Figure 5. Proportions of immune cell subsets during early (PROCLAIM) and long-term (ENDORSE integrated analysis) dimethyl fumarate (DMF) treatment.

PROCLAIM (n = 163) and the BG00012 Monotherapy Safety and Efficacy Extension Study in Multiple Sclerosis (ENDORSE) integrated analysis (n = 694) are shown. For each box plot, the top and bottom box edges correspond to the first and third quartiles. The black line inside the box represents the median. The top and bottom whisker lines mark the maximum and minimum values of the dataset, respectively. For PROCLAIM (shaded white), the box plots represent the longitudinal trajectory in lymphocyte subsets during early treatment (from baseline [BL] to week 24 [W24]). For the ENDORSE integrated analysis (shaded gray), the box plots represent the cross-sectional observations in lymphocyte subsets in patients who had been exposed to DMF for ∼5 years, stratified by absolute lymphocyte count (ALC) category. For the ENDORSE integrated analysis, data were stratified by ALC categories (ALC always ≥0.91 × 10⁹/L [≥lower limit of normal (LLN)]; ALC <0.8–0.5 × 10⁹/L for ≥6 months [moderate, prolonged lymphopenia, <0.8–0.5]; ALC <0.5 × 10⁹/L for ≥6 months [severe, prolonged lymphopenia, <0.5]). Patients were categorized as having moderate to severe, prolonged lymphopenia if they met these criteria at any time during the study. p values were calculated using Wilcoxon signed-rank test, compared the absolute change in relative proportion of lymphocyte subsets at week 24 with baseline for PROCLAIM, were calculated using a pairwise 2-sample Wilcoxon test, and compared the absolute change in relative proportion of lymphocyte subsets for moderate and severe, prolonged lymphopenia compared with ALCs ≥ LLN for the ENDORSE integrated analysis. Significant p values are marked with asterisks (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001) vs baseline for PROCLAIM week 24 or vs ≥LLN for ENDORSE integrated analysis ALC categories. (A) Transitional B cells (CD19⁺/CD24^hi/CD38^hi), naive B cells (CD19⁺/CD27⁻/IgD⁺), IgD⁺ memory B cells (non-class switched) (CD19⁺/CD27⁺/IgD⁺), IgD⁻ memory B cells (class switched) (CD19⁺/CD27⁺/IgD⁻), plasmablasts (CD19⁺/CD27⁺⁺/CD38⁺⁺), and CD138⁺ plasma cells (CD19⁺/CD27⁺⁺/CD38⁺⁺/CD138⁺). (B) CD4⁺ T cells (CD3⁺/CD4⁺), CD8⁺ T cells (CD3⁺/CD8⁺), B cells (CD19⁺), CD56^bright natural killer (NK) cells (CD19⁻/CD3⁻/CD16⁺/CD56^hi), and CD56^dim NK cells (CD19⁻/CD3⁻/CD16⁺/CD56^low). Ig = immunoglobulin.