Bruton’s tyrosine kinase inhibition reduces disease severity in a model of secondary progressive autoimmune demyelination

Table 1 Clinical outcomes of prophylactic and semi-therapeutic ibrutinib treatment in EAE Biozzi mice

Readout	Vehicle (n = 13)	Ibrutinib Day 0 (n = 13)	Post-test p value	Ibrutinib day 9 (n = 13)	Post-test p value	Test statistic _(d.f.)	Overall p value
Incidence	13/13	10/13	0.392	12/13	0.999	–	–
Time to onset (median day)	15.0	20.0	0.002	15.0	0.055	–	–
Maximum score	3.35 ± 0.77	1.58 ± 1.08	< 0.001	2.27 ± 1.13	0.004	H₍₂₎ = 19.2	< 0.001
Maximum score 1st wave	3.12 ± 0.62	1.54 ± 1.07	< 0.001	2.27 ± 1.13	0.009	H(₂) = 17.6	< 0.001
Maximum score 2nd wave	2.65 ± 1.36	0.42 ± 0.70	< 0.001	0.77 ± 1.39	0.001	H(₂) = 19.0	< 0.001
Relapse incidence	7/12	0/13	0.004	1/12	0.027	–	–
Time to relapse onset (median day)	34.0	> 36.0	0.002	> 36.0	0.006	–	–
End score	2.38 ± 1.52	0.12 ± 0.22	< 0.001	0.69 ± 1.42	0.003	H₍₂₎ = 19.3	< 0.001
Relative end body weight (%)	87.1 ± 11.8	107.6 ± 7.8	< 0.001	103.8 ± 9.6	< 0.001	F_(2,36) = 15.9	< 0.001

Analyses were performed on all mice from the experiment shown in Fig. 2a. Unless otherwise stated, values are shown as mean ± SD. Percent relative end body weight is relative to body weight on Day-1. The 1st wave of EAE was determined to be from Day 9 through 30, and the 2nd wave (relapse period) from Day 31 through 36. Significance for incidence and relapse incidence was tested using two-sided Fisher’s exact tests with p values adjusted for multiplicity using the Holm-Sidak approach. Significance for time to onset and time to relapse onset was tested using Gehan–Breslow–Wilcoxon tests between groups with p values adjusted for multiplicity using the Holm-Sidak approach. Significance for maximum score and end score was tested using Kruskal–Wallis tests followed by Dunn’s multiple comparisons tests. Significance for percent relative end body weight was tested using a one-way ANOVA followed by Dunnett's multiple comparisons test. Bold p values indicate a significant difference vs. the Vehicle group

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