A two-year observational study has confirmed the real-world safety and efficacy of higher-dose onabotulinumtoxinA for adults suffering from chronic migraine, providing valuable evidence that supports dosing flexibility in clinical practice.
The REPOSE study (NCT01686581), a prospective, observational trial conducted across 77 European centers, evaluated the effectiveness of onabotulinumtoxinA doses ranging from 155 U to 195 U in 641 enrolled participants with chronic migraine. The findings align with previous phase 3 PREEMPT clinical trials that established this dosing range as the licensed standard in Canada and Europe.
Significant Reduction in Headache Frequency
Patients receiving the higher dose range of 156-195 U experienced substantial reductions in monthly headache days (MHDs), with decreases ranging from 8.7 to 14.2 days from baseline. This compared favorably with the standard 155 U dose group, which showed reductions of 8.2 to 11.9 MHDs.
Dr. Andrew Blumenfeld, Director of The Headache Center of Southern California and a leading researcher in migraine treatments, noted, "These real-world findings are particularly valuable as they confirm what many clinicians have observed in practice—that some patients benefit from slightly higher doses within the approved range."
Quality of Life Improvements
The study measured patient outcomes using the Migraine-Specific Quality of Life Questionnaire (MSQ), which assesses the impact of migraine on daily functioning. Both dosing groups demonstrated meaningful improvements in MSQ domain scores across treatment visits, indicating enhanced quality of life with continued treatment.
"Chronic migraine significantly impairs patients' ability to function in daily life, affecting work productivity, social interactions, and overall wellbeing," explained Dr. Blumenfeld. "The consistent improvements in quality of life metrics observed in this study represent meaningful clinical benefits for patients."
Safety Profile Consistent with Previous Findings
The safety analysis revealed that higher doses maintained a favorable safety profile comparable to the standard dose. Among the 77 participants who received 156-195 U for four or more treatment visits, only 10 (13%) reported adverse drug reactions (ADRs), compared to 51 of 218 participants (23%) in the 155 U group.
The most commonly reported ADRs across both dosing groups were eyelid ptosis, neck pain, and musculoskeletal stiffness. Serious adverse drug reactions were rare, occurring in only 1 of 77 participants (1.3%) in the higher-dose group and 3 of 218 (1.4%) in the standard-dose group.
Study Design and Patient Population
REPOSE was designed as a noninterventional, open-label study that followed patients for 24 months after initiating treatment. Participants received onabotulinumtoxinA approximately every 12 weeks, with data collection occurring at each treatment visit.
For analysis purposes, participants were stratified into two groups based on the dosage received at four or more treatment visits: those receiving the standard 155 U dose and those receiving 156-195 U. Baseline characteristics were similar between the two groups, allowing for meaningful comparisons of outcomes.
Clinical Implications for Migraine Management
Chronic migraine, defined as headache occurring on 15 or more days per month for more than three months, affects approximately 2% of the global population. The condition places substantial burden on healthcare systems and significantly impairs patients' quality of life.
"The REPOSE study provides reassurance to clinicians that the approved dosing range of 155-195 U offers flexibility to tailor treatment to individual patient needs without compromising safety," said Dr. Blumenfeld. "This is particularly important for patients who may not achieve optimal response at the lower end of the dosing range."
Future Directions
While the REPOSE study provides valuable real-world evidence supporting the current dosing paradigm, researchers note that further investigation into personalized dosing strategies could help optimize outcomes for individual patients.
The study authors concluded that these real-world findings of the safety and efficacy of 155-195 U onabotulinumtoxinA doses are consistent with data from the PREEMPT clinical trials, confirming its role as an important treatment option for patients with chronic migraine in everyday clinical practice.
