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The chronic migraine preventive, despite falling short of efficacy end points, was safe and well-tolerated in a small cohort of patients aged 12 to 17 years.
Paul K Winner, DO
Despite failing to meet its efficacy end points, onabotulinumtoxinA (Botox, Allergan) was deemed well-tolerated in an adolescent population with chronic migraine, with prior data in the adult population providing enough to push for additional, modified study in adolescents.
All told, none of the 125-patient cohort discontinued treatment due to adverse events (AEs), with no serious adverse events (n = 3) considered related to treatment. All 3 resolved without sequelae. The most commonly reported treatment‐emergent AEs were neck pain (n = 8), upper respiratory tract infection (n = 7), migraine, and nasopharyngitis (n = 5 each).
The primary reason for discontinuing was a lack of efficacy, which occurred in 3.2% of patients (n = 4).
The work was conducted by Paul K. Winner, DO, director, Premiere Research Institute and the Palm Beach Headache Center, attending neurologist, Palm Beach Neurology, and clinical professor of neurology, Nova Southeastern University, and colleagues. “Additional studies with design modifications, including adequate statistical power, to assess the efficacy of multiple treatment cycles of onabotulinumtoxinA for CM prevention in adolescents may be informative,” they concluded.
OnabotulinumtoxinA was originally approved for the prevention of chronic migraine in adult patients in 2010.
The trial (NCT01662492) was a multicenter, double‐blind, parallel‐group, randomized trial evaluating a single dose of onabotulinumtoxinA, at either 155 U (n = 45) or 74 U (n = 43), compared to placebo (n = 37) patients aged 12 to <18 years. The primary efficacy outcome was the frequency of headache days from baseline at week 12; additional assessments included the change in frequency of headache days at weeks 4 and 8, and of severe headache days.
All of the treatments assessed ultimately reduced the frequency of headache days by week 12, with no significance between arms. The mean changes from baseline in the frequency of headache days were −6.3 days (95% CI, −8.5 to −4.2) for the 155 U dose, −6.4 days (95% CI, −8.8 to −4.0) for the 74 U dose, and −6.8 days (95% CI, −9.6 to −4.1) for the placebo group, respectively (P ≥ .474).
Treatment‐related AEs were reported by 23% (n = 10) patients in the 155 U group, 16% (n = 7) in the 74 U group, and 11% (n = 4) in the placebo group. The majority were mild in severity in the 155 U (n = 8; 80%) and 74 U (n = 5; 71%) groups, and mild for 50% (n = 2) in the placebo group.
“In adolescents, migraine is often undiagnosed or misdiagnosed and can present unique management challenges,” Winner and colleagues wrote. The authors noted that additionally, there are unique challenges to assessing migraine agents in this population in clinical trials, as well. In placebo-controlled trials in children and adolescents with migraine, placebo response levels have consistently been higher than observed with adults.
Winner and colleagues detailed that going forward, study design adjustments may be able to address this challenge, at least in part. They suggested assessing efficacy with larger sample sizes than what was planned for adult clinical trials, as well as allowing the identification and exclusion of placebo responders prior to randomization.
“Therefore, to fully assess the benefits of treatment in adolescents, we suggest that future pediatric trials evaluate at least 2 treatment cycles of onabotulinumtoxinA, enroll larger numbers of patients, and explore the use of a placebo run‐in or crossover design,” they wrote.
Winner PK, Kabbouche M, Yonker M, Wangsadipura V, Lum A, Brin MF. A Randomized Trial to Evaluate OnabotulinumtoxinA for Prevention of Headaches in Adolescents With Chronic Migraine. Headache. Published online February 9, 2020. doi: 10.1111/head.13754.