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.

Who was studied

Key inclusion criteria

  • Age 18–55 years
  • RMS diagnosis based on McDonald criteria 2005
  • 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 30 days before randomization

Key exclusion criteria

  • Other clinically relevant disease
  • Pregnancy, breastfeeding, or plans to conceive or father a child during the trial
  • Cytokine therapy, interferon, or glatiramer acetate within 3 months
  • Previous natalizumab or other immunosuppressive treatment

Participants at baseline

CharacteristicTeriflunomide 7 mgN=408Teriflunomide 14 mgN=372PlaceboN=389
Age, years — mean ± SD37.4 ± 9.438.2 ± 9.438.1 ± 9.1
Female sex — n (%)300 (74%)258 (69%)273 (70%)
Time since MS symptom onset, years — mean ± SD8.18 ± 6.758.18 ± 6.737.64 ± 6.70
EDSS — mean ± SD2.71 ± 1.392.71 ± 1.352.69 ± 1.36
Relapses in the previous year — mean ± SD1.4 ± 0.71.4 ± 0.71.4 ± 0.8
MS medication use in the previous 2 years — n (%)123 (30%)126 (34%)135 (35%)

SD: standard deviation; EDSS: Expanded Disability Status Scale.

Source: Confavreux et al., Lancet Neurology 2014, Table 1

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

TOWER independently reproduced teriflunomide’s relapse benefit and the disability result at 14 mg. Together with TEMSO, it strengthened the evidence for that dose across separate populations rather than relying on one pivotal trial.

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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