Here is My Question:
After 2 years on Tysabri my neurologist suggested that I start getting infusions each 6 weeks instead of each 4 weeks, even though I am JCV negative. What would be the benefit? What is the evidence about efficacy of 6 week or 8 week dosing regimen? Thanks!
Answer:
Good question.
The main reason such a change in dosing frequency (from every 4 weeks to every 6 or 8 weeks) is considered is based on preliminary evidence that doing so may reduce the risk of progressive multifocal leukoencephalopthy (PML) while maintaining the effectiveness of Tysabri.
The rationale behind this is that we know that Tysabri saturates alpha-4-beta-1 integrin receptor by >80% after the infusion, and the saturation remains above 75% when you go back to get your next infusion 4 weeks later. At 6-8 weeks after the infusion, the saturation drops to ~70% and then ~40% two weeks later. The interaction between this receptor on your white blood cells and the blood vessel wall allows the cell to get into the central nervous system and potentially lead to an MS relapse. Tysabri blocks this interaction which is presumably why it works so well in reducing the number of clinical attacks, MRI lesions, and attenuating disability over time.
This receptor-Tysabri interaction is a double-edged sword, however. The white blood cells are also needed to survey the central nervous system and eradicate foreign invaders (ie, the JC-virus that causes PML). So, by altering the dosing frequency of tysabri, we are hoping to allow enough saturation of the integrin receptor by tysabri to protect patients from MS but at the same time, allow enough opportunity for the white blood cells to gain access to the nervous system to "keep an eye" on foreign viruses--particularly the one that causes PML.
Preliminary data on this topic presented at the American Academy of Neurology meeting in 2014 can be found below:
After 2 years on Tysabri my neurologist suggested that I start getting infusions each 6 weeks instead of each 4 weeks, even though I am JCV negative. What would be the benefit? What is the evidence about efficacy of 6 week or 8 week dosing regimen? Thanks!
Answer:
Good question.
The main reason such a change in dosing frequency (from every 4 weeks to every 6 or 8 weeks) is considered is based on preliminary evidence that doing so may reduce the risk of progressive multifocal leukoencephalopthy (PML) while maintaining the effectiveness of Tysabri.
The rationale behind this is that we know that Tysabri saturates alpha-4-beta-1 integrin receptor by >80% after the infusion, and the saturation remains above 75% when you go back to get your next infusion 4 weeks later. At 6-8 weeks after the infusion, the saturation drops to ~70% and then ~40% two weeks later. The interaction between this receptor on your white blood cells and the blood vessel wall allows the cell to get into the central nervous system and potentially lead to an MS relapse. Tysabri blocks this interaction which is presumably why it works so well in reducing the number of clinical attacks, MRI lesions, and attenuating disability over time.
This receptor-Tysabri interaction is a double-edged sword, however. The white blood cells are also needed to survey the central nervous system and eradicate foreign invaders (ie, the JC-virus that causes PML). So, by altering the dosing frequency of tysabri, we are hoping to allow enough saturation of the integrin receptor by tysabri to protect patients from MS but at the same time, allow enough opportunity for the white blood cells to gain access to the nervous system to "keep an eye" on foreign viruses--particularly the one that causes PML.
Preliminary data on this topic presented at the American Academy of Neurology meeting in 2014 can be found below:
| Mitigating PML While Maintaining Efficacy |
This multicenter observational data is preliminary but so far suggests that extending the dosing of Tysabri to every 6 to 8 weeks appears to maintain the drug's effectiveness against MS and at the same time, they have not observed a case of PML. Of course, this is just preliminary, and they are continuing the observational study to confirm these findings.
Hope this helps.
A. Scott Nielsen MD MMSc
Virginia Mason Multiple Sclerosis Clinic
Hope this helps.
A. Scott Nielsen MD MMSc
Virginia Mason Multiple Sclerosis Clinic
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