Repopulators after CD20 depletion.

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The influence of CD20 on depletion is important as an element to control MS, but it has now got a new dimension with the COVID-19 pandemic and vaccination responses.

Anti-CD20 treatment got delayed due to COVID-19 and most studies have suggested that there was not disease breakthrough with a 3 month break. In terms of a vaccination response it has likewise been suggested that once your B cells are over 1-3% of lymphocytes you will make some form vaccination antibody response.

At 6 months after the first dose 41/155 (~26%) would have repleted to 1% B cells at 12 months of dosing 31/41 (FR) and 14/114 (SR) so 45/155 (29%) would have repleted…. Therefore this would predict about at 30% seroconversion in people recieving continual 6 monthly dosing.

The fast repopulators at 6 months after the first dose showed some disease breakthrough. So if you were thinking to dose for an IRT-like effect maybe more than one dose would be needed

Gianmarco Abbadessa, Giuseppina Miele, Paola Cavalla, Paola Valentino, Girolama Alessandra Marfia, Elisabetta Signoriello, Doriana Landi, Chiara Bosa, Marco Vercellino, Antonio De Martino, Rosanna Missione, Maddalena Sparaco, Luigi Lavorgna, Giacomo Lus, Simona Bonavita CD19 Cell Count at Baseline Predicts B Cell Repopulation at 6 and 12 Months in Multiple Sclerosis Patients Treated with Ocrelizumab. International Journal of Environmental Research and Public Health  (IF3.39),  DOI: 10.3390/ijerph18158163

Background: The kinetics of B cell repopulation in MS patients treated with Ocrelizumab is
highly variable, suggesting that a fixed dosage and time scheduling might be not optimal. We aimed
to investigate whether B cell repopulation kinetics influences clinical and radiological outcomes and
whether circulating immune asset at baseline affects B cell repopulation kinetics.

Methods: 218 MS patients treated with Ocrelizumab were included. Every six months we collected data on clinical and magnetic resonance imaging (MRI) activity and lymphocyte subsets at baseline. According to B cell counts at six and twelve months, we identified two groups of patients, those with fast repopulation
rate (FR) and those with slow repopulation rate (SR).
In line with previous studies, B cell reappearance was defined when CD19 cells reached 1% of lymphocyte count

Results: A significant reduction in clinical and radiological activity was found. One hundred fifty-five patients had complete data and received at least three treatment cycles (twelve-month follow-up). Over the twelve-month treatment period, in patients with a complete follow up and complete data (n = 155), a significant reduction in CD19 cells was revealed (12.94% at baseline vs. 0.45% after twelve months (p = 0.001)); we also found a significant decrease in total lymphocytes (p = 0.0012) and CD8 cell count (p = 0.01), but not CD4 cell count. After six months, the FR patients were 41/155 (26.45%) and 10/41 (29.27%) remained non-depleted after twelve months. In the SR group at six months, only 12.28% was not depleted after twelve months (p = 0.013). FR patients showed a significantly higher percentage of active MRI scan at twelve months (17.39% vs. 2.53%; p = 0.008). Furthermore, FR patients had a higher baseline B cell count compared to patients with an SR (p = 0.02 and p = 0.002, at the six- and twelve-month follow-ups, respectively). FR had a significantly higher CD19 cell count (15.76 ± 9.23% and 12.45 ± 7.29%, respectively; p = 0.02). It was determined that 12% of CD19 cells at baseline as the cut-off point, generating the best combination of sensitivity and specificity, for B cells reappearance at six months (AUC, 0.62 (0.52–0.73))

Conclusion: A considerable proportion of MS patients did not achieve a complete CD19 cell depletion and these patients had a higher baseline CD19 cell count. These findings, together with the higher MRI activity found in FR patients, suggest that the Ocrelizumab dosage could be tailored depending on CD19 cell counts at baseline in order to achieve complete disease control in all patients. Our results show a significant higher proportion of active MRI scans at twelve months in FR patients, compared to SR patients, suggesting that Ocrelizumab needs to be administered based on peripheral B cell count monitoring.

With regard to B cell kinetics, our results show the depletion of B cells after six- and twelve-months in most of the patients. However, 26% of them had an incomplete depletion at six months that was confirmed in 1/3 of them at twelve months.

Disclaimer: Please note that the opinions expressed here are those of the author 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 Univeristy of London.

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