Stovner, Lars Jacob

Background Anatomical and experimental data indicate that onabotulinimtoxin A could be more efficient and cost-effective for treating chronic migraine with injections targeting the cranial sutures, where collaterals from the meninges penetrate the skull. Methods A new injection paradigm (FollowTheSutures) was tested for safety, tolerability and feasibility in a Phase II, open-label, non-controlled, single-center pilot study. Ninety units of onabotulinimtoxin A (Botox®), were injected in 18 sites over the area of the cranial sutures. Adverse events and potential beneficial effects were recorded in a headache diary at least 4 weeks before, and for 12 weeks after the injections. A higher dilution than normal of onabotulinimtoxin A was used to get better diffusion. Results Nineteen (of 20 included) women with chronic migraine received the injections and were evaluable. There was only one treatment-related adverse event (reduced power of chewing for some weeks). Otherwise, the procedure was overall well tolerated. Patients improved on most efficacy parameters after the injections. There was little or no effect on glabellar or forehead lines. Conclusions The protocol was safe and well tolerated. Lower risk of unblinding due to the absence of cosmetic effects should make the injection procedure well suited for a large, randomized, placebo-controlled study. If efficacy is confirmed, it will be markedly less costly than the standard procedure. Trial registration: EUDRACT (2017-002516-13), ClinicalTrials.gov (NCT03543254).

Objective The main objective of this pilot study was to investigate the safety of administering onabotulinumtoxinA towards the sphenopalatine ganglion in 10 patients with intractable chronic migraine with an open, uncontrolled design. We also collected efficacy data to provide an indication as to whether future placebo-controlled studies should be performed. Method In a prospective, open-label, uncontrolled study after one-month baseline, we performed bilateral injections of 25 IU onabotulinumtoxinA (total dose 50 IU) toward the sphenopalatine ganglion in a single outpatient session in 10 patients with intractable migraine with a follow-up of 12 weeks. The primary outcome was adverse events and the main efficacy outcome was frequency of moderate and severe headache days in month 2 post-treatment compared to baseline. Results All 10 patients experienced a total of 25 adverse events. The majority of these were different types of local discomfort in the face and jaw, and none were classified as serious. In an intention-to-treat analysis of the main efficacy outcome, a statistically significant reduction of moderate and severe headache days in baseline versus month 2 was observed (16.3 ± 6.2 days baseline versus 7.6 ± 7.6 days month 2, p = 0.009). Eight out of 10 patients experienced an at least 50% reduction of moderate and severe headache days compared to baseline. Conclusion The result warrants randomised, placebo-controlled studies to establish both safety and efficacy of this potential novel treatment of chronic migraine.