Effects of onabotulinumtoxinA treatment in chronic migraine patients with and without daily headache at baseline: results from the COMPEL Study

Abstract

BackgroundOnabotulinumtoxinA is effective in preventing chronic migraine (CM); however, the benefit of onabotulinumtoxinA in patients with CM with daily headache is unknown because these patients are typically excluded from clinical trials. This subanalysis of the COMPEL Study assessed the efficacy and safety of onabotulinumtoxinA in people with CM with and without daily headache.MethodsIn total, 715 patients received onabotulinumtoxinA 155 U with or without concomitant oral preventive treatment. Patients who had complete daily diary records for the 28 days of the baseline period were stratified based on daily headache status. The primary outcome variable was reduction in headache-day frequency per 28-day period at 108 weeks (after 9 treatment cycles) relative to baseline. Exploratory outcomes included moderate to severe headache days, migraine disability (using the Migraine Disability Assessment [MIDAS] questionnaire), and health-related quality of life (Migraine-Specific Quality-of-Life Questionnaire v2 [MSQ]). Adverse events and their relatedness were recorded.ResultsOverall, 641 patients had complete daily diary records at baseline. In patients with daily headache (n = 138) versus without (n = 503), treatment with onabotulinumtoxinA was associated with a significant mean (SD) reduction in 28-day headache-day frequency relative to baseline at week 108 (− 10.5 [9.2] vs − 12.2 [6.7], respectively; both P < 0.001) with no significant between-group difference (P = 0.132). The mean (SD) reduction in moderate to severe headache days at week 108 was significant in patients with and without daily headache (− 11.5 [9.4] and − 9.9 [6.4]; P < 0.001) with no significant between-group difference (P = 0.153). Mean (SD) MIDAS scores significantly improved from baseline at week 108 (− 43.3 [73.4] and − 43.6 [46.7]; both P < 0.001), with no significant between-group difference (P = 0.962). Similarly, mean (SD) MSQ subscale scores significantly improved from baseline at week 108 for patients with and without daily headache. OnabotulinumtoxinA was well tolerated in patients with and without daily headache.ConclusionResults indicate that onabotulinumtoxinA is associated with reductions from baseline in headache-day frequency and improvements in disability and quality of life for up to 108 weeks in people with CM with daily headache; however, a longer duration of treatment was required to fully realize the treatment effect on headache. No new safety concerns were identified.Electronic supplementary materialThe online version of this article (10.1186/s10194-018-0953-0) contains supplementary material, which is available to authorized users.

Effectiveness, Safety, and Health-Related Quality of Life of Chronic Migraine Patients Treated with Onabotulinum Toxin A

“…In addition, our data support strong clinically and statistically significant associations between health-related quality of life in patients with CM and BONT-A. The results from this real-world study are consistent with the efficacy and safety profile of BNT-A established in clinical trials [4, 7] and other studies [9-11]. All these factors require the patient and physician to have a good understanding of the disease, its course, and to work together to achieve the best outcome.…”

“…At baseline, the median (Q1-Q3) number of migraine days was 12 (10)(11)(12)(13)(14)(15). The number of median migraine days reduced to 8 (6-9) at 6 months (p < 0.001) and to 5 (4-7) at 12 months (p < 0.001) ( Table 1).…”

OnabotulinumtoxinA in Chronic Migraine: A Profile of Its Use

“…In other analyses of BoNT/A efficacy in COMPEL [ 16 , 27 – 37 ] (post hoc [ 27 , 35 , 36 ], where stated): Assessments of migraine-related disability (MIDAS score) [ 28 ] and migraine-specific HR-QOL (all three MSQ domain scores) were improved ( p < 0.0001 vs baseline) at week 108 [ 28 ] Comorbid symptoms of depression [measured using the 9-item Patient Health Questionnaire (PHQ-9)] and anxiety (7-item Generalized Anxiety Disorder Assessment), and associated symptoms of sleep disturbance (Pittsburgh Sleep Quality Index) and fatigue (Fatigue Severity Scale), were improved ( p < 0.0001 vs baseline) at week 108; similar improvements were seen at all earlier assessments [ 29 ] Assessments of headache symptoms [ 16 , 30 – 34 ], headache-related impact (HIT-6 score) [ 16 , 30 , 33 ], migraine-related disability (MIDAS score) [ 31 , 32 , 34 ] and migraine-specific HR-QOL (all three MSQ domain scores) [ 32 , 34 ] were improved to a similar extent in patients with or without a history of acute medication overuse [ 30 , 31 ], those receiving or not receiving oral preventive treatments at baseline [ 16 ], those with or without daily headaches at baseline [ 32 , 33 ], and those with or without allodynia at baseline [ 34 ] The proportion of monthly headache-day frequency responders progressively increased over the course of the study (47%, 54%, 57% and 62% at weeks 24, 60, 84, 108, respectively). Among patients who completed all nine treatment cycles, a high proportion (76%) of monthly headache-day frequency responders at week 24 maintained this response through week 108 [ 35 ] Responder rates at week 108 were 62% for monthly headache-day frequency, 59% for HIT-6 score, 75% for MIDAS score and 66% for MSQ RR domain score; 87%, 72%, 52% and 27% of patients achieved at least one, at least two, at least three or all four of these outcomes, respectively [ 27 ] The proportion of patients who achieved treatment-controlled CM (defined as < 15 headache days/month in any of the 4-week periods ending at weeks 24, 60, 84 and 108) was high and increased progressively over the course of the study (56%, 69%, 70% and 74% at weeks 24, 60, 84 and 108, respectively) [ 36 ] Sustained treatment-controlled CM (defined as &...…”

“…Assessments of headache symptoms [ 16 , 30 – 34 ], headache-related impact (HIT-6 score) [ 16 , 30 , 33 ], migraine-related disability (MIDAS score) [ 31 , 32 , 34 ] and migraine-specific HR-QOL (all three MSQ domain scores) [ 32 , 34 ] were improved to a similar extent in patients with or without a history of acute medication overuse [ 30 , 31 ], those receiving or not receiving oral preventive treatments at baseline [ 16 ], those with or without daily headaches at baseline [ 32 , 33 ], and those with or without allodynia at baseline [ 34 ]…”

Botulinum Toxin in the Treatment of Headache

“…The COMPEL study, a large long-term open-label study funded by Allergan, further explored the type of chronic migraine patient who responded to OBTA. It found that in the long term, patients with daily headache had a very similar reduction in the number of moderate or severe headache days per month as patients without daily headache at baseline [ 22 ].…”