Comparing Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) and Targeted Approaches for OnabotulinumtoxinA in Chronic Migraine Treatment

Background: OnabotulinumtoxinA is a Food and Drug Administration–approved treatment for chronic migraine prophylaxis. The standard injection paradigm is derived from the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials, which use fixed injection sites and do not account for peripheral nerve trigger zones implicated in migraine pathogenesis. Anatomically targeted injection strategies directed at these trigger sites have shown promise, but direct comparative evaluation with PREEMPT-based approaches remains limited. Methods: A systematic review and meta-analysis was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Embase and PubMed were searched for studies evaluating onabotulinumtoxinA administered using either PREEMPT or anatomically targeted injection techniques in patients with chronic migraine. Eligible studies reported outcomes including headache days per month, migraine headache index, or symptom elimination rates. Independent t tests were used to compare changes in outcomes between groups. Results: Fifteen studies met inclusion criteria, including 13 PREEMPT-based studies (n = 1339) and 2 targeted injection studies (n = 48). Both strategies significantly reduced monthly headache frequency. In the PREEMPT cohort, headache days decreased from 23.3 ± 6.7 to 11.9 ± 7.9 per month ( P < 0.001). In the targeted cohort, headache days decreased from 15.1 ± 11.2 to 4.1 ± 5.4 per month ( P < 0.001). No significant difference was identified between groups in magnitude of improvement ( P = 0.75). The migraine headache index also improved significantly in the targeted cohort. Complications were mild and transient in both groups, with fewer adverse events reported in the targeted studies. Conclusions: Both PREEMPT and targeted onabotulinumtoxinA injections reduce migraine burden. Targeted treatment may offer advantages such as individualized therapy, lower toxin requirements, and fewer complications.