Chronic active MS lesions respond poorly to anti-CD20 antibodies

Anti-CD20 therapies do not fully resolve chronic active/smouldering lesions, visible on MRI as paramagnetic rim lesions (PRLs), after 2 years of follow-up. These findings may be partially explained by the low numbers of CD20+ B cells in chronic active lesions, the limited CD20+ B cells tissue turnover, and the inefficient passage of anti-CD20 antibodies across the blood-brain barrier.

Chronic active/smouldering lesions, visible as PRLs, are associated with clinical disease severity and neuro-axonal damage [1]. A new study aimed to assess the effects of anti-CD20 antibody therapy on these lesions. B-cell lineage lymphocytic subpopulations in chronic active lesions were also analysed, including the consequences of their depletion.

A longitudinal, clinical, MRI study was set up in which 4 European academic hospitals participated [2]. Included were 68 adults with relapsing-remitting MS or progressive MS; 42 received anti-CD20 treatment, while 26 chose not to be treated. All participants underwent longitudinal 3T susceptibility-based MRI for PRL detection and quantitative-susceptibility mapping (QSM) analysis. The median follow-up for treated and untreated participants was 26 and 31 months, respectively. Dr Pietro Maggi (Saint-Luc University Hospital, Belgium) presented the results.

A total of 346 white-matter lesions were studied: 185 PRLs (133 treated and 52 untreated) and 161 non-PRLs (110 treated and 51 untreated). At follow-up, the paramagnetic rim disappeared in none of the 133 treated PRLs. The researchers did not find a significant treatment effect on PRLs versus non-PRLs for log-lesion volume (P=0.16), QSM (P=0.56), or T1 values (P=0.34). PRLs were larger (P<0.0001) and expanded over time (P=0.009), “confirming their nasty, destructive phenotype,” Dr Maggi said.

In chronic active lesions, lymphocytes constituted 6.8% of all immune cells; they included 4.3% of CD20+ B cells, 20% of antibody-producing plasmablasts, 75.5% of activated T cells, and 0.2% of natural-killer cells. A gene-regulatory network (GRN) machine-learning analysis predicted that depletion of CD20+ B cells, plasmablasts, and T cells would each affect genes highly expressed by microglia and dendritic cells.

Thus, anti-CD20 therapies did not fully resolve PRLs after 2 years of follow-up. The lack of CD20+ B cells in chronic active lesions and the inefficient passage of anti-CD20 antibodies across the blood-brain-barrier could be possible explanations

1. Absinta M ,et al. JAMA Neurol. 2019;76(12):1474–1483.
2. Maggi P. Chronic active multiple sclerosis lesions are poorly responsive to anti-CD20 antibody treatment. Abstract O118, ECTRIMS 2022, 26–28 October, Amsterdam, Netherlands.

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Posted on 19 December, 202225 March, 2024