What you can’t pick in MS

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“Whatever choice you make makes you. Choose wisely” – Roy T Bennett, The Light in the Heart.

Unfortunately, you can’t pick your race or whether you get MS, nor whether you have to deal with both. Racial differences in treatment response for health conditions is not a novel concept. When I was a trainee I was taught that it was harder to control blood pressures in African-Americans than in Caucasian individuals, with poorer response to B-blockers and ACE inhibitors. To date this remains one of the most widely studied racial differences in response to medicines.

This April at AAN 2021, the NYU School of Medicine presented preliminary work demonstrating a difference in response to anti-CD20 therapies between African-American and Caucasian individuals with MS/NMO. They studied B-cell repopulation rates in 168 MS/NMO patients (71% female) treated with either rituximab or ocrelizumab.

Their main finding was that B cells repopulated faster in African-American individuals than Caucasians (unfortunately, I’m not able to show you their slides as it’s still unpublished work) – 76% versus 33% at 6-12 months, respectively. The B-cell subset composition was no different between the two groups, suggesting that this is purely an efficacy thing.

So what does this mean? It is likely that anti-CD20 treatments aren’t as effective in African-Americans than in Caucasians. We may have to do more frequent anti-CD20 dosing or higher total dose in this population to have the same effect as in Caucasians.

It should be noted that these are findings from a single study and a pooled analysis of the Phase III ocrelizumab clinical trials asking the same questions would be helpful.

AAN2021

Disclaimer: Please note that the opinions expressed here are those of the author NDG and do not reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust or Queen Mary University of London.

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Neuro Doc Gnanapavan

13 comments

    • Good question – needs to be looked at, Asians respond to medications differently to African-Americans and Caucasians.

  • Why would time to repopulate be a measure of efficacy as long as the CD-20 cells are depleted and allowed to reboot from the bone marrow? Does the study suggest that a lower percentage of CD-20 +B cells are actually depleted with similar doses of OCR/RTX between the two groups?

    • The reboot population would be naïve B cells from the bone marrow, but the memory B cells will be depleted. In terms of the type of B cell that is depleted there is no difference between the two races. If B-cells do repopulate faster then with time their will be breakthrough activity.

  • Hypotheses 1. Ocrelizumab works as an immune suppressant and suppression of repopulation with higher doses of Ocrelizumab or alcohol would be beneficial to pwMS on this treatment.
    Hypothesis 2. Ocrelizumab kills B cells (including those infected with EBV) and repopulation with B cells that aren’t infected with EBV doesn’t have any effect on MS outcome and reduces opportunistic infections.
    I would love to see a study looking at repopulation rates and clinical outcomes. This might persuade me away from hypothesis 2, and I would go back to poisoning my bone marrow with alcohol. I don’t think you can say, “ It is likely that anti-CD20 treatments aren’t as effective in African-Americans than in Caucasians”, until somebody does the the subgroup analysis, as this makes the unproven assumption that hypothesis 1 is correct.

          • So why does killing a B cell with anti CD20 not affect what comes back, but Cladribine and Alemtuzumab both do?

          • Anti-CD20 absolutely does affect what comes back, this was reportered at ECTRIMS in 2017 and it can be seen that the B cell repertoire is different, the T cell repertoir did not change much so I dont think in terms of the B cells there is much differencs between the three treatments indeed I have argued that the effect will be the same. Anti-CD20 is an IRT

  • I was wondering about race, MS and blood sugar levels. And a diet such as high in white rice consumption? As white rice can have a high GI score.

    • This is where things get complicated, cardiovascular risk is big contributor as far as MS progression is concerned. If the risk factors such as hypertension, diabetes are present (more than foods with high GI score) the additive risk of race (Asians have higher risk cardiovascular events) will compound matters.

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