Recapping Research From 2023 AHS Annual Scientific Meeting

In recent months, the NeurologyLive® team has been covering the news and conducting interviews with experts on the latest updates in the clinical care of patients with neurological diseases, such as dementia or Alzheimer, epilepsy, headache or migraine, movement disorders, multiple sclerosis, neuromuscular diseases, sleep medicine, and stroke.

To recap the 2023 American Headache Society (AHS) Annual Meeting, June 15-18, in Austin, Texas, the team has culminated some of the biggest pieces of news to offer updates on new developments in the literature about headache/migraine to spread awareness on prevention and treatment approaches.

Click here for more coverage of AHS 2023.

Latest Literature

Survey Shows Lack of Awareness of Medication-Overuse Headache in Patients with Migraine

Findings from a survey of patients with migraine and interviews with neurologists indicated that several patients, including those at higher risk, were unaware of medication-overuse headache. These results also suggest that clinicians are more likely to talk about medication-overuse headache with their patients only when a behavior or symptom reminiscent of overuse might be already happening.¹

Among 200 patients with migraine, 38.6% claimed they had never heard of 'medication overuse’ for headache. Notably, approximately 53.4% of patients who did hear of medication-overuse headache reported that they had talked about the condition with their current provider and 38.4% learned about the condition 5 or more years following their migraine diagnosis.

The mixed methods study included adult patients with migraine and practicing neurologists affiliated with 1 academic health center in Chicago, Illinois. The adult patients were English-speaking, had a diagnosis of migraine, and were enrolled from an electronic health record query. Using the same health system for recruitment, a sample of neurologists were asked by email to participate in an exploratory, qualitative interview that was conducted by trained research staff. The quantitative survey data was assessed using descriptive statistics and the qualitative data from the interviews was analyzed using a modified version of the Rapid Identification of Themes from Audio Recordings (RITA) procedures.

Enrolled patients were contacted through research coordinators that introduced the study to them, engaged them in the informed consent process, and administered the structured survey. Among the 200 adult patients, 82.9% were women, 57.4% were White, 31.8% made less than $50,000 annually, and 18.2% had limited health literacy. The patients had been diagnosed with migraine, on average, for over a decade, with 35.9% of respondents claim they took over-the-counter-pain reliever on at least 15 days in the past month.

Candesartan Shown to be Safe, Effective as Option to Prevent Migraine in Adolescents

Findings from a small-scale retrospective chart review study provided evidence that candesartan, an antihypertensive drug, was well-tolerated and may be helpful in reduction of mean monthly headache days in adolescents with a high baseline headache frequency.² Investigators concluded that patients may gain more benefit from the drug if used as a first-line treatment earlier in the disease course. Candesartan, an angiotensin receptor 2 blocker, has been typically used to treat high blood pressure and heart failure, but has also previously shown effectiveness for migraine prevention in randomized controlled trials.

Conducted between January 2016 and December 2022, the trial featured 24 complete records of adolescent patients followed at the Texas Children’s Hospital Headache Clinic. Patients had data on demographics, primary headache diagnosis, headache frequency in days per month prior to initiation and at first follow-up 2-6 months after initiation, frequency of moderate to severe headache days per week, number of preventive therapies being taken concurrently and tried prior to candesartan initiation, and reported adverse events.

Of the sample, chronic migraine was the most common diagnosis (54%), followed by new daily persistent headache (17%), episodic migraine (17%), and post-traumatic headache (12%). Mean monthly headache frequency, the primary outcome, was significantly reduced following treatment with candesartan, with patients experiencing an average of 23.3 days per month prior to initiation vs 19.6 days after (P = .04).

Following treatment, median headache days decreased from 30 (range, 3-30) to 19.5 (range, 0-30), with 5 individuals (21%) reporting at least a 50% reduction. Additionally, adolescents on the therapy saw statistically significant reductions in the mean frequency of moderate to severe headache days per week (pre-initiation: 3.3 days vs post-initiation: 2.6 days; P = .04). Investigators noted though that these data should be interpreted with caution because of subjective differences in patient reporting and note documentation. In terms of safety, Patniyot et al reported mild light-headedness and mild blood pressure decrease in 3 patients (12.5%).

Discontinuation of Peripheral Nerve Blocks and OnabotulinumtoxinA From Adverse Effects in Chronic Migraine

In a recent retrospective cohort study, patients who received both onabotulinumtoxinA (Botox; Allergan) and nerve blocks showed a statistically significant difference in the number of adverse events (AEs) leading to discontinuation of therapy in comparison with individuals on onabotulinumtoxinA alone. These results provide evidence of the subsequent administration of local anesthetic and onabotulinumtoxinA for the treatment of migraine during a single clinical encounter, and adds to the current lack of safety data.³

Although there was a significant difference in the number of AEs in patients on the combination therapy that led to discontinuation of therapy (0.8% [1/131] vs 4.6% [6/131], P = .065), the analysis showed no significant difference in total AEs between combination therapy compared to nerve blocks alone or onabotulinumtoxinA alone. Notably, the authors observed 1 patient out of the whole cohort (0.8%) that accounted for 67%, or 4 out of 6 AEs in the combination group.

The objective of the study was to explore the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA treatment during a single outpatient clinic visit. Anderson and colleagues hypothesized that the combined procedure would be a safe and well-tolerated therapy for patients with chronic migraine and other headache disorders.

Investigators used clinical data from 1 outpatient headache clinic over a 16-month time period to conduct the retrospective review. Adult patients with migraine were recruited by procedure codes and deemed eligible if they received peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter in the study period for their treatment of chronic migraine. Patients were ineligible if they were under the age of 18 years, received their treatment outside of the clinic, or were given sphenopalatine ganglion blocks. The controls for the study were age- and sex-matched patients that received either peripheral nerve block or onabotulinumtoxinA.

Migraine Treatment Atogepant Outperforms Rimegepant in Matching-Adjusted Indirect Comparison Analysis

New data from a matching-adjusted indirect comparison analysis showed that patients treated with atogepant (Qulipta; AbbVie) 60 mg once daily (QD) demonstrated significant improvements in both efficacy and quality of life end points compared with those treated with rimegepant (Nurtec ODT; Pfizer) 75 mg every other day (QOD).⁴ The analysis included data from 2 phase 3 atogepant trials (PROGRESS: NCT03855137; and ADVANCE: NCT024848326) and 1 phase 2/3 rimegepant trial (BHV3000-305: NCT). Of note, the analysis only included patients who met the BHV3000-305 inclusion/exclusion criteria for these factors: at least 6 monthly migraine days (MMDs) at baseline and less than 18 monthly headache days (MHDs) at baseline.

A Bucher comparison was performed utilizing the aggregated data for the reweighted atogepant trial sample vs the observed effects in BHV3000-305 using placebo as an anchor between the studies. In addition to change in MMDs, investigators observed between-group differences in Migraine-Specific Quality of Life Questionnaire (MSQ v2.1) Role Function-Restrictive (RFR) domain scores after 12 weeks of treatment. In total, the analysis included 252 patients in the pooled atoegpent 60 mg QD group and 348 patients in the rimegepant 75 mg QOD group, with baseline characteristics that were balanced after weighting. Across weeks 1-12, atogepant-treated patients demonstrated a statistically significant greater reduction in mean MMDs vs rimegepant (mean difference, ­­–1.65; 95% CI, –2.49 to –0.81; P <.001).

Despite the fact that the atogepant 60 mg QD group had similar odds of experiencing a treatment-emergent adverse event (OR, 0.91; 95% CI, 0.56-1.45; P = .7366) and numerically higher odds of discontinuation because of any reason (OR, 1.43; 95% CI, 0.69-3.06) vs rimegepant, neither difference was statistically significant. In addition to showing greater impact on MMDs, the atogepant group outperformed rimegepant in a scenario analysis across weeks 9-12, with statistically significant greater reduction in MMDs observed (mean difference, –1.5; 95% CI, –2.55 to –0.43; P <.01). Furthermore, atogepant 60 mg QD demonstrated a significantly higher MSQ v2.1 RFR domain score (mean difference, 7.36; 95% CI, 1.88-12.82; P <.01) vs rimegepant 75 mg QOD.

Intravenous Ketamine Significantly Reduces Pain in Refractory Pediatric Headache

Findings from a recent study of pediatric patients with refractory migraine demonstrated a significant reduction in pain at discharge using intravenous ketamine as a treatment with no serious adverse events. These results suggest that intravenous ketamine is an effective, safe, and well-tolerated option for treating refractory pediatric headaches and status migrainosus.⁵ All told, the median percent pain reduction at discharge was 50% (IQR -67% to +25%) among 58 encounters with pediatric patients with refractory migraine. Of note, 64% of patients did not have headache recurrence or exacerbation in 1 month after discharge. Notably, the median time to recurrence was 7 days (IQR, 3-12.5) for those that recurred and 9% had recurrence in 72 hours postdischarge.

Researchers conducted a retrospective chart review of patients between the ages of 5 and 21 years old. To be eligible, the patients had to be admitted to a tertiary pediatric referral center for the treatment of refractory headache. Patients were excluded if they received both ketamine and IV dihydroergotamine (DHE) in the same period, had a secondary etiology for headache, or had a pain score that was less than 3 on a verbal analogue scale at presentation. Investigators used the percentage of pain reduction at discharge ([Discharge Pain Score - Initial Pain Score]/Initial Pain Score*100) as the primary outcome, while also observing serious adverse events, medication adverse effects, headache recurrence in 72 hours, and headache recurrence in 30 days postdischarge. Investigators defined headache recurrence if patients made a phone call or representation of care for headache requiring rescue therapy. Demographic variables from the patients were also collected.

In the analysis, 58 encounters comprised of 38 unique pediatric patients with a median age of 15.8 years (IQR 13.42-17.41), 76% of which identified as women, were included. Seventy-eight percent of patients were diagnosed as chronic migraine without aura and he median duration of headache or headache pain exacerbation at presentation was 10 days (IQR, 3-26.5). Also, the median maximum dose of intravenous ketamine was 0.28 mg/kg/hour (IQR, 0.2-0.4), with the median duration of infusion being 3 days (IQR, 2-3). Although there were no serious adverse events reported in the analysis, the most common adverse effects were dizziness (19%), nausea (12%), hallucinations (12%), blurry vision (12%), cognitive fog (9%), dysphoria (5%) and vomiting (4%). Notably, only 7% of encounters had discontinued therapy early because of the adverse events the patients experienced.

REFERENCES
1. Curran Y, Pack A, Huang W, et al. Patient Awareness and Provider Communication about Medication-Overuse Headache among Patients with Migraine. Presented at: AHS Annual Meeting, 2023; June 15-18; Austin, TX. P-137.
2. Patniyot I, Duggan D, Holick M, Dudley-harrell H. A retrospective analysis of the use of candesartan for migraine prevention in adolescents. Presented at: 2023 AHS Annual Meeting; June 15-18; Austin, TX. Abstract P-09.
3. Iser C, Anderson C, Hirte I, et al. Sequential administration of peripheral nerve blocks and onabotulinumtoxinA for the treatment of chronic migraine and other headache disorders – A retrospective tolerability and safety study. Presented at: AHS Annual Meeting, 2023; June 15-18; Austin, TX. P-177.
4. Tassorelli C, Onishchenko K, Duan M, et al. Comparative efficacy, quality of life, and safety/tolerability of atogepant and rimegepant in migraine prevention: a matching-adjusted indirect comparison. Presented at: 2023 AHS Annual Meeting; June 15-18; Austin, TX. P-42.
5. Rosenthal S, Ackley E, Koehler A, Yonker M. The Safety and Efficacy of Intravenous Ketamine in the Treatment of Refractory Pediatric Headache. Presented at: AHS Annual Meeting, 2023; June 15-18; Austin, TX. P-193.