TOWER

Teriflunomide

TOWER independently confirmed the relapse efficacy of teriflunomide and showed reduced sustained disability accumulation with 14 mg.

Phase
Phase III
Population
Relapsing multiple sclerosis (RMS)
Controlled period
Aug 2008 — Apr 2012

What was compared

RandomizedDouble-blindPlacebo-controlled189 sites
Intervention

Teriflunomide 14 mg

Orally once daily

n=372
Comparator

Placebo

Matching oral tablet once daily

n=389

Additional randomized arm

Teriflunomide 7 mg

Orally once dailyn=408
1,169 randomizedVariable; at least 48 weeks controlled phase

Primary endpoint

Prespecified outcome

Annualized relapse rate

Variable-duration treatment period

Outcome figure

Primary endpoint results

Intervention Comparator or reference

Annualized relapse rate

Relapses per participant-year

Variable-duration treatment period
Teriflunomide 14 mg
0.32
Teriflunomide 7 mg
0.39
Placebo
0.50

36.3% lower with 14 mg (P=0.0001); the 7 mg reduction was smaller.

Selected secondary outcomes

12-week sustained disability accumulation

Risk was reduced 31.5% with 14 mg versus placebo (P=0.0442).

Severe relapses

The 14 mg dose reduced several prespecified measures of severe relapse burden.

Study population

Randomized
1,169 randomized
Age
Mean 37.9 years; eligible 18–55
Sex
831 women (71%)
Disability
Ambulatory relapsing MS
Disease definition
Relapsing MS with one relapse in 1 year or two in 2 years

Who entered the trial

Key inclusion criteria

  • Relapsing multiple sclerosis
  • At least one relapse in the prior year or two in the prior 2 years
  • Age 18–55 years

Key exclusion criteria

  • Major cardiovascular, hepatic, neurologic, endocrine, or systemic disease
  • Significant anemia, leukopenia, thrombocytopenia, or bone-marrow impairment
  • Pregnancy, breastfeeding, or prior specified immunosuppressant use

Safety signal

  • Hair thinning and liver-enzyme elevation were among the characteristic teriflunomide-associated events.
  • Serious adverse events were broadly similar across groups in the primary report.

Why it mattered

Together with TEMSO, TOWER provided replicated evidence for the approved 14 mg dose across relapse and disability outcomes.

Important limitation

Treatment duration varied because the study ended 48 weeks after the last participant enrolled, complicating simple cross-trial comparisons based on a fixed timepoint.

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