OnabotulinumtoxinA Reduces Health Resource Utilization in Chronic Migraine: PREDICT Study.

BACKGROUND: PREDICT was a Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA treatment for chronic migraine (CM). We descriptively assess health resource utilization, work productivity, and acute medication use. METHODS: OnabotulinumtoxinA (155-195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Participants completed a 4-item health resource utilization questionnaire and 6-item Work Productivity and Activity Impairment Questionnaire: Specific Health Problem V2.0. Acute medication use was recorded in daily headache diaries. Treatment-emergent adverse events were recorded throughout the study. RESULTS: A total of 197 participants were enrolled, and 184 received ≥1 treatment with onabotulinumtoxinA and were included in the analysis. Between baseline and the final visit, there were decreases in the percentage of participants who reported headache-related healthcare professional visit(s) (96.2% to 76.8%) and those who received headache-related diagnostic testing (37.5% to 9.9%). Reductions from baseline were also observed in the mean number of headache-related visits to an emergency room/urgent care clinic (2.5 to 1.4) and median headache-related hospital admissions (4.0 to 1.0). OnabotulinumtoxinA improved work productivity and reduced the mean (standard deviation) number of hours missed from work over a 7-day period (6.1 [9.7] to 3.0 [6.8]). Mean (standard deviation) acute medication use decreased from baseline (15.2 [7.6] to 9.1 [6.5] days). No new safety signals were identified. CONCLUSIONS: Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA treatment for CM in the Canadian population reduces health resource utilization and acute medication use and improves workplace productivity, supporting the long-term benefits of using onabotulinumtoxinA for CM.

Long-term efficacy and safety of erenumab in patients with chronic migraine in whom prior preventive treatments had failed: A subgroup analysis.

OBJECTIVE: To assess the long-term efficacy and safety of erenumab in the subgroup of patients with chronic migraine (CM) in whom prior preventive treatments had failed (TF) (≥1, ≥2, and ≥3 TF medication categories) and never failed (preventive naïve or prior preventive treatments had not failed), using the data from a 52-week, open-label treatment period (OLTP) of the parent study. BACKGROUND: Erenumab is a fully human monoclonal antibody that selectively binds to and inhibits the canonical calcitonin gene-related peptide receptor. There are limited long-term data evaluating the efficacy and safety of erenumab in patients with CM in whom prior preventive treatments had failed. METHODS: Patients who had completed the 12-week double-blind treatment period (DBTP) in the parent study were eligible to participate in the 52-week OLTP, during which they received erenumab every 4 weeks. The TF subgroups (≥1, ≥2, and ≥3 TF medication categories) were not mutually exclusive; patients in whom prior preventive treatments from ≥3 medication categories had failed were also counted in the ≥2 and ≥1 medication categories. Endpoints included monthly migraine days (MMD), monthly acute migraine-specific medication days (MSMD), achievement of ≥50%, ≥75%, and 100% reduction from baseline in MMD, and exposure-adjusted patient incidence rates of adverse events (AEs; per 100 patient-years). RESULTS: Erenumab treatment provided sustained mean reductions in MMD and MSMD relative to the parent study baseline throughout the 52 weeks of the OLTP across all TF subgroups. At Week 52, the mean MMD change was -8.6 (SD 6.6) (baseline: 18.4 [SD 4.5] days) in the ≥1 TF subgroup. A post hoc completer analysis (52 weeks [OLTP] erenumab) showed that compared with erenumab 70 mg, the 140 mg dose was associated with numerically greater reductions in the mean MMD (Week 40: -8.6 and -7.2 days; Week 52: -9.7 and -7.9 days [≥1 TF subgroup]) and a higher proportion of patients achieved ≥50%, ≥75%, and 100% response thresholds across all subgroups at Weeks 40 and 52. Overall the exposure-adjusted patient incidence rates of AEs did not increase during the OLTP versus the DBTP (≥1 TF subgroup: 141.9/100 versus 317.9/100 patient-years), and no new safety signals occurred. CONCLUSION: The long-term treatment with erenumab was well tolerated and showed sustained efficacy in patients with CM in whom prior preventive treatments had failed, with numerically greater treatment effects for 140 mg versus 70 mg.

OnabotulinumtoxinA Improves Quality of Life in Chronic Migraine: The PREDICT Study.

BACKGROUND: The PREDICT study assessed real-world, long-term health-related quality of life in adults with chronic migraine (CM) receiving onabotulinumtoxinA. METHODS: Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA for CM. OnabotulinumtoxinA (155-195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Primary endpoint: mean change in Migraine-Specific Quality of Life Questionnaire (MSQ) at treatment 4 (Tx4) versus baseline. Secondary endpoints: mean change in MSQ at final visit versus baseline, and headache days. RESULTS: 184 participants (average age 45 years; 84.8% female; 94.6% Caucasian) received ≥1 onabotulinumtoxinA treatment; 150 participants completed 4 treatments (1 year) and 123 completed all 7 treatment cycles (2 years). Mean (SD) onabotulinumtoxinA dose per treatment cycle was 171 (18) U and treatment interval was 13.2 (1.8) weeks. Baseline mean (SD) 20.9 (6.7) headache days/month decreased (Tx1: -3.5 [6.3]; Tx4: -6.5 [6.6]; p < 0.0001 versus baseline). Mean (SD) increased from baseline in MSQ at Tx4 (restrictive: 21.5 [24.3], preventive: 19.5 [24.7], emotional: 22.9 [32.9]) and the final visit (restrictive: 21.3 [23.0], preventive: 19.2 [23.7], emotional: 27.4 [30.7]), exceeding minimal important differences (all p < 0.0001). Seventy-seven (41.8%) participants reported 168 treatment-emergent adverse events (TEAEs); 38 TEAEs (12.0%) were considered treatment-related. Four (2.2%) participants reported six serious TEAEs; none were considered treatment-related. No new safety signals were identified. CONCLUSIONS: Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA for CM in Canada improved MSQ scores and reduced headache frequency and severity, adding to the body of evidence on the long-term safety and effectiveness of onabotulinumtoxinA for CM.

Efficacy and safety of erenumab (AMG334) in chronic migraine patients with prior preventive treatment failure: A subgroup analysis of a randomized, double-blind, placebo-controlled study.

Background Erenumab was effective and well tolerated in a pivotal clinical trial of chronic migraine. Here, we evaluated efficacy and safety of monthly erenumab (70 mg or 140 mg) versus placebo in the subgroup of patients who had previously failed preventive treatment(s) (≥ 1, ≥ 2 prior failed medication categories) and in patients who had never failed. Methods Subgroup analyses evaluated change from baseline in monthly migraine days; achievement of ≥ 50% and ≥ 75% reduction in monthly migraine days; and change in monthly acute migraine-specific medication days. Adverse events were evaluated for each subgroup. Results Treatment with both doses of erenumab resulted in greater reductions in monthly migraine days (primary endpoint) at Month 3 (treatment difference [95% CI], never failed subgroup: -2.2 [-4.1, -0.3] for 70 mg and -0.5 [-2.4, 1.5] for 140 mg; ≥ 1 prior failed medication categories subgroup: -2.5 [-3.8, -1.2], for 70 mg and -3.3 [-4.6, -2.1] for 140 mg; ≥ 2 prior failed medication categories subgroup: -2.7 [-4.2, -1.2], for 70 mg and -4.3 [-5.8, -2.8] for 140 mg). Similar results were observed in the monthly acute migraine-specific medication days endpoint, and in the achievement of ≥ 50% and ≥ 75% reduction in monthly migraine days. There were no new or unexpected safety issues. Conclusion Erenumab showed consistent efficacy in chronic migraine patients who had failed prior preventive treatments and was well tolerated across subgroups.

A Nursing Intervention Increases Quality of Life and Self-Efficacy in Migraine: A 1-Year Prospective Controlled Trial.

OBJECTIVES: To compare the impact of a combined nursing and medical approach to a medical follow-up only on headache outcomes, quality of life, and self-efficacy in a cohort of migraineurs. BACKGROUND: Interdisciplinary approaches have been proposed for migraine management. A nursing intervention could improve patient outcomes. METHODS: We prospectively studied new patients referred to our tertiary headache center for migraine. The control group was followed by a physician; the active group was also followed by a nurse with a personalized intervention including adaptation of the lifestyle. RESULTS: Two hundred patients (176 women and 24 men, mean age 40 years old) were included and classified according to headache frequency. Each group was followed for 12 months with daily headache diaries. One hundred and sixty-two completed the study. There were no significant differences between groups for the decrease in headache days, the percent of chronic patients reverting to episodic status or the cessation of medication overuse. Patients in the control group were more likely to find a successful prophylaxis (55.6 vs 27.7%, P = .002). Despite this, the mean decrease in HIT-6 scores at month 8 was 5.23 ± 9.18 for the active group compared with a decrease of 2.10 ± 9.27 for the control group (P = .030, clinically significant difference of 3.13). Headache Management Self-Efficacy Scale (HMSE) scores, representing the feeling of self-efficacy, increased by 14.35 ± 18.41 for the active group vs 4.69 ± 21.22 in the control group (P = .002). CONCLUSION: A nursing intervention can lower the impact of migraines on the patient's life. The improvement in the HIT-6 score in this study was correlated with improvements in self-efficacy.

Neurostimulation for Refractory Cervicogenic Headache: A Three-Year Retrospective Study.

BACKGROUND: Occipital nerve stimulation (ONS) has been used for the treatment of neuropathic pain conditions and could be a therapeutic approach for refractory cervicogenic headache (CeH). AIM: The aim of this study is to assess the efficacy and safety of unilateral ONS in patients suffering from refractory CeH. METHODS: We conducted a retrospective chart review on patients implanted from 2011 to 2013 at CHUM. The primary outcome was a 50% reduction in headache days per month. Secondary outcomes included change in EuroQol Group Visual Analog Scale rating of health-related quality of life (EQ VAS), six item headache impact test (HIT-6) score, hospital anxiety and depression scale (HADS) score, work status, and medication overuse. RESULTS: Sixteen patients fulfilled the inclusion criteria; they had suffered from daily moderate to severe CeH for a median of 15 years. At one year follow-up, 11 patients were responders (69%). There was a statistically significant improvement in the EQ VAS score (median change: 40 point increase, p = 0.0013) and HIT-6 score (median change: 17.5 point decrease, p = 0.0005). Clinically significant anxiety and depression scores both resolved amongst 60% of patients. At three years, six patients were responders (37.5%). Out of the 11 responders at one-year post implantation, five had remained headache responders (R-R) and one additional patient became a responder (NR-R). There was a statistically significant improvement in the EQ VAS score (median change: 15 point increase, p = 0.019) and HIT-6 score (median change: 7.5 point decrease, p = 0.0017) compared with baseline. Clinically significant anxiety and depression scores both, respectively, resolved among 22.5% and 33.9% of patients. Five out of seven disabled patients were back to work. CONCLUSION: ONS may be a safe and effective treatment modality for patients suffering from a refractory CeH. Further study may be warranted.

Early onset of efficacy with erenumab in patients with episodic and chronic migraine.

BACKGROUND: Subcutaneous erenumab reduced monthly migraine days and increased the likelihood of achieving a ≥ 50% reduction at all monthly assessment points tested in 2 pivotal trials in episodic migraine (EM) and chronic migraine (CM). Early efficacy of migraine preventive medications is an important treatment characteristic to patients. Delays in achievement of efficacy can result in failed adherence. The objective of these post-hoc analyses were to evaluate efficacy in the first 4 weeks after initial subcutaneous administration of erenumab 70 mg, erenumab 140 mg, or placebo. METHODS: There is no generally accepted methodology to measure onset of action for migraine preventive medications. We used a comprehensive approach with data from both studies to evaluate change from baseline in weekly migraine days (WMD), achievement of ≥ 50% reduction in WMD, and proportion of patients experiencing migraine measured on a daily basis. The 7-day moving averages were overlaid with observed data. RESULTS: In both studies (EM: N = 955; CM: N = 667), there was evidence of onset of efficacy of erenumab vs. placebo during the first week of treatment, which in some cases reached nominal significance. For EM the changes in WMD were (least squares mean [LSM] [95% CI]): placebo, - 0.1 (- 0.3, 0.0); erenumab 70 mg, - 0.3 (- 0.5, - 0.2) p = 0.130; erenumab 140 mg, - 0.6 (- 0.7, - 0.4) p < 0.001. For CM the changes were: placebo, - 0.5 (- 0.8, - 0.3); erenumab 70 mg, - 0.9 (- 1.2, - 0.7) p = 0.047; erenumab 140 mg, - 0.8 (- 1.1, - 0.5) p = 0.18. Achievement of ≥ 50% reduction in WMD was observed as early as Week 1 (adjusted OR [95% CI] erenumab vs placebo) in EM: erenumab 70 mg, 1.3 (1.0, 1.9) p = 0.097; erenumab 140 mg, 2.0 (1.4, 2.7) p < 0.001. A similar outcome was observed for CM: erenumab 70 mg, 1.8 (1.1, 2.8) p = 0.011; erenumab 140 mg, 1.9 (1.2, 2.9) p = 0.009. Seven-day moving averages of observed data showed each treatment arm differed from placebo by Week 1 (OR [95% CI]): in EM Day 3 for erenumab 140 mg, 0.7 (0.5, 1.0) p = 0.031 and at Day 7 for 70 mg, 0.6 (0.4, 0.8) p = 0.002; in CM: Day 6 for erenumab 70 mg, 0.6 (0.4, 0.9) p = 0.022 and at Day 7 for 140 mg, 0.7 (0.4, 1.0); p = 0.038. CONCLUSION: Erenumab showed early onset of efficacy with separation from placebo within the first week of treatment in both chronic and episodic migraine patients.

Pregabalin for the management of cervicogenic headache: a double blind study.

OBJECTIVES: The primary objective was to evaluate the effects of pregabalin relative to placebo in patients with chronic unilateral cervicogenic headache. Primary and secondary end points: To assess the change from baseline in the frequency of cervicogenic headache days per 28-day period between placebo and treatment group. To assess the change from baseline in the intensity of headache, and health outcome measures. STUDY DESIGN: This was a double-blind, randomized, placebo-controlled, parallel-group study, evaluating the efficacy and safety of pregabalin in patients with cervicogenic headache. PROCEDURES: The study consisted of two phases. A baseline of -28 days and a double-blind placebo-controlled phase: with an escalation and maintenance phase, during which patients remained at their highest dose until the end of the study, at Day 86. RESULTS: Forty one patients were randomized, predominantly females, with a mean age of 52 years old. At screening, both groups had, on average, 26 headache-days per month. By the final phase of the study, the number of headache days dropped to 16 per month for the pregabalin group while remaining stable for the placebo group (p=0.037). No serious adverse events were reported during the study. CONCLUSION: In this study, primary objectives were achieved with a statistically significant change of ten days in frequency of headache days; with minor side effects that were well tolerated.

Prophylactic onabotulinumtoxinA in patients with chronic migraine and comorbid depression: An open-label, multicenter, pilot study of efficacy, safety and effect on headache-related disability, depression, and anxiety.

BACKGROUND: Chronic migraine is associated with significant headache-related disability and psychiatric comorbidity. OnabotulinumtoxinA (BOTOX(®)) is effective and well tolerated in the prophylactic treatment of chronic migraine. This study aimed to provide preliminary data on the efficacy and safety of prophylactic onabotulinumtoxinA in patients with chronic migraine and comorbid depressive symptoms. METHODS: This was a prospective, open-label, multicenter pilot study. Eligible patients met International Classification of Headache Disorders 2nd edition Revision criteria for chronic migraine and had associated depressive symptoms, including Patient Health Questionnaire depression module scores of 5-19. Eligible participants received 155 units of onabotulinumtoxinA, according to the PREEMPT protocol, at baseline and week 12. Assessments included headache frequency, the Headache Impact Test™, the Migraine Disability Assessment, the Beck Depression Inventory(®)-II, the nine-item Patient Health Questionnaire depression module, and the seven-item Generalized Anxiety Disorder questionnaire. Adverse events were also monitored. RESULTS: Overall, 32 participants received treatment. At week 24, there were statistically significant mean (standard deviation [SD]) improvements relative to baseline in the number of headache/migraine-free days (+8.2 [5.8]) (P<0.0001) and in the number of headache/migraine days (-8.2 [5.8]) (P<0.0001) per 30-day period. In addition, there were significant improvements in Headache Impact Test scores (-6.3 [6.9]) (P=0.0001) and Migraine Disability Assessment scores (-44.2 [67.5]) (P=0.0058). From baseline to week 24, statistically significant improvements were also seen in Beck Depression Inventory-II (-7.9 [6.0]) (P<0.0001), Patient Health Questionnaire depression module (-4.3 [4.7]) (P<0.0001), and Generalized Anxiety Disorder questionnaire (-3.5 [5.0]) (P=0.0002) scores. No serious adverse events were reported. Adverse events considered related to treatment occurred in 30% of patients and were mild or moderate. CONCLUSION: Prophylactic onabotulinumtoxinA was well tolerated in patients with chronic migraine and comorbid depression, and was effective in reducing headache frequency, impact, and related disability, which led to statistically significant improvements in depression and anxiety symptoms.