Risk factors for reactivation of clinical disease activity in multiple sclerosis after stopping natalizumab

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You can all read the text, natalizumab seems to hold everything in check

Risk factors for reactivation of clinical disease activity in multiple sclerosis after natalizumab cessation. Mustonen T BM, Rauma I MD, Hartikainen P MD, PhD, Krüger J MD, PhD, Niiranen M MD, Selander T M.Sc, Simula S MD, PhD, Anne M R MD, PhD, Kuusisto H MD, PhD. Mult Scler Relat Disord. 2019 Nov 5;38:101498.

BACKGROUND:Natalizumab (NTZ) is widely used for highly active relapsing-remitting multiple sclerosis (MS). Inflammatory disease activity often returns after NTZ treatment discontinuation. We aimed to identify predictive factors for such reactivation in a real-life setting.

METHODS:We conducted a retrospective survey in four Finnish hospitals. A computer-based search was used to identify all patients who had received NTZ for multiple sclerosis. Patients were included if they had received at least six NTZ infusions, had discontinued treatment for at least three months, and follow-up data was available for at least 12 months after discontinuation. Altogether 89 patients were analyzed with Cox regression model to identify risk factors for reactivation, defined as having a corticosteroid-treated relapse.

RESULTS:At 6 and 12 months after discontinuation of NTZ, a relapse was documented in 27.0% and 35.6% of patients, whereas corticosteroid-treated relapses were documented in 20.2% and 30.3% of patients, respectively. A higher number of relapses during the year prior to the introduction of NTZ was associated with a significantly higher risk for reactivation at 6 months (Hazard Ratio [HR] 1.65, p < 0.001) and at 12 months (HR 1.53, p < 0.001). Expanded Disability Status Scale (EDSS) of 5.5 or higher before NTZ initiation was associated with a higher reactivation risk at 6 months (HR 3.70, p = 0.020). Subsequent disease-modifying drugs (DMDs) failed to prevent reactivation of MS in this cohort. However, when subsequent DMDs were used, a washout time longer than 3 months was associated with a higher reactivation risk at 6 months regardless of whether patients were switched to first-line (HR 7.69, p = 0.019) or second-line therapies (HR 3.94, p = 0.035). Gender, age, time since diagnosis, and the number of NTZ infusions were not associated with an increased risk for reactivation.

CONCLUSION: High disease activity and a high level of disability prior to NTZ treatment seem to predict disease reactivation after treatment cessation. When switching to subsequent DMDs, the washout time should not exceed 3 months. However, subsequent DMDs failed to prevent the reactivation of MS in this cohort

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  • Important question, and do not forget not only the repapses but the subacute inflammation is also important.

    My sis switched from Fingo to Alem. Her condition was stable while she took Fingo, but the washout was very bad to her. Her condition declined day by day (from EDSS3.0 to 3.5, posterior fossal sympthoms), after 38 days washout and 5cycles of Alem, she regained her energy and condition, and finally looks like very stable with Alem…
    Currently I do not know that continously decline was the result of relapse, or the subacute inflammation which returned after Fingo built off.
    But time is brain not only when we start to treat but also we switch to another treatment.

    • If she is truly rrms she should be totally stable other than temporary decline from relapses…edss 3.0-4.0 is where spms symptoms begin. Hopefully alem. can turn the clock back some..and then keep it there.

  • Yes that’s what we know this disease, but actually she was declining continously from 0.0 to 3.5 and she only needed 2years to reach it. She had cerebellar problems, and also brainstem sympthoms (nystagmus swallowing issues), and she really declined months by monts. (And her MRI proved it, cause showed new T2 spots and unfortunately T1 black holes as well)

    The first milestone was fingolimod.
    But before she got fingo, she had a vision examinaton and her ophthalmologist found her vision was like a 90yrs old wmn, and also found she had optic neuritis as well.

    After only 2-4wks with Fingo her diplopia cleared, her vision went good again. (Her ophthalmologist could not believe what she found, cause her vision also went near normal only after 1month) and meanwhile her walking speed was better and better day by day, after 6mnths with Fingo she was much more better.

    But switched to Alem. after 25 mnths because her potential family plans.
    And finally Alemtuzumab helped also. Her 9hole, 25w, 500m, and cognitive tests went better or were stable. And finally her neuro find her EDSS3.5 with fingo improved by 0.5 point by the end of the 1st year with Alem, and her neuro found she have a chance to reach the EDSS 2.5 by the end of the second year with alem.!
    Believe or not, she had 2documented relapses, but her current neuro suspected she had at least 8(!) but it was minor ones, and we more likely saw it as a continously decline. And unf. her first neuro was really not good. (Not like her current.)

    But this also prove: MS is not two or three diseases. She is younger, so after Fingo, and Alem switched off her brain inflammation, her brain got a chance to regenerate itself (brain reserve). But when the Fingo is built off her sympthoms started to grow again (like before Fingo), and cleared immedately after the first 5 cycles of Alemtuzumab. Alem looks like workin also very well. Maybe a bit better than Fingo. Hope it can continue for long-long time.

    And actually and unfortunately she presents her old sympthoms when the weather is hot, if her body temp grows.

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