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

Table 2 Clinical outcomes of late therapeutic ibrutinib treatment in EAE Biozzi mice

	Experiment 1			Experiment 2			Experiment 3
Readout	Vehicle (n = 18)	Ibrutinib Day 49 (n = 18)	Test statistic_(d.f.) (p value)	Vehicle (n = 10)	Ibrutinib Day 49 (n = 10)	Test statistic_(d.f.) (p value)	Vehicle (n = 13)	Ibrutinib Day 49 (n = 13)	Test statistic_(d.f.) (p value)
Balanced for enrollment
Day of onset	14.9 ± 2.0	14.7 ± 1.7	–	14.6 ± 2.5	14.4 ± 1.3	–	13.7 ± 1.2	13.9 ± 1.4	–
Score at onset	1.11 ± 0.72	1.25 ± 0.69	–	1.05 ± 0.72	1.10 ± 0.57	–	1.31 ± 0.66	1.27 ± 0.75	–
Score at enrollment	2.33 ± 0.42	2.31 ± 0.49	–	2.10 ± 0.66	2.10 ± 0.52	–	1.69 ± 0.48	1.65 ± 0.38	–
Maximum score through Day 49	3.25 ± 0.26	3.28 ± 0.31	–	3.25 ± 0.35	3.20 ± 0.48	–	3.65 ± 0.69	4.12 ± 0.87	–
Readouts of efficacy
Efficacy period maximum score	2.86 ± 0.45	2.47 ± 0.44	U = 93 (0.023)	2.80 ± 0.86	2.30 ± 0.35	U = 30 (0.131)	2.42 ± 0.73	1.67 ± 0.44	U = 29 (0.009)
End score	2.56 ± 0.48	2.14 ± 0.64	U = 100 (0.042)	2.55 ± 0.93	2.05 ± 0.60	U = 34 (0.197)	2.04 ± 0.86	1.50 ± 0.48	U = 43 (0.088)
Relative end body weight (%)	94.5 ± 13.4	101.9 ± 11.8	t₍₃₄₎ = 1.74 (0.091)	99.0 ± 14.7	103.2 ± 13.3	t₍₁₈₎ = 0.659 (0.518)	100.0 ± 16.6	109.8 ± 6.1	t₍₂₄₎ = 1.91 (0.069)

Analyses were performed on all mice from the experiments shown in Fig. 4. Values are shown as mean ± SD. Percent relative end body weight is relative to body weight on Day -1 (Experiment 1) or Day 0 (Experiments 2 and 3). Significance for efficacy period (period starting 15 days after treatment onset, i.e., Day 64, through study termination) maximum score and end score was tested using two-tailed Mann–Whitney tests. Significance for percent relative end body weight was tested using a two-tailed unpaired t test. Bold p values indicate a significant difference vs. the Vehicle group

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