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#Post#: 457--------------------------------------------------
Aubagio for patients w/1st clinical episode suggesting MS: TOPIC
phase 3 study
By: agate Date: September 5, 2014, 7:28 pm
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From Science Direct (September 3) citing The Lancet Neurology,
September 2, 2014:
[quote]
The Lancet Neurology
Available online 2 September 2014
In Press, Corrected Proof
Oral teriflunomide for patients with a first clinical episode
suggestive of multiple sclerosis (TOPIC): a randomised,
double-blind, placebo-controlled, phase 3 trial
Prof Aaron E Miller, MD, Prof Jerry S Wolinsky, MD, Ludwig
Kappos, MD, Prof Giancarlo Comi, MD, Prof Mark S Freedman, MDe,
Prof Tomas P Olsson, MDf, Deborah Bauer, MS, Myriam Benamor, MD,
Philippe Truffinet, MD, Prof Paul W O'Connor, MD, for the TOPIC
Study Group
Summary
Background
Teriflunomide is a once-daily oral immunomodulator approved for
the treatment of relapsing-remitting multiple sclerosis. We
aimed to assess the efficacy and safety of teriflunomide in
patients with a first clinical episode suggestive of multiple
sclerosis.
Methods
In this randomised, double-blind, placebo-controlled,
parallel-group study, we enrolled patients aged 18–55 years with
clinically isolated syndrome (defined as a neurological event
consistent with demyelination, starting within 90 days of
randomisation, and two or more T2-weighted MRI lesions ≥3
mm in diameter) from 112 centres (mostly hospitals) in 20
countries. Participants were randomly assigned (1:1:1) in a
double-blind manner (by an interactive voice response system) to
once-daily oral teriflunomide 14 mg, teriflunomide 7 mg, or
placebo, for up to 108 weeks. Patients, staff administering the
interventions, and outcome assessors were masked to treatment
assignment.
The primary endpoint was time to relapse (a new neurological
abnormality separated by ≥30 days from a preceding
clinical event, present for ≥24 h in the absence of fever
or known infection), which defined conversion to clinically
definite multiple sclerosis.
The key secondary endpoint was time to relapse or new
gadolinium-enhancing or T2 lesions on MRI, whichever occurred
first.
The primary outcome was analysed for the modified
intention-to-treat population; safety analyses included all
randomised patients who were exposed to the study drug, as
treated.
This trial is registered with ClinicalTrials.gov, number
NCT00622700.
Findings
Between Feb 13, 2008, and Aug 22, 2012, 618 patients were
enrolled and randomly assigned to teriflunomide 14 mg (n=216),
teriflunomide 7 mg (n=205), or placebo (n=197). Two patients in
each of the teriflunomide groups did not receive the study drug,
so the modified intention-to-treat population comprised 214
patients in the teriflunomide 14 mg group, 203 in the
teriflunomide 7 mg group, and 197 in the placebo group. Compared
with placebo, teriflunomide significantly reduced the risk of
relapse defining clinically definite multiple sclerosis at the
14 mg dose (hazard ratio [HR] 0·574 [95% CI 0·379–0·869];
p=0·0087) and at the 7 mg dose (0·628 [0·416–0·949]; p=0·0271).
Teriflunomide reduced the risk of relapse or a new MRI lesion
compared with placebo at the 14 mg dose (HR 0·651 [95% CI
0·515–0·822]; p=0·0003) and at the 7 mg dose (0·686
[0·540–0·871]; p=0·0020). During the study, six patients who
were randomly assigned to placebo accidently also received
teriflunomide at some point: four received 7 mg and two received
14 mg. Therefore, the safety population comprised 216 patients
on teriflunomide 14 mg, 207 on teriflunomide 7 mg, and 191 on
placebo.
Adverse events that occurred in at least 10% of patients in
either teriflunomide group and with an incidence that was at
least 2% higher than that with placebo were increased alanine
aminotransferase (40 [19%] of 216 patients in the 14 mg group,
36 [17%] of 207 in the 7 mg group vs 27 [14%] of 191 in the
placebo group), hair thinning (25 [12%] and 12 [6%] vs 15 [8%]),
diarrhoea (23 [11%] and 28 [14%] vs 12 [6%]), paraesthesia (22
[10%] and 11 [5%] vs 10 [5%]), and upper respiratory tract
infection (20 [9%] and 23 [11%] vs 14 [7%]). The most common
serious adverse event was an increase in alanine
aminotransferase (four [2%] and five [2%] vs three [2%]).
Interpretation
TOPIC is to our knowledge the first study to report benefits of
an available oral disease-modifying therapy in patients with
early multiple sclerosis. These results extend the stages of
multiple sclerosis in which teriflunomide shows a beneficial
effect.
Funding
Genzyme, a Sanofi company.
Correspondence to:
Prof Aaron E Miller, Icahn School of Medicine at Mount Sinai,
The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, 5
East 98th Street; Box 1138, New York, NY 10029, USA
[/quote]
The article is available here
HTML http://www.sciencedirect.com/science/article/pii/S1474442214701917.
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