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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.
“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.
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.
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.
“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.
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.
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.
“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.
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.
REPORTING FROM THE AHS ANNUAL MEETING
Key clinical point:
Major finding: The likelihood of at least a 50% reduction in headache days per month in chronic migraine patients during weeks 29-32 versus baseline was nearly 400% greater in those randomized to onabotulinumtoxinA than to topiramate.
Study details: The FORWARD trial was a randomized, multicenter, open-label, 36-week study in 282 chronic migraine patients.
Disclosures: FORWARD was sponsored by Allergan. The presenter 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.