CONFIRM

Dimethyl fumarate

CONFIRM showed that oral dimethyl fumarate reduced relapses and MRI activity versus placebo while including glatiramer acetate as an active reference.

Phase
Phase III
Population
Relapsing-remitting multiple sclerosis (RRMS)
Controlled period
Jun 2007 — Aug 2011

What was compared

RandomizedDouble-blindPlacebo-controlledActive reference
Intervention

Dimethyl fumarate 240 mg twice daily

Orally twice daily

n=359
Comparator

Placebo

Matching oral capsules

n=363

Additional randomized arms

Dimethyl fumarate 240 mg three times daily

Orally three times dailyn=345

Glatiramer acetate

20 mg subcutaneously once daily; active referencen=350
1,417 randomized96 weeks controlled phase

Primary endpoint

Prespecified outcome

Annualized relapse rate

2 years

Outcome figure

Primary endpoint results

Intervention Comparator or reference

Annualized relapse rate

Relapses per participant-year

2 years
Dimethyl fumarate twice daily
0.22
Dimethyl fumarate three times daily
0.20
Glatiramer acetate
0.29
Placebo
0.40

44% and 51% lower with dimethyl fumarate; 29% lower with glatiramer acetate.

Selected secondary outcomes

Disability progression

Reductions versus placebo were not statistically significant.

MRI lesions

Both dimethyl fumarate regimens and glatiramer acetate improved key MRI outcomes.

Study population

Randomized
1,417 randomized
Age
Mean 37.3 years; eligible 18–55
Sex
993 women (70%)
Disability
EDSS 0–5.0
Disease definition
Relapsing-remitting multiple sclerosis

Who entered the trial

Key inclusion criteria

  • Defined based on McDonald criteria 2005
  • Relapsing-remitting clinical course
  • Baseline EDSS 0–5.0

Key exclusion criteria

  • Other chronic immune disease or malignancy
  • Clinically important urologic, pulmonary, or gastrointestinal disease
  • Pregnancy or breastfeeding

Safety signal

  • Flushing and gastrointestinal events were more frequent with dimethyl fumarate.
  • Lymphocyte counts decreased with dimethyl fumarate; injection-related events were more frequent with glatiramer acetate.

Why it mattered

CONFIRM supplied a second large pivotal data set for dimethyl fumarate and contextualized its effect alongside a familiar active reference.

Important limitation

The study was not designed or powered to establish superiority or noninferiority between dimethyl fumarate and glatiramer acetate.

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