Starling, Amaal J

Aim Incorporating patient-reported outcomes (PROs) into clinical practice and real-world research is essential to enable a more holistic assessment of treatment effectiveness, beyond migraine frequency alone. Given the number of calcitonin gene-related peptide (CGRP)-targeted treatments available, switching between CGRP-targeted preventive therapies is a common practice. Real-world evidence on switching to intravenous eptinezumab in adults with migraine for whom prior subcutaneous or oral CGRP-targeted preventive therapies failed is limited. The ongoing INFUSE study was designed to evaluate the real-world effectiveness of switching to eptinezumab in US clinical practice among adults with migraine for whom ≥1 prior CGRP-targeted preventive therapy had failed. Methods INFUSE, a real-world, non-interventional study evaluating the effectiveness of eptinezumab in US clinical practice, included adults with migraine for whom ≥1 prior CGRP-targeted preventive therapy had failed and who were newly initiating eptinezumab treatment. PROs were collected electronically. To provide an overall assessment of the change in migraine disease, Patient Global Impression of Change (PGIC) was utilized. Other outcomes allowed for the evaluation of novel end points, such as brain fog and participant-defined good days. Results The baseline population included 190 participants (female, 88.9%; 35–54 years of age, 53.7%). At month 6, 44.1% (95% confidence interval (CI): 35.3–53.4%) of participants reported “much/very much improved” on PGIC, and 75.7% (95% CI: 66.9–82.7%) reported any improvement. Mean good days increased by 6.3 per month at month 6 ( P < 0.001). Among participants reporting brain fog at baseline (93.7%), 55.8% (95% CI: 46.2–64.9%) reported improvement at month 6. Conclusion This research provides insights into capturing the broader migraine burden and the holistic impact of preventive treatment and highlights the potential for achieving ambitious goals. In this population for whom ≥1 prior CGRP-targeted preventive therapy had failed, switching to eptinezumab was associated with participant-reported, clinically meaningful improvements in PROs, including frequency, disability, disease status, and brain fog.

Aim To determine whether there is a difference in the time to complete a rapid number naming task during the interictal state compared to prodrome, migraine headache, postdrome phases of migraine and non-migraine headache, and characterize non-headache symptoms experienced during these phases. Methods This prospective longitudinal cohort study evaluated 30 adults with migraine with or without aura who completed diary entries and a timed rapid number naming task at least three times daily for up to four months from October 2020 to July 2022 at a tertiary headache center. Diary entries included self-report of current migraine phase (having a migraine headache, non-migraine headache, prodrome, postdrome, or interictal baseline) and detailed symptoms experienced. The outcome of interest for the timed rapid number naming task was the time to complete the task with zero errors. Results Compared to the interictal baseline, the time with zero errors for the rapid number naming task was significantly slower during the prodrome (median (Q1, Q3) 1.0 s slower (0.4, 2.9), p -value 0.010), migraine headache (median (Q1, Q3) 3.8 s slower (2.6, 7.5), p -value <0.001), and postdrome (median (Q1, Q3) 0.9 s slower (0.2, 2.1), p -value 0.011) phases of migraine, and non-migraine headache attacks (median (Q1, Q3) 1.2 s slower (0.1, 3.1), p -value 0.006). For those with migraine with aura (N = 15), the time with zero errors was significantly slower during all phases compared to interictal phase. For those with migraine without aura (N = 15), the time with zero errors was significantly slower only during the migraine headache, but not other phases compared to the interictal phase. The top 5 most reported non-headache symptoms during any phase of migraine and non-migraine headache attacks included fatigue, neck stiffness, light sensitivity, blurred vision/vision changes, and difficulty concentrating. Conclusions Among the overall participant cohort, the time with zero errors to complete a rapid number naming task was significantly slower during all ictal phases compared to interictal phase. This was also the case in the migraine with aura cohort but in the migraine without aura cohort there was only a significant difference during the migraine headache phase versus interictal phase. There is overlap in non-headache symptoms between the prodrome, migraine headache, postdrome, and non-migraine headache phases, which may make distinguishing between these phases difficult. Combining subjective data, such as symptom diaries, with objective measures, such as rapid number naming tasks, may allow for more refined assessment of migraine phases and distinguishing migraine from non-migraine headache attacks.

ABSTRACT Background This post hoc analysis examined the reduction in monthly headache days ( MHDs ) by frequency category shifts and associated improvements following eptinezumab treatment. Methods The DELIVER trial evaluated eptinezumab in adults with migraine for whom 2–4 previous preventive treatments failed. During a 24‐week, double‐blind, placebo‐controlled period followed by a 48‐week extension period, participants received IV eptinezumab 100 mg, 300 mg, or placebo every 12 weeks, with all receiving eptinezumab beginning Week 25 (dose‐blinded). Participants were categorized by MHD frequency: > 14, 8–14, 4 to < 8, 1 to < 4, 0. MHD category shifts were evaluated in the total population and several subgroups (including participants with > 14 baseline MHDs and early ≥ 50% responders). In participants reporting < 8 MHDs after all doses, the associated changes in headache intensity and disease status were evaluated. Results Of randomized participants, 88% (782/890) completed the trial. The percentage of participants randomized initially to eptinezumab who reported < 4 MHDs was 23% (138/592) over Weeks 1–12 and 47% (236/498) over Weeks 61–72; 9% reported 0 MHDs after the final dose. Of participants randomized initially to eptinezumab who shifted from ≥ 8 MHDs at baseline to < 8 over Weeks 1–12, 71% (170/241) reported < 8 MHDs for the rest of the trial; of those who shifted from > 14 to < 8 MHDs, 66% (49/74) reported < 8 MHDs for the rest of the trial. Reduction to < 8 MHDs was associated with robust improvements in headache intensity and disease burden. Conclusions Eptinezumab was associated with sustained reduction in MHD category, with some achieving headache/migraine freedom in patients with a history of preventive treatments that failed. Trial Registration ClinicalTrials.gov (identifier: NCT04418765; https://www.clinicaltrials.gov/ct2/show/NCT04418765 ) and EudraCT (identifier: 2019‐004497‐25; https://www.clinicaltrialsregister.eu/ctr‐search/search?query=2019‐004497‐25 )

Tools used for the identification, evaluation, and monitoring of concussion have not been sufficiently studied in youth or real-world settings. Normative and reliability data on sideline concussion assessment measures in the youth athlete population is needed. Pre-season normative data for 515 athletes (93.5% male) aged 5 to 16 on the Standardized Assessment of Concussion (SAC/SAC-Child), modified Balance Errors Scoring System (mBESS), Timed Tandem Gait (TTG), and the King–Devick Test (KDT) are provided. A total of 212 non-injured athletes repeated the measures post-season to assess test–retest reliability. Mean performance on the SAC-C, mBESS, TTG, and KDT tended to improve with age. KDT was the only measure that demonstrated good to excellent stability across age ranges (ICC = 0.758 to 0.941). Concentration was the only SAC/SAC-C subtest to demonstrate moderate test–retest stability (ICC = 0.503 to 0.706). TTG demonstrated moderate to good (ICC = 0.666 to 0.811) reliability. mBESS demonstrated poor to moderate reliability (ICC = −0.309 to 0.651). Commonly used measures of concussion vary regarding test–retest reliability in youth. The data support the use of at least annual sport concussion baseline assessments in the pediatric population to account for the evolution in performance as the child ages. Understanding the variation in the stability and the evolution of baseline performance will enable improved identification of possible injury.

Abstract Objective To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. Background Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. Methods A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16‐month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age‐ and sex‐matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. Results In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0–3.2]; p = 0.338). Conclusions In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.

Introduction Access to headache consultations by a headache specialist is limited. E‐consultations are an efficient approach shown to reduce costs and improve continuity of care with the primary care provider. Indications, suitability, and uptake in the headache population are not well studied. Methods This quality improvement pilot aims to explore the appropriateness of e‐consultations for patients referred to a headache specialist. E‐consultation feasibility was explored through (1) retrospective review of completed face‐to‐face consultations; (2) prospective survey of providers to identify face‐to‐face consultations appropriate for e‐consultation; (3) cross‐sectional review of the current waiting list to assess theoretical triaging to face‐to‐face vs e‐consultation; and (4) prospective review of all e‐consultations requested from an academic headache clinic to improve the understanding of e‐consultation feasibility and referral triage. Results The retrospective review included 75 face‐to‐face consultations with a mean (SD) wait time of 33 (39.4) days for consultations, of which 28/75 (37.3%) were deemed to be feasible e‐consultations. The prospective survey of providers identified 10 face‐to‐face consultations that were felt to be theoretically appropriate for e‐consultation. The cross‐sectional review identified 20 patients on the clinic waiting list, of whom 5/20 (25%) were theoretically triaged to e‐consultation. Finally, the prospective review found 12 requested e‐consultations, of which 6/12 (50%) were for migraine prophylaxis recommendations. Chart data often lacked details for complete assessments, with 5/12 (41.7%) converted to face‐to‐face consultations and only 4/12 (33.3%) deemed appropriate for e‐consultation. Conclusion E‐consultation in headache medicine could be considered if appropriately triaged. Pathways are needed to reach patients earlier in their disease course to ensure headache care meets guideline recommendations, and e‐consultation is 1 option. However, better communication with primary care is required for system optimization.

Background Erenumab, a calcitonin gene‐related peptide (CGRP) receptor monoclonal antibody, has been well tolerated with good efficacy for the preventive treatment of episodic and chronic migraine in phase 2 and phase 3 clinical trials. Limited post‐market observations are available to validate these findings in a real‐world tertiary headache clinic population with complex comorbidities and refractory migraine. Objective The goal of this study is to demonstrate the real‐world performance of erenumab among patients in a tertiary care headache clinic by describing patient selection, experience, and clinical characteristics after 6 months of erenumab therapy. Methods A retrospective, exploratory, observational study was conducted on patients receiving at least 1 erenumab injection (70 or 140 mg). Baseline data obtained by chart review and telephone calls were compared to 6‐month follow‐up telephone calls. The primary outcome was the reduction in self‐reported headache days per month at baseline compared to 6 months for those with complete 6‐month data. The significance level was set at P < .05. Secondary analyses explored the distribution of headache severity, responder rates, Migraine Disability Assessment scores, adverse effects, ineffective preventives, comorbidities, wearing‐off, and discontinuation. Results Of the 101 patients who consented to participate, 89.1% (90/101) were women, and the mean age of all patients was 49 years (range, 19‐80 years). At baseline, 94.1% (95/101) of patients had chronic migraine, 5.0% (5/101) had episodic migraine, and 18.8% (19/101) had medication overuse headache. The mean (SD) number of baseline headache and migraine days per month for the entire cohort were 24.3 (8.2) and 18.2 (9.3) days, respectively. Participants had numerous comorbidities and had tried a mean of 11.2 unique oral medications and 4.8 unique medication categories before receiving erenumab, including 83.2% (84/101) who had also received onabotulinumtoxinA. Six‐month post‐erenumab follow‐up data were available for 42.6% (43/101) of participants. For these 43 participants, the number of headache days per month decreased significantly by 6.5 days from a baseline mean (SD) of 24.8 (6.47) days to 18.3 (12) days at 6‐month follow‐up ( P < .001); similarly, the monthly migraine days decreased significantly by 8.4 days from a baseline mean of 19.1 (9.3) days to 10.7 days at 6‐month follow‐up ( P < .001). The 50% responder rate was 34.9% (15/43) for monthly headache days and 54.8% (23/43) for monthly migraine days. Of all 101 participants, 28 (27.7%) discontinued erenumab, primarily because it was ineffective (39.3%, 11/28) or because of adverse effects (42.9%, 12/28). Conclusion This post‐market observational study of patient experience describes response to erenumab in a real‐world tertiary headache clinic with a complex patient population. Overall, these complex patients had a significant positive clinical response to erenumab, but with high rates of discontinuation. This study also noted a 1‐week wearing‐off response and high rates of constipation. Further post‐market studies are needed to better characterize patient selection and real‐world response to erenumab.

Objective To summarize the current literature on non‐steroidal anti‐inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID‐19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. Background The use of non‐steroidal anti‐inflammatory drugs and corticosteroids in patients during the COVID‐19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID‐19 pandemic. Methods A detailed search of the scientific and popular literature was performed. Results There is limited literature pertaining to the safety of non‐steroidal anti‐inflammatory drugs and corticosteroids during the COVID‐19 pandemic. To date, there are no clear scientific data that preclude the use of non‐steroidal anti‐inflammatory drugs in the general population who may acquire COVID‐19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. Conclusion Scientific information regarding the COVID‐19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non‐steroidal anti‐inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID‐19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.