TOPIC

Teriflunomide

TOPIC tested early teriflunomide after a first demyelinating event and delayed a relapse defining clinically definite MS.

Phase: Phase III
Population: First clinical episode suggestive of multiple sclerosis (CIS)
Controlled period: Feb 2008 — Dec 2012

What was compared

RandomizedDouble-blindPlacebo-controlled112 centers

Intervention

Teriflunomide 14 mg

Orally once daily

n=216

Comparator

Placebo

Matching oral tablet once daily

n=197

Additional randomized arm

Teriflunomide 7 mg

Orally once dailyn=205

618 randomizedUp to 108 weeks controlled phase

Primary endpoint

Prespecified outcome

Time to relapse defining clinically definite MS

Up to 108 weeks

Outcome figure

Primary endpoint results

Intervention Comparator or reference

Risk of relapse defining clinically definite MS

Hazard ratio (95% CI)

Up to 108 weeks

Teriflunomide 14 mg vs placebo0.574 (0.379–0.869)

Teriflunomide 7 mg vs placebo0.628 (0.416–0.949)

Risk reductions were significant for 14 mg (P=0.0087) and 7 mg (P=0.0271).

Selected secondary outcomes

Relapse or new MRI lesion

HR 0.651 with 14 mg and 0.686 with 7 mg versus placebo.

Study population

Randomized: 618 randomized
Age: Mean 32.7 years; eligible 18–55
Sex: 419 women (68%)
Disability: First demyelinating event; ambulatory population
Disease definition: Clinically isolated syndrome with MRI lesions

Who entered the trial

Key inclusion criteria

First acute or subacute neurologic event consistent with demyelination
Symptom onset within 90 days of randomization
At least two characteristic T2 lesions measuring at least 3 mm

Key exclusion criteria

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

Safety signal

Liver-enzyme elevation, hair thinning, diarrhea, paresthesia, and upper-respiratory infection were more frequent in at least one teriflunomide group.
The most common serious adverse event was increased alanine aminotransferase.

Why it mattered

TOPIC extended pivotal oral-therapy evidence to the earliest clinically recognizable stage of the MS disease course.

Important limitation

The conversion endpoint reflects the diagnostic framework of its era; later McDonald criteria may classify some comparable patients as having MS at baseline.