How Does Nerivio Work?
A 2019 study published in the clinical journal Headache showed that Nerivio lessened migraine symptoms within two hours for most participants, and completely alleviated head pain for over a third
How it Works
How Does Nerivio Work?
A 2019 study published in the clinical journal Headache showed that Nerivio lessened migraine symptoms within two hours for most participants, and completely alleviated head pain for over a third
66.7% of
patients
achieve pain relief at 2 hours
(Yarnitsky et al., Headache)
Non-invasive
Non-addictive
Non-pharmacological
Smart &
Personalized
From the arm to the brain
Nerivio stimulates small nerves in the upper arm. The message from the arm is received by a brainstem pain regulation center that can inhibit pain signals by releasing neurotransmitters, resulting in significant pain relief which can end the migraine attack.
Clinical Data
Nerivio was evaluated in several clinical studies to evaluate its effect in episodic and chronic migraine patients and in adolescence. The following section summarizes the studies performed by Theranica:
The pilot study was a single-center, prospective, double-blind, randomized, crossover, sham-controlled pilot study aimed to assess the safety and efficacy of non-invasive remote electrical neuromodulation (REN) with the Nerivio device for the acute treatment of migraine. In this study, 86 people with migraine with or without aura (in accordance with International Classification of Headache Disorders [ICHD] classification criteria) who had 2–8 attacks per month without preventive medications for at least 2 months were recruited. The participants were requested to treat migraine episodes at home using the device, which randomly provided one of four different stimuli programs differentiating in pulse width and one sham stimulus. Pain levels were self-reported via a smartphone application at stimulation onset and again at 10, 20, and 120 minutes after stimulation onset. The primary endpoint was the proportion of participants reporting pain decrease of at least 50% at 2 hours post-treatment in at least 50% of completed treatments. The analysis of the primary endpoint was performed on 71 participants who successfully treated at least one migraine attack and have not used rescue medications concurrently with REN treatments. This analysis revealed a 64% rate of at least 50% pain reduction at 2 hours post-treatment, in at least 50% of completed active treatments. This rate was significantly higher than the 26% rate found for the sham treatment (p=0.005). In this study, no device-related adverse events and no side effects were reported.
The pivotal study (TCH-003) was a prospective, randomized, double-blind, sham controlled multi-center study aimed to demonstrate the safety and efficacy of the Nerivio remote electrical neuromodulation device for the acute treatment of migraine with or without aura. This study was conducted from December 2017 to October 2018 at 12 sites, 7 in the US and 5 in Israel.
296 participants with migraine with or without aura (in accordance with ICHD classification criteria) who had 2–8 attacks per month, ≤12 headache days per month, and were on either no or stable migraine preventive medications in the last two months prior to recruitment were enrolled. 252 participants were randomized to active (n=126) or sham stimulation (n=126). Headache pain levels were reported at baseline, 2 hours and 48 hours post-treatment. The primary efficacy endpoint of the study was the percentage of participants reporting reduction in their pain level, without use of medication, from severe or moderate to mild or no pain or from mild to no pain within 2 hours. Sustained pain relief or pain-free status was defined as having a headache response at 2 hours post-treatment with no use of rescue medication and no return to baseline or relapse of headache pain within 48 hours. The analyses were performed on 202 participants (99 in the active group and 103 in the sham group) who treated an attack within one hour from symptoms onset and reported pain level at 2 hours post-treatment. At 2 hours post-treatment, active stimulation was significantly more effective than sham stimulation in reducing headache pain (66.7% vs. 38.8%, p<0.0001)), in completely relieving headaches (37.4% vs 18.4%, p=0.005), in reducing the most bothersome symptom (MBS) of the associated symptoms of nausea, sensitivity to light and sensitivity to sound (46.3%% vs. 22.2%, p=0.001) and in reducing the combination of headache and MBS (40.0% vs. 15.2%, p<0.001). The 2-hours pain relief and pain-free superiority of the active treatment were sustained 48 hours post-treatment; sustained pain relief at 48 hours post-treatment was achieved by 39.1% of the participants in the active group versus 16.9% in the sham group (p<0.005) and sustained pain free status at 48 hours post-treatment was achieved by 20.7% of the participants in the active group versus 7.9% in the sham group (p<0.005)
Moreover, pain relief at 2 hours post-treatment was consistent across multiple treatments (62.6% of the participants in the active group achieved pain relief in at least 50% of their attacks vs. 45.6% in the sham group, p<0.05).
This study also demonstrated a favorable safety profile for Nerivio. The incidence of device-related adverse events was low (3.6% of participants) and the event rate was similar between the active (Nerivio) and sham treatment groups. During 773 treatments, 23 (2.7%) device-related adverse events were reported, 14 in the active group and 9 in the sham group. All device-related adverse events were mild, did not require treatment and resolved within 24 hours. No device-related serious adverse events were reported and none of the participants withdrew from the study due to adverse events.
In conclusion, the results of the pivotal study indicate that Nerivio is safe and effective for the acute treatment of migraine. The findings of this study were robust and clinically meaningful. Nerivio, thus, offers a novel alternative for current pharmacological and non-pharmacological treatments that combines effective treatment with minimal side effects.
The pilot study (TCH-005) was prospective, open-label, single arm, dual-center study aimed to demonstrate the safety and efficacy of Nerivio remote electrical neuromodulation device for the acute treatment of migraine with or without aura in patients with chronic migraine (>15 headache days/month). This study was conducted from September 2019 to February 2020 at 2 sites (USA -1, Israel – 1).
42 participants were enrolled, and 38 participants were evaluable for analyses. A total of 210 evaluable treatments (excluding the training treatment) of qualifying migraine headaches were conducted by the 38 participants included in the analyses, with an average of 5.5±2.6 evaluable treatments per patient per 4 weeks.
The primary, secondary and exploratory endpoints of a single attack were conducted on the test treatment of the final analysis set of 38 participants. Pain relief and pain-free at 2 hours were achieved by 50.0% (19/38; CI95% 33.4-66.6%) and 26.3% (10/38; CI95% 13.4-43.1%) participants, respectively. Pain relief was sustained for 24 hours in 83.3% (10/12; CI95% 51.6-97.9%) of the participants who achieved relief at 2 hours (7 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 58.8% (10/17; CI95% 32.9-81.6%), 37.5% (9/24; CI95% 18.8-59.4%), and 50.0% (8/16; CI95% 24.7-75.3%) participants, respectively. Furthermore, 46.7% (14/30; CI95% 28.3-65.7%) participants experienced improvement in functional ability at 2 hours and 72.7% (16/22; CI95% 49.8-89.3%) participants experienced improvement in functional ability at 24 hours (8 participants with missing data at 24 hours were excluded from the analysis).
Consistency analyses across all attacks (excluding the training treatment) demonstrated that 73.7% (28/38) of the participants experienced pain relief in at least 50% of their treated attacks. Mean pain relief rate across subjects was 58.8%, median pain relief rate across subjects was 60% and the inter quartiles rang (IQR) was 43.67 – 87.50%.
According to the safety analyses, the percentage of participants experiencing at least one adverse event was 4.7% (2/42) with 95% confidence interval of (0.6 – 16.2%). A single device-related adverse event was reported (2.3% [1/4])). The device-related adverse event was moderate, resolved within 48 hours following drug therapy (triptan). There were no serious adverse device-related events and none of the participants withdrew from the study due to adverse events.
Endpoint |
Result |
Pain relief at 2 hours post-treatmenta (in the test treatment) |
50.0% (19/38) |
Pain-free at 2 hours post-treatmentb (in the test treatment) |
26.3% (10/38) |
Disappearance of associated symptoms at 2 hours post-treatment | |
Disappearance of nausea and/or vomiting |
58.8% (10/17) |
Disappearance of photophobia |
37.5% (9/24) |
Disappearance of phonophobia |
50.0% (8/16) |
Sustained pain relief at 24 hours post-treatment (in the test treatment) |
83.3% (10/12) |
Improvement in functional ability at 2 hoursd |
46.7% (14/30) |
Improvement in functional ability at 24 hoursd |
72.7% (16/22) |
Within-subject consistency of pain reliefc |
73.7% (28/38) |
The findings of the study demonstrated 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-free rates were generally similar to those found in people with non-chronic migraine as reported in the Nerivio pivotal clinical study TCH003. Overall, the data reveal consistent response rates from treatment to treatment, with no evidence of reduction in therapeutic benefits over time. Specifically, over 73% of the patients achieved pain relief at 2 hours in more than half of their attacks. The findings of this study also show that the device is safe and well-tolerated. No safety issues were associated with the more frequent use of the device in patients with chronic migraine.
The main study (TCH-006) was prospective, open-label, single arm, multi-center study aimed to demonstrate the safety and efficacy of Nerivio remote electrical neuromodulation device for the acute treatment of migraine with or without aura in patients with chronic migraine (>15 headache days/month). This study was conducted from November 2019 to June 2020 at 9 sites in the USA.
Participants entered a 4-week “Run-in” phase in which they had to report their migraine attacks and continue with their usual treatment care. Participants who reported at least 6 qualifying migraine headaches with pain data at baseline and 2 hours post-treatment were eligible to continue to the “Treatment” phase
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; CI95% 46.3-67.4%) of the participants experienced pain relief in at least 50% of their treated attacks. Mean pain relief rate across subjects was 50.4%, and median pain relief rate across subjects was 50%. Pain relief in at least 2 of 3 consecutive treatments (first 3 treatments excluding the training treatment) was reported by 64.4% (47/73; CI95% 52.3-75.3%) of the participants.
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 vomiting | 48.8% (20/41) |
Disappearance of photophobia | 40.5% (30/74) |
Disappearance of phonophobia | 44.6% (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 relief | 57.1% (52/91) |
The percentage of participants experiencing at least one adverse event was 9.1% (9/99) with 95% confidence interval of (4.2 – 16.6%). 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, resolved within 24 hours without medication. The other adverse events which were deemed unrelated to the device.
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-free 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.
The study was a prospective, open-label, single arm, multicenter study of the Nerivio device in adolescent patients (age 12-17, inclusive), aiming to assess the performance of Nerivio in the adolescent migraine population. study was conducted from October 2019 to May 2020 (Clinicaltrials.gov number – NCT04089761).
Study design and procedures
Eligible participants were enrolled based on the inclusions/exclusions criteria. Following enrollment, participants entered a 4-week “Run-in” phase in which they had to report their migraine attacks and continue with their usual treatment care. Participants who reported at least 3 qualifying migraine headaches with pain data at baseline and 2 hours post-treatment were eligible to continue to the “Treatment” phase.
During the “Treatment” phase, participants were asked to treat their migraine attacks at home for 8 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 within the first two hours post-treatment. Pain scores (none, mild, moderate, or severe), absence/presence of migraine associated symptoms including nausea/vomiting, photophobia and phonophobia, and functional disability were recorded at baseline, 2- and 24-hours post-treatment in electronic diary application included in the Nerivio mobile application that was installed on the participants’ smartphones.
Participants who completed the “Treatment” phase were offered to continue to an 8-week follow-up phase in which they could incorporate the device into their usual care. Following the 8 weeks of “Follow up” phase, participants fill out their end of study questionnaire and completed the study.
Safety and efficacy endpoints
The primary endpoints of this study were the safety and tolerability of Nerivio. Safety was assessed by the incidence of adverse events in general and by seriousness, severity and association to the device. Treatment tolerability was assessed by the percent of subjects who fail to complete the study because of adverse events.
The secondary endpoints were related to device efficacy and included the proportion of participants who achieved pain relief at 2 hours post-treatment, defined as improvement from severe or moderate pain to mild or none, or improvement from mild pain to none; proportion of participants who achieved pain-free (improvement from mild, moderate, or severe pain to none) at 2 hours, and disappearance of associated symptoms (nausea/vomiting, photophobia, and phonophobia) at 2 hours post-treatment. Exploratory endpoints included sustained pain relief at 24 hours, sustained pain-free at 24 hours, and improvement in functional ability at 2 hours and at 24 hours. Within-subject consistency of pain relief and pain-free responses, defined as the proportion of participants achieving pain relief/pain-free at 2 hours post-treatment in at least 50% of their treated headaches, were also assessed.
Results
60 patients were enrolled, of which 1 participant was lost to follow-up during the run-in phase, and 14 completed the run-in but were not eligible to continue according to protocol specifications.
Among the 45 participants who entered the treatment phase, all participants completed at least one treatment (the training treatment) and 39 participants completed the test treatment, forming the final analysis set (two participants had missing data at 2 hours post-treatment, three participants did not have migraine headaches and one participant was a lost to follow-up).
The participants demographic information is shown in table 1.
Characteristic | |||
Age, y (SD) | 15.4 (1.8) | ||
Female, % (n/N) | 60.0% (36/60) | ||
Race, % (n/N) | |||
Caucasian (including Hispanic) | 86.6% (52/60) | ||
African/ Eastern Arab | 1.66% (1/60) | ||
African American | 10.0% (6/60) | ||
American Indian or Alaskan Native | 1.66% (1/60) | ||
Average number of headache days per month | 9.6 (4.6) | ||
Average number of migraine headache days per month | 7.9 (3.9) | ||
Triptan users, % (n/N) | 30.0% (18/60) | ||
Migraine with aura, % (n/N) | 31.7% (19/60) | ||
MBS % (n/N)* | |||
Nausea | 35.0% (21/60) | ||
Photophobia | 43.3% (26/60) | ||
Phonophobia | 16.7% (10/60) | ||
None | 5.0% (3/60) |
Table 1 – Participants demographic information
Run-in phase
A total of 267 qualifying migraine attacks were reported during the run-in phase by 54 of the 60 enrolled patients (6 patients did not report any migraines during the run-in phase), with an average of 4.9 migraine attacks per participant.
The characteristics of the reported migraine headaches in the “Run-in” phase are presented in Table 2.
All patients | ||
Headache level at baseline |
Mild | 22.1% (59/267) |
Moderate | 46.4% (124/267) | |
Severe | 31.5% (84/267) | |
Headache level at 2 hours |
No Pain | 17% (40/235) |
Mild | 45.5% (107/235) | |
Moderate | 23.4% (55/235) | |
Severe | 14% (33/235) | |
Use of medication within 2h | 60 % (141/235) | |
Aura at baseline | 23.2% (62/267) | |
Nausea at baseline | 48.3% (129/267) | |
Photophobia at baseline | 78.65% (210/267) | |
Phonophobia at baseline | 53.5% (143/267) | |
Nausea at 2 hours | 38.7% (91/235) | |
Photophobia at 2 hours | 62.9% (148/235) | |
Phonophobia at 2 hours | 37.4% (88/235) |
Table 2 – Characteristics of migraine attacks reported during the “Run-in” phase.
Treatment phase
Safety
Safety analyses were performed on all 45 participants who used the device at least once. 10 participants (22.2%) reported at least one adverse event. There was one device-related adverse event reported (2.2%) in which a temporary feeling of pain in the arm was felt. This adverse event was mild and resolved after the treatment without requiring medication or any other intervention. The other adverse events which were deemed unrelated to the device included common cold (1 participant), chest congestion (2 participants), influenza (2 patients), leg pain (1 patient), streptococcus pharyngitis (1 participant), upper respiratory infection (1 patient), and worsened migraine (1 patient). There were no device-related serious adverse events and none of the participants withdrew from the study due to device-related adverse events.
Efficacy
A total of 159 qualifying migraine headaches were treated with Nerivio for which pain data was recorded at baseline and at 2 hours post-treatment (average of 3.5 treatments per participant). Pain severity of treated migraine headaches was mostly moderate (48.4% [77/159]). 57/159 (35.8%) of the treated migraine headaches were severe and 25/159 (15.7%) of the treated migraine headaches were mild.
Pain relief and pain-free at 2 hours were achieved by 71.8% (28/39) and 35.9% (14/39) participants, respectively. Pain relief was sustained for 24 hours in 90.9% (20/22) of the participants, and pain freedom was sustained for 24 hours in 90.9% (10/11) of the participants. Nausea, photophobia, and phonophobia disappeared at 2 hours in 54.5% (12/22), 41.9% (13/31), and 40.0% (10/25) participants, respectively. Furthermore, 69.7% (23/33) participants experienced improvement in functional ability at 2 hours and 69.0% (20/29) participants experienced improvement in functional ability at 24 hours.
a consistency analyses was conducted across all treated attacks (excluding the training treatment). This analysis demonstrated that 66.7% (26/39) of the participants experienced pain relief in at least 50% of their treated attacks, and 33.3% (13/39) of the participants experienced pain-free in at least 50% of their treated attacks.
Safety analyses were performed on all 45 participants who used the device at least once. 10 participants (22.2%) reported at least one adverse event. There was one device-related adverse event reported (2.2%) in which a temporary feeling of pain in the arm was felt. This adverse event was mild and resolved after the treatment without requiring medication or any other intervention. The other adverse events which were deemed unrelated to the device.
The findings of the study show that Nerivio is effective for the acute treatment of migraine in the adolescent population. The results of the study show that Nerivio is safe to use and is well-tolerated by adolescence migraineurs. The incidence of device-related adverse events was low with no device-related serious adverse events.
Efficacy outcome summary is demonstrated in table 3.
Endpoint |
Result |
Pain-free at 2 hours post-treatment (in the test treatment) | 71.8% (28/39) |
Disappearance of associated symptoms at 2 hours post-treatment | 35.9% (14/39) |
Disappearance of nausea | 54.5% (12/22) |
Disappearance of photophobia | 41.9% (13/31) |
Disappearance of phonophobia | 40.0% (10/25) |
Sustained pain relief at 24 hours post-treatment (in the test treatment) | 90.9% (20/22) |
Sustained pain free at 24 hours post-treatment (in the test treatment) | 90.9% (10/11) |
Improvement in functional ability at 2 hours | 69.7% (23/33) |
Improvement in functional ability at 24 hours | 69.0% (20/29) |
Table 3 – Efficacy outcome
Conclusions
The results of the study show that Nerivio is safe and effective for the acute treatment of migraine in adolescents. There was one device-related adverse event in which a temporary feeling of pain in the arm was felt. This adverse event was mild and resolved after the treatment without requiring medication or any other intervention. This rate of device-related adverse events compares favorably to the reported rates for current pharmacological treatments. Importantly, the safety profile of Nerivio is also favorable with respect to new pharmacological developments such as ditans and gepants, though these have not been assessed in adolescents yet.
Acute treatment of migraine headaches resulted in clinically meaningful benefits. Pain relief and pain-free rates were generally similar to those found in adults, indicating that Nerivio provides an alternative acute migraine treatment independent of age.
Post HOC Analysis
In addition, a post hoc analysis (TCH-004) of comparison between the Nerivio treatment (REN) and Standard-Care Medications for Acute Treatment of Migraine was performed.
Four efficacy endpoints were tested: pain freedom and pain relief (severe to mild or no pain, or moderate to no pain—two-step improvement) after a single treatment, and pain freedom and pain relief consistency across treatments. All endpoints refer to 2 hours after treatment. For the single-treatment endpoints. The analyzed test treatment for REN was defined as the first REN treatment after a training treatment, and the test treatment for medications was defined as the first treatment in the run-in phase in which medication was used. For the consistency endpoints, consistent response was defined as response (pain freedom or relief) in at least 50% of the first four treatments. All participants had completed four evaluable REN treatments. The number of medication treatments varied among participants, and consistency was calculated on the basis of all available data (up to four treatments) for each participant.
Results
Participants
During the medication phase, eight participants (22.8%) used oral triptans only (five rizatriptan, one eletriptan,
one zolmitriptan, and one sumatriptan), two participants (5.7%) alternated between oral triptans and
OTC analgesics, and 26 participants (71.4%) used OTC analgesics only (11 ibuprofen, seven naproxen sodium,
five acetaminophen, and three acetaminophen-aspirin/caffeine combination).
Efficacy Results
Single Treatment Pain freedom in the REN phase was reported by 37.1% (13/35) of the participants, vs 8.6% (3/35) in the medication phase, with a statistically significant difference: P¼0.004 (OR¼11.0, 95% CI 1.60–473).
Pain relief in the REN phase was reported by 71.4% (25/35) of the participants, vs 57.1% (20/35) in the medication phase: P¼0.225 (OR¼1.83, 95% CI 0.62–6.04). The single-treatment results are depicted in Figure 2.
Consistent Efficacy
Consistent pain freedom in the REN phase was reported by 40.0% (14/35) of the participants, vs 8.6% (3/35) in
the medication phase, with a statistically significant difference: P<0.001 (proportion difference¼0.314,
0.144–0.473). OR was not applicable because there were zero participants in the group that achieved pain freedom
with medications but not with REN, and thus the paired proportion difference was estimated instead.
Consistent pain relief in the REN phase was reported by 80.0% (28/35) of the participants, vs 57.1% (20/35)
in the medication phase, with a statistically significant difference: P¼0.033 (OR¼3.67, 95% CI 0.97–20.47).
Response Rates by Medication Class Response rates were subanalyzed by medication class. Statistical comparison was not performed because of sample size limitations of the subgroups, and response rates are presented for reporting purposes only. Twentysix participants used OTC analgesic medications, of whom 38.4% (10/26) achieved pain freedom with REN, vs 11.5% (3/26) with medications. Pain relief was achieved by 76.9% (20/26) with REN, vs 65.3% (17/26) with medications. Nine participants used oral triptans, of whom 33.3% (3/9) achieved pain freedom with REN, vs 0% (0/9) with medications. Pain relief with REN was achieved by 55.5% (5/9), vs 33.3% (3/9) with medications.
The results of the post hoc analysis provides a preliminary indication that REN may be as effective as, if not more effective than, certain standard-Care medications in adolescents with migraine. Specifically, REN was found to be superior to the tested medications (oral triptans and OTC analgesic medications) in pain freedom after a single treatment, pain freedom consistency across treatments, and pain relief.
The study was a prospective, open-label, single arm, multicenter study of the Nerivio device in adolescent patients (age 12-17, inclusive), aiming to assess the performance of Nerivio in the adolescent migraine population. study was conducted from October 2019 to May 2020 (Clinicaltrials.gov number – NCT04089761).
Study design and procedures
Eligible participants were enrolled based on the inclusions/exclusions criteria. Following enrollment, participants entered a 4-week “Run-in” phase in which they had to report their migraine attacks and continue with their usual treatment care. Participants who reported at least 3 qualifying migraine headaches with pain data at baseline and 2 hours post-treatment were eligible to continue to the “Treatment” phase.
During the “Treatment” phase, participants were asked to treat their migraine attacks at home for 8 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 within the first two hours post-treatment. Pain scores (none, mild, moderate, or severe), absence/presence of migraine associated symptoms including nausea/vomiting, photophobia and phonophobia, and functional disability were recorded at baseline, 2- and 24-hours post-treatment in electronic diary application included in the Nerivio mobile application that was installed on the participants’ smartphones.
Participants who completed the “Treatment” phase were offered to continue to an 8-week follow-up phase in which they could incorporate the device into their usual care. Following the 8 weeks of “Follow up” phase, participants fill out their end of study questionnaire and completed the study.
Safety and efficacy endpoints
The primary endpoints of this study were the safety and tolerability of Nerivio. Safety was assessed by the incidence of adverse events in general and by seriousness, severity and association to the device. Treatment tolerability was assessed by the percent of subjects who fail to complete the study because of adverse events.
The secondary endpoints were related to device efficacy and included the proportion of participants who achieved pain relief at 2 hours post-treatment, defined as improvement from severe or moderate pain to mild or none, or improvement from mild pain to none; proportion of participants who achieved pain-free (improvement from mild, moderate, or severe pain to none) at 2 hours, and disappearance of associated symptoms (nausea/vomiting, photophobia, and phonophobia) at 2 hours post-treatment. Exploratory endpoints included sustained pain relief at 24 hours, sustained pain-free at 24 hours, and improvement in functional ability at 2 hours and at 24 hours. Within-subject consistency of pain relief and pain-free responses, defined as the proportion of participants achieving pain relief/pain-free at 2 hours post-treatment in at least 50% of their treated headaches, were also assessed.
Results
60 patients were enrolled, of which 1 participant was lost to follow-up during the run-in phase, and 14 completed the run-in but were not eligible to continue according to protocol specifications.
Among the 45 participants who entered the treatment phase, all participants completed at least one treatment (the training treatment) and 39 participants completed the test treatment, forming the final analysis set (two participants had missing data at 2 hours post-treatment, three participants did not have migraine headaches and one participant was a lost to follow-up).
The participants demographic information is shown in table 1.
Characteristic | |||
Age, y (SD) | 15.4 (1.8) | ||
Female, % (n/N) | 60.0% (36/60) | ||
Race, % (n/N) | |||
Caucasian (including Hispanic) | 86.6% (52/60) | ||
African/ Eastern Arab | 1.66% (1/60) | ||
African American | 10.0% (6/60) | ||
American Indian or Alaskan Native | 1.66% (1/60) | ||
Average number of headache days per month | 9.6 (4.6) | ||
Average number of migraine headache days per month | 7.9 (3.9) | ||
Triptan users, % (n/N) | 30.0% (18/60) | ||
Migraine with aura, % (n/N) | 31.7% (19/60) | ||
MBS % (n/N)* | |||
Nausea | 35.0% (21/60) | ||
Photophobia | 43.3% (26/60) | ||
Phonophobia | 16.7% (10/60) | ||
None | 5.0% (3/60) |
Table 1 – Participants demographic information
Run-in phase
A total of 267 qualifying migraine attacks were reported during the run-in phase by 54 of the 60 enrolled patients (6 patients did not report any migraines during the run-in phase), with an average of 4.9 migraine attacks per participant.
The characteristics of the reported migraine headaches in the “Run-in” phase are presented in Table 2.
All patients | ||
Headache level at baseline |
Mild | 22.1% (59/267) |
Moderate | 46.4% (124/267) | |
Severe | 31.5% (84/267) | |
Headache level at 2 hours |
No Pain | 17% (40/235) |
Mild | 45.5% (107/235) | |
Moderate | 23.4% (55/235) | |
Severe | 14% (33/235) | |
Use of medication within 2h | 60 % (141/235) | |
Aura at baseline | 23.2% (62/267) | |
Nausea at baseline | 48.3% (129/267) | |
Photophobia at baseline | 78.65% (210/267) | |
Phonophobia at baseline | 53.5% (143/267) | |
Nausea at 2 hours | 38.7% (91/235) | |
Photophobia at 2 hours | 62.9% (148/235) | |
Phonophobia at 2 hours | 37.4% (88/235) |
Table 2 – Characteristics of migraine attacks reported during the “Run-in” phase.
Treatment phase
Safety
Safety analyses were performed on all 45 participants who used the device at least once. 10 participants (22.2%) reported at least one adverse event. There was one device-related adverse event reported (2.2%) in which a temporary feeling of pain in the arm was felt. This adverse event was mild and resolved after the treatment without requiring medication or any other intervention. The other adverse events which were deemed unrelated to the device included common cold (1 participant), chest congestion (2 participants), influenza (2 patients), leg pain (1 patient), streptococcus pharyngitis (1 participant), upper respiratory infection (1 patient), and worsened migraine (1 patient). There were no device-related serious adverse events and none of the participants withdrew from the study due to device-related adverse events.
Efficacy
A total of 159 qualifying migraine headaches were treated with Nerivio for which pain data was recorded at baseline and at 2 hours post-treatment (average of 3.5 treatments per participant). Pain severity of treated migraine headaches was mostly moderate (48.4% [77/159]). 57/159 (35.8%) of the treated migraine headaches were severe and 25/159 (15.7%) of the treated migraine headaches were mild.
Pain relief and pain-free at 2 hours were achieved by 71.8% (28/39) and 35.9% (14/39) participants, respectively. Pain relief was sustained for 24 hours in 90.9% (20/22) of the participants, and pain freedom was sustained for 24 hours in 90.9% (10/11) of the participants. Nausea, photophobia, and phonophobia disappeared at 2 hours in 54.5% (12/22), 41.9% (13/31), and 40.0% (10/25) participants, respectively. Furthermore, 69.7% (23/33) participants experienced improvement in functional ability at 2 hours and 69.0% (20/29) participants experienced improvement in functional ability at 24 hours.
a consistency analyses was conducted across all treated attacks (excluding the training treatment). This analysis demonstrated that 66.7% (26/39) of the participants experienced pain relief in at least 50% of their treated attacks, and 33.3% (13/39) of the participants experienced pain-free in at least 50% of their treated attacks.
Safety analyses were performed on all 45 participants who used the device at least once. 10 participants (22.2%) reported at least one adverse event. There was one device-related adverse event reported (2.2%) in which a temporary feeling of pain in the arm was felt. This adverse event was mild and resolved after the treatment without requiring medication or any other intervention. The other adverse events which were deemed unrelated to the device.
The findings of the study show that Nerivio is effective for the acute treatment of migraine in the adolescent population. The results of the study show that Nerivio is safe to use and is well-tolerated by adolescence migraineurs. The incidence of device-related adverse events was low with no device-related serious adverse events.
Efficacy outcome summary is demonstrated in table 3.
Endpoint |
Result |
Pain-free at 2 hours post-treatment (in the test treatment) | 71.8% (28/39) |
Disappearance of associated symptoms at 2 hours post-treatment | 35.9% (14/39) |
Disappearance of nausea | 54.5% (12/22) |
Disappearance of photophobia | 41.9% (13/31) |
Disappearance of phonophobia | 40.0% (10/25) |
Sustained pain relief at 24 hours post-treatment (in the test treatment) | 90.9% (20/22) |
Sustained pain free at 24 hours post-treatment (in the test treatment) | 90.9% (10/11) |
Improvement in functional ability at 2 hours | 69.7% (23/33) |
Improvement in functional ability at 24 hours | 69.0% (20/29) |
Table 3 – Efficacy outcome
Conclusions
The results of the study show that Nerivio is safe and effective for the acute treatment of migraine in adolescents. There was one device-related adverse event in which a temporary feeling of pain in the arm was felt. This adverse event was mild and resolved after the treatment without requiring medication or any other intervention. This rate of device-related adverse events compares favorably to the reported rates for current pharmacological treatments. Importantly, the safety profile of Nerivio is also favorable with respect to new pharmacological developments such as ditans and gepants, though these have not been assessed in adolescents yet.
Acute treatment of migraine headaches resulted in clinically meaningful benefits. Pain relief and pain-free rates were generally similar to those found in adults, indicating that Nerivio provides an alternative acute migraine treatment independent of age.
Post HOC Analysis
In addition, a post hoc analysis (TCH-004) of comparison between the Nerivio treatment (REN) and Standard-Care Medications for Acute Treatment of Migraine was performed.
Four efficacy endpoints were tested: pain freedom and pain relief (severe to mild or no pain, or moderate to no pain—two-step improvement) after a single treatment, and pain freedom and pain relief consistency across treatments. All endpoints refer to 2 hours after treatment. For the single-treatment endpoints. The analyzed test treatment for REN was defined as the first REN treatment after a training treatment, and the test treatment for medications was defined as the first treatment in the run-in phase in which medication was used. For the consistency endpoints, consistent response was defined as response (pain freedom or relief) in at least 50% of the first four treatments. All participants had completed four evaluable REN treatments. The number of medication treatments varied among participants, and consistency was calculated on the basis of all available data (up to four treatments) for each participant.
Results
Participants
During the medication phase, eight participants (22.8%) used oral triptans only (five rizatriptan, one eletriptan,
one zolmitriptan, and one sumatriptan), two participants (5.7%) alternated between oral triptans and
OTC analgesics, and 26 participants (71.4%) used OTC analgesics only (11 ibuprofen, seven naproxen sodium,
five acetaminophen, and three acetaminophen-aspirin/caffeine combination).
Efficacy Results
Single Treatment Pain freedom in the REN phase was reported by 37.1% (13/35) of the participants, vs 8.6% (3/35) in the medication phase, with a statistically significant difference: P¼0.004 (OR¼11.0, 95% CI 1.60–473).
Pain relief in the REN phase was reported by 71.4% (25/35) of the participants, vs 57.1% (20/35) in the medication phase: P¼0.225 (OR¼1.83, 95% CI 0.62–6.04). The single-treatment results are depicted in Figure 2.
Consistent Efficacy
Consistent pain freedom in the REN phase was reported by 40.0% (14/35) of the participants, vs 8.6% (3/35) in
the medication phase, with a statistically significant difference: P<0.001 (proportion difference¼0.314,
0.144–0.473). OR was not applicable because there were zero participants in the group that achieved pain freedom
with medications but not with REN, and thus the paired proportion difference was estimated instead.
Consistent pain relief in the REN phase was reported by 80.0% (28/35) of the participants, vs 57.1% (20/35)
in the medication phase, with a statistically significant difference: P¼0.033 (OR¼3.67, 95% CI 0.97–20.47).
Response Rates by Medication Class Response rates were subanalyzed by medication class. Statistical comparison was not performed because of sample size limitations of the subgroups, and response rates are presented for reporting purposes only. Twentysix participants used OTC analgesic medications, of whom 38.4% (10/26) achieved pain freedom with REN, vs 11.5% (3/26) with medications. Pain relief was achieved by 76.9% (20/26) with REN, vs 65.3% (17/26) with medications. Nine participants used oral triptans, of whom 33.3% (3/9) achieved pain freedom with REN, vs 0% (0/9) with medications. Pain relief with REN was achieved by 55.5% (5/9), vs 33.3% (3/9) with medications.
The results of the post hoc analysis provides a preliminary indication that REN may be as effective as, if not more effective than, certain standard-Care medications in adolescents with migraine. Specifically, REN was found to be superior to the tested medications (oral triptans and OTC analgesic medications) in pain freedom after a single treatment, pain freedom consistency across treatments, and pain relief.
The Retrospective Survey Study (TCH-009) evaluated the self-reported effectiveness and tolerability of the Nerivio device for the acute treatment of menstrual migraine, via a retrospective structured survey that was sent to adult female Nerivio users.
Women aged 18–55 years who experience menstrually related or pure menstrual migraine and have completed at least four Remote Electrical Neuromodulation (REN) treatments with the Nerivio device, participated in this retrospective, observational survey study. Participants completed a short online survey assessing effectiveness, satisfaction, and safety outcomes. The survey was sent to 455 female patients aged 18–55 across the United States who used Nerivio between October 1, 2019, and October 18, 2020, and completed at least four REN treatment sessions.
Before taking the survey, patients provided informed consent. The consent form appeared as the first page of the survey, and participants clicked either ‘‘agree’’ or ‘‘disagree’’ to the consent statement (those who clicked ‘‘agree’’ proceeded to the survey, and those who clicked ‘‘disagree’’ were brought to an exit page).
Figure 1 – Survey disposition chart
Results
Effectiveness
Participants were predominantly white (92.3% [84/91]), had a mean age of 35.2 ± 8.1, had an average number of 13.3 ± 8.7 headache days per month, and treated 4.9 ± 4.8 menstrual migraines with Nerivio.
74.7% (68/91) of the participants reported that the treatment was at least moderately effective (moderately effective 37.4%, very effective 26.4%, extremely effective 11.0%). The treatment was reported not effective in 25.3% (23/91) of the participant (slightly effective: 20.9%, not effective 4.4%).
45.1% (41/91) of the participants reported satisfaction from REN (slightly satisfied 33%, extremely satisfied 12.1%), while 34.1% (31/91) were neutral, and 20.9% (19/91) were not satisfied (slightly dissatisfied 16.5%, not at all satisfied 4.4%).
82.4% (75/91) of the participants indicated that they experience menstrual cramps. Out of these 75, 38.7% (29/75) reported that REN was at least moderately effective (moderately effective 28.0%, very effective 8%, extremely effective 2.7%) in treating the cramps. The treatment was reported not effective for cramps in 61.3% (46/75) of the participant (slightly effective: 29.3%, not effective 32.2%).
38 patients (41.8%) indicated that they experience pelvic pain during menstruation. Out of these 38, 36.8% (14/38) reported that REN was at least moderately effective for the pelvic pain (moderately effective 28.9%, very effective 2.6%, extremely effective 5.3%). The treatment was reported not effective for pelvic pain by 63.2% (24/38) of the participant (slightly effective: 28.9%, not effective 34.2%).
Safety
Twelve patients (13.2%) reported mild short term side effects: sore arm for several days after treatment (n = 1), bruise on the arm (n = 1), nausea (n = 2), dizziness (n = 1), drowsiness (n = 1), muscle twitching (n = 3), numbness in the arm during treatment (n = 2), and tingling in the arm and hand (n = 1).
100% (91/91) of the participants reported that the treatment was at least moderately tolerable (moderately tolerable 8.8%, very tolerable 20.9%, extremely tolerable 70.3%).
The current survey study suggests that REN may offer an effective, well-tolerated treatment option for menstrual migraine, indicates that REN may provide a safe, non-pharmacological treatment option for women with menstrual migraine
You can see how this popup was set up in our step-by-step guide: https://wppopupmaker.com/guides/auto-opening-announcement-popups/
You are being redirected to UpScript, our telemedicine partner.
Register and create an UpScript account to get your prescription.
[contact-form-7 id=”1401″ title=”Contact Form”]
Click the link below to access Mychart download page
mychartplus.orgClick the link below to access Mychart download page
mychartplus.orgClick the link below to access Mychart download page
mychartplus.orgClick the link below to access Mychart download page
mychartplus.orgYou are being redirected to UpScript, our telemedicine partner.
Register and create an UpScript account to get your prescription.
You are being redirected to UpScript, our telemedicine partner.
Register and create an UpScript account to get your prescription.
You are being redirected to ProCare, our mail-order and specialty pharmacy partner.
Register and create a patient account at ProCare to get your prescription.
You are being redirected to ProCare Rx, our PBM systems partner.
Register and create a patient account with ProCare Rx to get your prescription.
You are being redirected to SteadyMD, our telemedicine partner.
Register and create a SteadyMD account to get your prescription.
You are being redirected to SteadyMD, our telemedicine partner.
Register and create a SteadyMD account to get your prescription.
[contact-form-7 id=”6996″ title=”HCP_Contact Form”]