Alemtuzumab replay

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Sometimes it’s better the devil you know than the one you don’t.

Alemtuzumab came into disfavor following the European Medicines Agency (EMA) Article 20 procedure surrounding certain rare side effects. There couldn’t have been a deeper grave to crawl out of.

In my mind the group most to gain from alemtuzumab have always been those early on in their disease before disability sets in. I stand corrected.

Real life data from Israel suggests that even at an average EDSS score of 4.8 (the first milestone where there is limitation of walking) there is stabilization of disability progression within 2 years of starting (see Figure below).

figure1
Figure: The median EDSS score one year before treatment was 4.0 (IQR 1.5–5.1), and EDSS at baseline was 4.0 (IQR 2.5–6.0). EDSS after 1 year of treatment was 4.8 (IQR 2.9–6.0), and EDSS after 2 years was 3.0 (IQR 2.5–6.5). The EDSS change from baseline was not statistically significant (p = 0.632)

How is alemtuzumab achieving this?

Most likely through a reduction in relapse rate. In the year preceding treatment the average relapse rate was 2, which later became 0 after 2 years of treatment (see figure below).

figure2
Figure: Median relapse rate was 2.0 (IQR 1.0–3.9) in the year leading up to alemtuzumab treatment. At 1-year follow-up, the median relapse rate was 0.0 (IQR 0.0–1.0); at 2-year follow-up the median relapse rate was 0.0 (IQR 0.0–0.0). The change in the number of relapses was 2.0 (IQR 1.0–3.0) (p < 0.0001)

Abstract

Acta Neurol Belg. 2020 May 23. doi: 10.1007/s13760-020-01375-6. Online ahead of print.

Efficacy and Safety of Alemtuzumab Treatment in a Real-World Cohort of Patients With Multiple Sclerosis

Ofir ZmiraAlex I Halpern Lital Abraham Anat Achiron

Alemtuzumab is a monoclonal anti-CD52 antibody prescribed to treat relapsing-remitting multiple sclerosis (RRMS). Alemtuzumab affects the balance of the immune system by depleting circulating lymphocytes, leading to the formation of a new immune repertoire less likely to induce autoimmune attack against CNS myelin. We collected real-world data of RRMS patients treated with alemtuzumab. We assessed relapse rate, disability progression, and MRI-related disease activity over a 24 month period. Our study included 35 RRMS patients (19 female and 16 male) with a mean age of 37.3 years (SD = 10.5). The patient cohort had a mean disease duration of 10.4 years, median previous disease modifying treatments (DMTs) of 3.0, and a median expanded disability status scale (EDSS) score of 4.0 (IQR 2.5-6.0). Neurological disability remained stable during treatment and there was no statistically significant change in EDSS score. Prior to treatment, the median relapse rate was 2.0 (IQR 1.0-3.0); after treatment the median relapse rate was 0.0. This 2.0 decrease in relapse rate is statistically significant (p < 0.0001). Moreover, the treated patients exhibited a statistically significant decrease in gadolinium (GD) enhancing lesions on MRI [both in number (p < 0.005) and volume (p < 0.005)]. Thirty-three percent of patients reached NEDA-3 (no evidence of disease activity) status by the end of treatment. In a real-world setting, alemtuzumab treatment significantly decreased relapse rate and GD-enhancing lesions while preventing disability progression. Tolerability of treatment was high, with patients experiencing only minor adverse events.

About the author

Neuro Doc Gnanapavan

5 comments

  • This effect seems to be unique to Alemtuzumab. Ocrelizumab reduces relapses to the same extant yet doesn’t reverse disability. What is alemtuzumab doing that no other Ms drug is doing? Something is happening to ms outcomes that has not been explained when alemtuzumab is used. When correctly explained, I suspect may lead to the biggest breakthrough in ms to date. Can no one else wake up and smell the coffee?

      • Thanks Prof G. Great article. I remembering scanning through it bit read it completely. Makes sense to me that T cells as well as driving MS also are involved in the repair mechanisms. If I remember correctly wasn’t there t cell study from Dublin proved conclusively a subset of the cells were directly involved in directing mylination. After depletion could these t cells also be rejuvenated ?

  • Makes me wish that the EMA had heeded the letter ProfG wrote to them.
    Makes me hurt to know there are those who will have had treatment put on hold due to Covid and those who have to wait to receive treatment after a point at which they will have increased disability due to the EMA decision.
    Makes me glad there are so many who’ve benefitted from treatment and I hope that the positive info contained in this report will be encouraging to many PwMS waiting for Alem or considering having it.

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