IFNβ-1b subcutaneous pivotal trial

Interferon beta-1b

The trial established subcutaneous interferon beta-1b as an effective relapse-reducing therapy for ambulatory people with relapsing-remitting multiple sclerosis.

Phase
Phase III
Population
Relapsing-remitting multiple sclerosis (RRMS)
Controlled period
Jun 1988 — Jun 1990

What was compared

RandomizedDouble-blindPlacebo-controlledMulticenter
Intervention

Interferon beta-1b

250 μg (8 MIU) subcutaneously every other day

n=124
Comparator

Placebo

Matching subcutaneous injection every other day

n=123

Additional randomized arm

Lower-dose interferon beta-1b

50 μg (1.6 MIU) subcutaneously every other dayn=125
372 randomized2 years controlled phase

Primary endpoint

Prespecified outcome

Annualized exacerbation rate

2 years

Outcome figure

Primary endpoint results

Intervention Comparator or reference

Annualized exacerbation rate

Exacerbations per participant-year

2 years
Interferon beta-1b 250 μg
0.84
Placebo
1.27

34% lower annual exacerbation rate with the approved high dose (P<0.001).

Selected secondary outcomes

Exacerbation-free status

31% with high-dose interferon beta-1b versus 16% with placebo at 2 years.

Disability

The 2-year trial was not conclusive for disability progression.

Study population

Randomized
372 randomized
Age
18–50 years eligible
Disability
EDSS 0–5.5
Disease definition
Ambulatory relapsing-remitting multiple sclerosis

Who entered the trial

Key inclusion criteria

  • Ambulatory relapsing-remitting multiple sclerosis
  • At least two exacerbations during the previous 2 years
  • Baseline EDSS no higher than 5.5

Key exclusion criteria

  • Progressive disease without relapses
  • Major illness or treatment likely to confound immune or neurologic assessment
  • Pregnancy

Safety signal

  • Injection-site reactions and influenza-like symptoms were characteristic treatment-emergent effects.
  • Laboratory monitoring identified treatment-related hematologic and hepatic abnormalities.

Why it mattered

This was the pivotal evidence behind the first interferon beta treatment for MS and helped establish relapse rate as a central controlled-trial outcome.

Important limitation

The trial was powered around relapses, not long-term disability. Its 2-year controlled phase could not establish the durability of benefit or uncommon harms.

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