BERLIN – Rizatriptan fought migraine more effectively in children and adolescents when it was dosed according to body weight in a randomized, double-blind parallel group trial.
Previous industry-sponsored rizatriptan studies in children revealed no significant treatment effects, Dr. Tony W. Ho said. For example, in one study of 291 adolescents, the 2-hour response rate was 66% with treatment versus 56% with placebo. The lack of significant efficacy could be due to all patients receiving the same 5-mg tablets, a dose that can be insufficient given the increase in body mass index among 12- to 17-year-olds, he added.
"If you think about it, many adolescents are as heavy as some adults nowadays but may receive a lower dose," said Dr. Ho, a researcher at Merck Sharp & Dohme Corp., Whitehouse Station, N.J., a subsidiary of Merck & Co., which markets rizatriptan as Maxalt.
In the current study, Dr. Ho and his associates tried weight-based dosing in children aged 12-17 years with a history of moderate to severe attacks. Those who weighed less than 40 kg received 5-mg of rizatriptan orally disintegrating tablets (ODT; Maxalt-MLT), and those 40 kg or heavier received 10 mg within 30 minutes of a moderate to severe attack.
"These teenagers were heavier than we expected, with a mean BMI of 22.6 [kg/m2]. The majority of patients were from the U.S.," Dr. Ho said at the International Headache Congress, which was sponsored by the International Headache Society and the American Headache Society.
A total 570 of the 702 participants were evaluable for efficacy analyses and were studied further. The researchers found 31% of the treatment group (87 of 284 participants) reported freedom from pain at 2 hours (the primary outcome), compared with 22% (63 of 286) of the placebo group. The odds ratio favoring rizatriptan was 1.55. Patients rated their pain from 1 (a happy face meaning no head pain) up to 5 (a frowning face reflecting very bad head pain).
"Weight-based rizatriptan ODT treatment demonstrated a statistically significant difference versus placebo in eliminating pain," Dr. Ho said.
The study featured a double-blind, run-in phase design. "Even with a design to reduce the placebo effect, we still had a 22% rate," Dr. Ho said.
Patients randomized to rizatriptan also experienced significantly less nausea, vomiting, and impairment of activities of daily living, compared with those who received placebo, Dr. Ho said. "This supports a weight-based approach to treating pediatric migraine."
A meeting attendee questioned the incidence of vomiting reported in the study, stating that "usually the rate of severe vomiting is 60%-70%, but you had lower than 15%."
The children rated severity of associated symptoms, including vomiting, using a five-face scale, Dr. Ho replied. "I don’t know how that is related to other definitions of severity."
There was no statistically significant difference in 2-hour pain relief, a secondary outcome experienced by 59% of the treated group and 51% of the placebo group.
Rizatriptan use is off label in pediatric patients. The Food and Drug Administration cleared this selective 5-hydroxytryptamine1B/1D receptor agonist for acute treatment of migraine attacks with or without aura in adults 18 years and older.
Rizatriptan was generally well tolerated, Dr. Ho said. The overall adverse event rate within 14 days was 24% in the treatment group and 23% in the placebo group.
Of the 702 patients enrolled, 91% were female. All participants had a history of migraine (with or without aura) for at least 6 months. They also reported one to eight moderate to severe migraine attacks per month and a lack of satisfactory relief with the use of nonsteroidal anti-inflammatory drugs.
Dr. Ho said additional data on children 6 years and older are forthcoming.