SAN FRANCISCO – The odds of at least a 50% reduction in headache days per month in chronic migraine patients 32 weeks after randomization to onabotulinumtoxinA for prophylaxis were 394% greater than with topiramate in the multicenter, open-label FORWARD trial, Andrew M. Blumenfeld, MD, reported at the annual meeting of the American Headache Society.
Bruce Jancin/MDedge News
Dr. Andrew M. Blumenfeld
“Impressively, onabotulinumtoxinA showed a more favorable effect on depressive symptoms,” he added. “The overall results suggest that the beneficial effects of onabotulinumtoxinA on a range of PROs may lead to improved adherence.”
The FORWARD trial was a multicenter, open-label, prospective, 36-week study which randomized 282 adult chronic migraine patients to fixed-dose onabotulinumtoxinA at the approved dose of 155 U every 12 weeks or to topiramate (Topamax) titrated over the course of 12 weeks to the approved dose of 50-100 mg/day. However, after 12 weeks on topiramate, patients could elect to discontinue the drug and switch to onabotulinumtoxinA.
This was a trial designed to evaluate effectiveness, which Dr. Blumenfeld defined as the combination of efficacy plus treatment adherence. And treatment adherence with topiramate was poor: 63% of patients discontinued that medication, mainly because of adverse events or lack of efficacy, compared with just 7.9% of the onabotulinumtoxinA group.
The primary endpoint was the proportion of patients who achieved at least a 50% reduction in headache days per month beginning at week 32, compared with their rate during 4 weeks at baseline. Of 142 patients randomized to topiramate, 25 completed 36 weeks of therapy, and 17 of those 25 (68%) achieved at least a 50% reduction in headache days per month. That’s one way to look at it. The other is to examine effectiveness: 17 of 142 topiramate-treated patients (12%) met the primary endpoint. In contrast, 99 of 140 patients assigned to onabotulinumtoxinA completed treatment, and 56 of those 99 (57%) met the primary endpoint. Thus, the neurotoxin therapy had a 40% effectiveness rate. The odds of being at least a 50% responder were 394% greater in the onabotulinumtoxinA group, according to Dr. Blumenfeld.
Secondary endpoints consisted of four PROs: the Headache Impact Test of migraine-related disability (HIT-6), the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP), the Patient Health Questionnaire–9 (PHQ-9), and a cutting edge, not yet fully validated instrument known as the Functional Impact of Migraine Questionnaire, or FIMQ.
The onabotulinumtoxinA group fared significantly better than the topiramate group on all four PROs. But Dr. Blumenfeld singled out the PHQ-9 results as of particular clinical importance. A score of 5 or more is considered evidence of at least mild depression; on average, both groups were depressed at baseline, with a mean score of 6.5 in the onabotulinumtoxinA group and 7.6 in the topiramate group. At week 12, the scores were 5.2 and 6.7, respectively. At week 24, 4.5 versus 7.2. At week 36, the average PHQ-9 score in the onabotulinumtoxinA group was 4.4 – meaning no depression – compared with 7.1 in the topiramate group.