Fig. 4

Late therapeutic ibrutinib treatment ameliorates clinical severity of EAE in Biozzi mice. a–f SCH/CFA-immunized Biozzi mice were treated with vehicle or ibrutinib daily from Day 49 (dotted lines in a, c, and e) through the day before study termination. Arrows indicate the final day of each experiment (Day 83, Day 78, or Day 75, respectively). Experiment 1 had n = 18 mice/group, Experiment 2 had n = 10 mice/group, and Experiment 3 had n = 13 mice/group. a, c, e Clinical scores, and percent body weights relative to Day-1 (a) or Day 0 (c, e). Gray areas represent the efficacy period of treatment (period starting 15 days after treatment onset, i.e., Day 64, through study termination), during which clinical scores and relative body weight areas under the curves were compared. b, d, f Maximum EAE scores during the efficacy period of treatment. Data in a, c, and e are shown as mean + SEM and data in b, d, and f are shown as mean ± SEM. Significance was tested using an unpaired two-tailed t test (relative body weight area under the curve and relative end body weight), two-tailed Mann–Whitney test (end score and maximum score), or two-tailed Mann–Whitney test followed by the Benjamini and Hochberg procedure (clinical scores on individual days, false discovery rate (FDR) = 5%, bars and asterisks above clinical score graphs indicate FDR-adjusted significance level of individual days). *p < 0.050, **p < 0.010, ***p < 0.001, n.s. = not significant