The future is looking more clear and less painful for migraineurs and the clinicians who treat them. Complete results from 2 phase 3 trials examining the effects of 2 humanized monoclonal antibodies in patients with episodic and chronic migraine were published simultaneously in the New England Journal of Medicine. Data from both studies showed significant improvements in migraine frequency, and demonstrated positive effects on quality of life and use of migraine prophylaxis.
The first study, led by Stephen D. Silberstein, MD, of Thomas Jefferson University in Philadelphia, and colleagues, examined the preventive effects of quarterly or monthly subcutaneous injection of fremanezumab (675 mg) in patients with chronic migraine (defined as any headache ≥15 days/month or migraine ≥8 days/month).
The study enrolled 1130 patients, of which 376 were randomly assigned to receive fremanezumab quarterly, 379 monthly, and 375 to placebo. Average headache days per month were 13.2, 12.8, and 13.3, respectively.
Mean reduction in average number of headache days per month was 4.3±0.3 in the quarterly group; 4.6±0.3 in the monthly group; and 2.5±0.3 in the placebo group (P <.001 for both when compared with placebo). The percent of patients who experienced ≥50% reduction in average headache days per month was 38% in the quarterly group, 41% in the monthly group, and 18% in the placebo group (P <.001 for both when compared with placebo).
Adverse events were reported in 70% and 71% of patients receiving fremanezumab quarterly and monthly, respectively, and 64% in the placebo group; most of which were graded as mild to moderate in severity. Injection site reactions were reported in 47% of patients in the treatment arms compared with 40% in the placebo group, with injection-site pain the most commonly reported adverse event. Notably, the researchers reported 10 cases of abnormal hepatic function in the treatment arms and 3 cases in the placebo group. Most cases were transient and reverted to normal levels without trial discontinuation. The researchers noted that all patients with elevated liver enzymes had a history of nonsteroidal anti-inflammatory drug, acetaminophen, or antidepressant usage.
The second study examined a similar monoclonal antibody, erenumab, for the prevention of episodic migraine.
Researchers, led by Peter J. Goadsby, MD, PhD, of King’s College Hospital, London, United Kingdom, randomly assigned 955 patients with episodic migraine to receive subcutaneous injections of 70 mg erenumab (n=317), 140 mg erenumab (n=319), or placebo (n=319) monthly for 6 months. Endpoints included change in mean number of migraine days per month, ≥50% reduction in mean migraine days per month, change in number of days using migraine medication, and change in domains measuring physical impairment and everyday activities indicative of migraine burden.
Overall, the mean number of migraine days per month at baseline was 8.3; by months 4-6, the reduction in mean number of migraine days was 3.2 in the 70 mg group, 3.7 in the 140 mg group, and 1.8 in the placebo group (P <.001 for both when compared with placebo). Fifty percent of patients in the 140 mg group experienced a ≥50% reduction in mean number of migraine days per month, compared with 43.3% in the 70 mg group and 26.6% in the placebo group (P <.001 for both when compared with placebo). Reductions in the use of migraine-specific medication were 1.1 days in the 70 mg group, 1.6 days in the 140 mg group, and 0.2 days in the placebo group (P <.001 for both when compared with placebo).
Physical impairment and everyday activities scores on the Migraine Physical Function Impact Diary scale improved by 4.2 and 5.5, and 4.8 and 5.9 points, respectively, in the 70 and 140 mg groups, compared with 2.4 and 3.3 points in the placebo group.
Over 90% of patients randomly assigned to receive erenumab received all 6 doses. Frequency and severity of adverse events were similar across both treatment groups and placebo; however, injection-site pain was more commonly reported in the 70 mg treatment group than placebo.
The researchers noted that treatment response was recorded as early as month 1 in the treatment arms, and that the overall reduction in migraine days translated to a reduced effect of migraine on patients.
Future trials will examine long-term safety and efficacy of both treatments. Both erenumab and fremanezumab are currently under review by the FDA.
Disclosures: Fremanezumab trial was funded by Teva Pharmaceuticals; theerenumab trial was funded by Amgen and Novartis.
- Silberstein SD, Dodick DW, Bigal ME, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017;377:2113-2122.
- Goadsby PJ, Reuter U, Hallstrom Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377:2123-2132.