#MSBlog: Natalizumab starts working within 2-3 months. Therefore any relapse destined to happen in the first 2-3months will probably occur.
Epub: Kappos et al.Clinical effects of natalizumab on multiple sclerosis appear early in treatment course.J Neurol. 2013 Jan.
Background: In clinical practice natalizumab is typically used in MSers who have experienced breakthrough disease during treatment with interferon beta (IFNβ) or glatiramer acetate. In these MSers 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.
Objectives and methods: 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).
Results: 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 MSers 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 MSers 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).
Conclusion: Natalizumab resulted in rapid, sustained reductions in disease activity in both AFFIRM and in clinical practice. This decrease in disease activity occurred within the first 3 months of treatment even in patients with more active disease.
"These results are well known from the natalizumab development program and it is good to see that they are also observed in real-life clinical practice with the TOP study. I always tell MSers that natalizumab takes 2-3 months to have an effect and that any relapse destined to happen in the few months after starting treatment will happen. This means that if we had to apply the definition of NEDA (no evidence of disease-activity) to natalizumab-treated MSers we would have to rebaseline them at 3 months; new MRI and set the relapse and disability counter to zero. The time when to rebaseline will depend on the mechanism of action of the drug; for example for glatiramer acetate you would probably choose 6 to 9 months and for alemtuzumab 13 months, i.e. after the second course of treatment. All these issues are up for debate. The good thing is that they concept of NEDA is now on the table so let's hope it generates some healthy discussion and debate; you the MSers deserve it!"