Sustained reduction in chronic migraine with onabotulinumtoxinA

Continuous onabotulinumtoxinA treatment led to a sustained reduction in chronic migraine, according to pooled analysis of the double-blind and open-label phases of the PREEMPT* trial.

The findings were based on pooled analysis of the modified last observation carried forward (mLOCF) data from the PREEMPT trial (a 24-week, two onabotulinumtoxinA cycle [day 0 and week 12], double-blind, placebo-controlled phase, followed by a 32-week, three onabotulinumtoxinA cycle [weeks 24, 36, and 48], open-label phase). In the double-blind phase, 1,384 individuals with chronic migraine (15 monthly headache days [MHD]) were randomized to receive onabotulinumtoxinA (n=688) or placebo (n=696), a majority of whom proceeded to the open-label phase (607 and 629 in the onabotulinumtoxinA/onabotulinumtoxinA and placebo/onabotulinumtoxinA groups, respectively).

Reduction in MHD to <15 per month occurred in more patients on onabotulinumtoxinA compared with placebo during the last month of the double-blind phase (66.7 percent vs 59.1 percent; p=0.003) and at any 3 consecutive months of the double-blind phase (63.5 percent vs 54.2 percent; p<0.001), and/or treatment-controlled chronic migraine at the end of the double-blind phase (56.1 percent vs 49.1 percent; p=0.010).

Patients treated with onabotulinumtoxinA also had fewer MHDs during the last month of the double-blind phase than those treated with placebo (mean 7.2 vs 7.9; p=0.013) as well as fewer treatment-controlled chronic migraines at the end of the double-blind phase (mean 6.8 vs 7.4; p=0.017).

Among those who received onabotulinumtoxinA in the open-label phase, 81.1 percent experienced <15 MHDs during the last month (mean 5.6 MHDs), 79.4 percent at any 3 consecutive months of the entire study (mean 8.1 MHDs), and/or 60.9 percent sustained treatment-controlled chronic migraine for the entire open-label phase (mean 5.0 MHDs).

Fewer consecutive headache days

In a separate post hoc pooled analysis of the two identically designed PREEMPT trials, long-term treatment with onabotulinumtoxinA also reduced the number of consecutive headache-free days in individuals with chronic migraine.

“PREEMPT study patients treated with onabotulinumtoxinA experienced more consecutive days without moderate/severe headache or migraine/probable migraine compared with placebo at week 24, and the benefits were sustained throughout the entire 56 weeks of the study,” noted the researchers.

Participants used headache diaries to document their consecutive days without moderate/severe headache or migraine/probable migraine, with a headache day defined as a headache lasting ≥4 continuous hours/day. At baseline (28-day screening phase), mean number of headache days was comparable between patients in the onabotulinumtoxinA and placebo groups (19.9 vs 19.8; p=0.498).

At week 24, the number of consecutive days without moderate/severe headache was greater among onabotulinumtoxinA vs placebo recipients (mean 22.5 vs 18.5), as was the number of consecutive days without migraine/probable migraine (mean 21.6 vs 17.6; p<0.01 for both).

The results remained in favour of onabotulinumtoxinA at week 56, where patients who received onabotulinumtoxinA in both phases had more consecutive headache-free days than those who received placebo in the double-blind phase and onabotulinumtoxinA in the open-label phase (mean 46.7 vs 40.4 [moderate/severe headache] and mean 45.7 vs 38.9 [migraine/probable migraine]).

“An increased number of consecutive days without headache as a result of long-term onabotulinumtoxinA treatment has the potential to improve the daily lives of patients with chronic migraine. These data support the long-term benefits associated with the use of onabotulinumtoxinA for treatment of chronic migraine in clinical practice,” said the researchers.