Triptan efficacy does not predict onabotulinumtoxinA efficacy but improves with onabotulinumtoxinA response in chronic migraine patients

Chronic migraine (CM) is a highly disabling primary headache. Botulinum toxin (onabotulinumtoxinA) is effective for treatment of CM, with similar to 50% of patients responding after 24 weeks. A response predictor would prevent unnecessary treatments. Inhibiting calcitonin gene related peptide (CGRP) release from trigeminal nociceptive fibres is one of the modes of acting discussed for onabotulinumtoxinA in CM. Therefore, we hypothesized that the response to triptans might predict response to onabotulinumtoxinA. Contrariwise, onabotulinumtoxinA treatment might affect triptan efficacy. 49 CM patients scheduled for their first onabotulinumtoxinA treatment were included. Before (T0) and three months after (T1) onabotulinumtoxinA treatment, patients rated triptan efficacy and indicated number of headache days/month. At T1, patients additionally rated onabotulinumtoxinA efficacy. Headache days/month were on average reduced by 7.1 +/- 7.0 days from T0 to T1 (p < 0.001). Triptan efficacy ratings at T0 did not predict onabotulinumtoxinA efficacy ratings at T1 (p = 0.19) or reduction of headache days (p = 0.37). However, triptan efficacy significantly improved from T0 to T1 in onabotulinumtoxinA responders (p < 0.001) but not in non-responders (p = 1.00). Triptan efficacy did not predict response to onabotulinumtoxinA in CM. However, triptan efficacy increased after successful onabotulinumtoxinA treatment. This supports the hypothesis that efficacy of acute migraine treatment with triptans improves with effective migraine prophylaxis

Effects of non-invasive vagus nerve stimulation on attack frequency over time and expanded response rates in patients with chronic cluster headache: a post hoc analysis of the randomised, controlled PREVA study

Background: In the PREVention and Acute treatment of chronic cluster headache (PREVA) study, attack frequency reductions from baseline were significantly more pronounced with non-invasive vagus nerve stimulation plus standard of care (nVNS + SoC) than with SoC alone. Given the intensely painful and frequent nature of chronic cluster headache attacks, additional patient-centric outcomes, including the time to and level of therapeutic response, were evaluated in a post hoc analysis of the PREVA study. Findings: After a 2-week baseline phase, 97 patients with chronic cluster headache entered a 4-week randomised phase to receive nVNS + SoC (n = 48) or SoC alone (n = 49). All 92 patients who continued into a 4-week extension phase received nVNS + SoC. Compared with SoC alone, nVNS + SoC led to a significantly lower mean weekly attack frequency by week 2 of the randomised phase;the attack frequency remained significantly lower in the nVNS + SoC group through week 3 of the extension phase (P = 25%, >= 50%, and >= 75% from baseline (>= 25% and >= 50%, P = 75%, P = 0.009). The 100% response rate was 8% with nVNS + SoC and 0% with SoC alone. Conclusions: Prophylactic nVNS led to rapid, significant, and sustained reductions in chronic cluster headache attack frequency within 2 weeks after its addition to SoC and was associated with significantly higher >= 25%, >= 50%, and >= 75% response rates than SoC alone. The rapid decrease in weekly attack frequency justifies a 4-week trial period to identify responders to nVNS, with a high degree of confidence, among patients with chronic cluster headache

Burden of Migraine in Patients With Preventive Treatment Failure Attending European Headache Specialist Centers: Real-World Evidence From the BECOME Study

Migraña; Fracaso del tratamiento; Productividad laboralMigraine; Treatment failure; Work productivityMigranya; Fracàs del tractament; Productivitat laboralIntroduction Migraine is consistently ranked as one of the most disabling neurological conditions in the world, often causing a substantial impairment of daily activities and quality of life. It also carries a high economic burden of direct and indirect healthcare costs. Patients with difficult-to-treat migraine often cycle through different preventive therapies, but real-world prospective evidence describing the burden of migraine in patients with prior preventive treatment failure (PPTF) in Europe is limited. In BECOME, we aimed to characterize and assess the prevalence and burden of migraine in patients with PPTF attending specialist headache centers in Europe and Israel. Furthermore, we assessed this burden in pre-specified subgroups based on the frequency of monthly migraine days (MMD) and number of PPTFs. Methods BECOME was a prospective, non-interventional study conducted in two concurrent parts across 17 countries in Europe and Israel. In part 1, patients visiting the centers over a 3-month period were screened for frequency of PPTF, MMD, and other characteristics. In part 2, patients from part 1 with ≥ 1 PPTF and ≥ 4 MMD were enrolled, and impact of migraine on patient-reported outcomes, and healthcare resource utilization (HRU) were examined. Results In part 1 (n = 20,837), 62.2% of patients reported ≥ 1 PPTF. In part 2 (n = 2419), 15.3% of patients reported ≥ 4 PPTF. In part 2, the migraine burden measured by the EuroQoL 5 dimensions 5 level (EQ-5D-5L) questionnaire indicated an impact of at least moderate severity in performing usual activities in 26.5% of patients, pain/discomfort in 51.2%, and 26.1% reported being at least moderately anxious/depressed. Most patients reported a severe impact on daily activities and disability due to migraine. Abnormal Hospital Anxiety and Depression subscale scores of ≥ 11 were observed in 29% (anxiety) and 19.8% (depression) of the population. In part 2, analysis of HRU showed 21.2% patients visited an emergency department and 8.4% were hospitalized for headache/migraine in the past year. Conclusions This study provides real-world evidence of the high personal, social, and HRU burden of migraine in Europe and Israel.This study was funded by Novartis Pharma AG, Basel, Switzerland. The study sponsor participated in the study design, data collection, data review, data analysis and writing of the report. The Rapid Service Fee was funded by Novartis Pharma AG, Basel, Switzerland

Prednisone for the treatment of withdrawal headache in patients with medication overuse headache: A randomized, double-blind, placebo-controlled study

Purpose: To investigate the efficacy of prednisone for treatment of withdrawal headache in patients with medication overuse headache (MOH). Patients and methods: In this prospective double-blind, placebo-controlled, parallel designed multicentre trial, 96 consecutive patients with MOH were randomized to withdrawal treatment with either 100 mg prednisone or placebo over 5 days. Patients were enrolled if they met the International Headache Society criteria for MOH and were diagnosed with migraine or episodic tension-type headache as primary headache. Exclusion criteria comprised significant neurological or psychiatric disorders. Withdrawal symptoms, including headache severity and intake of rescue medication, were documented for 14 days after randomization. Results: Patients treated with prednisone did not experience fewer hours of moderate or severe headache than patients receiving placebo. However, patients requested less rescue medication within the first 5 days. Conclusions: During withdrawal in MOH, prednisone reduces rescue medication without decreasing the severity and duration of withdrawal headache

Cost-effectiveness analysis of non-invasive vagus nerve stimulation for the treatment of chronic cluster headache

Background: Cluster headache (CH) is a debilitating condition that is generally associated with substantial health care costs. Few therapies are approved for abortive or prophylactic treatment. Results from the prospective, randomised, open-label PREVA study suggested that adjunctive treatment with a novel non-invasive vagus nerve stimulation (nVNS) device led to decreased attack frequency and abortive medication use in patients with chronic CH (cCH). Herein, we evaluate whether nVNS is cost-effective compared with the current standard of care (SoC) for cCH. Methods: A pharmacoeconomic model from the German statutory health insurance perspective was developed to estimate the 1-year cost-effectiveness of nVNS + SoC (versus SoC alone) using data from PREVA. Short-term treatment response data were taken from the clinical trial;longer-term response was modelled under scenarios of response maintenance, constant rate of response loss, and diminishing rate of response loss. Health-related quality of life was estimated by modelling EQ-5D T data from PREVA;benefits were defined as quality-adjusted life-years (QALY). Abortive medication use data from PREVA, along with costs for the nVNS device and abortive therapies (i.e. intranasal zolmitriptan, subcutaneous sumatriptan, and inhaled oxygen), were used to assess health care costs in the German setting. Results: The analysis resulted in mean expected yearly costs of (sic)7096.69 for nVNS + SoC and (sic)7511.35 for SoC alone and mean QALY of 0.607 for nVNS + SoC and 0.522 for SoC alone, suggesting that nVNS generates greater health benefits for lower overall cost. Abortive medication costs were 23 % lower with nVNS + SoC than with SoC alone. In the alternative scenarios (i.e. constant rate of response loss and diminishing rate of response loss), nVNS + SoC was more effective and cost saving than SoC alone. Conclusions: In all scenarios modelled from a German perspective, nVNS was cost-effective compared with current SoC, which suggests that adjunctive nVNS therapy provides economic benefits in the treatment of cCH. Notably, the current analysis included only costs associated with abortive treatments. Treatment with nVNS will likely promote further economic benefit when other potential sources of cost savings (e.g. reduced frequency of clinic visits) are considered

More Attacks and Analgesic Use in Old Age: Self-Reported Headache Across the Lifespan in a German Sample

Background: Reliable population-based data on the prevalence and characteristics of primary headache across the lifespan are essential. However, robust data are lacking. Methods: We utilized questionnaire data from a random general population sample in Germany, that comprised 2,478 participants aged ≥14 years. A standardized questionnaire addressing headache and headache treatment was filled in during the face-to-face survey. Results: The 6-month prevalence of self-reported headache in the total sample amounted to 39.0% (known diagnosis of migraine 7.2%; tension-type headache 12.4%; another diagnosis or unknown diagnosis 23.4%). Age-specific prevalence rates were 37.9% (14-34 years), 44.6% (35-54 years), 38.5% (55-74 years), and 26.9% (≥75 years). Compared to age group 14-34, participants aged 35-54 were more (OR = 1.29, 95%-CI 1.05-1.60, p = 0.018) and those aged ≥75 were less (OR = 0.55, 95%-CI 0.40-0.76, p 14 days per month. The frequency of headache did not differ significantly between age groups in men [χ2(3, N = 384) = 1.45, p > 0.05], but in women [χ2(3, N = 651) = 21.57, p 14 days per month: 1.8 (14-34 years), 2.5 (35-54 years), 3.2 (55-74 years), and 3.4 (≥75 years), respectively 7.9 (14-34 years), 11.4 (35-54 years), 18.4 (55-74 years), and 22.8 (≥75 years). Conclusions: In general, the prevalence of headache decreases with age. However, older women suffer from more frequent attacks and older participants take analgesics on more days per month than younger participants. This might put them at risk of medication overuse which may lead to medication overuse headache. More research is needed to understand these specifics in headache frequency and treatment behavior in older people

Use of outpatient medical care by headache patients in Germany: a population-based cross-sectional study

Background: Headache sufferers in need of professional health care often do not utilize the care available, and factors influencing headache-specific physician consultation are not yet understood. Objectives of this study are (1) to assess self-reported headache-specific physician consultations and (2) to identify headache-related and sociodemographic predictors. Methods: Data of a random sample of the general population in Germany aged ≥14 years were analyzed (N = 2461). A multivariate binary logistic regression was conducted to identify a parsimonious model to predict physician consultation. Results: 50.7% of the participants with headache reported at least one headache-specific physician consultation during lifetime. Of these, 53.6% had seen one, 26.1% two, and 20.3% more than two physicians because of their headaches. The odds of physician consultation increased with the number of headache days per month (HDM) (reference HDM 1) HDM 1–3 (OR = 2.29), HDM 4–14 (OR = 2.41), and HDM ≥15 (OR = 4.83) and increasing Headache Impact Test score (HIT-6) (reference “no or little impact”) moderate impact (OR = 1.74), substantial impact (OR = 3.01), and severe impact (OR = 5.08). Middle-aged participants were more likely to have consulted than younger and older ones (reference 14–34 years) 35–54 years (OR = 1.90), 55–74 years (OR = 1.96), ≥75 years (OR = 1.02). The odds of physician consultation among self-employed subjects were lower than among employed manual workers (OR = 0.48). The living environment (rural versus urban) did not have an influence on the consultation frequency. Conclusion: The results indicate that apart from burden-related factors (headache frequency; headache impact), health care utilization patterns are also influenced by patients’ occupational status and age. Further research is needed to analyze whether the lower consultation rate means that the self-employed have a higher risk of chronification or that they have more effective self-management strategies regarding headache