Real-World Evidence for the Safety and Efficacy of CGRP Monoclonal Antibody Therapy Added to OnabotulinumtoxinA Treatment for Migraine Prevention in Adult Patients With Chronic Migraine.

Background: OnabotulinumtoxinA and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) target different migraine pathways, therefore, combination treatment may provide additional effectiveness for the preventive treatment of chronic migraine (CM) than either treatment alone. The objective of this study was to collect real-world data to improve the understanding of the safety, tolerability, and effectiveness of adding a CGRP mAb to onabotulinumtoxinA treatment for the preventive treatment of CM. Methods: This was a retrospective, longitudinal study conducted using data extracted from a single clinical site's electronic medical records (EMR) of adult patients (≥18 years) with CM treated with ≥2 consecutive cycles of onabotulinumtoxinA before ≥1 month of continuous onabotulinumtoxinA and CGRP mAb (erenumab, fremanezumab, or galcanezumab) combination treatment. Safety was evaluated by the rate of adverse events (AE) and serious adverse events (SAE). The proportion of patients who discontinued either onabotulinumtoxinA, a CGRP mAb, or combination treatment, and the reason for discontinuation, if available, was collected. The effectiveness of combination preventive treatment was assessed by the reduction in monthly headache days (MHD). Outcome data were extracted from EMR at the first CGRP mAb prescription (index) and up to four assessments at ~3, 6, 9, and 12 months post-index. The final analyses were based on measures consistently reported in the EMR. Results: EMR were collected for 192 patients, of which 148 met eligibility criteria and were included for analysis. Erenumab was prescribed to 56.7% of patients, fremanezumab to 42.6%, and galcanezumab to 0.7%. Mean (standard deviation [SD]) MHD were 20.4 (6.6) prior to onabotulinumtoxinA treatment and 14.0 (6.9) prior to the addition of a CGRP mAb (baseline). After real-world addition of a CGRP mAb, there were significant reductions in MHD at the first assessment (~3 months) (mean -2.6 days/month, 95% CI -3.7, -1.4) and at all subsequent visits. After ~12 months of continuous combination treatment, MHD were reduced by 4.6 days/month (95% CI -6.7, -2.5) and 34.9% of patients achieved ≥50% MHD reduction from index. AEs were reported by 18 patients (12.2%), with the most common being constipation (n = 8, 5.4% [onabotulinumtoxinA plus erenumab only]) and injection site reactions (n = 5, 3.4%). No SAEs were reported. Overall, 90 patients (60.8%) discontinued one or both treatments. The most common reason for discontinuing either treatment was lack of insurance coverage (40%); few (~14%) patients discontinued a CGRP mAb and none discontinued onabotulinumtoxinA due to safety/tolerability. Conclusion: In this real-world study, onabotulinumtoxinA was effective at reducing MHD and the addition of a CGRP mAb was safe, well-tolerated and associated with incremental and clinically meaningful reductions in MHD for those who stayed on the combination treatment. No new safety signals were identified. Of those who discontinued, the majority reported lack of insurance coverage as a reason. Prospective real-world and controlled trials are needed to further evaluate the safety and potential benefits of this combination treatment paradigm for people with CM.

Effect of Headache-Free Days on Disability, Productivity, Quality of Life, and Costs Among Individuals with Migraine.

BACKGROUND: The functional impairment associated with migraine can cause physical, emotional, and economic ramifications that can affect occupational, academic, social, and family life. Understanding the relationship between headache-free days (HFDs) and the disease burden of migraine may help with decisions regarding treatment and management of migraine. OBJECTIVE: To determine the relationship between burden of disease measures and HFDs among individuals with migraine experiencing ≥ 4 headache days in the previous 30 days. METHODS: The 2016 U.S. National Health and Wellness Survey (N = 97,503) was self-administered to a nationally representative sample of adults. Respondents with a migraine diagnosis who reported ≥ 4 headache days a month were included in the analysis. The primary independent variable was the number of HFDs assessed as both a continuous (HFDs in the previous 30 days) and categorical (0-10, 11-20, and 21-26 HFDs) measure. HFDs were used to predict outcomes using separate generalized linear models. Outcomes included effect on functional status and well-being, measured by the 6-item Headache Impact Test (HIT-6) score; number of days of work and/or household activities missed due to migraine; annualized indirect costs due to work productivity loss (assessed via the Work Productivity and Activity Impairment questionnaire); and annualized direct costs due to health care resource use (health care provider visits, emergency room visits, and hospitalizations). RESULTS: The survey included 372 respondents with diagnosed migraine and ≥ 4 headache days per month. Using HFDs as a continuous variable, each additional HFD was associated with a 0.15-point reduction in HIT-6 scores, a 5% reduction in both number of work days and household activities missed, and a 4% reduction in indirect costs; thus, a 5-day increase in HFDs would lead to a 0.75-point reduction in HIT-6 scores, 25% reduction in days of work or household activities missed, and 20% reduction in indirect costs. Analyzing HFDs as a categorical variable, respondents experiencing 21-26 HFDs had lower HIT-6 total scores than those with 0-10 HFDs (adjusted means: 66.59 vs. 63.91; P = 0.001) or those with 11-20 HFDs (65.66 vs. 63.91, P = 0.015). Respondents experiencing 21-26 HFDs missed fewer work days than those with 0-10 HFDs (4.44 vs. 1.46, P = 0.002) or those with 11-20 HFDs (3.36 vs. 1.46, P = 0.009). Similarly, respondents with 11-20 HFDs (22.99 vs. 9.72, P < 0.001) and those with 21-26 HFDs (22.99 vs. 7.34, P = 0.001) were associated with fewer days of household activities missed due to migraine compared with respondents with 0-10 HFDs. Respondents with 21-26 HFDs per month had significantly lower indirect costs ($16,975 vs. $6,919, P = 0.025) than those with 0-10 HFDs. CONCLUSIONS: A higher number of HFDs is associated with decreased headache-related disability among those with migraine. Interventions that increase the total number of HFDs may reduce the burden and cost associated with migraine. DISCLOSURES: This study was funded by Teva Pharmaceutical Industries (Petach Tikva, Israel). Cohen is an employee of Teva Branded Pharmaceutical Products R&D (USA); Bell was employed by Teva Pharmaceutical Industries at the time of this study and has stock/stock options in Teva Pharmaceutical Industries. Lee is employed by Kantar, which received payment from Teva Pharmaceutical Industries for data analyses performed for this study. Lipton has received research support from the NIH, the Migraine Research Foundation, and the National Headache Foundation. He has reviewed for the NIA and NINDS; holds stock options in eNeura Therapeutics and Biohaven Holdings; and serves as consultant, advisory board member, or has received honoraria from the American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Dr. Reddy's, electroCore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, and Vedanta. Saikali serves on the advisory board and as speaker for Allergan, Amgen, Promius, Supernus, and Teva Pharmaceuticals. He serves as a speaker for Assertio, Avanir, Cefaly, Egalet, Eli Lilly, Gammacore, and Pernix. This study has been presented as a poster at the American Academy of Neurology 2018 Annual Meeting, April 21-27, 2018, in Los Angeles, CA; Headache Update 2017, July 13-16, 2017, in Lake Buena Vista, FL; and the American Headache Society 2017 Annual Meeting, June 8-11, 2017, in Boston, MA.

Sphenopalatine ganglion block in primary headaches: An American Headache Society member survey.

BACKGROUND: The sphenopalatine ganglion (SPG), in the pterygopalatine fossa, is a known current and historical target for therapeutic intervention in headache disorders because of its role in cranial autonomics and vasodilation. There remains an overall lack of well-established SPG treatment protocols, particularly with the advent of newer commercial devices. METHODS: A 22 multiple-choice question survey was created to evaluate clinical practice patterns with SPG block and sent to members of the American Headache Society (AHS). Questions focused on determining indications, preferred applicators, medications applied, perceived efficacy, tolerability, and reimbursement. RESULTS: One hundred seventy-two of 1,346 (12.8%) AHS members participated. Ninety-three respondents (56.3%) had performed SPG blocks on 50 or fewer patients. The SphenoCath (42.4%) and the Tx360 (41.8%) were the most common methods of application. Ease of use was the top reason for provider preference in applicator type. SPG blocks were mostly used as an as-needed one-time procedure. When a scheduled protocol was used, twice weekly for 6 weeks was most common. Chronic migraine was the most commonly treated headache disorder and rated the most likely to respond to SPG block. Experienced clinicians found SPG more helpful as a stand-alone treatment and tended to report that acute relief was not predictive of enduring response. CONCLUSIONS: The variety of responses strongly suggests that clinicians would benefit from formalized protocols for SPG blocks. More experienced clinicians may have developed individualized protocols that they feel are more effective. The lack of evidence-based protocols contribute to clinicians not performing SPG blocks more frequently.

Novel treatment for radiation optic neuropathy with intravenous bevacizumab.

Radiation optic neuropathy is a devastating form of vision loss that can occur months to years after radiation therapy for tumors and other lesions located in close proximity to the visual pathways. We present the case of a 24-year-old woman who underwent external beam radiation for treatment of a tectal pilocytic astrocytoma, and 5 years later she developed bilateral radiation optic neuropathy and radiation necrosis of the right temporal lobe. We opted to treat her with intravenous bevacizumab with 3 doses every 3 weeks, as well as dexamethasone and pentoxifylline. After the first infusion of bevacizumab, the patient noted improvement in vision and color vision, and a follow-up magnetic resonance imaging study showed that the previous enhancement of the optic nerves and chiasm was diminishing. Her vision improved dramatically and has remained stable over a 3-year period.