Remote electrical neuromodulation (REN) in the acute treatment of migraine: a comparison with usual care and acute migraine medications

DOI: https://doi.org/10.1186/s10194-019-1033-9

Abstract-Summary The results reported herein compare the efficacy of REN with current standard of care in the acute treatments of migraine.

We performed a post-hoc analysis on a subgroup of participants with migraine from a randomized, double-blind, parallel-group, sham-controlled, multicenter study on acute care.

The original study included a 2–4 weeks run-in phase, in which migraine attacks were treated according to patient preference (i.e., usual care) and reported in an electronic diary; next, participants entered a double-blind treatment phase in which they treated the attacks with an active or sham device.

The efficacy of REN was compared to the efficacy of usual care or pharmaco- logical treatments in the run-in phase in a within- subject design that included par- ticipants who treated at least one attack with the active REN device and reported pain intensity at 2 h post-treatment.

At 2 h post-treatment, pain relief was achieved in 66.7% of the participants using

REN versus 52.5% participants with usual care (p < 0.05).

REN and usual care were similarly effective for pain-free status at 2  h. The results also demonstrate the non-inferiority of REN compared with acute pharma- cological treatments and its non-dependency on preventive medication use.

REN is an effective acute treatment for migraine with non-inferior efficacy com-

pared to current acute migraine therapies.

Extended: REN is an effective acute treatment of migraine attacks, with non- inferior efficacy compared with usual care and various pharmacological treatments in this analysis.

Along with its favorable safety and tolerability profiles and its non-pharmacolog- ical nature that alleviates the adverse events and medical risks associated with some current migraine pharmacological treatments, our findings suggest that REN may be useful as an alternative or adjunctive acute migraine treatment.

Introduction A recent randomized, double-blind, sham-controlled, multicenter study has demon- strated that REN provides superior, clinically meaningful relief of migraine pain and complete pain freedom at 2 h post-treatment compared to sham stimulation.

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Active stimulation was more effective than sham stimulation in achieving pain relief (66.7% vs. 38.8%, p < 0.001), pain freedom (37.4% vs. 18.4%, p < 0.005) and relief of most bothersome symptom (MBS) (46.3% vs. 22.2%, p < 0.001) at 2 h post-treatment.

The pain relief and pain freedom superiorities of the active treatment were sus-

tained for 48 h post-treatment [471].

The current report describes an exploratory, within-subject, post-hoc analysis of the aforementioned study, aiming to examine whether REN is as effective as usual care and pharmacotherapies in the acute treatment of migraine.

Methods After enrollment, participants were trained to use an electronic diary, and then com- pleted a one-month run-in phase, during which the attacks were treated according to usual care and pain scores (none, mild, moderate, or severe) were recorded at base- line and 2 h post-treatment.

Participants treated their migraine attacks with the device for 4–6 weeks (double- blind treatment phase), as soon as possible after a migraine attack began and always within 1 h of onset.

Within-subject comparisons between REN and usual care or pharmacological treatments were performed on a subgroup of participants who treated at least one attack with the active REN device and reported pain intensity at 2 h post-treatment.

Additional analyses were performed on participants who had treated at least two attacks (and reported pain intensity at 2 h post-treatment) in the run-in phase and treated at least two attacks (and reported pain intensity at 2 h post-treatment) with the active REN device in the double-blind treatment phase.

Results Ninety of the ninety-nine participants had treated at least two attacks with pain intensity reported at 2 h post-treatment in the run-in phase and at least two attacks with pain intensity reported at 2 h post-treatment with the active REN device.

Pain relief and pain-free responses at 2 h post-treatment of the first attack reported in the run-in phase were compared with REN responses in the test treatment in the double-blind treatment phase.

For the 90 participants who treated at least two attacks in both the run-in and the double-blind treatment phases, pain relief and pain-free responses at 2 h post-treat- ment in at least one of two attacks in the run-in phase were compared with REN responses at 2 h in at least one of two attacks.

Discussion The overall results demonstrate that REN is an effective acute treatment for migraine with non-inferior efficacy to usual care in general and to acute migraine pharmaco- logical treatments specifically.

The within-subject pos-hoc analysis presented in this paper extends these find- ings by providing direct evidence that the efficacy of REN is non-inferior to indi- vidual usual care and to current acute migraine pharmacological treatments.

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In the context of this study, usual care (which included either no pharmacological treatment or migraine specific and non- specific pharmacological treatments) and pharmacological treatment (which included any type of acute medication) provided a window into real-life management and experiences without producing expecta- tions about the efficacy of a particular treatment approach.

Although direct comparisons between this exploratory post-hoc analysis and randomized clinical trials must be made cautiously, pain relief and pain-free response rates across pharmacological treatments in the current study are in the same range as those reported in previous studies [109, 472].

Conclusions REN is an effective acute treatment of migraine attacks, with non-inferior efficacy compared with usual care and various pharmacological treatments in this analysis. Along with its favorable safety and tolerability profiles and its non-pharmacolog- ical nature that alleviates the adverse events and medical risks associated with some current migraine pharmacological treatments, our findings suggest that REN may be useful as an alternative or adjunctive acute migraine treatment.

Acknowledgement A machine generated summary based on the work of Rapoport, Alan M.; Bonner, Jo H.; Lin, Tamar; Harris, Dagan; Gruper, Yaron; Ironi, Alon; Cowan, Robert P. 2019 in The Journal of Headache and Pain.

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