Currently Viewing:
Supplements Noninvasive Vagus Nerve Stimulation for Migraine and Primary Headache Disorders: Efficacy, Cost, and Impact on Quality of Life
Review of Evidence on Noninvasive Vagus Nerve Stimulation for Treatment of Migraine: Efficacy, Safety, and Implications
Mkaya Mwamburi, MD, PhD; Andrew T. Tenaglia, BA; Eric J. Leibler; and Peter S. Staats, MD, MBA
Currently Reading
Noninvasive Vagus Nerve Stimulation in a Primary Care Setting: Effects on Quality of Life and Utilization Measures in Multimorbidity Patients With or Without Primary Headache
Iain Strickland, PhD, BSc; Mkaya Mwamburi, MD, PhD; Steven Davis BSc; James C.R. Ward, MBBS; Janet Day, MBChB; Andrew T. Tenaglia, BA; Eric J. Leibler; and Peter S. Staats, MD, MBA
Participating Faculty

Noninvasive Vagus Nerve Stimulation in a Primary Care Setting: Effects on Quality of Life and Utilization Measures in Multimorbidity Patients With or Without Primary Headache

Iain Strickland, PhD, BSc; Mkaya Mwamburi, MD, PhD; Steven Davis BSc; James C.R. Ward, MBBS; Janet Day, MBChB; Andrew T. Tenaglia, BA; Eric J. Leibler; and Peter S. Staats, MD, MBA
Participants were followed between 4 to 60 weeks with a median follow up duration of 28 weeks. Patient self-reported adherence to gammaCore use after the week 4 visit, who continued gammaCore treatment was between 84% and 100% of patients complying to the prescribed gammaCore regimen as evaluated at the respective timepoints with the mean cumulative doses of gammaCore used, increasing to 955 doses at 40 weeks. In the LOCF analysis, the mean difference in EQ-5D index was +0.114 (P <.001) for all patients (n = 233), +0.113 (P <.001) for primary headache patients (n = 132), and +0.114 (P <.001) for nonheadache patients (n = 101). In the persistent gammaCore user analysis, the mean EQ-5D index increased from 0.58 at baseline to 0.74 at 12 weeks (n = 125) after which the index plateaued and was 0.77 at week 40 (n = 61). The increase in the EQ-5D index at week 40 (n = 61) was +0.156 (P <.001) for all patients, was +0.151 (P <.001) for primary headache patients (n = 37) and was +0.164 (P <.001) for nonheadache patients (n = 24). These findings for all primary headache and nonheadache patients are shown in Figures 2a, 2b, and 2c.

Changes in Utilization and Productivity Measures

In LOCF analysis, the mean percentage changes observed for all patients in number of consults and referrals were -19.3% (P <.001) from baseline mean of 4.10, and -23.2% (P =.02) from baseline mean of 0.78, respectively. The mean percentage change observed for primary headache patients in number of GP consults was -20.4% (P =.004) from baseline mean of 4.08. The mean percentage changes observed for non-headache patients in number of GP consults and referrals were -17.8% (P = .05) from baseline mean of 4.12, and -36.5% (P = .04) from baseline mean of 0.73, respectively.

In persistent gammaCore user analysis, mean percentage changes observed for all patients in number of GP consults and medical codes used were -28.5% (P = .002) from baseline mean of 7.31 and -40.0% (P = .002) from baseline mean of 3.52, respectively. The mean percentage changes observed for primary headache patients in number of GP consults, medical codes and sick notes issued were -29.5% (P = .01) from baseline mean of 6.41, -38.8% (P = .04) from baseline mean of 3.41, and -34.6% (P = .06) from baseline mean of 0.78, respectively. The mean percentage changes observed for nonheadache patients in the number of GP consults and medical codes were -37.3% (P = .06) from baseline mean of 8.71 and -41.5% (P = .01) from baseline mean of 3.71, respectively. These findings are shown in Table 2.

Changes in Utilization Measures by GammaCore Use Patterns

Of the 233 participants, the mean number of baseline GP consults were 7.3 versus 4.0 versus 1.0, respectively (P <.001) for persistent gammaCore users (n = 61), patients who used gammaCore for more than 4 weeks but less than 40 weeks (n = 111), and patients who used gammaCore for just 4 weeks (n = 61) respectively; number of baseline referrals were 1.1 versus 0.9 versus 0.2, respectively (P <.001); and number of baseline diagnosis codes used were 3.5 versus 2.0 versus 0.6, respectively (P <.001). The observed mean changes among persistent gammaCore users who used gammaCore for more than 4 weeks but less than 40 weeks and patients who used gammaCore for just 4 weeks were –2.08 versus –0.36 versus –0.27 respectively for number of GP consults (P = .003); –0.30 versus –0.21 versus 0.00 (no change) respectively for number of referrals (P = .33); and –1.41 versus +0.31 versus -0.14 respectively for number of diagnosis codes used (P <.001). These findings are illustrated in Figure 3.

Discussion

This analysis shows that a significant proportion of multimorbidity patients with MUS were persistent and adherent with gammaCore for more than 6 months. It also demonstrated that those considered high-demand patients (ie, those who had the highest healthcare resource utilization at baseline) were more likely to become the persistent gammaCore users and experienced the most robust improvements in QOL and reductions in utilization. Therefore, the high-demand patents that needed gammaCore the most were self-selecting and benefited from the greatest reduction in symptoms and health resource utilization. The gammaCore response was rapid and observed within 2 to 3 months of initiating treatment. The impact of gammaCore in patients with multiple comorbid conditions were somewhat similar among those with or without a primary headache disorder, indicating its potential suitability for any patient with comorbidities. This observation may be due to an existing common, yet unexplained pathology associated with vagal tone insufficiency or some other latent causation, that is potentially highlighted in those who benefited most dramatically due to persistent gammaCore use. The significant reduction in the utilization measures (–29%) and symptom codes used (–40%) among persistent gammaCore users suggest that nVNS may result in significantly lower healthcare costs and allow the potential for an effective pay-for-performance (value-based) platform for insurance coverage policies in the United States and similar healthcare environments.

These findings represent real-world evidence based on practical observations without strict clinical study requirements and designed to show how patients will respond to gammaCore use now that the device is being launched more broadly. We believe this is the first piece of evidence characterizing the effect of gammaCore in documented multimorbidity patients. Multimorbidity patients with MUS, who typically represent high-demand patients, can cost payers up to 3 times than patients without MUS and related comorbidities.7-9,16 The observed reduction in utilization (ie, the reduction in GP consults and number of diagnosis codes used) translates to a significant decrease in the costs associated with fewer GP visits, fewer laboratory tests, fewer requests for imaging diagnostic tests, and a decrease in a range of other related costs. The choice to use the number of GP consults, referrals, diagnosis codes used, and sick notes issued as measures of utilization and productivity was dictated by previously published studies and the availability of data in these primary care clinics.16 In considering the reduced GP consults (–30%) for which patients seek care for fewer diagnosis codes (–40%), it is reasonable to conclude that the additive effects could result in significantly lower future cost of care, reduced by as much as 50% (at least more than 30% or 40% in this case) and these savings may be more dramatic if there are subsequent reductions in laboratory and imaging test requests. This would be supported in findings by Polson et al (2018), demonstrating that in migraine patients with other MUS, there were higher utilization rates and the costs associated with the individual utilization events (eg, doctors’ visits, laboratory tests, imaging tests, emergency department [ED] visits) were higher for migraine/MUS patients than controls.

Of the 233 patients prescribed gammaCore, 93 patients (40%), a significant proportion, who persisted on gammaCore for up to 40 weeks with associated benefits, suggest clinical effectiveness. The voluntary persistence and adherence to gammaCore among the patients are indications that patients identified and appreciated measurable clinical and QOL benefits. The patients who persisted on and adhered to gammaCore were self-driven and self-selective and not dictated by a study protocol. This suggests that the observed rate of persistent use was very high and likely facilitated by the alleviation of symptoms together with ease of use, safety, practicality of gammaCore use, and offers robust evidence supporting the persistent use of gammaCore in the real world. This has been documented in primary headache studies.13,17-19 Patients benefited in a range of meaningful ways, including improvements in QOL measured using the validated EuroQol EQ-5D-5L index instrument.15 Patients showed significant benefits in questions in the EQ-5D instrument pertaining to usual activities, pain and discomfort, and anxiety and depression, but not in mobility or self-care. These observations align well with illness profiles of the patients included and further validate the patterns elicited for this population. These patients typically are relatively healthy physically and can take care of themselves. Therefore, even at baseline, these patients understandably scored well on mobility or self-care. Typically, the symptoms for these comorbid functional disorders of MUS predominantly affect activities of daily living, such as employment, exposure to pain, or anxiety/depression. Accordingly, at baseline, these patients scored poorly on usual activities, pain and discomfort, and anxiety and depression. This is consistent in our results, in which a significant response to gammaCore use was observed. Our interpretation is that persistent gammaCore use resulted in improved symptoms to the extent that it reduced the need for patients to seek as many GP consults and to seek treatment for fewer symptoms in their last 4 weeks compared to their respective initial 4 weeks and required fewer sick notes. Persistent gammaCore users benefited the most in those measures and even though the numbers of patients (n = 61 for all patients; n = 37 for primary headache patients; and n = 24 for nonheadache patients) were small, the findings were even more clinically and statistically significant. Of note, the improvements in QOL among the persistent gammaCore users were rapid and most dramatic in the initial 2 to 3 months and then sustained, thus, perpetuating the voluntary persistence and adherence to gammaCore. Those not experiencing the benefit within this time frame likely opted to stop treatment.

 
Copyright AJMC 2006-2019 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
x
Welcome the the new and improved AJMC.com, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up