CAMMS223
Alemtuzumab
CAMMS223 showed marked efficacy of annual alemtuzumab courses versus high-dose subcutaneous interferon beta-1a, while exposing important autoimmune risk.
- Phase
- Phase II
- Population
- Early, active relapsing-remitting multiple sclerosis (RRMS)
- Controlled period
- Dec 2002 — Sep 2007
What was compared
Alemtuzumab
12 or 24 mg/day IV in annual treatment cycles
Interferon beta-1a
44 μg subcutaneously three times weekly
Primary endpoint
Sustained disability accumulation and annualized relapse rate
36 months
Primary endpoint results
Sustained disability accumulation
Participants with progression (%)
Annualized relapse rate
Relapses per participant-year
HR 0.29 for disability and 0.26 for relapse rate (P<0.001 for both).
Selected secondary outcomes
Improved 0.39 point with alemtuzumab and worsened 0.38 with interferon.
T2 lesion burden and brain-volume change favored alemtuzumab.
Study population
- Randomized
- 334 randomized
- Age
- Mean 32.3 years; eligible 18–50
- Sex
- 214 women (64% of 333 with posted baseline data)
- Disability
- EDSS 0–3.0
- Disease definition
- Previously untreated, early active relapsing-remitting MS
Who entered the trial
Key inclusion criteria
- First MS symptoms within 3 years
- At least two clinical episodes in the preceding 2 years
- EDSS 0–3.0 plus at least one gadolinium-enhancing lesion during screening
Key exclusion criteria
- Prior MS immunotherapy other than corticosteroids
- Personal history of clinically important autoimmune disease
- Malignancy or non-MS disability that interfered with assessment
Safety signal
- Thyroid disorders occurred in 23% with alemtuzumab versus 3% with interferon.
- Immune thrombocytopenic purpura occurred in 3% versus 1%; one affected participant died.
- Infections occurred in 66% versus 47%, and alemtuzumab dosing was suspended during the trial.
Why it mattered
The trial demonstrated the potential of pulsed immune depletion to produce unusually large efficacy effects, while making long-term autoimmune surveillance inseparable from the treatment concept.
Important limitation
CAMMS223 was phase II, not phase III, and treatment suspension plus limited sample size complicate safety interpretation, especially for uncommon events.