CARE-MS I

Alemtuzumab

CARE-MS I confirmed superior relapse control with two annual alemtuzumab courses versus subcutaneous interferon beta-1a in treatment-naïve early RRMS.

Phase
Phase III
Population
Treatment-naïve relapsing-remitting multiple sclerosis (RRMS)
Controlled period
Aug 2007 — Apr 2011

What was compared

RandomizedRater-blindedActive-controlledMulticenter
Intervention

Alemtuzumab

12 mg/day IV for 5 days at baseline and 3 days at month 12

n=386 randomized
Comparator

Interferon beta-1a

44 μg subcutaneously three times weekly

n=195 randomized
581 randomized; 563 in primary analyses24 months controlled phase

Primary endpoint

Prespecified outcome

Relapse and 6-month sustained disability accumulation

2 years

Outcome figure

Primary endpoint results

Intervention Comparator or reference

Participants with a relapse

Participants with relapse (%)

2 years
Alemtuzumab
22%
Interferon beta-1a
40%

6-month sustained disability accumulation

Participants with progression (%)

2 years
Alemtuzumab
8%
Interferon beta-1a
11%

Relapse rate was 54.9% lower (P<0.0001); disability accumulation did not differ significantly (HR 0.70; P=0.22).

Selected secondary outcomes

Relapse-free status

78% with alemtuzumab versus 59% with interferon beta-1a at 2 years.

Who was studied

Key inclusion criteria

  • Age 18–50 years
  • RRMS diagnosis based on McDonald criteria 2005
  • MS symptoms for no more than 5 years
  • Baseline EDSS ≤ 3.0
  • At least 2 relapses in the previous 2 years, including at least 1 in the previous year
  • MRI abnormalities consistent with MS

Key exclusion criteria

  • Progressive MS
  • Previous MS treatment other than corticosteroids
  • Previous immunosuppressive, investigational, or monoclonal-antibody treatment
  • Clinically significant autoimmune disease other than MS

Participants at baseline

CharacteristicAlemtuzumabN=376IFNβ-1aN=187
Age, years — mean ± SD33.0 ± 8.033.2 ± 8.5
Female sex — n (%)243 (65%)122 (65%)
Time since MS symptom onset, years — mean ± SD2.1 ± 1.42.0 ± 1.3
EDSS — mean ± SD2.0 ± 0.82.0 ± 0.8
Relapses in previous 12 months — mean ± SD1.8 ± 0.81.8 ± 0.8
Gadolinium-enhancing lesions present — n/N (%)171/371 (46%)94/183 (51%)

SD: standard deviation; EDSS: Expanded Disability Status Scale; IFNβ: interferon beta.

Source: Cohen et al., Lancet 2012, Table 1

Safety signal

  • Infusion-associated reactions occurred in 90% of alemtuzumab-treated participants; 3% were serious. Reactions were less common during the second treatment course.
  • Most thyroid-associated adverse events were mild or moderate; autoimmune thyroid events required structured follow-up.
  • Infections were more frequent with alemtuzumab and were predominantly mild or moderate.

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

CARE-MS I confirmed a relapse advantage for two annual alemtuzumab courses over subcutaneous interferon beta-1a in previously untreated RRMS. The nonsignificant disability endpoint and autoimmune monitoring requirements tempered the interpretation of an effective induction strategy.

Important limitation

The trial met the relapse but not the disability coprimary endpoint, and rater blinding could not fully remove differences in treatment experience.

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