AFFIRM
Natalizumab
AFFIRM showed large effects of natalizumab monotherapy on relapses, disability progression, and MRI activity in relapsing MS.
- Phase
- Phase III
- Population
- Relapsing-remitting multiple sclerosis (RRMS)
- Controlled period
- Nov 2001 — Nov 2004
What was compared
Natalizumab
300 mg intravenous infusion every 4 weeks
n=627Placebo
Matching intravenous infusion every 4 weeks
n=315Primary endpoint
Clinical relapse and sustained disability progression
Relapse at 1 year; disability at 2 years
Primary endpoint results
Annualized clinical relapse rate
Relapses per participant-year
12-week sustained disability progression
Participants with progression (%)
68% lower clinical relapse rate at 1 year and 42% lower risk of sustained disability progression at 2 years.
Selected secondary outcomes
Mean 1.9 with natalizumab versus 11.0 with placebo over 2 years.
92% fewer with natalizumab at years 1 and 2.
Study population
- Randomized
- 942 randomized
- Age
- 18–50 years eligible
- Disability
- EDSS 0–5.0
- Disease definition
- Relapsing-remitting multiple sclerosis with recent relapse
Who entered the trial
Key inclusion criteria
- Defined based on McDonald criteria 2001
- At least one relapse in the preceding 12 months
- MRI lesions consistent with MS and EDSS 0–5.0
Key exclusion criteria
- Primary progressive, secondary progressive, or progressive-relapsing MS
- Relapse within 50 days without subsequent stabilization
- Clinically important infection, immune disorder, or major systemic disease
Safety signal
- Fatigue and allergic reactions were more frequent with natalizumab.
- Serious hypersensitivity occurred in 1% of natalizumab-treated participants.
- The controlled trial was not large or long enough to define rare opportunistic infection risk.
Why it mattered
AFFIRM demonstrated that blocking leukocyte adhesion could produce substantially larger effects than the platform-therapy era had typically shown.
Important limitation
Rare but serious risks cannot be inferred from AFFIRM alone; its efficacy findings must be separated from safety knowledge accumulated outside this monotherapy trial.