A few days ago we had the the effect of ozanimod on lymphocyte subsets and whilst T cells subsets were examined, B cells subsets were not…I said how can you understand how ozanimod works if you do not look at memory B cells.
Sadly this view falls on deaf ears or is that blinkered eyes
We made the point that all agents that inhibit MS also inhibit memory B cell activity. So far we have yet to see data that argues against this. When it does I will modify my view.
Ocrelizumab and rituximab selectivly target B cells. These are dosed every 6 months but we have made the point that if you consider memory B cells to be important targets then based on their repopulation kinetics, you should not have to dose every 6 months in everyone. We showed that based on the ocrelizumab phase II study. It is shown again here. Rather than dose every six months, the re-dose occurs when the memory B cells reach a set level, This way they can keep people in remision, whilst reducing the dose-requirement.
This now says the same as neuromyelitis optica, rheumatoid arthrits, myasthenia gravis, etc, etc, etc ,
If we can find the pathogenic cell characteritisics one could refine this further, but at some point I suspect we can stop the dosing and ocrelizumab becomes like alemtuzumab.
Tailoring B cell depletion therapy in MS according to memory B cell monitoring.Novi G, Bovis F, Fabbri S, Tazza F, Gazzola P, Maietta I, Currò D, Bruschi N, Roccatagliata L, Boffa G, Lapucci C, Pesce G, Cellerino M, Solaro C, Laroni A, Capello E, Mancardi G, Sormani M, Inglese M, Uccelli A.Neurol Neuroimmunol Neuroinflamm. 2020 Aug 4;7(5):e845. doi: 10.1212/NXI.0000000000000845. Print 2020 Sep.
Objective: We wanted to evaluate efficacy on inflammatory parameters of rituximab (RTX)-personalized reinfusion scheme using a memory B cell-based treatment regimen.
Methods: This is a prospective, uncontrolled, open-label study including patients with MS treated with RTX in 2 Italian MS units. All patients were treated with RTX induction, followed by maintenance infusion at the dosage of 375 mg/m2, according to memory B cell repopulation (0.05% of peripheral-blood mononuclear cells [PBMCs] for the first 2 years, 0.1% of PBMC for the third year). MS activity was assessed as clinical or MRI activity.
Results: One hundred two patients were included in the analysis. Mean follow-up was 2.40 years (range 0.57-7.15 years). The annualized relapse rate (ARR) was 0.67 in the year before RTX start and decreased to 0.01 in the 3 years after RTX initiation (global ARR). The proportion of patient with MS activity (i.e., relapse or MRI activity) was 63.16% in the year before RTX start and decreased to 8.7% (0-6 months), 1.3% (6-12 months), 0% (12-24 months), and 0% (24-36 months). Annualized RTX infusion rates were 1.67 (95% confidence interval [CI]: 1.43-1.94), 0.76 (95% CI: 0.58-0.98), and 0.78 (95% CI: 0.52-1.12) for the first 3 years after RTX initiation, respectively. Patients were reinfused with a mean infusion interval of 367 days (range 181-839 days).
Conclusion: The results of this study show that the memory B cell-based RTX reinfusion protocol is able to reduce the mean number of RTX reinfusions with persistent reduction of disease activity.