| Studies |
Year |
Country |
Population |
Participant |
Method |
Intervention |
Results |
| PREEMPT1 |
2010 |
North America sites |
Men or women aged 18–65 years with a history of CM meeting the diagnostic criteria listed in ICHD-II, with the exception of complicated migraine (hemiplegic migraine, basilar-type migraine, ophthalmoplegic migraine, and migrainous infarction) were eligible. |
Onabotulinumtoxin A (n 341)
Mean age 41.2
Placebo (n 332)
Mean age 42.1 |
24-week, double-blind, parallel group, placebo-controlled phase. |
Subjects were randomized (1:1) to injections every 12 weeks of onabotulinumtoxin A (155-195 U) or placebo (2 cycles) |
The study showed a greater reduction in MHDs in the intervention group (−7.6 onabotulinumtoxinA vs −6.1 placebo P = 0.002, 95% CI −1.5 (−2.6 to 0.59)) |
| PREEMPT2 |
2010 |
66 Global sites (50 North America and 16 European) |
Men or women aged 18–65 years with a history of CM meeting the diagnostic criteria listed in ICHD-II, with the exception of complicated migraine (hemiplegic migraine, basilar type migraine, ophthalmoplegic migraine, migraineurs infarction) were eligible |
Onabotulinumtoxin A (n 347)
Mean age 41
Placebo (n 358)
Mean age 40.9 |
24-week, phase 3, double-blind, parallel group, placebo-controlled phase. |
Subjects were randomized (1:1) to injections every 12 weeks of onabotulinumtoxin A (155–195 U) or placebo (2 cycles) |
The study showed a greater reduction in MHDs in the intervention group (−8.7 days onabotulinumtoxinA vs −6.3 placebo, P < 0.01, 95% CI −2.4 (−3.31 to −1.36)) |
| Epitnezumab (PROMISE-2) |
2020 |
128 sites in 13 countries (USA, Spain, Ukraine, Russia, United Kingdom, Republic of Georgia, Hungary, Italy, Slovakia, Germany, Czech Republic, Denmark, and Belgium) |
Adults 18–65 years, with a diagnosis of CM at or before 50 years of age were eligible for participation if they had a history of CM for ≥12 months before screening and experienced ≥ 15 to ≤ 26 headache days and ≥ 8 migraine during the 28-day screening period. |
Eptinezumab 100 mg (n 356)
Mean age 41.0
Epitinezumab 300 mg (n 350)
Mean age 41.0
Placebo (n 366)
Mean age 39.6 |
Phase 3, multicenter, randomized double-blind, parallel group, placebo-controlled phase. The primary endpoint was change from baseline in MMDs over wk 1 to 12 |
Subjects were randomized to receive eptinezumab 100, 300 mg, or placebo (1:1:1) administered on day 0 and week 12. |
Epitinezumab 100 and 300 mg was associated with significant reductions in MMDs across weeks 1 to 12 compared with placebo (placebo −5.6, 100 mg −7.7, P < 0.01 vs placebo; 300 mg – 8.2, P < 0.01 vs placebo) |
| Erenumab |
2017 |
69 headache and clinical research centers in North America (Canada and USA) and Europe (Czech Republic, Denmark, Finland, Germany, Norway, Poland, Sweden, and United Kingdom) |
Men or women aged 18–65 years with a history of CM (with or without aura). Patient had to have migraine for 15 or more days per month, or 8 or more of those days were migraine days |
Erenumab 70 mg (n 191)
Mean age 41.4
Erenumab 140 mg (n 190)
Mean age 42.9
Placebo (n 286)
Mean age 42.1 |
Phase 2, multicenter, randomized double-blind, parallel group, placebo-controlled phase.
The primary endpoint was change from baseline in MMDs over weeks 1 to 12 |
Patients were randomly assigned (3:2:2) to subcutaneous placebo, erenumab 70 mg, or erenumab 140 mg |
Erenumab 70 and 140 mg reduce MMDs vs placebo (both doses −6.6 days vs placebo −4.2 days, difference −2.5, P < 0.01, 95% CI (−3.5 to −1.4) |
| Galcanezumab (REGAIN) |
2018 |
116 headache and clinical research in 12 countries (Argentina, Canada, Czech Republic, Germany, Israel, Italy, Mexico, the Netherlands, Spain, Taiwan, United Kingdom, and USA) |
Adults 18–65 years with CM meeting the diagnostic criteria listed in ICHD-II.
The continuation or start of any additional migraine preventive treatment was not permitted |
Galcanezumab 120 mg (n 278)
Mean age 39.6
Galcanezumab 240 mg (n 277)
Mean age 41.05
Placebo (n 555)
Mean age 41.5 |
Phase 3, multicenter, randomized double-blind, parallel group, placebo-controlled phase with 12 weeks. |
Randomized in a 1:1:2 ratio received a subcutaneous injection of galcanezumab 120 mg/month (after an initial loan of 240 mg) or 240 mg/month or placebo |
Both galcanezumab groups demonstrated a greater reduction in MHDs compared with placebo (P < 0.001; placebo −2.7; galcanezumab 120 mg −4.8; 240 mg −4.6) |
| Fremanezumab |
2017 |
132 sites in 9 countries |
Adults 18–70 years with CM meeting the diagnostic criteria listed in ICHD-II. |
Fremanezumab quarterly (n 376)
Mean age 42.0
Fremanezumab monthly (n 379)
Mean age 40.6
Placebo (n 375)
Mean age 41.4 |
Randomized double-blind, placebo-controlled phase with a screening visit, a 28-day preintervention period and a 12-week intervention period |
Randomized in a ratio 1:1:1 to receive fremanezumab quarterly (a single dose 675 mg at baseline and placebo at week 4 and 8), fremanezumab monthly (625 mg at baseline and 225 mg at week 4 and 8) or matching placebo |
There was a reduction in the average number of monthly MHDs with fremanezumab quarterly (4.9 days) and fremanezumab monthly (5.0) superior than with placebo (3.2) (P > 0.001 in both comparisons) |
| Topiramate |
2007 |
46 U.S. sites |
Adults 18–65 years with 15 or more headache days per month, at least half of those were migraine/migrainous headaches |
Topiramate 100 mg (153)
Mean age 37.8
Placebo (n 153)
Mean age 38.6 |
Randomized double-blind, placebo-controlled, multicenter study with 16 weeks of treatment |
Randomized 1:1 to receive topiramate 100 mg or placebo. An initial dose of topiramate 25 mg/d was titulated upward in weekly increments of 25 mg/d to a maximum 100 mg/d (or to the maximum tolerated dose) |
Topiramate treatment results in a statistically significant mean reduction of migraine and reduction of MHDs relative to baseline (topiramate −5.6 vs placebo −4.1; P = 0.032) |
