In the 2-year AFFIRM pivotal trial:

Relapsing MS patients received 300 mg TYSABRI IV every 28 days (n=627) or placebo (n=315). Patients with PPMS, SPMS, and PRMS were excluded.

83% of patients taking TYSABRI had no sustained physical disability progression for 12 weeks vs 71% with placebo (primary endpoint: 17% vs 29%; p<0.001)1,2

TYSABRI demonstrated 67% relative reduction in ARR vs placebo (secondary endpoint: 0.22 vs 0.67; p<0.001)1,2

EXPLORE THE ONSET OF EFFICACY OF TYSABRI

In a post hoc analysis of the AFFIRM trial:

Rapid and sustained reductions in disease activity with TYSABRI3,a

Onset of efficacy as early as 2 months and maintained over 2 years

Study description: A post hoc analysis of the AFFIRM pivotal trial was performed to look at time to onset of clinical effects following initiation of TYSABRI. ARR was measured at 3-month intervals.3,b

Study limitations:

  • Because this post hoc analysis is retrospective in nature, there are no prospectively defined endpoints
  • Post hoc analyses are performed after study completion and cannot be used to demonstrate statistically significant differences between treatment groups

CUMULATIVE PROBABILITY OF RELAPSE OVER 2 YEARS FOR ALL PATIENTSc

Cumulative Probability of Relapse Over 2 Years for All Patients
Cumulative Probability of Relapse Over 2 Years for All Patients

Copyright © 2013 Kappos L, et al; licensee Springer Nature is adapted under CC by 4.0.

Rapid onset of efficacy first observed soon after the second infusionc

Difference in risk of relapse between TYSABRI and placebo at:

  • Day 42 in patients overall (5.4% vs 9.3% [HR: 0.56, 95% CI 0.34-0.93; p=0.0238])c
  • Day 45 in patients with highly active disease (6.8% vs 16.6% [HR: 0.35, 95% CI 0.14-0.87; p=0.0243)]d

Efficacy maintained over 2 years

Reduced risk of relapse was sustained over 2 years

  • By 58% in the overall population (28.7% vs 55.7% [HR: 0.42, 95% CI 0.34-0.52; p<0.0001])
  • By 75% in patients with highly active disease (29.3% vs 76.0% [HR: 0.25, 95% CI 0.17-0.39; p<0.0001])d

ARR OVER 2 YEARS FOR ALL PATIENTS

ARR Over 2 Years for All Patients
ARR Over 2 Years for All Patients

Copyright © 2013 Kappos L, et al; licensee Springer Nature is adapted under CC by 4.0.

Rapid onset of efficacy demonstrated by 3-month ARRe

TYSABRI reduced ARR within 3 months vs placebo:

  • By 58% in the overall population (0.3 [95% CI 0.23-0.4] vs 0.71 [95% CI 0.55-0.91]; p<0.0001)f
  • By 68% in patients with highly active disease (0.3 [95% CI 0.17-0.53] vs 0.94 [95% CI 0.55-1.63]; p=0.0039)d,g

Efficacy maintained over 2 years

Reductions in ARR were sustained to 2 years:

  • By 69% in the overall population (TYSABRI ARR was 0.31 RR of placebo, 95% CI 0.19-0.5; p<0.0001)
  • By 80% in patients with highly active disease (TYSABRI ARR was 0.20 RR of placebo, 95% CI 0.09-0.46; p<0.001)d

Corresponding placebo groups also showed sizable reductions.

ARR=annualized relapse rate; EDSS=Expanded Disability Status Scale; Gd+=gadolinium-enhancing; RR=rate ratio.

aPer protocol, patients in the pivotal trial were assessed at 12-week intervals for change in EDSS. Unscheduled visits occurred only in the event of new neurologic symptoms.
bThe AFFIRM (NAtalizumab Safety and EFFlcacy in Relapsing-Remitting MS) study was a pivotal 2-year, double-blind, randomized, controlled trial with 942 relapsing MS patients who received either TYSABRI® (natalizumab) monotherapy (300 mg by intravenous infusion [n=627]) or placebo (n=315) every 4 weeks for up to 28 months (30 infusions), which excluded patients with primary progressive, secondary progressive, or progressive relapsing MS.1,2
cTreatment effects on time to first relapse (in days) at a specific time point were assessed using hazard ratios (HRs) estimated from a Cox proportional hazards model, adjusting for the number of relapses in the year before study entry. The cumulative probability of relapse was estimated using the Kaplan-Meier method, and 95% confidence bands were derived using the equal precision approach. A log-rank test was used to determine the first day a significant difference in the cumulative probability of relapse emerged between study groups.3
dPost hoc subgroup analysis of data from AFFIRM defined highly active disease as ≥2 relapses in the year before study entry and ≥1 T1 Gd+ MRI lesion at study entry. A total of 209 patients (148 TYSABRI and 61 placebo) in AFFIRM met the criteria for highly active MS.3
eRelapses were defined as new or recurrent neurologic symptoms not associated with fever or infection that lasted ≥24 hours and were accompanied by new neurologic signs found by the examining neurologist.3
f58% reduction calculated based on rate of 0.3 with TYSABRI vs 0.71 with placebo: 0.71-0.3=0.41 difference/0.71=0.58 decrease.3
g68% reduction calculated based on rate of 0.3 with TYSABRI vs 0.94 with placebo: 0.94-0.3=0.64 difference/0.94=0.68 decrease.3