Early Intervention with Midazolam Nasal Spray and Efficacy in Patients with Seizure Clusters: Post- Hoc Analysis of an Open-label Extension Trial
Abstract number :
3.273
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2021
Submission ID :
1826034
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:51 AM
Authors :
James Wheless, MD - University of Tennessee Health Science Center & Le Bonheur Children’s Hospital; Marcus Brunnert, Dr. rer. nat. - UCB Pharma, Monheim am Rhein; Florin Floricel, MD, PhD - UCB Pharma, Monheim am Rhein; Svetlana Dimova, MD, PhD - UCB Pharma, Brussels; Brandi Fannon, PharmD - UCB Pharma, Smyrna
Rationale: Delay in treatment of seizure clusters (SCs) may lead to worse patient outcomes (Almohaish et al. J Clin Med 2021;10:1754); however, there are no standard SC treatment guidelines, including when to administer a rescue medication, and no studies to date have evaluated the effect of time to treatment on outcomes with approved nasal rescue sprays. This analysis assessed the impact of early intervention with midazolam nasal spray (MDZ-NS) on its efficacy in patients with SCs during repeated intermittent use.
Methods: ARTEMIS-2/P261-402 (NCT01529034) is a Phase III open‐label extension trial in patients with SCs aged ≥ 12 years who completed the randomized controlled trial ARTEMIS‐1/P261-401 (NCT01390220). Caregivers administered MDZ-NS 5 mg when patients experienced an SC; a second dose could be given if seizures did not terminate within 10 min or recurred within 10 min–6 h. This post-hoc analysis assessed efficacy outcomes (seizure termination within 10 min, no seizure recurrence between 10 min and 24 h) by time from seizure cluster episode (SCE) identification to administration of the first MDZ-NS dose. For SCEs treated with two doses, outcomes were assessed after the second dose.
Results: A total of 1996 SCEs in 161 patients were included; 60.1% and 39.9% of SCEs were treated with one and two MDZ-NS doses, respectively. Overall, MDZ-NS treatment was administered at a median of 3 min (Q1–Q3 1.0–7.0 min) after SCE identification (< 1 min: 18.5% of SCEs, median 0 min; 1–3 min: 35.9% of SCEs, median 2 min; 4–10 min: 28.3% of SCEs, median 5 min; > 10 min: 17.3% of SCEs, median 24 min). Overall, 92.4% of SCEs terminated within 10 min of MDZ-NS administration (95.6% of SCEs treated with one dose, 87.7% of SCEs treated with two doses). In 85.1% of SCEs, no seizure recurrence was observed between 10 min and 24 h after MDZ-NS administration (84.2% of SCEs treated with one dose, 86.6% of SCEs treated with two doses). The time from SCE identification to MDZ-NS administration did not substantially impact the proportion of SCEs that terminated within 10 min (Fig. 1). Sustained 24-h seizure control was achieved more often in SCEs for which treatment was administered sooner after SCE identification (Fig. 1). The time from SCE identification to MDZ-NS administration had a more pronounced effect on sustained 24-h seizure control after the first dose, but it appeared that it may also have impacted the sustained 24-h seizure control after the second dose (Fig. 1).
Conclusions: This analysis showed high overall efficacy for MDZ-NS, with seizure termination within 10 min and no recurrence between 10 min and 24 h for a large majority of SCEs. The time from SCE identification to initial treatment with MDZ-NS did not affect the proportion of SCEs that terminated within 10 min after administration of the first or second dose. However, sustained 24-h seizure control was more likely when MDZ-NS treatment was administered earlier after SCE identification, highlighting the importance of early treatment of SCs.
Funding: Please list any funding that was received in support of this abstract.: UCB Pharma-funded.
Anti-seizure Medications