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Extending Tysabri Dosing Intervals Reduces the Risk of PML.

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    Extending Tysabri Dosing Intervals Reduces the Risk of PML.

    Extending natalizumab dosing intervals reduces the risk of PML

    Quoting a Friday, March 9, 2018 post at:

    multiple-sclerosis-research.blogspot.com/

    “Natalizumab extended interval dosing (EID) is associated with a significant reduction in PML risk compared with standard interval dosing (SID) in the TOUCH® Prescribing Program

    Natalizumab, a highly efficacious medication approved for relapsing forms of MS, is used to prevent relapses, slow worsening disability, and may improve the quality of life for some patients. The medication is indicated to be prescribed as 300-milligram infusion dosed every four weeks.

    However, taking the medication longer than two years may increase risk of PML, which is caused by JCV. There have been 756 PML cases reported worldwide as of December 2017, with a global incidence rate of 4.19 per 1,000 PML cases in people treated with natalizumab. Patients who test JCV antibody-positive and therefore are presumed to have been infected with the virus, which comprises roughly half of the world population, are typically either told to not to start natalizumab, or have had treatment stopped after two years, when risk is deemed to be too high.

    Our new study… adds an important caveat to known PML risk in natalizumab users. According to the comprehensive analysis of TOUCH database, which includes all natalizumab users in the Unites States, the risk of PML is very significantly lower in JCV Antibody positive patients whose natalizumab infusions have been extended from 4 weeks to 5-12 weeks.

    The results showed clinically meaningful and statistically significant risk reductions… – there were no PML cases among 815 patients who met the inclusion criteria as compared to 96 cases noted in standard interval group (comprised of 23,168 patients). The average dosing interval extension ranged from 35 to 42 days. It is important to note that patients with dosing gaps over 12 weeks were excluded since numerous studies have demonstrated loss of drug efficacy after 3 months period.

    The TOUCH database does not capture efficacy data. Key outstanding question at this point is whether the efficacy of monthly natalizumab could be maintained with less frequent dosing (e.g. q 6 weeks). Our prior retrospective work found that extending the dose up to 8 weeks did not negatively affect the medication’s efficacy in a retrospective review of 2,000 patients in 6 MS Centers across the US.

    In the meantime, our recent findings could influence how neurologists prescribe the medication. Neurologists have been looking for safer ways to administer natalizumab infusions to their patients, but there hasn’t been clear data on whether decreasing dosing frequency improves safety. The large risk reduction seen with extending natalizumab infusions by just 2 weeks is potentially practice-changing since it could give neurologists an opportunity to prescribe a highly efficacious medication in a safer way.

    Our research team includes I. Kister, J.D. Goldberg, X. Li from New York University Langone Medical Center, J. Foley and R. Metzger from Rocky Mountain Multiple Sclerosis Clinic, G Cutter from University of Alabama at Birmingham School of Medicine, and I. Chang, B. Yu, Z. Ren, C. Hotermans, P.R. Ho, and N. Campbell from Biogen.

    Post by Lana Zhovtis”

    #2
    All this info came out a few years ago at the National Neurology seminar. I cannot remember if it was in Philly ?? I read about it on this site. I was excited and talked to my neuro - we decided to go 56 days after I had already changed from 4 weeks to 6.
    Linda

    Comment


      #3
      Hi Linda,

      Tysabri is tremendously effective. It has halted the progression of MS in so many pwMS that I felt the need to emphasize once again Tysabri's biggest safety concern can be de-risked by extending time between doses.

      From speaking with those getting Tysabri infusions over a period of years I have noticed that very few report any side effects at all from it. Tysabri is such a blessing to so many MSers that I wanted to keep current the knowledge that it can be de-risked by going longer than 4 weeks between infusions.

      It is a great DMT for MS. I have absolutely no doubt Tysabri is primarily responsible for my wife's present good health and I want others with MS to know that a highly effective treatment is available and is now safe even for those who are JC virus positive.

      Not a single JC positive person taking Tysabri has ever gotten PML on dose extension. Someday, possibly someone will, but it has been years now and the fact that not one doing dose extension has is tremendously significant. There have been several cases of PML on Gilyena and Tecfidera, too; but zero on Tysabri in dose extension.

      Tysabri is far more effective against MS than those two. To me, Tysabri on dose extension appears much safer than those and with less nasty side effects. In my experience at the infusion center, people on Tysabri seldom report any side effects.

      I just want pwMS to know that Tysabri is highly effective and very safe going 5,6,7 or 8 weeks between doses!

      Comment


        #4
        You are absolutely correct in doing this, Myoak! Tysabri has been a blessing for your wife, me and so many others and now for the extended dosing..YEA!! I am so thankful the National Academy of Neurology gave us this info.
        Linda

        Comment


          #5
          Linda,

          I looked back to see when we first began posting MS World about dose extension and noticed one from 2013. Sometimes older posts are worth reviewing and refreshing because newer people may not realize dose extension for many JCV+ has been going on for over 4 years and there have been no cases of PML in that group! So, from 2013, I quote...

          "The science behind dose extension, going from 4 weeks to 5,6,7, or 8 weeks… is to provide more capability for your body’s immune system to handle JCV. The majority of our population has JC virus but it is only a problem for those with a weakened immune system, including those taking an immunosuppressant like Tysabri.

          The serum concentration of Tysabri decreases over time, that’s why you have to get another dose every few weeks.

          Extending the time between doses of Tysabri allows your immune system to work better because there is less immunosuppressant present; the serum concentration decreases."

          I posted these stats from an early dose extension study in October of 2014...

          'Data from extending time between doses of Ty was collected from 6 MS centers in the USA. After an initial 6 month period of infusions at 4 weeks patients were placed in 4 treatment groups.

          1. Standard Dosing (SD) every 4 weeks (n=674)
          2. Early Extended Dosing (EED) 4 weeks 3 days to 6 weeks 6 days (n=231)
          3. Late Extended Dosing (LED) 7 weeks to 8.5 weeks (n=245)
          4. Variable Extended Dosing (VED) those who alternated between EED and LED (n=208)

          Results: “NEDA (No Evidence of Disease Activity) including both clinical and MRI criteria ranged from 49% in VED, 57% in EED to 77% in LED. ARR (annual relapse rate) and NEDA were significantly better in LED compared to EED and VED, possibly reflecting selection bias.”

          Just a note on selection bias… neuros may have selected their "most well" patients for the longest extension between doses out of caution; fear of negatively affecting their health. In any case, those who extended time longest did the best. Really a surprising finding.

          As the abstract states, the hypothesis behind dose extension is dose “adequate to exclude autoreactive T cells from entry into CNS (MS-protective) but nevertheless sufficiently permissive to enable CNS lymphocyte scavenging of JC virus to occur (PML-protective).”

          Zero cases of PML occurred in the 684 involved in dose extension.
          2 cases of PML occurred in the Standard Dosing group of 674 patients.

          This study is ongoing. They note that “We are approaching the 1248 person-years needed to reach statistical significance at 0.05 level.”

          If the current pattern holds for a few more months of no PML cases in extended dose then this technique of extending dose will have scientific proof it does reduce PML risk.

          Possibly, the present pattern will hold, the study concluded, written up and put into practice by clinicians who are aware of it. And I imagine most are, including the ones who say there are no studies backing the idea of dose extension to reduce PML risk.

          It is exciting to think about the possibility of dose extension reducing risk of PML to the point of eliminating it entirely. So far, so good.'

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