MIMS

Mitoxantrone

MIMS evaluated an intensive immunosuppressive strategy in people with worsening relapsing-remitting or secondary progressive multiple sclerosis.

Phase: Phase III
Population: Worsening relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS)
Controlled period: Jun 2, 1993 — Jul 10, 1997

What was compared

RandomizedDouble-blindPlacebo-controlledMulticenter

Intervention

Mitoxantrone

12 mg/m² intravenously every 3 months

n=60

Comparator

Placebo

Matching intravenous infusion every 3 months

n=64

Additional randomized arm

Exploratory mitoxantrone dose

5 mg/m² intravenously every 3 monthsn=70

194 randomized; 188 assessable24 months controlled phase

Primary endpoint

Prespecified outcome

Multivariate composite of five clinical measures

24 months

Outcome figure

Primary endpoint results

Intervention Comparator or reference

Multivariate composite treatment difference

Composite treatment difference (95% CI)

24 months

Mitoxantrone 12 mg/m² vs placebo0.30 (0.17–0.44)

Composite treatment difference 0.30 (95% CI 0.17–0.44; P<0.0001).

Selected secondary outcomes

EDSS change

Preplanned univariate analysis favored mitoxantrone (P=0.0194).

Treated relapses

Adjusted total treated relapses favored mitoxantrone (P=0.0002).

Study population

Randomized: 194 randomized; 188 assessable
Age: 18–65 years eligible
Disability: EDSS 3.0–6.0
Disease definition: Worsening relapsing-remitting or secondary progressive MS

Who entered the trial

Key inclusion criteria

Secondary progressive or worsening relapsing-remitting MS
Documented neurologic deterioration before entry
Baseline EDSS 3.0–6.0

Key exclusion criteria

Clinically important cardiac dysfunction
Bone-marrow compromise or major systemic illness
Pregnancy or prior cumulative anthracenedione exposure that increased risk

Safety signal

The controlled trial reported no drug-related serious adverse events or clinically significant cardiac dysfunction.
The sample and follow-up were too limited to define delayed cumulative cardiotoxicity or therapy-related leukemia risk.

Why it mattered

MIMS supplied controlled evidence for treatment in worsening and secondary progressive disease at a time when options were extremely limited.

Important limitation

The primary endpoint was an unusual multivariate composite, and the 2-year observation could not characterize the major cumulative toxicities that constrain mitoxantrone use.