Table 1.

Efficacy of intramuscular onabotulinumtoxinA (Botox^®) for prevention of headaches in adults with chronic migraine. Intent-to-treat results from the multicentre PREEMPT 1 [38] and 2 [39] studies and pooled analyses [40, 41, 49] of these trials

	Week 24a						Week 56a
	PREEMPT 1 [38]		PREEMPT 2 [39]		Pooled analysis [40, 41, 49]		Pooled analysis [41]
	OnabotA (n = 341)	PL (n = 338)	OnabotA (n = 347)	PL (n = 358)	OnabotAb (n = 688)	PLb (n = 696)	OnabotA → onabotAb (n = 688)	PL → onabotAb (n = 696)
HA days/monthc	− 7.8**	− 6.4	− 9.0***d	− 6.7d	− 8.4***d	− 6.6d	− 11.7*d	− 10.8d
Moderate to severe HA days/monthc	− 7.2**	− 5.8	− 8.3***	− 5.8	− 7.7***	− 5.8	− 10.7*	− 9.9
Cumulative h of HA on HA days/monthc	− 106.7**	− 70.4	− 132.4***	− 90.0	− 119.7***	− 80.5	− 169.1*	− 145.7
HA episodes/monthc	− 5.2d	− 5.3d	− 5.3**	− 4.6	− 5.2**	− 4.9	− 7.4	− 7.5
Migraine days/monthc,e	− 7.6**	− 6.1	− 8.7***	− 6.3	− 8.2***	− 6.2	− 11.2*	− 10.3
Migraine episodes/monthc	− 4.8	− 4.9	− 4.9**f	− 4.2f	− 4.9**	− 4.5	− 6.8	− 7.0
Acute HA pain medication intakes/monthc	− 10.3	− 10.4	− 9.9	− 8.4	− 10.1	− 9.4	− 15.4	− 15.7
Acute HA pain medication intake days/monthc	− 5.7f	− 5.8f	− 6.4***f	− 4.8f	− 6.1*	− 5.3	− 8.4	− 8.5
Triptan medication intakes/monthc	− 3.3*	− 2.5	− 3.0***	− 1.7	− 3.2***	− 2.1	− 4.2	− 3.8
HIT-6 scorec,g	− 4.7***	− 2.4	− 4.9***	− 2.4	− 4.8***	– 2.4	− 7.7	− 7.0
Pts with severe HIT-6 scoreg (%)	68.9***	79.9	66.3**	76.5	67.6***	78.2	50.6	51.9
MSQ RR subscale scorec,h	16.8***f	8.8f	17.2***f	8.4f	17.0***	8.6	25.2*	21.8
MSQ RP subscale scorec,h	12.6**f	7.6f	13.5***f	5.4f	13.1***	6.4	19.0	17.3
MSQ EF subscale scorec,h	16.9***f	10.0f	19.0***f	9.1f	17.9***	9.5	25.0	22.1

EF emotional functioning, HA headache, HIT-6 Headache Impact Test-6, MID minimal important difference, MSQ Migraine-Specific Quality-of-Life Questionnaire (v2.1), OnabotA onabotulinumtoxinA, PL placebo, pts patients, RP role preventive, RR role restrictive

*p < 0.05, **p < 0.01, ***p ≤ 0.001 vs (corresponding) PL

^aResults at week 24 (end of the double-blind phase) and week 56 (end of the open-label phase) were assessed over a 4-week period ending at week 24 and week 56, respectively

^bOf the 688 pts originally randomized to onabotA in the double-blind phase, 607 entered the open-label phase (and continued to receive onabotA). Of the 696 pts originally randomized to PL in the double-blind phase, 629 entered the open-label phase (and crossed over to receive onabotA)

^cMean change from baseline (week 0) (values at baseline were assessed over the prior 4-week period)

^dPrimary efficacy endpoint

^eDefinite or probable migraine days or episodes

^fData derived from the Medicines and Healthcare Products Regulatory Agency UK public assessment report [37]

^gScore of ≥ 60 indicates a severe impact. The established clinically meaningful MID (between-group) is 2.3; the established clinically meaningful MID from baseline (within-group) is − 5

^hOn a 0–100 scale, with higher scores indicating better health-related quality of life. The established clinically meaningful MIDs (between-group) are 3.2, 4.6 and 7.5 for the RR, RP and EF subscales, respectively; the established clinically meaningful MIDs from baseline (within-group) are 10.9, 8.3 and 12.2 for the RR, RP and EF subscales, respectively