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#Post#: 177--------------------------------------------------
(Abstr.) TOWER study, phase 3--oral teriflunomide for relapsing
MS
By: agate Date: February 18, 2014, 12:54 pm
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From the Lancet Neurology, February 18, 2014:
[quote]Oral teriflunomide for patients with relapsing multiple
sclerosis (TOWER): a randomised, double-blind,
placebo-controlled, phase 3 trial
Prof Christian Confavreux MD a *, Prof Paul O'Connor MD b, Prof
Giancarlo Comi MD c, Prof Mark S Freedman MD d, Prof Aaron E
Miller MD e, Prof Tomas P Olsson MD f, Prof Jerry S Wolinsky MD
g, Teresa Bagulho MD h, Jean-Luc Delhay MD i, Deborah Dukovic MS
h, Philippe Truffinet MD i, Prof Ludwig Kappos MD j
Corresponding Author, for the TOWER Trial Group†
Background
Teriflunomide is an oral disease-modifying therapy approved for
treatment of relapsing or relapsing—remitting multiple
sclerosis. We aimed to provide further evidence for the safety
and efficacy of teriflunomide in patients with relapsing
multiple sclerosis.
Methods
This international, randomised, double-blind,
placebo-controlled, phase 3 study enrolled adults aged 18—55
years with relapsing multiple sclerosis, one or more relapse in
the previous 12 months or two or more in the previous 24 months
but no relapse in the previous 30 days, and an Expanded
Disability Status Scale (EDSS) score of 5·5 points or less.
Patients were recruited from 189 sites in 26 countries and
randomly assigned (1:1:1) to once-daily placebo, teriflunomide 7
mg, or teriflunomide 14 mg via an interactive voice recognition
system. Treatment duration was variable, ending 48 weeks after
the last patient was included. The primary endpoint was
annualised relapse rate (number of relapses per patient-year)
and the key secondary endpoint was time to sustained
accumulation of disability (an EDSS score increase of at least 1
EDSS point sustained for a minimum of 12 weeks), both analysed
in the modified intention-to-treat population (all patients who
received at least one dose of assigned study medication). This
study is registered with ClinicalTrials.gov, number NCT00751881.
Findings
Between Sept 17, 2008, and Feb 17, 2011, 1169 patients were
randomly assigned to a treatment group, of whom 388, 407, and
370 patients received at least one dose of placebo,
teriflunomide 7 mg, or teriflunomide 14 mg, respectively. By the
end of the study, the annualised relapse rate was higher in
patients assigned to placebo (0·50 [95% CI 0·43—0·58]) than in
those assigned to teriflunomide 14 mg (0·32 [0·27—0·38];
p=0·0001) or teriflunomide 7 mg (0·39 [0·33—0·46]; p=0·0183).
Compared with placebo, teriflunomide 14 mg reduced the risk of
sustained accumulation of disability (hazard ratio [HR] 0·68
[95% CI 0·47—1·00]; log-rank p=0·0442); however, teriflunomide 7
mg had no effect on sustained accumulation of disability (HR
0·95 [0·68—1·35]; log-rank p=0·7620). The most common adverse
events were alanine aminotransferase increases (32 [8%] of 385
patients in the placebo group vs 46 [11%] of 409 patients in the
teriflunomide 7 mg group vs 52 [14%] of 371 patients in the
teriflunomide 14 mg group), hair thinning (17 [4%] vs 42 [10%]
vs 50 [13%]), and headache (42 [11%] vs 60 [15%] vs 46 [12%]).
Incidence of serious adverse events was similar in all treatment
groups (47 [12%] vs 52 [13%] vs 44 [12%]). Four deaths occurred,
none of which was considered to be related to study drug
(respiratory infection in the placebo group, traffic accident in
the teriflunomide 7 mg group, and suicide and septicaemia due to
Gram-negative infection complicated by disseminated
intravascular coagulopathy in the teriflunomide 14 mg group).
Interpretation
Teriflunomide 14 mg was associated with a lower relapse rate and
less disability accumulation compared with placebo, with a
similar safety and tolerability profile to that reported in
previous studies. These results confirm the dose effect reported
in previous trials and support the use of teriflunomide 14 mg in
patients with relapsing multiple sclerosis.
Funding
Genzyme, a Sanofi company.
____________________
a University Claude Bernard Lyon 1, Lyon, France
b University of Toronto, Toronto, ON, Canada
c University Vita-Salute San Raffaele, Milan, Italy
d University of Ottawa and the Ottawa Hospital Research
Institute, Ottawa, ON, Canada
e Icahn School of Medicine at Mount Sinai, New York, NY, USA
f Karolinska Institute, Stockholm, Sweden
g University of Texas Health Science Center at Houston, Houston,
TX, USA
h Genzyme, a Sanofi company, Bridgewater, NJ, USA
i Genzyme, a Sanofi company, Chilly Mazarin, France
j University Hospital Basel, Basel, Switzerland
Corresponding Author Information Correspondence to: Prof Ludwig
Kappos, University Hospital, Petersgraben 4, CH-4031 Basel,
Switzerland
* Prof Confavreux died in September, 2013
† Additional members are listed in the appendix[/quote]
The abstract can be seen here
HTML http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(13)70308-9/fulltext?elsca1=ETOC-NEUROLOGY&elsca2=email&elsca3=J34S35F.
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