Long-term safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis: Results from the TOWER extension study.


Journal

Multiple sclerosis and related disorders
ISSN: 2211-0356
Titre abrégé: Mult Scler Relat Disord
Pays: Netherlands
ID NLM: 101580247

Informations de publication

Date de publication:
Nov 2020
Historique:
received: 26 02 2020
revised: 30 07 2020
accepted: 31 07 2020
pubmed: 11 9 2020
medline: 15 5 2021
entrez: 10 9 2020
Statut: ppublish

Résumé

In the phase 3 TOWER core study (NCT00751881), the efficacy and safety of teriflunomide compared with placebo were demonstrated in patients with relapsing forms of multiple sclerosis (RMS). Here, the long-term safety and efficacy outcomes from the TOWER extension study (NCT00751881) are reported. All patients who entered the extension (N = 751) were assigned to teriflunomide 14 mg and assessed for long-term safety and efficacy. Of 751 patients in the TOWER extension study, 253, 265, and 233 patients received placebo/teriflunomide 14 mg, teriflunomide 7 mg/14 mg, and teriflunomide 14 mg/14 mg, respectively. Median teriflunomide exposure was 4.25 years (maximum 6.3 years). The overall frequency of adverse events (AEs) was comparable across treatment groups, but a higher proportion of patients in the teriflunomide 7 mg/14 mg (12.4%) and 14 mg/14 mg (12.4%) groups had serious AEs compared with the placebo/teriflunomide 14 mg group (6.4%). Alanine aminotransferase increase and hair thinning occurred at a higher frequency in the placebo/teriflunomide 14 mg group (11.2% and 14.3%, respectively) compared with the teriflunomide 7 mg/14 mg (3.0% and 4.5%, respectively) and 14 mg/14 mg groups (5.2% and 4.3%, respectively). The incidences of AEs of interest (hematologic and hepatic effects, peripheral neuropathy, hypertension, and malignancy) were low and comparable across treatment arms. Disability worsening and adjusted annualized relapse rates were low and stable over time, and mean Expanded Disability Status Scale scores were unchanged over time, for all treatment groups. In the TOWER extension study, the efficacy of teriflunomide 14 mg was maintained in patients with RMS. No new or unexpected AEs were observed with teriflunomide treatment, supporting a safety profile in the extension that was consistent with the core trial. These findings support the positive benefit:risk profile of teriflunomide as a long-term immunomodulatory therapy.

Sections du résumé

BACKGROUND BACKGROUND
In the phase 3 TOWER core study (NCT00751881), the efficacy and safety of teriflunomide compared with placebo were demonstrated in patients with relapsing forms of multiple sclerosis (RMS). Here, the long-term safety and efficacy outcomes from the TOWER extension study (NCT00751881) are reported.
METHODS METHODS
All patients who entered the extension (N = 751) were assigned to teriflunomide 14 mg and assessed for long-term safety and efficacy.
RESULTS RESULTS
Of 751 patients in the TOWER extension study, 253, 265, and 233 patients received placebo/teriflunomide 14 mg, teriflunomide 7 mg/14 mg, and teriflunomide 14 mg/14 mg, respectively. Median teriflunomide exposure was 4.25 years (maximum 6.3 years). The overall frequency of adverse events (AEs) was comparable across treatment groups, but a higher proportion of patients in the teriflunomide 7 mg/14 mg (12.4%) and 14 mg/14 mg (12.4%) groups had serious AEs compared with the placebo/teriflunomide 14 mg group (6.4%). Alanine aminotransferase increase and hair thinning occurred at a higher frequency in the placebo/teriflunomide 14 mg group (11.2% and 14.3%, respectively) compared with the teriflunomide 7 mg/14 mg (3.0% and 4.5%, respectively) and 14 mg/14 mg groups (5.2% and 4.3%, respectively). The incidences of AEs of interest (hematologic and hepatic effects, peripheral neuropathy, hypertension, and malignancy) were low and comparable across treatment arms. Disability worsening and adjusted annualized relapse rates were low and stable over time, and mean Expanded Disability Status Scale scores were unchanged over time, for all treatment groups.
CONCLUSION CONCLUSIONS
In the TOWER extension study, the efficacy of teriflunomide 14 mg was maintained in patients with RMS. No new or unexpected AEs were observed with teriflunomide treatment, supporting a safety profile in the extension that was consistent with the core trial. These findings support the positive benefit:risk profile of teriflunomide as a long-term immunomodulatory therapy.

Identifiants

pubmed: 32911306
pii: S2211-0348(20)30513-7
doi: 10.1016/j.msard.2020.102438
pii:
doi:

Substances chimiques

Crotonates 0
Hydroxybutyrates 0
Nitriles 0
Toluidines 0
teriflunomide 1C058IKG3B

Banques de données

ClinicalTrials.gov
['NCT00751881']

Types de publication

Clinical Trial, Phase III Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

102438

Informations de copyright

Copyright © 2020. Published by Elsevier B.V.

Auteurs

Aaron E Miller (AE)

Department of Neurology, Icahn School of Medicine at Mount Sinai, 5 East 98th Street-Box 1138, New York, NY, 10029, United States. Electronic address: aaron.miller@mssm.edu.

Tomas P Olsson (TP)

Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, L8:04, Karolinska Hospital, 17176 Stockholm, Sweden.

Jerry S Wolinsky (JS)

Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), 6431 Fannin Street, Houston, TX, 77030, United States.

Giancarlo Comi (G)

Ospedale San Raffaele, Milan, Italy.

Ludwig Kappos (L)

Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital and University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland.

Xueqiang Hu (X)

Neurology, Hospital of Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, China.

Xianhao Xu (X)

Beijing Hospital, No. 1 Dahua Road, Beijing, China.

Alex L Lublin (AL)

Sanofi, Cambridge, MA, United States.

Philippe Truffinet (P)

Sanofi, Chilly-Mazarin, France.

Jeffrey Chavin (J)

Sanofi, Cambridge, MA, United States.

Jean-Luc Delhay (JL)

Sanofi, Chilly-Mazarin, France.

Myriam Benamor (M)

Sanofi, Chilly-Mazarin, France.

Annie Purvis (A)

Sanofi, Cambridge, MA, United States.

Mark S Freedman (MS)

The Ottawa Hospital Ontario, 501 Smyth Road, Box 601, Ottawa, ON, Canada.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH