Efficacy and safety of Nerivio, a remote electrical neuromodulation device, for acute treatment of migraine in people with chronic migraine: an open label, single arm, multicenter study (NCT 04161807)

This was a prospective, open-label, single arm, multicenter study conducted at 9 sites in the USA. Eligible participants were adults (18–75 years old) who met the International Classification of Headache Disorders (ICHD-3) criteria for chronic migraine (at least 15 headache days a month, with at least eight days a month on which their headaches and associated symptoms meet diagnostic criteria for migraine).

Following a 4 weeks “Run-in” phase, eligible participants were asked to treat their migraine attacks at home for 4 weeks with their optimal stimulation intensity, as soon as possible after migraine headache began and always within one hour of attack onset. Participants were instructed to avoid taking rescue medications prior or within the first two hours post-treatment. Pain scores, absence/presence of migraine associated symptoms, and functional disability were recorded at baseline, 2- and 24-hours post-treatment using the electronic diary application.

The primary efficacy endpoint was the proportion of participants who achieved pain relief at 2 hours post-treatment in the test treatment, defined as improvement from severe or moderate pain to mild or none, or, improvement from mild pain to none.

97 participants completed at least one treatment of a qualifying migraine headache (the training treatment) and 91 participants completed the test treatment with evaluable data at baseline and at 2 hours, forming the final analysis set (5 participants did not have qualifying migraine headaches and 3 participants had missing data in the test treatment at baseline or at 2 hours).

Figure 1 – Participant disposition

Results

Run-in phase

A total of 997 qualifying migraine attacks were reported during the run-in phase by the 126 enrolled patients, with an average of 7.9 attacks per participant. Of these, pain level at baseline was reported on 993 reported attacks.

Treatment phase

A total of 493 evaluable treatments (excluding the training treatment) of qualifying migraine headaches were conducted by the 91 participants included in the analyses, with an average of 5.4±2.8 evaluable treatments per patient per 4 weeks. Medication at 2 hours was used in 54 of the 493 treatments (89.0% compliance rate). Use of medication was considered a treatment failure.

The primary, secondary, and exploratory endpoints of a single attack were conducted on the test treatment of the final analysis set of 91 participants. Pain relief and pain-free at 2 hours were achieved by 59.3% (54/91; CI95% 48.5-69.5%) and 20.9% (19/91; CI95% 13.0-30.6%) of the participants, respectively. Pain relief was sustained for 24 hours in 73.3% (33/45; CI95% 58.0-85.3%) of the participants (9 participants did not report pain level at 24 hours and were thus excluded from the analysis). Nausea, photophobia, and phonophobia disappeared at 2 hours in 48.8% (20/41; CI95% 32.8-64.8%), 40.5% (30/74; CI95% 29.2-52.5%), and 44.6% (29/65; CI95% 32.2-57.4%) participants, respectively. Furthermore, 59.4% (19/32; CI95% 40.6-76.3%) of the participants experienced improvement in functional ability at 2 hours (participants with missing data at baseline or at 2 hours were excluded from the analysis) and 50.0% (7/14; CI95% 23.0-76.9%) of the participants experienced improvement in functional ability at 24 hours (participants with missing data at baseline or at 24 hours were excluded from the analysis).

Consistency analyses across all attacks (excluding the training treatment) demonstrated that 57.1% (52/91) of the participants experienced pain relief in at least 50% of their treated attacks.

Endpoint

Result

Pain relief at 2 hours post-treatment (in the test treatment)59.3% (54/91)Pain-free at 2 hours post-treatment (in the test treatment)20.9% (19/91)Disappearance of associated symptoms at 2 hours post-treatment (in the test treatment) Disappearance of nausea and/or vomiting48.8% (20/41)Disappearance of photophobia40.5% (30/74)Disappearance of phonophobia44.6% (29/65)Sustained pain relief at 24 hours post-treatment (in the test treatment)73.3% (33/45)Improvement in functional ability at 2 hours (in the test treatment)59.4% (19/32)Improvement in functional ability at 24 hours (in the test treatment)50.0% (7/14)Within-subject consistency of pain relief57.1% (52/91)

Table 1 – Efficacy outcome

One device-related adverse event was reported (1.0% [1/99]) in which pain in the arm was felt following the use of the device on that arm. The device-related adverse event was mild, and resolved within 24 hours without medication.

Conclusions

The findings of the study show that Nerivio is effective for the acute treatment of migraine in people with chronic migraine. Acute treatment of migraine headaches resulted in clinically meaningful benefits. Pain relief and pain freedom rates were generally similar to those found in people with non-chronic migraine, indicating that Nerivio provides an alternative acute migraine treatment independent of the frequency and severity of migraine headaches.

The results of the study show that Nerivio is safe to use and is well-tolerated. The incidences of device-related adverse events were low with no device-related serious adverse events. The rate of all device-related adverse events was below 2%, which compares favorably to the reported rates for current pharmacological treatments.

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