Clinical effects of Tysabri (natalizumab) on multiple sclerosis appear early in treatment course
In clinical practice natalizumab is typically used in patients who have
experienced breakthrough disease during treatment with interferon beta
(IFNβ) or glatiramer acetate. In these patients it is important to
reduce disease activity as quickly as possible. In a phase II study,
differences between natalizumab and placebo in MRI outcomes reflecting
inflammatory activity were evident after the first infusion and
maintained through a 6-month period, suggesting a rapid onset of
natalizumab treatment effects. To explore how soon after natalizumab
initiation clinical effects become apparent, annualized relapse rates
per 3-month period and time to first relapse were analyzed in the phase
III AFFIRM study (natalizumab vs. placebo) and in the multinational
Tysabri® Observational Program (TOP). In AFFIRM, natalizumab
reduced the annualized relapse rate within 3 months of treatment
initiation compared with placebo in the overall population (0.30 vs.
0.71; p < 0.0001) and in patients with highly active disease (0.30 vs. 0.94; p = 0.0039).
The low annualized relapse rate was maintained throughout the 2-year
study period, and the risk of relapse in AFFIRM patients treated with
natalizumab was reduced [hazard ratio against placebo 0.42 (95 % CI
0.34–0.52); p < 0.0001]. Rapid reductions in annualized relapse rate also occurred in TOP (baseline 1.99 vs. 0–3 months 0.26; p < 0.0001). Natalizumab resulted in rapid, sustained reductions in disease activity in both AFFIRM and in clinical practice.
