Modifications to the PREEMPT Protocol for OnabotulinumtoxinA Injections for Chronic Migraine in Clinical Practice

Abstract

ObjectiveTo assess the PREEMPT protocol modifications that have developed in clinical practice over time.BackgroundThe United States Food and Drug Administration approved the 155‐unit fixed‐dose, fixed‐site PREEMPT protocol of onabotulinumtoxinA (BoNT‐A) injections for migraine prevention 9 years ago.MethodsThis is an anonymous survey with free text response options of Headache Medicine clinicians.ResultsOut of the 878 contacted Headache Medicine clinicians, 182 (20.7%) completed the survey. Of the 182 respondents, 141 (77.5%) reported that they did not always follow the PREEMPT protocol. Of the 182 respondents, 128 (70%) changed the number of injections, 115 (63%) changed the total units of BoNT‐A injected, 105 (57.7%) altered the location of injection sites (58%); 101 (55.5%) do not aspirate to ensure the absence of blood return; 22 (12.1%) changed the dilution; and 4 (2.2%) added lidocaine. The main reported reasons for changes in number, dose, and location of injections included adapting to the patients’ pain, anatomy, and preferences.ConclusionsThe wide inter‐ and intra‐personal variations in BoNT‐A injections for chronic migraine prevention seen in this survey raise concerns about the standardization of the procedure and suggest that an advisory protocol containing more evidence and discussion of the reasoning behind the recommendations might be more helpful than the current prescriptive protocol.

Response to “Modifications to the PREEMPT Protocol for OnabotulinumtoxinA Injections for Chronic Migraine in Clinical Practice”

“…[17][18][19] These results demonstrate more than 10 years of robust efficacy, safety, and clinical and real-world effectiveness data supporting the use of onabotulinum-toxinA for the treatment of chronic migraine using the PREEMPT protocol. Although the authors pose the question "whether evidence-based advisory statements might be more helpful than a proscriptive protocol," 1 we suggest that, in contrast, there is robust evidence to support the PREEMPT protocol and its specific instructions and flexibility in dosing and injection sites that allow clinicians to use their judgment and tailor treatment to their individual patients.…”

“…The authors conclude that over two-thirds of surveyed clinicians are altering the PREEMPT protocol, which calls into question the standardized nature of the protocol and suggests the creation of evidence-based advisory statements to discuss the protocol rationale. 1 We thank the authors for highlighting this important issue but believe that further clarification is needed about the evidence-based guidance and follow-thepain strategy described in previous PREEMPT injection protocol publications in Headache. 2,3 The authors report that 141/182 (78%) clinicians who responded to the survey (out of 878 contacted) reported not always following the PREEMPT protocol.…”

“…Furthermore, over three-quarters of the respondents to this survey indicated that they had at least 3 years' experience with onabotulinumtoxinA injections. 1 We are encouraged to see that these experienced clinicians are following the evidence-based recommendations and are comfortable using their judgment to adapt the dose and number of injection sites to fit the needs of their patients. Rather than describing these as deviations, we believe that these results show that experienced clinicians are following the pain of their patients and, therefore, utilizing the PREEMPT injection protocol.…”

“…In the Discussion of their article, the authors suggest that the reduced clinician adherence to the PREEMPT protocol is because the rationale for a standardized approach is perceived as arbitrary, and the authors further suggest that published evidence supporting this approach is lacking. 1 However, the protocol used in the PREEMPT trials was based on evidence from multiple clinical studies in episodic migraine, 10 tension-type headache, 11 and phase 2 trials in chronic daily headache. 2,12 Specifically, these phase 2, exploratory, randomized, placebo-controlled trials recruited over 1000 patients, and provided critical insights into the optimal dose and injection protocol for onabotulinumtoxinA.…”

Botulinum Neurotoxin Therapy for Depression: Therapeutic Mechanisms and Future Perspective

“…Preclinical and clinical evidence have showed that BoNTs therapy had analgesic effects on neuropathic pain, trigeminal neuralgia, and chronic migraine (32). Notably, BoNT/A has been given official approval for preventive therapy of chronic migraine by Food and Drug Administration (FDA) in pain medicine (33). BoNTs can alleviate trigeminal neuralgia and can last for 6 months or more (34).…”