A Randomized Trial to Evaluate OnabotulinumtoxinA for Prevention of Headaches in Adolescents With Chronic Migraine

Abstract

Objective As a post‐approval commitment, this dose‐ranging study was undertaken to evaluate efficacy and safety of onabotulinumtoxinA in adolescents. Background In adolescents, migraine is often undiagnosed or misdiagnosed and can present unique management challenges. OnabotulinumtoxinA was approved for prevention of chronic migraine (CM) in adults in 2010. Methods This multicenter, double‐blind, parallel‐group, randomized trial assessed a single treatment of onabotulinumtoxinA (155 U or 74 U) vs placebo (intramuscular saline) administered via the recommended fixed‐dose fixed site paradigm in adolescents with CM aged 12 to <18 years. The primary efficacy measure was change in frequency of headache days from baseline at week 12; other measures included change in frequency of headache days at weeks 4 and 8 and change in frequency of severe headache days. Safety and tolerability were assessed. Results Of 125 randomized patients (onabotulinumtoxinA 155 U, n = 45; onabotulinumtoxinA 74 U, n = 43; placebo, n = 37), all were included in the primary efficacy analysis, and 115 (92.0%) completed the study. Lack of efficacy was the primary reason for discontinuing (n = 4; 3.2%); no patients discontinued because of adverse events. All treatments reduced frequency of headache days at week 12, with no significant differences between treatments. The mean (95% confidence interval) changes from baseline in the frequency of headache days during the 28‐day period ending at week 12 (primary endpoint) were −6.3 (−8.5, −4.2), −6.4 (−8.8, −4.0), and −6.8 (−9.6, −4.1) days in the onabotulinumtoxinA 155 U, onabotulinumtoxinA 74 U, and placebo groups, respectively (P ≥ .474). All treatments reduced frequency of severe headache days and were well‐tolerated; serious adverse events (n = 3) were considered unrelated to treatment and resolved without sequelae. The most commonly reported treatment‐emergent adverse events were neck pain (n = 8), upper respiratory tract infection (n = 7), migraine, and nasopharyngitis (n = 5 each). Conclusion Although this study did not meet its efficacy endpoints, onabotulinumtoxinA was well tolerated in this adolescent population. Given previous data demonstrating the benefits of onabotulinumtoxinA in adults with CM, 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.

The Efficacy of Botulinum Toxin in Pediatric Chronic Migraine: A Literature Review

“…The other excluded studies did not meet inclusion criteria as noted above. In total, 2 retrospective analyses, 9,37 3 case series, 38 -40 1 case report, 41 and 1 randomized control trial 42 were included in this review (Table 1).…”

“…Studies enrolled between 1 and 30 patients and the randomized controlled trial enrolled 125 patients. Dosing and injection paradigms varied, with 1 study 39 and the randomized controlled trial 42 having fixed protocols whereas the majority 9,37,38,40,41 had a combination of fixed with “followed the pain.” Even among those with a standardized approach, no studies had the same injection protocol; 2 9,37 followed the PREEMPT protocol, 43 adding injections in sites of further benefit, whereas others 38 -40 used less sites than the PREEMPT protocol. The protocols ranged widely in dose injected into the frontalis (2.5-30 U), corrugator supercilii (5-15 U), procerus (2.5-10 U), temporalis (15-50 U), trapezius (20-50 U), and splenius capitis (20-40 U) muscles.…”

“…Three studies 38,39,41 included the presence of other subtypes of chronic daily headache or comorbidities. The randomized controlled trial 42 followed the PREEMPT protocol, varying only the dose between groups with one receiving the adult dose (155 U), another injected with a little less than half (74 U), and the other group receiving placebo (0 U).…”

The unique demands of childhood migraine

“…They found some evidence for a small benefit of the prophylactic medications propranolol and topiramate in the first five months of treatment, but in the longer term the drugs performed no better than placebo. In another study this year 7 , an injected medication called onabotulinumtoxin A was also found to work no better than placebo in adolescents. And in an as-yet-unpublished analysis, Powers's group found that three years after the CHAMP trial ended, young people who got better during the study tended to stay better, The power of placebo at preventing migraines in young people has presented clinicians with a conundrum, Powers says.…”

Safety and Efficacy of Fremanezumab for the Prevention of Migraine: A Meta-Analysis From Randomized Controlled Trials

“…The prevention of migraines is not to prevent the illness but to reduce the frequency of migraine attacks (9). The traditional preventive medications on migraines frequently lead to an early suspension of treatment due to their poor efficacy and tolerability in migraine people (10,11).…”