A reduction in HIT-6 scores of more than 2.5 points is considered to represent clinically significant improvement in migraine-related disability. At week 6, the HIT-6 score had fallen by an average of 4.0 points from baseline in the onabotulinumtoxinA group, compared with –2.2 points with topiramate. At week 18, the margin of improvement was –5.1 versus –1.6 points, while at week 36 the average improvement was –5.6 points in the onabotulinumtoxinA group, compared with –1.4 points in the topiramate arm in a last-observation-carried-forward analysis.
Mean baseline scores on the WPAI-SHP were 4.8 in the onabotulinumtoxinA group and 5.1 in those on topiramate. At week 12, the scores had improved to 3.3 and 4.4, respectively, and at week 36, to 3.5 and 4.4, respectively, a significant and clinically meaningful difference.
Mean baseline scores on the FIMQ were 59.8 and 53.9 in the onabotulinumtoxinA and topiramate groups. By week 30, the scores were 37.1 and 47.5, respectively.
The main reasons half of the topiramate patients discontinued were the adverse events classically associated with the drug: paresthesia, cognitive impairment, nausea, and fatigue. None of these were reported by more than 0.5% of onabotulinumtoxinA recipients.
This is not the first study to show superior outcomes with neurotoxin therapy for the prevention of chronic migraine.
“There is a disconnect between the published data and what happens in the community,” Dr. Blumenfeld observed. “In clinical practice, topiramate is listed as first-line therapy for chronic migraine, while onabotulinumtoxinA is third or fourth line.”
Insurers normally balk at covering neurotoxin therapy because it is relatively expensive. But in an era when PROs have taken on new weight with regulatory agencies and payers, the ground may be soon be shifting.
One audience member noted that in the relatively small subgroup of patients who could tolerate topiramate sufficiently to stay on the drug, the outcomes were quite good. Dr. Blumenfeld concurred.
“It’s something that we all see in clinical practice: Those patients who can stay on topiramate, who can tolerate it, do very well. So for the 17 of 25 who stayed on it and had a 50% reduction in headache days, that 68% is a good number, and I think it matches our clinical experience,” he said. “But the key message of this study – and I think this is a different way of looking at the way we assess medications – is to look at efficacy, but also at tolerability and long-term adherence. And the problem with topiramate-treated patients, particularly in chronic migraine, is they have a difficult time staying on the medication long enough to see that good effect.”
The FORWARD trial was sponsored by Allergan. Dr. Blumenfeld serves as a consultant to that company and a half-dozen others.
SOURCE: Blumenfeld AM et al. Headache. 2018 Jun;58(52):75. Abstract IOR06.