MSCRG

Intramuscular interferon beta-1a

MSCRG tested whether once-weekly intramuscular interferon beta-1a could delay sustained disability progression in relapsing multiple sclerosis.

Phase: Phase III
Population: Relapsing multiple sclerosis (RMS)
Controlled period: Nov 1990 — 1993

What was compared

RandomizedDouble-blindPlacebo-controlledMulticenter

Intervention

Interferon beta-1a

30 μg intramuscularly once weekly

n=158

Comparator

Placebo

Matching intramuscular injection once weekly

n=143

301 randomizedUp to 104 weeks controlled phase

Primary endpoint

Prespecified outcome

Sustained disability progression

Kaplan–Meier estimate at 104 weeks

Outcome figure

Primary endpoint results

Intervention Comparator or reference

Sustained disability progression

Participants with progression (%)

Kaplan–Meier estimate at 104 weeks

Interferon beta-1a

21.9%

Placebo

34.9%

Time to sustained EDSS progression was significantly delayed (P=0.02).

Selected secondary outcomes

Relapses among 2-year completers

Annual relapse rate was 0.61 with interferon beta-1a and 0.90 with placebo.

MRI activity

Gadolinium-enhancing lesion activity favored interferon beta-1a.

Who was studied

Key inclusion criteria

Age 18–55 years
Definite relapsing MS (Poser criteria), present for at least 1 year
Baseline EDSS 1.0–3.5
At least 2 relapses in the previous 3 years
No relapse for at least 2 months before entry

Key exclusion criteria

Chronic progressive MS
Previous immunosuppressive or interferon treatment
ACTH or corticosteroids in the previous 2 months
Pregnancy, breastfeeding, or absence of required contraception
Other disease compromising organ function

Participants at baseline

Characteristic	IFNβ-1aN=158	PlaceboN=143
Age, years — mean ± SEM	36.7 ± 0.57	36.9 ± 0.64
Female sex — n (%)	118 (75%)	103 (72%)
MS duration, years — mean ± SEM	6.6 ± 0.46	6.4 ± 0.49
EDSS — mean ± SEM	2.4 ± 0.06	2.3 ± 0.07
Prestudy annual relapse rate — mean ± SEM	1.2 ± 0.05	1.2 ± 0.05

SEM: standard error of the mean; EDSS: Expanded Disability Status Scale; IFNβ: interferon beta.

Source: Jacobs et al., Annals of Neurology 1996, Table 1

Safety signal

Influenza-like symptoms, headache, muscle ache, and injection-related effects were associated with interferon treatment.
Laboratory monitoring was required for blood counts and hepatic measures.

Why it mattered

MSCRG made sustained EDSS progression the primary clinical outcome, showing that an MS trial could evaluate disability as well as relapse activity. It supplied pivotal evidence for weekly intramuscular interferon beta-1a, linking a treatment regimen to a patient-relevant disability measure.

Important limitation

Enrollment ended before every participant could complete 2 years, producing variable follow-up and making the 104-week estimate dependent on time-to-event methods.