Over a year treatment period, patients maintained their subscale scores assessing medication effects, energy and fatigue, and cognition, all of which might be expected to be sensitive to a new treatment.
Recently published findings showed that adults with seizure clusters either maintained or improved quality of life (QoL) after being treated with diazepam nasal spray (Valtoco; Neurelis) for a year period. Using the Quality of Life in Epilepsy (QOLIE)-31-P questionnaire, investigators found several changes among different subscales, suggesting differences in the sensitivity with use of an intermittent treatment.1
The data showed that mean QOLIE-31-P scores, among all patients with data at any time point, were stable or increased across time points, with maximum at day 365. From day 0 to the end of the treatment period, mean total QOLIE-31-P scores increased from 57.3 to 62.5, meeting the definition of clinically important improvement (minimally important change [MIC], 5.19 points). Furthermore, Seizure Worry and Social Functioning, two subscales of the questionnaire, demonstrated the greatest numerical increases in points (Seizure Worry: 8.7 points; from 46.3 to 55.0; MIC, 7.4 points; Social Functioning: 8.1 points; from 52.9 to 61.0; MIC, 4.0 points).
Senior investigator Adrian Rabinowicz, MD, senior vice president, Clinical Development and Medical Affairs, Neurelis, and colleagues concluded that the "availability of diazepam nasal spray for out-of-hospital seizure treatment has the potential to improve patients’ and caregivers’ sense of empowerment to treat and control seizure clusters. In this population with intractable epilepsy, maintained or increased QoL scores may show stability or a lack of decline."
In the open-label safety study, 74 of 85 (87.1%) adults provided QOLIE-31-P data, and 72 of those patients were included in the analyses. The QOLIE-31-P, recorded at days 30, 150, 270, and 365, included 7 subscales: Seizure Worry, Overall QoL, Emotional Wellbeing, Energy/Fatigue, Cognitive Functioning, Medication Effects, and Social Functioning. Higher scores indicated better QoL, with an overall score calculated as a weighted composite of the 7 subscales.
Among those who had follow-up data for all 5 time points (n = 48; 64.9%), mean total QOLIE-31-P scores increased from day 0 to day 365 by 2.2 points (from 59.5 to 61.7), with mean changes of 5.9 (from 48.4 to 54.3) and 6.3 (from 55.3 to 61.6) in Seizure Worry and Social Functioning, respectively. For noncompleters (n = 26; 35.1%), or those who only had data for 2 to 4 time points, mean scores were also similar or increased across time points; however, the number of patients decreased over time, with only 5 patients contributing data to the day 365 means.
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In total, 41 patients administered diazepam nasal spray frequently for at least 2 doses per month while the remaining 31 individuals used it less often. Despite the differences in dosage, overall QOLIE-31-P scores, as well as mean Seizure Worry and Social Functioning scores, were similar and slightly higher by the end of the year treatment period. Changes from baseline showed numerically small but statistically significant improvements between groups in the Social Functioning score at day 270 (P = .045; 2-sided, 2-sample t test), but not for any other subscales or time points.
Between those who self-administered at least 1 dose of diazepam nasal spray (n = 25) vs those who had only care partner administration (n = 47), there were no statistically significant difference in QOLIE-31-P overall scores. Although self-administrators’ scores were generally higher throughout, the difference between the groups declined over time.
Of the 72 patients who completed follow-up, 76.4% (n = 55) had at least 1 treatment-emergent adverse event (TEAE). Treatment-related TEAEs were reported in 17 patients (23.6%), the most common of which were nasal discomfort (11.1%) and headache (5.6%). There was 1 death, attributable to sudden death in epilepsy, and 1 discontinuation because of TEAE (major depression) in the frequent-usage group, neither of which were treatment-related.
Rabinowicz et al concluded, "the hypothesis-generating results presented here are suggestive of effects of intermittent treatment on the QoL of patients with seizure clusters that could be further investigated using objective measurement with an appropriate instrument specifically developed for these patients and caregivers."