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
In a post hoc analysis of the AFFIRM trial:
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
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