The wide variance in onabotunlinumtoxinA use for migraine prevention raises the question of whether evidence-based advisory statements might be more helpful than a proscriptive protocol.
Olivia Begasse de Dhaem, MD
Results from an anonymous survey questioning the treatment procedures with the FDA-approved PREEMPT protocol of onabotunlinumtoxinA (BoNT-A) injections for migraine prevention revealed wide inter- and intrapersonal variations, ultimately raising concerns about the standardization of the procedure.1
Of the 182 clinician respondents to the survey, 141 (77.5%) reported that they did not always follow the PREEMPT protocol, suggesting that an advisory protocol containing more evidence and discussion of the reasoning behind the recommendations might be more helpful than the current prescriptive protocol.
Olivia Begasse de Dhaem, MD, clinical fellow in neurology, Brigham and Women's Hospital and Harvard University, and colleagues, wrote in the study that as the protocol is agency-approved for BoNT-A injections for chronic migraine, the results are compelling enough to push for “further investigations of the reasons why the protocol was seldom followed in clinical practice.” Additionally, they noted that in light of a lack of published evidence providing reasoning for the PREEMPT protocol, “current guidelines may be perceived as arbitrary, giving providers the freedom to develop deviations.”
To improve the advisory protocol, Begasse De Dhaem told NeurologyLive “We need evidence and reasoning on the currently recommended location and number of injections. Although the protocol mentions that 45 extra units can be added according to a follow-the-pain paradigm, more easily accessible information thoroughly describing these potential extra locations is also needed. If we think onabotulinumtoxinA works for migraine prevention on terminal trigeminal and occipital nerve fibers, we need a reasoning for the trapezius injections.”
“We also need more evidence on the dilution and the impact of dilution on onabotulinumtoxinA diffusion,” she added.
In October 2010, BoNT-A was approved by the FDA as a preventive strategy for patients having headaches on most days of the month, lasting at least 4 hours per day. A standardized set of injections called the PHASE 3 Research Evaluating Migraine Prophylaxis Therapy, or PREEMPT, protocol was used in the 2 randomized, placebo-controlled trials that became the basis of the FDA’s decision.2
The protocol calls for 31 small injections of 5 units each in prescribed locations over the forehead, sides of the head, and back of the head and neck. Additionally, the amount of medicine approved by the FDA for chronic migraine prevention, and administered in the PREEMPT protocol, is 155 units.
BoNT-A is produced in vials of 100 and 200 units, so clinicians use a treatment strategy called “follow the pain” to administer remainder of the units. The injection process typically takes 10 to 15 minutes and patients oftentimes need 2 to 3 cycles to truly see benefit.
Contrary to standardized protocol, results from the survey from Begasse de Dhaem et al. revealed that 128 (70%) changed the number of injections, 115 (63%) changed the total units of BoNT-A injected, and 105 (57.7%) altered the location of injection sites.
Out of the 182 surveyed clinicians, 96 (52.8%) frequently made alterations and 32 (17.6%) rarely made such alterations. Additionally, 108 (59.3%) participants sometimes administered more than 31 injections. The follow-the-pain paradigm accounted for 35.7% of the main reasons for performing an increased number of injections—the most of any reported. Temporomandibular dysfunction and attempts at increasing efficacy and longevity of the injections accounted for 16.5% and 13.7% of the reasons for increasing number of injections, respectively.
Results from the survey also showed that 115 (63.2%) of the 182 clinicians said they modified the total units of BoNT-A. Injections of more than 155 units occurred in 99 (54.4%) od clinicians, compared with 39 (21.4%) clinicians who injected BoNT-A with less than 155 units.
1. Begasse de haem O, Gharedaghi MH, Rizzoli P. Modifications to the PREEMPT protocol for onabotulinumtoxinA injections for chronic migraine in clinical practice. Headache. Published online April 25, 2020. doi: 10.1111/head.13823.
2. Tepper D. Onabotunlinum A (Botox). Headache. Published online 2014. doi: 10.1111/head.1234