Tepper, Stewart J.

Objective To evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation (sTMS) for the preventive treatment of migraine. Background sTMS was originally developed for the acute treatment of migraine with aura. Open label experience has suggested a preventive benefit. The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention. Methods The eNeura SpringTMS Post-Market Observational U.S. Study of Migraine (ESPOUSE) Study was a multicenter, prospective, open label, observational study. From December 2014 to March 2016, patients with migraine (n = 263) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment. The treatment protocol consisted of preventive (four pulses twice daily) and acute (three pulses repeated up to three times for each attack) treatment. Patients reported daily headache status, medication use, and device use with a monthly headache diary. The primary endpoint, mean reduction of headache days compared to baseline, was measured over the 28-day period during weeks 9 to 12. The primary endpoint was compared to a statistically-derived placebo estimate (performance goal). Secondary endpoints included: 50% responder rate, acute headache medication consumption, HIT-6, and mean reduction in total headache days from baseline of any intensity. Results Of a total of 263 consented subjects, 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set. For the primary endpoint, there was a −2.75 ± 0.40 mean reduction of headache days from baseline (9.06 days) compared to the performance goal (−0.63 days) ( p < 0.0001). The 50% responder rate of 46% (95% CI 37%, 56%) was also significantly higher ( p < 0.0001) than the performance goal (20%). There was a reduction of −2.93 (5.24) days of acute medication use, headache impact measured by HIT-6, −3.1 (6.4) ( p < 0.0001), and total headache days of any intensity −3.16 days (5.21) compared to the performance goal (−0.63 days) ( p < 0.0001). The most common adverse events were lightheadedness (3.7%), tingling (3.2%), and tinnitus (3.2%). There were no serious adverse events. Conclusions This open label study suggests that sTMS may be an effective, well-tolerated treatment option for migraine prevention. Trial registration number NCT02357381

Objective To further characterize the clinical utility of AVP‐825 based on additional prespecified outcomes and post hoc analyses of COMPASS, a Phase 3 comparative efficacy trial of AVP‐825 vs 100 mg oral sumatriptan (NCT01667679). AVP‐825 was approved in January 2016 by the US Food and Drug Administration under the name ONZETRA ® Xsail ® (sumatriptan nasal powder) for the acute treatment of migraine with or without aura in adults. Background AVP‐825 is a delivery system that uses a patient's own breath to deliver low‐dose sumatriptan powder to the upper posterior regions of the nasal cavity beyond the narrow nasal valve, areas lined with vascular mucosa conducive to rapid drug absorption into the systemic circulation. The recommended dose of AVP‐825 is 22 mg sumatriptan powder administered as one 11 mg nosepiece in each nostril, which delivers approximately 15‐16 mg of sumatriptan intranasally. The COMPASS trial compared AVP‐825 22‐100 mg oral sumatriptan across multiple migraine attacks for efficacy, safety, and tolerability endpoints. Design/Methods COMPASS was a randomized, multicenter, double‐dummy, crossover, multiattack, comparative efficacy study with two 12‐week double‐blind periods. Patients with 2‐8 migraine attacks/month were randomized 1:1 to AVP‐825 (22 mg) plus oral placebo or an identical placebo delivery system plus 100 mg oral sumatriptan for the first period, and then patients switched treatments for the second period. Patients treated up to 5 qualifying migraines per period within 1 h of onset, even if the intensity of the attack was mild. Results from the primary endpoint (SPID‐30, defined as the sum of pain intensity differences from dosing to 30 minutes), key secondary efficacy endpoints and safety assessments have been reported in the primary publication (Tepper et al., 2015). This article reports additional prespecified outcomes, including the SPID‐30 for attacks treated when baseline severity was mild vs moderate/severe, measures of sustained response and consistency of effect in patients who experienced multiple migraine attacks, and the results of post hoc analyses performed to assess total migraine freedom (defined as no pain and no migraine‐associated symptoms, including nausea, vomiting, photophobia, and phonophobia), time to pain freedom, time to meaningful pain relief, and local (occurring at the site of administration in the nose) vs systemic treatment‐emergent adverse events (TEAEs). Results A total of 185 patients completed both treatment periods, yielding 1,531 migraine attacks which were treated and assessed (765 AVP‐825, 766 oral sumatriptan). Treatment with AVP‐825 provided greater reduction in migraine pain intensity which was statistically significant vs oral sumatriptan in the first 30 minutes postdose regardless of whether attacks were treated when pain was mild (least squares mean SPID‐30 = 3.90 vs 0.24, P = .0013) or moderate/severe (least squares mean SPID‐30 = 13.83 vs 10.07, P = .0002). At every time point from 15 to 90 minutes postdose, the proportion of attacks achieving total migraine freedom was greater and statistically significant after treatment with AVP‐825 vs 100 mg oral sumatriptan. AVP‐825 treatment resulted in greater odds of achieving pain freedom (odds ratio, OR = 1.29, P < .01) and meaningful pain relief (OR = 1.32, P < .0001), which were also statistically significant compared with oral sumatriptan. In addition, a greater proportion of attacks treated with AVP‐825 vs oral sumatriptan was associated with sustained pain freedom, achieving statistical significance when assessed from 1 h postdose through 24 hours postdose (33.3% vs 27.9%; P < .05) and through 48 hours postdose (32.7% vs 27.4%; P < .05). For patients who treated multiple migraine attacks in both treatment periods, a greater proportion had consistent pain relief and pain freedom following treatment with AVP‐825 compared to oral sumatriptan across multiple attacks, a difference that achieved statistical significance at 30 minutes postdose. Local TEAEs of abnormal taste and nasal discomfort were more common following AVP‐825 treatment. Of the patients experiencing either of these TEAEs, about 90% described the intensity as mild, and only one discontinued treatment because of either of these two TEAEs. Conclusions These results from the COMPASS study further demonstrate that treatment with AVP‐825 provides earlier onset and more consistent across‐episode improvement of pain and migraine‐associated symptoms compared with oral sumatriptan, highlighting the clinical advantages of this newly approved intranasal delivery system for low‐dose sumatriptan powder.

Objective The purpose of this study was to evaluate the frequency of migraine headache in a large cohort of patients with fibromyalgia using a brief migraine headache‐screening tool. Background Several studies report a high prevalence of fibromyalgia among patients with migraine headaches, but there is a dearth of research evaluating the frequency of migraine headaches in patients with fibromyalgia, despite clinical observations suggesting that migraine headaches are common in patients with fibromyalgia. Design and Methods This was a cross‐sectional survey study. Patients (N = 3717) with a previous diagnosis of fibromyalgia who were members of the M ayo C linic F ibromyalgia R egistry were contacted by electronic survey and asked to complete a brief demographic and medical history questionnaire and the validated ID ‐ M igraine screener. Results A total of 1730 patients (46.5%) completed the electronic survey. The majority of participants were white (97.2%), female (92.5%), with a mean age of 56.2 (±13.1) years. Of the respondents, 966 (55.8%) met criteria for migraine headaches. Hypertension (309 [32.3%] vs 294 [40.1%], P = .004), asthma (312 [32.5%] vs 189 [25.9%], P = .011), irritable bowel syndrome (520 [54.6%] vs 348 [47.6], P = .017), chronic fatigue syndrome (486 [50.7%] vs 271 [37.1], P < .0001), depression (634 [66.5%] vs 413 [56.7%], P = .0002), anxiety (415 [43.5%] vs 252 [34.7%], P = .0011), and post‐traumatic stress disorder (172 [18.0%] vs 96 [13.2%], P = .006) were all significantly more common in those who met criteria for migraine headaches than those who did not. Conclusion The results of this study suggest that migraine headaches are common in patients with fibromyalgia. Clinicians who care for either population must be aware that these conditions commonly overlap and can significantly increase a patient's cumulative disease burden.