granella, Maria Trojano, Roberto Bergamaschi, Eugenio Pucci, Recai Turkoglu, Pamela A McCombe, Vincent Van Pesch, Bart Van Wijmeersch, Claudio Solaro, Cristina Ramo-Tello, Mark Slee, Raed Alroughani, Bassem Yamout, Vahid Shaygannejad, Daniele Spitaleri, José Luis Sánchez-Menoyo, Radek Ampapa, Suzanne Hodgkinson, Rana Karabudak, Ernest Butler, Steve Vucic, Vilija Jokubaitis, Tim Spelman, Helmut Butzkueven

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: Oral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.

METHODS: We identified all patients with relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).

RESULTS: The eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fumarate (0.20 vs 0.26; p=0.01) and similar on dimethyl fumarate and teriflunomide (0.19 vs 0.22; p=0.55). No differences in disability accumulation (p≥0.59) or improvement (p≥0.14) were found between the therapies. In patients with ≥3-month treatment persistence, subsequent discontinuations were less likely on fingolimod than teriflunomide and dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.68).

CONCLUSION: The effect of fingolimod on relapse frequency was superior to teriflunomide and dimethyl fumarate. The effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment. Persistence on fingolimod was superior to the two comparator drugs.

Original languageEnglish
Pages (from-to)458-468
Number of pages11
JournalJournal of neurology, neurosurgery, and psychiatry
Volume90
Issue number4
DOIs
Publication statusPublished - Apr 2019

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Multiple Sclerosis
Recurrence
Relapsing-Remitting Multiple Sclerosis
Therapeutics
Propensity Score
Statistical Models
Fingolimod Hydrochloride
Dimethyl Fumarate
teriflunomide
Immunotherapy
Cohort Studies
Survival
Pharmaceutical Preparations

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Kalincik, T., Kubala Havrdova, E., Horakova, D., Izquierdo, G., Prat, A., Girard, M., ... Butzkueven, H. (2019). Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis. Journal of neurology, neurosurgery, and psychiatry, 90(4), 458-468. https://doi.org/10.1136/jnnp-2018-319831

Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis. / Kalincik, Tomas; Kubala Havrdova, Eva; Horakova, Dana; Izquierdo, Guillermo; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Grammond, Pierre; Onofrj, Marco; Lugaresi, Alessandra; Ozakbas, Serkan; Kappos, Ludwig; Kuhle, Jens; Terzi, Murat; Lechner-Scott, Jeannette; Boz, Cavit; Grand'Maison, Francois; Prevost, Julie; Sola, Patrizia; Ferraro, Diana; Granella, Franco; Trojano, Maria; Bergamaschi, Roberto; Pucci, Eugenio; Turkoglu, Recai; McCombe, Pamela A; Pesch, Vincent Van; Van Wijmeersch, Bart; Solaro, Claudio; Ramo-Tello, Cristina; Slee, Mark; Alroughani, Raed; Yamout, Bassem; Shaygannejad, Vahid; Spitaleri, Daniele; Sánchez-Menoyo, José Luis; Ampapa, Radek; Hodgkinson, Suzanne; Karabudak, Rana; Butler, Ernest; Vucic, Steve; Jokubaitis, Vilija; Spelman, Tim; Butzkueven, Helmut.

In: Journal of neurology, neurosurgery, and psychiatry, Vol. 90, No. 4, 04.2019, p. 458-468.

Research output: Contribution to journalArticle

Kalincik, T, Kubala Havrdova, E, Horakova, D, Izquierdo, G, Prat, A, Girard, M, Duquette, P, Grammond, P, Onofrj, M, Lugaresi, A, Ozakbas, S, Kappos, L, Kuhle, J, Terzi, M, Lechner-Scott, J, Boz, C, Grand'Maison, F, Prevost, J, Sola, P, Ferraro, D, Granella, F, Trojano, M, Bergamaschi, R, Pucci, E, Turkoglu, R, McCombe, PA, Pesch, VV, Van Wijmeersch, B, Solaro, C, Ramo-Tello, C, Slee, M, Alroughani, R, Yamout, B, Shaygannejad, V, Spitaleri, D, Sánchez-Menoyo, JL, Ampapa, R, Hodgkinson, S, Karabudak, R, Butler, E, Vucic, S, Jokubaitis, V, Spelman, T & Butzkueven, H 2019, 'Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis', Journal of neurology, neurosurgery, and psychiatry, vol. 90, no. 4, pp. 458-468. https://doi.org/10.1136/jnnp-2018-319831
Kalincik, Tomas ; Kubala Havrdova, Eva ; Horakova, Dana ; Izquierdo, Guillermo ; Prat, Alexandre ; Girard, Marc ; Duquette, Pierre ; Grammond, Pierre ; Onofrj, Marco ; Lugaresi, Alessandra ; Ozakbas, Serkan ; Kappos, Ludwig ; Kuhle, Jens ; Terzi, Murat ; Lechner-Scott, Jeannette ; Boz, Cavit ; Grand'Maison, Francois ; Prevost, Julie ; Sola, Patrizia ; Ferraro, Diana ; Granella, Franco ; Trojano, Maria ; Bergamaschi, Roberto ; Pucci, Eugenio ; Turkoglu, Recai ; McCombe, Pamela A ; Pesch, Vincent Van ; Van Wijmeersch, Bart ; Solaro, Claudio ; Ramo-Tello, Cristina ; Slee, Mark ; Alroughani, Raed ; Yamout, Bassem ; Shaygannejad, Vahid ; Spitaleri, Daniele ; Sánchez-Menoyo, José Luis ; Ampapa, Radek ; Hodgkinson, Suzanne ; Karabudak, Rana ; Butler, Ernest ; Vucic, Steve ; Jokubaitis, Vilija ; Spelman, Tim ; Butzkueven, Helmut. / Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis. In: Journal of neurology, neurosurgery, and psychiatry. 2019 ; Vol. 90, No. 4. pp. 458-468.
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abstract = "OBJECTIVE: Oral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.METHODS: We identified all patients with relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).RESULTS: The eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fumarate (0.20 vs 0.26; p=0.01) and similar on dimethyl fumarate and teriflunomide (0.19 vs 0.22; p=0.55). No differences in disability accumulation (p≥0.59) or improvement (p≥0.14) were found between the therapies. In patients with ≥3-month treatment persistence, subsequent discontinuations were less likely on fingolimod than teriflunomide and dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.68).CONCLUSION: The effect of fingolimod on relapse frequency was superior to teriflunomide and dimethyl fumarate. The effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment. Persistence on fingolimod was superior to the two comparator drugs.",
author = "Tomas Kalincik and {Kubala Havrdova}, Eva and Dana Horakova and Guillermo Izquierdo and Alexandre Prat and Marc Girard and Pierre Duquette and Pierre Grammond and Marco Onofrj and Alessandra Lugaresi and Serkan Ozakbas and Ludwig Kappos and Jens Kuhle and Murat Terzi and Jeannette Lechner-Scott and Cavit Boz and Francois Grand'Maison and Julie Prevost and Patrizia Sola and Diana Ferraro and Franco Granella and Maria Trojano and Roberto Bergamaschi and Eugenio Pucci and Recai Turkoglu and McCombe, {Pamela A} and Pesch, {Vincent Van} and {Van Wijmeersch}, Bart and Claudio Solaro and Cristina Ramo-Tello and Mark Slee and Raed Alroughani and Bassem Yamout and Vahid Shaygannejad and Daniele Spitaleri and S{\'a}nchez-Menoyo, {Jos{\'e} Luis} and Radek Ampapa and Suzanne Hodgkinson and Rana Karabudak and Ernest Butler and Steve Vucic and Vilija Jokubaitis and Tim Spelman and Helmut Butzkueven",
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TY - JOUR

T1 - Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis

AU - Kalincik, Tomas

AU - Kubala Havrdova, Eva

AU - Horakova, Dana

AU - Izquierdo, Guillermo

AU - Prat, Alexandre

AU - Girard, Marc

AU - Duquette, Pierre

AU - Grammond, Pierre

AU - Onofrj, Marco

AU - Lugaresi, Alessandra

AU - Ozakbas, Serkan

AU - Kappos, Ludwig

AU - Kuhle, Jens

AU - Terzi, Murat

AU - Lechner-Scott, Jeannette

AU - Boz, Cavit

AU - Grand'Maison, Francois

AU - Prevost, Julie

AU - Sola, Patrizia

AU - Ferraro, Diana

AU - Granella, Franco

AU - Trojano, Maria

AU - Bergamaschi, Roberto

AU - Pucci, Eugenio

AU - Turkoglu, Recai

AU - McCombe, Pamela A

AU - Pesch, Vincent Van

AU - Van Wijmeersch, Bart

AU - Solaro, Claudio

AU - Ramo-Tello, Cristina

AU - Slee, Mark

AU - Alroughani, Raed

AU - Yamout, Bassem

AU - Shaygannejad, Vahid

AU - Spitaleri, Daniele

AU - Sánchez-Menoyo, José Luis

AU - Ampapa, Radek

AU - Hodgkinson, Suzanne

AU - Karabudak, Rana

AU - Butler, Ernest

AU - Vucic, Steve

AU - Jokubaitis, Vilija

AU - Spelman, Tim

AU - Butzkueven, Helmut

N1 - © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2019/4

Y1 - 2019/4

N2 - OBJECTIVE: Oral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.METHODS: We identified all patients with relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).RESULTS: The eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fumarate (0.20 vs 0.26; p=0.01) and similar on dimethyl fumarate and teriflunomide (0.19 vs 0.22; p=0.55). No differences in disability accumulation (p≥0.59) or improvement (p≥0.14) were found between the therapies. In patients with ≥3-month treatment persistence, subsequent discontinuations were less likely on fingolimod than teriflunomide and dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.68).CONCLUSION: The effect of fingolimod on relapse frequency was superior to teriflunomide and dimethyl fumarate. The effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment. Persistence on fingolimod was superior to the two comparator drugs.

AB - OBJECTIVE: Oral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.METHODS: We identified all patients with relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).RESULTS: The eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fumarate (0.20 vs 0.26; p=0.01) and similar on dimethyl fumarate and teriflunomide (0.19 vs 0.22; p=0.55). No differences in disability accumulation (p≥0.59) or improvement (p≥0.14) were found between the therapies. In patients with ≥3-month treatment persistence, subsequent discontinuations were less likely on fingolimod than teriflunomide and dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.68).CONCLUSION: The effect of fingolimod on relapse frequency was superior to teriflunomide and dimethyl fumarate. The effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment. Persistence on fingolimod was superior to the two comparator drugs.

U2 - 10.1136/jnnp-2018-319831

DO - 10.1136/jnnp-2018-319831

M3 - Article

VL - 90

SP - 458

EP - 468

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

SN - 0022-3050

IS - 4

ER -