IHSS Proves Effective at Measuring IH Symptoms

Research presented at Virtual SLEEP 2021 suggests the Idiopathic Hypersomnia Severity Scale (IHSS) is a reliable and comprehensive measure of excessive daytime sleepiness, sleep inertia, and self-reported global symptoms among individuals with idiopathic hypersomnia (IH).

“IH is a central hypersomnolence disorder characterized by excessive daytime sleepiness, prolonged nighttime sleep, and sleep inertia,” explained presenting author Yves Dauvilliers, MD, PhD, a professor at the Sleep and Wake Disorders Centre in the department of Neurology at Gui de Chauliac Hospital in France.

The IHSS, a 14-item, self-reported questionnaire, was designed to assess core IH symptom severity. “In a previous study we found that IHSS total scores were associated with the Epworth Sleepiness Scale (ESS) in patients with IH, untreated and treated subjects. However, the relationship between IHSS scores and other symptoms of IH measured with all the tools has not been formally established,” Dauvilliers said.

To address this knowledge gap, researchers conducted a post hoc analysis of data from a clinical trial (NCT03533114) evaluating lower-sodium oxybate (LXB, Xywav). IHSS efficacy served as a key secondary endpoint in the double-blind, placebo controlled randomized withdrawal period study.

Currently, LXB is approved for treatment of cataplexy and excessive daytime sleepiness among patients with narcolepsy in the United States.

At baseline, patients completed the IHSS and ESS, while the IHSS, ESS, and Patient Global Impression of Change (PGIc) were completed during an open label treatment titration and optimization period (OLTTOP). All 3 measures were also completed after the OLTTOP, after a stable-dose period (SDP), and after a double-blind, randomized withdrawal period (DBRWP). In addition, the sleep inertia visual analog scale (VAS-SI) was completed during screening, SDP, and DBRWP.

“This complex design was decided [on] to reduce the number of participants in it, which is important when studying a rare disease, and also to reduce the amount of time [patients are] taking the placebo,” Dauvilliers said.

Analyses revealed:

• IHSS scores correlated positively with ESS scores (correlation coefficient [r] = 0.77; 95% CI, 0.73-0.81) and VAS-SI scores (r = 0.69; 95% CI, 0.63-0.75)
• IHSS total score change was correlated with PGIc rank (chi-square with 6 degrees of freedom = 595.8; nominal P <.001)
• The linear mixed model showed that a 3-point change in ESS score corresponded to an average 3.99- point change in IHSS score; a 10-point change in VAS-SI score corresponded to an average 3-point change in IHSS score
• Participants very much improved in the PGIc had a −12.13 (95% CI, −13.23 to −11.04) expected change in IHSS score
• Participants much improved in the PGIc had a −8.39 (95% CI, −9.30 to −7.48) expected change in IHSS score

At least 10% of trial participants reported treatment emergent adverse events including nausea, headache, dizziness, anxiety and vomiting.

“In conclusion, in this study, LXB, low-sodium oxidate, demonstrated clinically meaningful effects on the ESS, PGIc, IHSS, and VAS-SI in participants with IH. The overall safety profile of LXB was consistent with what is known with sodium oxybate,” Dauvilliers said.

Reference

Dauvilliers Y, Arnulf I, Foldvary-Schaefer N, et al. Correlation of the idiopathic hypersomnia severity scale with other measures of sleep parameters in a phase 3 trial. Presented at: Virtual SLEEP 2021; June 10-13, 2021; Virtual. Abstract 500.