Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study

Paul O'Connor, Giancarlo Comi, Mark S Freedman, Aaron E Miller, Ludwig Kappos, Jean-Pierre Bouchard, Christine Lebrun-Frenay, Jan Mares, Myriam Benamor, Karthinathan Thangavelu, Jinjun Liang, Philippe Truffinet, Victoria J Lawson, Jerry S Wolinsky, Teriflunomide Multiple Sclerosis Oral (TEMSO) Trial Group and the MRI-AC in Houston, Texas, Egon Stenager (Medlem af forfattergruppering)

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Resumé

OBJECTIVE: To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563).

METHODS: A total of 742 patients entered the extension. Teriflunomide-treated patients continued the original dose; those previously receiving placebo were randomized 1:1 to teriflunomide 14 mg or 7 mg.

RESULTS: By June 2013, median (maximum) teriflunomide exposure exceeded 190 (325) weeks per patient; 468 patients (63%) remained on treatment. Teriflunomide was well-tolerated with continued exposure. The most common adverse events (AEs) matched those in the core study. In extension year 1, first AEs of transient liver enzyme increases or reversible hair thinning were generally attributable to patients switching from placebo to teriflunomide. Approximately 11% of patients discontinued treatment owing to AEs. Twenty percent of patients experienced serious AEs. There were 3 deaths unrelated to teriflunomide. Soon after the extension started, annualized relapse rates and gadolinium-enhancing T1 lesion counts fell in patients switching from placebo to teriflunomide, remaining low thereafter. Disability remained stable in all treatment groups (median Expanded Disability Status Scale score ≤2.5; probability of 12-week disability progression ≤0.48).

CONCLUSIONS: In the TEMSO extension, safety observations were consistent with the core trial, with no new or unexpected AEs in patients receiving teriflunomide for up to 9 years. Disease activity decreased in patients switching from placebo and remained low in patients continuing on teriflunomide.

CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that long-term treatment with teriflunomide is well-tolerated and efficacy of teriflunomide is maintained long-term.

OriginalsprogEngelsk
TidsskriftNeurology
Vol/bind86
Udgave nummer10
Sider (fra-til)920-30
ISSN0028-3878
DOI
StatusUdgivet - 2016

Fingeraftryk

Safety
Placebos
Gadolinium
Hair
Liver
Enzymes

Citer dette

O'Connor, Paul ; Comi, Giancarlo ; Freedman, Mark S ; Miller, Aaron E ; Kappos, Ludwig ; Bouchard, Jean-Pierre ; Lebrun-Frenay, Christine ; Mares, Jan ; Benamor, Myriam ; Thangavelu, Karthinathan ; Liang, Jinjun ; Truffinet, Philippe ; Lawson, Victoria J ; Wolinsky, Jerry S ; Teriflunomide Multiple Sclerosis Oral (TEMSO) Trial Group and the MRI-AC in Houston, Texas ; Stenager, Egon. / Long-term safety and efficacy of teriflunomide : Nine-year follow-up of the randomized TEMSO study. I: Neurology. 2016 ; Bind 86, Nr. 10. s. 920-30.
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title = "Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study",
abstract = "OBJECTIVE: To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563).METHODS: A total of 742 patients entered the extension. Teriflunomide-treated patients continued the original dose; those previously receiving placebo were randomized 1:1 to teriflunomide 14 mg or 7 mg.RESULTS: By June 2013, median (maximum) teriflunomide exposure exceeded 190 (325) weeks per patient; 468 patients (63{\%}) remained on treatment. Teriflunomide was well-tolerated with continued exposure. The most common adverse events (AEs) matched those in the core study. In extension year 1, first AEs of transient liver enzyme increases or reversible hair thinning were generally attributable to patients switching from placebo to teriflunomide. Approximately 11{\%} of patients discontinued treatment owing to AEs. Twenty percent of patients experienced serious AEs. There were 3 deaths unrelated to teriflunomide. Soon after the extension started, annualized relapse rates and gadolinium-enhancing T1 lesion counts fell in patients switching from placebo to teriflunomide, remaining low thereafter. Disability remained stable in all treatment groups (median Expanded Disability Status Scale score ≤2.5; probability of 12-week disability progression ≤0.48).CONCLUSIONS: In the TEMSO extension, safety observations were consistent with the core trial, with no new or unexpected AEs in patients receiving teriflunomide for up to 9 years. Disease activity decreased in patients switching from placebo and remained low in patients continuing on teriflunomide.CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that long-term treatment with teriflunomide is well-tolerated and efficacy of teriflunomide is maintained long-term.",
keywords = "Journal Article",
author = "Paul O'Connor and Giancarlo Comi and Freedman, {Mark S} and Miller, {Aaron E} and Ludwig Kappos and Jean-Pierre Bouchard and Christine Lebrun-Frenay and Jan Mares and Myriam Benamor and Karthinathan Thangavelu and Jinjun Liang and Philippe Truffinet and Lawson, {Victoria J} and Wolinsky, {Jerry S} and {Teriflunomide Multiple Sclerosis Oral (TEMSO) Trial Group and the MRI-AC in Houston, Texas} and Egon Stenager",
note = "{\circledC} 2016 American Academy of Neurology.",
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doi = "10.1212/WNL.0000000000002441",
language = "English",
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publisher = "Lippincott Williams & Wilkins",
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O'Connor, P, Comi, G, Freedman, MS, Miller, AE, Kappos, L, Bouchard, J-P, Lebrun-Frenay, C, Mares, J, Benamor, M, Thangavelu, K, Liang, J, Truffinet, P, Lawson, VJ, Wolinsky, JS, Teriflunomide Multiple Sclerosis Oral (TEMSO) Trial Group and the MRI-AC in Houston, Texas & Stenager, E 2016, 'Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study', Neurology, bind 86, nr. 10, s. 920-30. https://doi.org/10.1212/WNL.0000000000002441

Long-term safety and efficacy of teriflunomide : Nine-year follow-up of the randomized TEMSO study. / O'Connor, Paul; Comi, Giancarlo; Freedman, Mark S; Miller, Aaron E; Kappos, Ludwig; Bouchard, Jean-Pierre; Lebrun-Frenay, Christine; Mares, Jan; Benamor, Myriam; Thangavelu, Karthinathan; Liang, Jinjun; Truffinet, Philippe; Lawson, Victoria J; Wolinsky, Jerry S; Teriflunomide Multiple Sclerosis Oral (TEMSO) Trial Group and the MRI-AC in Houston, Texas ; Stenager, Egon (Medlem af forfattergruppering).

I: Neurology, Bind 86, Nr. 10, 2016, s. 920-30.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Long-term safety and efficacy of teriflunomide

T2 - Nine-year follow-up of the randomized TEMSO study

AU - O'Connor, Paul

AU - Comi, Giancarlo

AU - Freedman, Mark S

AU - Miller, Aaron E

AU - Kappos, Ludwig

AU - Bouchard, Jean-Pierre

AU - Lebrun-Frenay, Christine

AU - Mares, Jan

AU - Benamor, Myriam

AU - Thangavelu, Karthinathan

AU - Liang, Jinjun

AU - Truffinet, Philippe

AU - Lawson, Victoria J

AU - Wolinsky, Jerry S

AU - Teriflunomide Multiple Sclerosis Oral (TEMSO) Trial Group and the MRI-AC in Houston, Texas

A2 - Stenager, Egon

N1 - © 2016 American Academy of Neurology.

PY - 2016

Y1 - 2016

N2 - OBJECTIVE: To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563).METHODS: A total of 742 patients entered the extension. Teriflunomide-treated patients continued the original dose; those previously receiving placebo were randomized 1:1 to teriflunomide 14 mg or 7 mg.RESULTS: By June 2013, median (maximum) teriflunomide exposure exceeded 190 (325) weeks per patient; 468 patients (63%) remained on treatment. Teriflunomide was well-tolerated with continued exposure. The most common adverse events (AEs) matched those in the core study. In extension year 1, first AEs of transient liver enzyme increases or reversible hair thinning were generally attributable to patients switching from placebo to teriflunomide. Approximately 11% of patients discontinued treatment owing to AEs. Twenty percent of patients experienced serious AEs. There were 3 deaths unrelated to teriflunomide. Soon after the extension started, annualized relapse rates and gadolinium-enhancing T1 lesion counts fell in patients switching from placebo to teriflunomide, remaining low thereafter. Disability remained stable in all treatment groups (median Expanded Disability Status Scale score ≤2.5; probability of 12-week disability progression ≤0.48).CONCLUSIONS: In the TEMSO extension, safety observations were consistent with the core trial, with no new or unexpected AEs in patients receiving teriflunomide for up to 9 years. Disease activity decreased in patients switching from placebo and remained low in patients continuing on teriflunomide.CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that long-term treatment with teriflunomide is well-tolerated and efficacy of teriflunomide is maintained long-term.

AB - OBJECTIVE: To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563).METHODS: A total of 742 patients entered the extension. Teriflunomide-treated patients continued the original dose; those previously receiving placebo were randomized 1:1 to teriflunomide 14 mg or 7 mg.RESULTS: By June 2013, median (maximum) teriflunomide exposure exceeded 190 (325) weeks per patient; 468 patients (63%) remained on treatment. Teriflunomide was well-tolerated with continued exposure. The most common adverse events (AEs) matched those in the core study. In extension year 1, first AEs of transient liver enzyme increases or reversible hair thinning were generally attributable to patients switching from placebo to teriflunomide. Approximately 11% of patients discontinued treatment owing to AEs. Twenty percent of patients experienced serious AEs. There were 3 deaths unrelated to teriflunomide. Soon after the extension started, annualized relapse rates and gadolinium-enhancing T1 lesion counts fell in patients switching from placebo to teriflunomide, remaining low thereafter. Disability remained stable in all treatment groups (median Expanded Disability Status Scale score ≤2.5; probability of 12-week disability progression ≤0.48).CONCLUSIONS: In the TEMSO extension, safety observations were consistent with the core trial, with no new or unexpected AEs in patients receiving teriflunomide for up to 9 years. Disease activity decreased in patients switching from placebo and remained low in patients continuing on teriflunomide.CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that long-term treatment with teriflunomide is well-tolerated and efficacy of teriflunomide is maintained long-term.

KW - Journal Article

U2 - 10.1212/WNL.0000000000002441

DO - 10.1212/WNL.0000000000002441

M3 - Journal article

C2 - 26865517

VL - 86

SP - 920

EP - 930

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 10

ER -