Wednesday, 9 January 2013

Research: natalizumab works within a few months

#MSBlog: Natalizumab starts working within 2-3 months. Therefore any relapse destined to  happen in the first 2-3months will probably occur. 


Background: In clinical practice natalizumab is typically used in MSers who have experienced breakthrough disease during treatment with interferon beta (IFN╬▓) 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!"

CoI: multiple

6 comments:

  1. Does that mean the first 6-9 months on GA and the first 13 months on alemt you are as good as untreated? Isnt that dangerous for patients with v active disease? (accumulating damage)

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  2. Yes, but this is not good: http://chefarztfrau.de/?page_id=716

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    1. as you will seeon blog prof g provides regular updates on PML risks from tysabri

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  3. Ok, it seems that you can proudly explain why Tysabri "works" as described here. You also use these results as an argument in favour of the viral/autoimmune theory. The same with Gilenya and Lemtrada. But, you are in a completely awkward position when you need to explain why the same drugs don't "work" for other patients (who happen to be the majority). This renders your theories of "working" mechanisms absolutely irrelevant to the true nature of MS.

    If you had a consistent and truthful theory for the origin of MS you should explain both positive and negative results regarding drug use. Yet, when it comes to negative results you fall back and hide behind unproven conjectures about "neurodegenerative" processes, which of course is no explanation since neurodegeneration is self evident in MS. In other words if a theory can not explain the negative outcomes, there is no logical support for any explanation of the positive ones.

    This is just an epistemological remark, I know prof GG has an interest in philosophy.

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  4. Do you think I can discuss the NEDA concept with my neurologist when I next see him? Are they all 'in the loop'? And I suppose the next question to him would be: 'How is my progression/non-progression being calculated?' I'd value your input - I don't like being pushy but I will if I need to.

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    1. You can ask him if he buys into the concept. This is new for MS and at the moment no many in the field have adopted it.

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