Effects of onabotulinumtoxinA treatment in patients with and without allodynia: results of the COMPEL study

Abstract

BackgroundOnabotulinumtoxinA is effective in treating chronic migraine (CM), but there are limited data assessing how allodynia affects preventive treatment responses. This subanalysis of the 108-week, multicenter, open-label COMPEL Study assessed the efficacy and safety of onabotulinumtoxinA in people with CM with and without allodynia.MethodsPatients (n = 715) were treated with onabotulinumtoxinA 155 U every 12 weeks for 9 treatment cycles. The Allodynia Symptom Checklist was used to identify patients with allodynia (scores ≥3). The primary outcome for this subanalysis was reduction in monthly headache days from baseline for weeks 105 to 108 in groups with and without allodynia. Other outcomes included assessments of moderate to severe headache days, disability (using the Migraine Disability Assessment [MIDAS] questionnaire), and health-related quality of life (Migraine-Specific Quality-of-Life Questionnaire [MSQ] v2). Adverse events and their relation to treatment were recorded.ResultsOnabotulinumtoxinA was associated with a significant mean (SD) reduction in headache day frequency at week 108 relative to baseline in patients with (n = 289) and without (n = 426) allodynia (− 10.8 [7.1] and − 12.5 [7.4], respectively; both P < 0.001) that was significantly greater in patients without allodynia (P = 0.044 between-subgroup comparison). Moderate to severe headache days were significantly reduced at week 108 in patients with and without allodynia (− 9.6 [6.9] and − 10.5 [7.2]; both P < 0.001); reduction was similar between groups. MIDAS scores improved significantly at week 108 (− 53.0 [50.3] and − 37.7 [53.0]; both P < 0.001), with a significant between-group difference in favor of those with allodynia (P = 0.005). Similarly, MSQ subscale scores (Role Function Preventive, Role Function Restrictive, Emotional Function) significantly improved at week 108 for patients with and without allodynia: 20.6 (21.9) and 16.9 (20.7), 28.0 (23.3) and 24.7 (22.7), and 27.6 (26.5) and 24.9 (26.1), respectively (all P < 0.001). OnabotulinumtoxinA was well tolerated in patients with and without allodynia.ConclusionResults indicate that onabotulinumtoxinA is associated with reductions from baseline in multiple efficacy outcomes for up to 108 weeks whether or not allodynia is present. The allodynia group showed a smaller treatment response for reduction in headache days, but a similar or greater treatment response for improvement in other measures. No new safety concerns were identified.Electronic supplementary materialThe online version of this article (10.1186/s10194-018-0952-1) contains supplementary material, which is available to authorized users.

Photophobia and allodynia in persistent post-traumatic headache are associated with higher disease burden

“…In the clinical setting, sensory features in PTH are both prominent and clinically actionable (34) aspects of headache-related disease burden. Importantly, our data highlights the presence of multimodal sensory hypersensitivity in non-migraine type, as well as in migraine-like, PTH subjects (Figures 2 and 3(c)).…”

Mechanisms of Botulinum Toxin Type A Action on Pain

“…Another group found that the plasma level of CGRP was higher in responders compared to non-responders, and a decrease of CGRP by treatment could also be demonstrated [134,135]. On the other hand, the presence of cutaneous allodynia did not prove to be a predicting factor for the efficacy of BoNT/A, even though it is considered to reflect the presence of central sensitization [132,133,136]. A recent study on Korean patients also suggested that longer disease duration could be associated with a poorer response [137].…”

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 ]…”