Halker, Rashmi

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.

The sphenopalatine ganglion (SPG) has attracted the interest of practitioners treating head and face pain for over a century because of its anatomical connections and role in the trigemino‐autonomic reflex. In this review, we discuss the anatomy of the SPG, as well as what is known about its role in the pathophysiology of headache disorders, including cluster headache and migraine. We then address various therapies that target the SPG, including intranasal medication delivery, new SPG blocking catheter devices, neurostimulation, chemical neurolysis, and ablation procedures.

Background Occipital nerve (ON) injections with corticosteroids and/or local anesthetics have been employed for the acute and preventive treatment of migraine for decades. However, to date there is no randomized, placebo-controlled evidence to support the use of occipital nerve block (ONB) for the prevention of migraine. Objective The objective of this article is to determine the efficacy of ONB with local anesthetic and corticosteroid for the preventive treatment of migraine. Participants and methods Patients between 18 and 75 years old with ICHD-II-defined episodic (> 1 attack per week) or chronic migraine (modified ICHD-II as patients with > 10 days with consumption of acute medications were permitted into the study) were randomized to receive either 2.5 ml 0.5% bupivacaine plus 0.5 ml (20 mg) methylprednisolone over the ipsilateral (unilateral headache) or bilateral (bilateral headache) ON or 2.75 ml normal saline plus 0.25 ml 1% lidocaine without epinephrine (placebo). Patients completed a one-month headache diary prior to and after the double-blind injection. The primary outcome measure was defined as a 50% or greater reduction in the frequency of days with moderate or severe migraine headache in the four-week post-injection compared to the four-week pre-injection baseline period. Results Thirty-four patients received active and 35 patients received placebo treatment. Because of missing data, the full analysis of 33 patients in the active and 30 patients in the placebo group was analyzed for efficacy. In the active and placebo groups respectively, the mean frequency of at least moderate (mean 9.8 versus 9.5) and severe (3.6 versus 4.3) migraine days and acute medication days (7.9 versus 10.0) were not substantially different at baseline. The percentage of patients with at least a 50% reduction in the frequency of moderate or severe headache days was 30% for both groups (10/30 vs nine of 30, Δ 0.00, 95% CI –0.22 to 0.23). Conclusions Greater ONB does not reduce the frequency of moderate to severe migraine days in patients with episodic or chronic migraine compared to placebo. The study was registered with ClinicalTrial.gov (NCT00915473).

Objective To identify factors associated with triptan discontinuation among migraine patients. Background It is unclear why many migraine patients who are prescribed triptans discontinue this treatment. This study investigated correlates of triptan discontinuation with a focus on potentially modifiable factors to improve compliance. Methods This multicenter cross‐sectional survey (n = 276) was performed at US tertiary care headache clinics. Headache fellows who were members of the American Headache Society Headache Fellows Research Consortium recruited episodic and chronic migraine patients who were current triptan users (use within prior 3 months and for ≥1 year) or past triptan users (no use within 6 months; prior use within 2 years). Univariate analyses were first completed to compare current triptan users to past users for: migraine characteristics, other migraine treatments, triptan education, triptan efficacy, triptan side effects, type of prescribing provider, Migraine Disability Assessment ( MIDAS ) scores and Beck Depression Inventory ( BDI ) scores. Then, a multivariable logistic regression model was selected from all possible combinations of predictor variables to determine the factors that best correlated with triptan discontinuation. Results Compared with those still using triptans (n = 207), those who had discontinued use (n = 69) had higher rates of medication overuse (30 vs 18%, P = .04) and were more likely to have ever used opioids for migraine treatment (57 vs 38%, P = .006) as well as higher MIDAS (mean 63 vs 37, P = .001) and BDI scores (mean 10.4 vs 7.4, P = .009). Compared with discontinued users, current triptan users were more likely to have had their triptan prescribed by a specialist (neurologist, headache specialist, or pain specialist) (74 vs 54%, P = .002) and were more likely to report headache resolution (53 vs 14%, P < .001) or a reduction in pain intensity (71 vs 28%, P < .001) most of the time from their triptan. On a 1‐5 scale (1 = disagree, 5 = agree), triptan users felt they had more: control over their migraine attacks (2.9 vs 2.1), confidence in their prescribing provider (4.5 vs 4.0), and were more educated about triptan use (4.2 vs 3.7) compared with triptan discontinuers ( P < .001 for all comparisons). Although both current and prior users reported similar rates of side effects (48 vs 43%, P = .44), of those who discontinued use, the main reasons were for lack of effect (44%) and side effects (29%). Our multivariable modeling revealed that the strongest correlate of triptan discontinuation was lack of efficacy (odds ratio = 17, 95% confidence interval [8.8, 33.0]). Other factors associated with discontinuation included MIDAS > 24 (2.6, [1.5, 4.6]), BDI >4 (2.5, [1.4, 4.5]), and a history of ever using opioids for migraine therapy (2.2, [1.3, 3.8]). Having a triptan prescribed by a specialist and using at least 1 other abortive medication with the triptan were associated with a decreased likelihood of triptan discontinuation (0.41, [0.2‐0.7] and 0.44 [0.3, 0.8], respectively). Conclusions As expected, discontinuation was most correlated with lack of efficacy, but other important factors associated with those who had discontinued use included greater migraine‐related disability, depression, and the use of opioids for migraine attacks. Compared with patients who had discontinued triptans, current triptan users felt more: educated about their triptan, control over their migraine attacks, and confidence in their prescribing provider. Current triptan users had their triptan prescribed by a specialist and used other abortive medications with their triptan more often compared with patients who had discontinued triptans. Given the cross‐sectional nature of this study, we cannot determine if these factors contributed to triptan discontinuation or reflect the impact of such discontinuation. Interventions that address modifiable risk factors for triptan discontinuation may decrease the likelihood of triptan discontinuation and thus improve overall migraine control. Because lack of efficacy was most strongly associated with triptan discontinuation, future research should determine why triptans are effective for some patients but not others.