Authors :
Presenting Author: Megan Barra, PharmD – Marinus Pharmaceuticals, Inc.
Sri Saikumar, MS, MBA – Trinity Life Sciences; Saloni Shah, BS, LLB, MBA – Trinity Life Sciences; Dushyant Katariya, BE – Trinity Life Sciences; Adrienne Lovink, MASc – Trinity Life Sciences; Henrikas Vaitkevicius, MD – Marinus Pharmaceuticals, Inc.; Eva Rybak, PharmD – Marinus Pharmaceuticals, Inc.
Rationale:
Status epilepticus (SE) is a common life-threatening neurological emergency; early recognition and treatment initiation leads to a better response and may improve outcomes. Patients (pts) who do not respond to standard first and second line treatments are in refractory SE (RSE) requiring additional pharmacotherapies including escalation to IV anesthesia (IVA). Ongoing controversy on optimal timing, depth of IVA, and its impact on pt outcomes remains unelucidated. There is a lack of data on the SE pt journey in recent years, including epidemiology, outcomes, and the changing healthcare landscape during the COVID-19 pandemic.
Methods:
Hospital-based, service-level, all-payer US data from PINC AI™ Healthcare Database (2018-2022) and Komodo Health Healthcare Map (2017-2022) were analyzed. Hospitalizations were flagged based on the appearance of an SE ICD-10 CM code at the admit, primary, or secondary diagnostic position.
Episodes were categorized as the following: SE (received benzodiazepine [BZD] therapy only); established SE (ESE; received 1 BZD and 1 IV antiseizure medication [ASM]); and RSE (≥ 2 IV ASMs without IVA [RSE-noIVA] or ≥ 1 ASM with IVA and concomitant mechanical ventilation [MV, RSE-IVA]). Super-refractory SE (SRSE) described RSE with IVA and ≥ 2 days of MV.Results:
This cross-sectional pt journey study examined a total of 140,538 SE episodes in 113,229 unique patients (median [IQR] age 51 [27, 66] years) during the five year study period. Baseline epilepsy diagnosis was reported in 67% of pts. SE was the admit, primary or secondary diagnosis in 35%, 55% and 41% of episodes, respectively. Most episodes were categorized as SE (n=51.0K, 36%), ESE (n=26.6K, 19%), and RSE (n=63.0K, 45%). In pts with RSE, 41% received RSE-IVA and 11% progressed to SRSE. Pts with RSE-IVA had longer ICU length of stay (LOS) vs RSE-noIVA or ESE (median 5.0, 3.0 and 2.0 days, respectively), hospital LOS (9.0, 6.0 and 3.0 days), and in-hospital mortality (25%, 12%, 5%). Even in the absence of IVA, pts with RSE who received ≥ three IV ASMs had more ICU admissions (72% vs 62%) and longer ICU (median 4.0 vs 2.0 days) and hospital (9.0 vs 5.0 days) LOS than those responsive to two IV ASMs. Inter-hospital transfers were associated with 32% of episodes; 76% of transfers occurred after first/second line therapy. Approximately 41% of pts with RSE were treated at multiple institutions during an episode and ~2/3 ultimately received care at a tertiary academic medical center. Pts with RSE-IVA had the highest rate of transfers (46%), followed by those with RSE-noIVA (35%) and ESE (30%). Recurrent SE was observed in 20% of pts.
Conclusions:
Pts with SE have complex care pathways requiring specialized care and multi-institutional interactions. Increased treatment refractoriness and exposure to IVA in SE is associated with longer ICU and hospital LOS and overall worse outcomes. Rapidly effective anti-SE treatments remain an urgent unmet need in this patient population.
Funding:
Marinus Pharmaceuticals, Inc.