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
Interferon beta-1b
250 μg (8 MIU) subcutaneously every other day
n=124Placebo
Matching subcutaneous injection every other day
n=123Additional randomized arm
Lower-dose interferon beta-1b
50 μg (1.6 MIU) subcutaneously every other dayn=125Primary endpoint
Annualized exacerbation rate
2 years
Primary endpoint results
Annualized exacerbation rate
Exacerbations per participant-year
34% lower annual exacerbation rate with the approved high dose (P<0.001).
Selected secondary outcomes
31% with high-dose interferon beta-1b versus 16% with placebo at 2 years.
The 2-year trial was not conclusive for disability progression.
Who was studied
Key inclusion criteria
- Age 18–50 years
- RRMS diagnosis: clinically definite or laboratory-supported definite MS (Poser criteria), present for at least 1 year
- Baseline EDSS ≤ 5.5; ambulatory
- At least 2 acute relapses in the previous 2 years
- Clinically stable for at least 30 days
Key exclusion criteria
- Previous azathioprine or cyclophosphamide treatment
- ACTH or prednisone in the previous 30 days
Participants at baseline
| Characteristic | IFNβ-1b 8 MIUN=124 | IFNβ-1b 1.6 MIUN=125 | PlaceboN=123 |
|---|---|---|---|
| Age, years — mean ± SEM | 35.2 ± 0.6 | 35.3 ± 0.7 | 36.0 ± 0.6 |
| Female sex — n | 86 | 85 | 88 |
| Time since MS diagnosis, years — mean ± SEM | 4.7 ± 0.4 | 4.7 ± 0.4 | 3.9 ± 0.3 |
| EDSS — mean ± SEM | 3.0 ± 0.1 | 2.9 ± 0.1 | 2.8 ± 0.1 |
| Relapses in previous 2 years — mean ± SEM | 3.4 ± 0.2 | 3.3 ± 0.1 | 3.6 ± 0.1 |
| Time since last relapse, days — mean ± SEM | 157.9 ± 10.8 | 140.8 ± 10.2 | 134.9 ± 10.3 |
SEM: standard error of the mean; EDSS: Expanded Disability Status Scale; IFNβ: interferon beta; MIU: million international units.
Source: IFNB Multiple Sclerosis Study Group, Neurology 1993, Table 2
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 trial provided the pivotal evidence for interferon beta-1b, the first FDA-approved disease-modifying therapy for MS in 1993, and helped establish relapse reduction as a treatment goal.
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.