AAN2019. We have made a suggestion that memory B cell depletion may be an important therapeutic target and Luis has been doing over-time going through the abstracts to ask questions. So thanks for the hard work.
One question that comes from this is can you monitor memory B cell levels in the blood to get an idea of disease activity and when to retreat. This has been done in NMO and so the 6 monthly dosing has been extended to 8 or more months. In MS I suspect one needs to dose even less for many people, but a trial is needed. However, the issue of memory B cells monitoring will surface. Some will say no, some will any say yes. However you can relapse in arthritis without virtually no peripheral B cells so you can relapse with MS without B cells.
Anyway what happens in another MS-like condition. When antibodies to a myelin protein compared to an astrocyte water channel in NMO. Can you monitor memory B cells?.
Depletion of memory B cells is effective to prevent relapses in AQP4 antibody NMOSD but not in MOG antibody disorder Pierre Durozard et al.
Objective: To assess if monitoring of memory B cells is relevant to individualize the frequency of rituximab administration in MOG-antibody disorder as previously demonstrated for AQP4-antibody disorder. Background: NA
Design/Methods: 16 adult patients with MOG-antibody disorder and 29 adult patients with AQP4-antibody disorder were included in a prospective monocentric observational study. All patients were treated with rituximab using an individualized dosing schedule according to memory B cells count. Memory B cells were measured monthly from the second month after rituximab infusion and in case of relapse. Memory B cells were considered to be depleted if their frequency was less than 0.05% in peripheral blood mononuclear cells by flow cytometric analysis. Relapses, memory B cells count during relapses and EDSS were collected.
Results: Mean follow-ups were 38 months (13-79) in AQP4-positive patients and 19 months (9-38) in MOG positive patients. After rituximab initiation, 13 relapses occurred in 7 out of 29 AQP4-positive patients (24%). In MOG-positive patients, 10 relapses occurred in 6 out of 16 patients (37.5%). While memory B cells have reemerged in 12 out of 13 relapses (92.5%) occurring in AQP4-positive patients, they have reemerged in only 2 out of 10 relapses (20%) occurring in MOG-positive patients (p<0.001). These relapses occurred after a median time of 2.6 months (range 0.6 – 5.8), since the last infusion, in MOG positive patients, and 7 months (range 0.8 – 13) in AQP4 positive patients (p < 0.001). Conclusions: Identification of patients with short reemergence of memory B cells occurring before 6 months appears relevant to improve the efficacy of rituximab in AQP4-antibody disorder but not in MOG-antibody disorder where most relapses occur despite accurate depletion of memory B cells. This argues for a distinct pathophysiological mechanisms underlying relapses in MOG- vs AQP4-antibody disorder providing another clue to individualize MOG-antibody disorder as a novel disease entity.
The occrance of relapse was not statistically different between the NMO and the MOG-mediated antibody disease. Memory cells reemerged in most of the people with NMO who relapsed but they only re-emerged in 20% in people with MOG-disease.
However, the relapses occurred at 2.6 months compared to the 7 months for NMO. This is very quick. So it is possible that the relapses were going to happen anyway because they occured before the next cycle of rituxumab. How many cycles had they had because in MS trials there is a re-baselining at 6 months to allow for this. Alternatively is this a subgroup, where the B cells are protective and you are removing the B regulatory cells as has been suggested to be a possibility in MS. However, one thing that has to be said is that the methodology is flawed. This because they set memory B cells as being 0.05% of the blood cells, It is a percentage it needs to be an absolute number because if the T cell number increases then the B cell pool stays down. However, if mean the diagnosis needs to spot-on.