PMID- 32911306
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20220531
IS  - 2211-0356 (Electronic)
IS  - 2211-0348 (Linking)
VI  - 46
DP  - 2020 Nov
TI  - Long-term safety and efficacy of teriflunomide in patients with relapsing 
      multiple sclerosis: Results from the TOWER extension study.
PG  - 102438
LID - S2211-0348(20)30513-7 [pii]
LID - 10.1016/j.msard.2020.102438 [doi]
AB  - 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: All patients who entered the extension (N = 751) were assigned to 
      teriflunomide 14 mg and assessed for long-term safety and efficacy. 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: 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.
CI  - Copyright (c) 2020. Published by Elsevier B.V.
FAU - Miller, Aaron E
AU  - Miller AE
AD  - 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.
FAU - Olsson, Tomas P
AU  - Olsson TP
AD  - Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, 
      Center for Molecular Medicine, L8:04, Karolinska Hospital, 17176 Stockholm, 
      Sweden.
FAU - Wolinsky, Jerry S
AU  - Wolinsky JS
AD  - Department of Neurology, McGovern Medical School, The University of Texas Health 
      Science Center at Houston (UTHealth), 6431 Fannin Street, Houston, TX, 77030, 
      United States.
FAU - Comi, Giancarlo
AU  - Comi G
AD  - Ospedale San Raffaele, Milan, Italy.
FAU - Kappos, Ludwig
AU  - Kappos L
AD  - Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and 
      Biomedical Engineering, University Hospital and University of Basel, Petersgraben 
      4, CH-4031 Basel, Switzerland.
FAU - Hu, Xueqiang
AU  - Hu X
AD  - Neurology, Hospital of Sun Yat-Sen University, 107 Yan Jiang West Road, 
      Guangzhou, China.
FAU - Xu, Xianhao
AU  - Xu X
AD  - Beijing Hospital, No. 1 Dahua Road, Beijing, China.
FAU - Lublin, Alex L
AU  - Lublin AL
AD  - Sanofi, Cambridge, MA, United States.
FAU - Truffinet, Philippe
AU  - Truffinet P
AD  - Sanofi, Chilly-Mazarin, France.
FAU - Chavin, Jeffrey
AU  - Chavin J
AD  - Sanofi, Cambridge, MA, United States.
FAU - Delhay, Jean-Luc
AU  - Delhay JL
AD  - Sanofi, Chilly-Mazarin, France.
FAU - Benamor, Myriam
AU  - Benamor M
AD  - Sanofi, Chilly-Mazarin, France.
FAU - Purvis, Annie
AU  - Purvis A
AD  - Sanofi, Cambridge, MA, United States.
FAU - Freedman, Mark S
AU  - Freedman MS
AD  - The Ottawa Hospital Ontario, 501 Smyth Road, Box 601, Ottawa, ON, Canada.
CN  - TOWER investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT00751881
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20200801
PL  - Netherlands
TA  - Mult Scler Relat Disord
JT  - Multiple sclerosis and related disorders
JID - 101580247
RN  - 0 (Crotonates)
RN  - 0 (Hydroxybutyrates)
RN  - 0 (Nitriles)
RN  - 0 (Toluidines)
RN  - 1C058IKG3B (teriflunomide)
SB  - IM
MH  - Crotonates/adverse effects
MH  - Humans
MH  - Hydroxybutyrates
MH  - *Multiple Sclerosis
MH  - *Multiple Sclerosis, Relapsing-Remitting/drug therapy
MH  - Nitriles
MH  - Recurrence
MH  - Toluidines/adverse effects
OTO - NOTNLM
OT  - Efficacy
OT  - Extension
OT  - Long-term
OT  - Safety
OT  - Teriflunomide
EDAT- 2020/09/11 06:00
MHDA- 2021/05/15 06:00
CRDT- 2020/09/10 20:16
PHST- 2020/02/26 00:00 [received]
PHST- 2020/07/30 00:00 [revised]
PHST- 2020/07/31 00:00 [accepted]
PHST- 2020/09/11 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/09/10 20:16 [entrez]
AID - S2211-0348(20)30513-7 [pii]
AID - 10.1016/j.msard.2020.102438 [doi]
PST - ppublish
SO  - Mult Scler Relat Disord. 2020 Nov;46:102438. doi: 10.1016/j.msard.2020.102438. 
      Epub 2020 Aug 1.