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#Post#: 457--------------------------------------------------
Aubagio for patients w/1st clinical episode suggesting MS: TOPIC
phase 3 study
DIR 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
>
--- End Quote ---
The article is available here
HTML http://www.sciencedirect.com/science/article/pii/S1474442214701917.
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