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
n=223 randomized: 113 at 12 mg/day; 110 at 24 mg/dayInterferon beta-1a
44 μg subcutaneously three times weekly
n=111 randomizedPrimary 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.
Who was studied
Key inclusion criteria
- RRMS diagnosis based on McDonald criteria 2001
- Symptom onset within 36 months
- Baseline EDSS ≤ 3.0
- At least 2 clinical episodes in the previous 2 years
- At least 1 enhancing lesion on up to 4 monthly MRI scans
Key exclusion criteria
- Previous DMT
- Clinically significant autoimmune disease
- Serum anti-thyrotropin-receptor antibodies
Participants at baseline
| Characteristic | Alemtuzumab 12 mgN=112 | Alemtuzumab 24 mgN=110 | IFNβ-1aN=111 |
|---|---|---|---|
| Age, years — mean ± SD | 31.9 ± 8.0 | 32.2 ± 8.8 | 32.8 ± 8.8 |
| Female sex — % | 64.3% | 64.5% | 64.0% |
| Time since first relapse, years — median (range) | 1.3 (0.1–3.5) | 1.2 (0.3–3.2) | 1.4 (0.2–6.3) |
| EDSS — mean ± SD | 1.9 ± 0.74 | 2.0 ± 0.73 | 1.9 ± 0.83 |
| At least 3 relapses in previous 2 years — n (%) | 46 (41.1%) | 40 (36.4%) | 30 (27.0%) |
SD: standard deviation; EDSS: Expanded Disability Status Scale; IFNβ: interferon beta.
Source: CAMMS223 Trial Investigators, NEJM 2008, Table 1
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.
Later safety context
Later FDA warning (2018): post-marketing reports identified rare serious stroke and cervicocephalic arterial dissection shortly after alemtuzumab infusion. These reports extend beyond the controlled-trial findings above.
FDA, Alemtuzumab safety communication, November 29, 2018 ↗Why it mattered
CAMMS223 showed that intermittent immune-depleting treatment could produce large relapse and disability effects in early, untreated RRMS. Its autoimmune complications also demonstrated that efficacy and delayed safety surveillance had to be considered together.
Important limitation
CAMMS223 was phase II, not phase III, and treatment suspension plus limited sample size complicate safety interpretation, especially for uncommon events.