The spectrum of response to erenumab in patients with chronic migraine and subgroup analysis of patients achieving ≥50%, ≥75%, and 100% response.

OBJECTIVE: To assess the efficacy of erenumab across the spectrum of response thresholds (≥50%, ≥75%, 100%) based on monthly migraine days (MMD) reduction in patients with chronic migraine from a 12-week, randomized study (NCT02066415). METHODS: Patients (n = 667) received (3:2:2) placebo or erenumab 70/140 mg once-monthly. The proportion of patients achieving a given response threshold was assessed. A post-hoc analysis was conducted to contextualize the actual treatment benefit in subgroups of patients achieving (or not) specified response thresholds. Outcome measures included MMD, acute migraine-specific medication treatment days (MSMD) and disability. RESULTS: The proportion of patients responding to erenumab exceeded that of placebo at the ≥50% and ≥75% response thresholds. At month 3, 39.9% and 41.2% of patients on erenumab 70 and 140 mg, respectively, achieved ≥50% response versus placebo (23.5%). Similarly, at month 3, 17.0% and 20.9% of patients on erenumab 70 and 140 mg, respectively, achieved ≥75% response versus placebo (7.8%). Compared with the overall erenumab-treated population (change in MMD: -6.6 [both 70 and 140 mg]), ≥50% responders showed MMD reductions of -12.2/-12.5 for 70 mg/140 mg versus -2.6/-2.2 for those not achieving ≥50% response. ≥75% responders showed MMD reductions of -13.9/-14.8 for 70 mg/140 mg versus -5.0/-4.3 for those not achieving ≥75% response. Relative improvements in MSMD and disability were observed in responders versus overall erenumab-treated population. CONCLUSION: For erenumab-treated patients achieving ≥50% response, the actual reduction in MMD was almost twice that of the overall population. These findings provide context for setting realistic expectations regarding actual treatment benefit experienced by patients responding to treatment.

Long-term study of the efficacy and safety of OnabotulinumtoxinA for the prevention of chronic migraine: COMPEL study.

BACKGROUND: OnabotulinumtoxinA is approved for the prevention of headache in those with chronic migraine (CM); however, more clinical data on the risk-benefit profile for treatment beyond one year is desirable. METHODS: The Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open Label (COMPEL) Study ( ClinicalTrials.gov , NCT01516892) is an international, multicenter, open-label long-term prospective study. Adults with CM received 155 U of onabotulinumtoxinA (31 sites in a fixed-site, fixed-dose paradigm across 7 head/neck muscles) every 12 weeks (±7 days) for 9 treatment cycles (108 weeks). The primary outcome was headache day reductions at 108 weeks; secondary outcomes were headache day reductions at 60 weeks and change in the 6-item Headache Impact Test (HIT-6) score. Safety and tolerability were assessed by reviewing the frequency and nature of adverse events (AEs). AEs were determined at each visit through patient self-report, general non-directed and, for specific AEs, directed questioning, and physical examination. Subgroup analyses for safety and efficacy included, but were not limited to, patients with/without concomitant oral preventive treatment and acute medication overuse at baseline. RESULTS: Enrolled patients (N = 716) were 18-73 years old and most were female (n = 607, 84.8%). At baseline, patients reported an average 22.0 (SD = 4.8) headache days per month. 52.1% of patients (n = 373) completed the study. By 60 and 108 weeks, a significant reduction in headache days (- 9.2 days and - 10.7 days, respectively, P < 0.0001) was observed. Significant improvements (P < 0.0001) in HIT-6 scores (- 7.1 point change at week 108) were also demonstrated. 131 patients (18.3%) reported ≥1 treatment-emergent adverse events; most frequently reported was neck pain (n = 29, 4.1%). One patient reported a serious treatment-related adverse event (rash). No deaths were reported. CONCLUSIONS: The COMPEL Study provides additional clinical evidence for the consistency of the efficacy and for the long-term safety and tolerability of onabotulinumtoxinA for the prevention of headache in those with CM who have been treated with onabotulinumtoxinA every 12 weeks over 2 years (9 treatments) with the fixed-site, fixed-dose injection paradigm. TRIAL REGISTRATION: Trial registration number: NCT01516892 . Name of registry: clinicaltrials.gov . Date of registration: January 20 2012. Date of enrollment of first patient: December 2011.

Preventing Episodic Migraine With Caloric Vestibular Stimulation: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the safety and efficacy of a novel solid-state, caloric vestibular stimulation (CVS) device to provide adjuvant therapy for the prevention of episodic migraine in adult migraineurs. BACKGROUND: Migraine causes significant disability in ∼12% of the world population. No current migraine preventive treatment provides full clinical relief, and many exhibit high rates of discontinuation due to adverse events. Thus, new therapeutic options are needed. CVS may be an effective and safe adjuvant-therapy for the prevention of episodic migraine. METHODS: In a multicenter, parallel-arm, block-randomized, placebo-controlled clinical trial (clinicaltrials.gov: NCT01899040), subjects completed a 3-month treatment with the TNM™ device for CVS (refer to Fig. 2 for patient enrollment and allocation). The primary endpoint was the change in monthly migraine days from baseline to the third treatment month. Secondary endpoints were 50% responder rates, change in prescription analgesic usage and difference in total subjective headache-related pain scores. Device safety assessments included evaluation of any impact on mood, cognition, or balance. RESULTS: Per-protocol, active-arm subjects showed immediate and continued steady declines in migraine frequency over the treatment period. After 3 months of treatment, active-arm subjects exhibited significantly fewer migraine days (-3.9 ± 0.6 from a baseline burden of 7.7 ± 0.5 migraine days). These improvements were significantly greater than those observed in control subjects (-1.1 ± 0.6 from a baseline burden = 6.9 ± 0.7 migraine days) and represented a therapeutic gain of -2.8 migraine days, CI = -0.9 to -4.7, P = .012. Active arm subjects also reported greater reductions in acute medication usage and monthly pain scores compared to controls. No adverse effects on mood, cognition, or balance were reported. Subjects completed the trial with an average rate of 90% treatment adherence. No serious or unexpected adverse events were recorded. The rate of expected adverse events was similar across the active and the placebo groups, and evaluation confirmed that subject blinding remained intact. CONCLUSION: The TNM™ device for CVS appears to provide a clinically efficacious and highly tolerable adjuvant therapy for the prevention of episodic migraine.

OnabotulinumtoxinA for treatment of chronic migraine: pooled analyses of the 56-week PREEMPT clinical program.

OBJECTIVE: To evaluate safety and efficacy of onabotulinumtoxinA (BOTOX(®) ) as headache prophylaxis in adults with chronic migraine. BACKGROUND: Chronic migraine is a prevalent, disabling, and undertreated neurological disorder. OnabotulinumtoxinA is the only approved prophylactic therapy in this highly disabled patient population. DESIGN AND METHODS: Two phase III, 24-week, double-blind, parallel-group, placebo-controlled studies, followed by a 32-week, open-label, single-treatment, onabotulinumtoxinA phase, were conducted (January 23, 2006 to August 11, 2008). Qualified subjects were randomized (1:1) to injections of onabotulinumtoxinA (155-195 U) or placebo every 12 weeks for 5 cycles (double-blind: 2, open-label: 3). The pooled primary variable was mean change from baseline in frequency of headache days. Secondary variables included proportion of patients with severe Headache Impact Test-6 score (≥ 60) and mean changes from baseline in frequencies of migraine days, moderate/severe headache days, and migraine episodes; cumulative hours of headache on headache days; and acute headache medication intakes. The primary time point was week 24. Assessments for the open-label phase (all patients treated with onabotulinumtoxinA) compared double-blind treatment groups (onabotulinumtoxinA/onabotulinumtoxinA vs placebo/onabotulinumtoxinA) and are summarized to give a descriptive view of consistent study results, with inferences regarding statistical significance only examined for week 56. RESULTS: A total of 1384 patients were randomized to onabotulinumtoxinA (n = 688) or placebo (n = 696) in the double-blind phase; 607 (88.2%) onabotulinumtoxinA/onabotulinumtoxinA and 629 (90.4%) placebo/onabotulinumtoxinA patients continued into the open-label phase. OnabotulinumtoxinA/onabotulinumtoxinA treatment statistically significantly reduced headache-day frequency vs placebo/onabotulinumtoxinA in patients with chronic migraine at week 56 (-11.7 onabotulinumtoxinA/onabotulinumtoxinA, -10.8 placebo/onabotulinumtoxinA; P = .019). Statistically significant reductions also favored onabotulinumtoxinA/onabotulinumtoxinA for several secondary efficacy variables at week 56, including frequencies of migraine days (-11.2 onabotulinumtoxinA/onabotulinumtoxinA, -10.3 placebo/onabotulinumtoxinA; P = .018) and moderate/severe headache days (-10.7 onabotulinumtoxinA/onabotulinumtoxinA, -9.9 placebo/onabotulinumtoxinA; P = .027) and cumulative headache hours on headache days (-169.1 onabotulinumtoxinA/onabotulinumtoxinA, -145.7 placebo/onabotulinumtoxinA; P = .018). After the open-label phase (all treated with onabotulinumtoxinA), statistically significant within-group changes from baseline were observed for all efficacy variables. Most patients (72.6%) completed the open-label phase; few discontinued because of adverse events. No new safety or tolerability issues emerged. CONCLUSIONS: Repeated treatment with ≤ 5 cycles of onabotulinumtoxinA was effective, safe, and well tolerated in adults with chronic migraine.

Electronic medical record system in a headache specialty practice: a patient satisfaction survey.

BACKGROUND: Since November 2002, Headache Wellness Center, a specialty headache practice in Greensboro, NC, has used exclusively an electronic medical record (EMR) system for all patient clinical contacts. OBJECTIVE: To assess patient satisfaction and perceptions regarding this new office technology and to better understand the EMR-patient-physician relationship. METHODS: An EMR satisfaction survey was administered from February to June 2006 and was completed by 394 patients. All patients were known to the practice and completed the survey at the time of a headache revisit evaluation. RESULTS: The majority of respondents believed that EMR system use was not intrusive; did not draw attention away from patient contact; provided more efficient and accurate interactions; and preferred an EMR system in this particular headache setting. CONCLUSION: Patient satisfaction with an EMR system in a headache specialty practice was high.

Efficacy of duloxetine as a migraine preventive medication: possible predictors of response in a retrospective chart review.

OBJECTIVE: This case series is a retrospective chart analysis conducted to evaluate the efficacy of duloxetine as a migraine preventive medication and to suggest possible predictors of response. BACKGROUND: Duloxetine, a relatively new selective serotonin and norepinephrine reuptake inhibitor, is FDA-approved for treatment of depression and diabetic peripheral neuropathic pain. The efficacy of duloxetine as a headache preventive medication is currently unknown. METHOD: A retrospective chart review was performed using the electronic medical records of Headache Wellness Center, a headache specialty practice in Greensboro, North Carolina. From January 2004 to December 2006, 65 patients were identified who were prescribed duloxetine for migraine prevention for at least 2 months. Doses ranged from 30 mg qd to 90 mg qd. Frequency, severity, and impact of migraine disability were measured at baseline and compared to values obtained after 2 months of treatment. RESULTS: The total patient sample demonstrated a reduction in mean monthly headache frequency from 19.40 (SD=7.1) to 15.70 (SD=8.2) (P= .01). The 50% responder rate was 22%. In subset analysis, individuals with abnormal baseline Zung anxiety scores demonstrated a greater reduction in mean monthly headache frequency (4.28, P= .03) and a greater responder rate (25%) than those in the total patient sample. Non-statistically significant trends were observed in those patients with abnormal baseline Zung Depression scores exhibiting a less robust mean monthly migraine reduction (2.75, P= .18) than those with normal baseline depression scores (3.42, P= .07). CONCLUSIONS: Duloxetine demonstrates minimal effectiveness as a headache preventive medication. An interesting trend suggests that the presence of anxiety may be a positive predictor in treatment with duloxetine.

Pharmacoeconomics: the cost of prophylactic migraine treatments.

Migraine preventive medications considered effective reduce headache frequency by 50 percent in approximately 50 percent of treated patients. In spite of similar effectiveness, these medications vary tremendonsly in their prices. Knowledge of medication prices and employing cost-effective strategies may greatly reduce treatment costs.

Cost considerations of acute migraine treatment.

OBJECTIVE: To provide medication price data and cost-reducing strategies for the acute treatment of migraine. METHODS: Retail prices for common acute care medications were found at http://www.drugstore.com. Cost-reduction tactics were obtained from literature searches and clinical experience. RESULTS: Several strategies can reduce cost without sacrificing treatment outcome. In mild to moderate migraine, low-priced nonsteroidal anti-inflammatory drugs can be used as first-line medications due to their proven efficacy and favorable tolerability. For patients with more severe migraine, implementing a stratified care approach-using migraine-specific medications early in acute treatment-is cost-effective for most patients. Stratified care not only improves outcome and decreases disability, but also reduces cost. Pill splitting and early administration of triptans within an attack enhance their value. Supplying rescue medications, such as opioids, sedatives, and phenothiazines, can prevent emergency department visits. Minimizing multiple dosing of triptans and reducing utilization of expensive health care resources are key factors in reducing the cost of effective migraine treatment. An important affordability factor for patients with co-payments is the number of triptan pills per package. Sumatriptan, naratriptan, and frovatriptan each contain 9 tablets per package, while most other triptan packages contain 6. Current triptan retail prices (per unit) include: Amerge 1 and 2.5 mg, 17.78 dollars; Axert 6.25 and 12.5 mg, 16.31 dollars; Frova 2.5 mg, 13.89 dollars; Imitrex 50 mg, 14.96 dollars; Imitrex 100 mg, 14.41 dollars; Imitrex Nasal Spray 20 mg, 21.61 dollars; Imitrex SQ 6 mg, 50.26 dollars; Maxalt 5 and 10 mg, 15 dollars; Maxalt-MLT 5 and 10 mg, 15 dollars; Relpax 40 mg, 13.58 dollars; Zomig 2.5 mg, 13.67 dollars; Zomig 5 mg, 15.89 dollars; Zomig-ZMT 2.5 mg, 13.67 dollars; and Zomig-ZMT 5 mg, 15.89 dollars. CONCLUSIONS: Practitioners can optimize the use of health care dollars without compromising quality of care through awareness of cost-saving treatment strategies, as well as price variations among medications.