TEMSO

Teriflunomide

TEMSO established once-daily oral teriflunomide as a relapse-reducing therapy and showed a disability effect at the 14 mg dose.

Phase
Phase III
Population
Relapsing multiple sclerosis (RMS)
Controlled period
Sep 2004 — Jul 2010

What was compared

RandomizedDouble-blindPlacebo-controlledMulticenter
Intervention

Teriflunomide 14 mg

Orally once daily

Comparator

Placebo

Matching oral tablet once daily

Additional randomized arm

Teriflunomide 7 mg

Orally once daily
1,088 randomized108 weeks controlled phase

Primary endpoint

Prespecified outcome

Annualized relapse rate

108 weeks

Outcome figure

Primary endpoint results

Intervention Comparator or reference

Annualized relapse rate

Relapses per participant-year

108 weeks
Teriflunomide 14 mg
0.37
Teriflunomide 7 mg
0.37
Placebo
0.54

31.5% and 31.2% relative reductions (P<0.001 for both doses).

Selected secondary outcomes

12-week confirmed disability progression

20.2% with 14 mg versus 27.3% with placebo (P=0.03).

MRI

Both doses were superior to placebo across prespecified MRI outcomes.

Who was studied

Key inclusion criteria

  • Age 18–55 years
  • RMS diagnosis based on McDonald criteria 2001
  • Baseline EDSS ≤ 5.5
  • At least 1 relapse in the previous year or at least 2 in the previous 2 years
  • No relapse in the 60 days before randomization

Key exclusion criteria

  • Other systemic disease
  • Pregnancy or plans to conceive during the trial

Participants at baseline

CharacteristicTeriflunomide 7 mgN=366Teriflunomide 14 mgN=359PlaceboN=363
Age, years — mean ± SD37.4 ± 9.037.8 ± 8.238.4 ± 9.0
Female sex — n (%)255 (69.7%)255 (71.0%)275 (75.8%)
Time since MS symptom onset, years — mean ± SD8.8 ± 6.88.7 ± 6.78.6 ± 7.1
EDSS — mean ± SD2.68 ± 1.342.67 ± 1.242.68 ± 1.34
Relapses in the previous year — mean ± SD1.4 ± 0.71.3 ± 0.71.4 ± 0.7
DMT use in the previous 2 years — n (%)102 (27.9%)102 (28.4%)90 (24.8%)
Gadolinium-enhancing T1 lesions present — n/N (%)127/360 (35.3%)125/355 (35.2%)137/359 (38.2%)

SD: standard deviation; EDSS: Expanded Disability Status Scale; DMT: disease-modifying therapy.

Source: O’Connor et al., NEJM 2011, Table 1

Safety signal

  • Diarrhea, nausea, and hair thinning were more common with teriflunomide.
  • Mild alanine aminotransferase elevation was more frequent; marked elevation and serious infection rates were similar among groups.

Why it mattered

TEMSO supplied pivotal evidence that an oral immunomodulator could reduce relapses, with a confirmed-disability benefit at the 14 mg dose. It broadened oral treatment options without using the S1P-modulator mechanism tested in the fingolimod programs.

Important limitation

The study tested two doses and several MS courses; interpretation of the disability result is specific to the 14 mg comparison.

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