American Academy of Neurology annual meeting – 13-18 April 2024
The following summarizes some of the highlights from Day 3 of AAN 2024.
April 18 Edition
April 16 Edition
April 15 Edition
Cenobamate in focal-onset seizures and refractory epilepsy: real-world data
Donanemab in early Alzheimer disease
Ocrelizumab efficacy in African-Americans and Hispanics
Utility of biomarkers in RIS
CONGRESS HIGHLIGHTS – WEDNESDAY EDITION
Cenobamate in focal-onset seizures and refractory epilepsy: real-world data
Cenobamate was approved by Health Canada last November as an adjunctive therapy for the management of partial-onset seizures in patients who are not satisfactorily controlled with conventional therapy. Two new database analyses have compared outcomes in patients receiving cenobamate or another adjunctive therapy. The two studies indicated that treatment with cenobamate may significantly reduce morbidity and healthcare utilization in patients with focal-onset epilepsy and refractory epilepsy post-surgery.
The first study (N=58,786; mean age 42 years) compared adjunctive cenobamate versus brivaracetam, clobazam, eslicarbazepine, lacosamide, lamotrigine, levetiracetam, or perampanel in patients with focal epilepsy (Urban et al. AAN 2024;S29.003). Overall, 62.8% had a history of intractable seizures and 39.5% had a history of status epilepticus (SE). Over the observation period (116,859 person-years), adjunctive cenobamate was associated with significantly lower rates of in-patient days and emergency room visits. The mean increase in in-patient days relative to cenobamate ranged from 1.7/100 patient-years with lamotrigine to 6.4/100 PY with lacosamide. The mean increase in ER visits relative to cenobamate ranged from 2.0/100 PY for brivaracetam to 8.8/100 PY for levetiracetam.
A separate analysis examined health utilization in patients (N=7,835; mean age 39 years) receiving adjunctive antiepileptic therapy following epilepsy surgery (Pellinen et al. AAN 2024;P8.004). Surgical procedures included epilepsy-related surgical resection, or implantation of a vagus nerve stimulator or a responsive neurostimulation device. A total of 73.0% had intractable seizures and 46.7% had a history of SE. During the observation period (14,874 person-years), the overall rate of in-patient days was 202.7/100 PY; the rate of ER visits was 47.3/100 PY. The lowest rate of in-patient days was seen with eslicarbazepine. Cenobamate use was associated with significantly lower rates of in-patient days compared to the other six adjunctive therapies. Relative to cenobamate, the mean increase in in-patient days ranged from 0.004/100 patient-years with lamotrigine to 10.3/100 PY with lacosamide. Cenobamate was associated with the lowest rate of emergency room visits. The mean increase in ER visits relative to cenobamate ranged from 3.4/100 PY for brivaracetam to 9.2/100 PY for levetiracetam. A prior analysis reported a 100% reduction in seizure frequency at 12 months in 29.2% of patients with refractory focal seizures despite prior surgery (Abou-Khalil et al. Epilepsy Res 2022;184:106952).
Donanemab in early Alzheimer disease
The TRAILBLAZER-ALZ2 trial recently demonstrated a modest clinical benefit with donanemab 1400 mg q4wk IV in early symptomatic AD patients (mean age 73 years) with amyloid and tau pathology (Sims et al. JAMA 2023;330:512-527). The least-squares mean (LSM) change in iADRS scale score at 76 weeks was -6.02 with donanemab vs. -9.27 with placebo in the low/medium tau cohort, and -10.19 vs. -13.11, respectively, in the combined study population. LSM change in CDR-SB score was 1.20 with donanemab vs. 1.88 with placebo at week 76. A post-hoc analysis examined the clinical relevance of donanemab-associated changes (Atri et al. AAN 2024;S1.004). Benefits were seen on ADRS items such as episodic memory, executive function and instrumental ADL related to communication; and all CDR-SB cognitive and functional domains, including memory, orientation, judgment/problem solving and personal care. Donanemab was associated with a higher incidence of serious adverse events (17.4% vs. 15.8% with placebo) and mortality (1.9% vs. 1.1%). A separate analysis presented at AAN noted that if inclusion/exclusion criteria from the study were applied to the Mayo Clinic Study of Aging cohort, only 13 of 817 patients (1.6%) would qualify for a trial of anti-amyloid therapy (Jones et al. AAN 2024;N4.001).
There were three deaths in donanemab-treated patients who developed amyloid-related imaging abnormalities (ARIA). A post-hoc analysis of the donanemab clinical trial program examined factors predictive of ARIA-edema and effusions (ARIA-E), which occurred in 22% of donanemab-treated patients (Greenberg et al. AAN 2024;P1.001). Baseline risk factors for ARIA-E were APOE ε4 homozygosity, greater amyloid burden, higher number of microhemorrhages, presence of cortical superficial siderosis and higher arterial pressure. The authors concluded that genotyping and a baseline MRI may be useful prior to starting treatment.
Ocrelizumab efficacy in African-Americans and Hispanics
CHIMES is an open-label phase IV study in African-Americans and Hispanic Americans, two populations that are underrepresented in DMT trials (Amezcua et al. AAN 2024;PL5.004). The primary endpoint was no evidence of disease activity (NEDA) at 48 weeks. NEDA was defined as no relapses, no 24-week confirmed disability progression and no new lesions. Data were reported for 251 patients; mean age was 35.5 years; mean body-mass index was 31.0 kg/m2; and mean baseline EDSS score was 2.4. The mean time from first MS symptoms to diagnosis was two years. At 48 weeks, 46% of African-Americans and 58% of Hispanic Americans achieved NEDA. A total of 46.0% and 63.8% of the two groups, respectively, had no new T2 lesions. The rate of serious adverse events was 5.5%. No new safety signals were identified.
Utility of biomarkers in RIS
A study at St. Michael’s Hospital, Toronto, analysed serum levels of NfL and glial fibrillary acidic protein (GFAP) in 52 individuals with radiologically isolated syndrome compared to 21 healthy controls (Martin et al. AAN 2024;P7.002). MRIs were obtained at baseline and at 12 months. Median sNfL levels were significantly higher in RIS vs. controls (10.8 vs. 8.5 pg/mL). There was no significant difference in GFAP level between the two groups. sNfL level was significantly correlated with the number of black holes, number of spinal cord lesions and number of lesions positive for the central vein sign (CVS+). Baseline sNfL was not correlated with any MRI findings at 12 months.
GFAP at baseline was correlated with the number of black holes, number of infratentorial lesions and the number of CVS+ lesions. Baseline GFAP was also prognostic for the development of white matter lesions, black holes and CVS+ lesions at 12 months.
April 18 Edition
April 16 Edition
April 15 Edition