DMF alters the T cell repertoire, and emerging evidence suggests it also impacts B cells. Given the putative role of memory B cells in MS pathophysiology, characterizing DMF’s effect on B cells may provide insight into DMF’s therapeutic benefit.

In PROCLAIM (EUDRA CT 20015-001973-42), an open-label, multicenter, 96-week, Phase 3b study, patients aged 18-65 years with RRMS (n=218) were treated with DMF. Change from baseline (CFB) for total B-cell and B-cell subset counts, IgA/G/M levels and apoptosis markers (Ki67/AnnexinV/cCAS3/cPARP) was assessed by flow cytometry based on baseline, and week (W) 4, 8, 12, 24, 36, 48, 72 and 96 measurements.

Decreased total CD19⁺B cell counts were observed at W4 after treatment initiation (-10.2% CFB, p<0.001), earlier than for T cells. Total B cells reached nadir at W24 (-30.5% CFB, p<0.0001). After W48, a gradual increase was observed though levels never reached baseline (W96:-13.4% CFB, p<0.05). Naïve CD27^-IgD⁺B cells changed less relative to memory CD27⁺IgD⁺non-class-switched B cells and CD27⁺⁺CD38⁺⁺plasmablasts (-21%; -43%, -57% CFB at W48, respectively, p<0.0001). Transitional CD24^hiCD38^hiB cells were the only B-cell subset to increase during DMF treatment (+54% CFB at W48; +50% at W96, P<0.0001). All IgA/G/M levels remained stable during treatment (within ±10% CFB, P=NS). Circulating B cells exhibited no evidence of increased apoptosis.

Selective changes across key B-cell subsets during 2 years of DMF treatment resulted in a relative proportional increase in transitional and naïve B cells with concomitant decrease in memory B cells, and stable Ig levels. Results suggest DMF modulates a shift away from memory B cells and towards a naïve repertoire that does not impair protective humoral immunity, potentially contributing to DMF’s therapeutic benefits on MS.

Study Supported by: Biogen