Poster Number-53 - Response to Treatment with Lemborexant in Older Subjects with Insomnia Disorder and Comorbid Pain at Baseline

Response to Treatment with Lemborexant in Older Subjects with Insomnia Disorder and Comorbid Pain at Baseline

Purpose:

Although the prevalence of insomnia among the elderly varies globally, most reports estimate that 25%-50% are affected in most countries.¹ Chronic pain is also prevalent among the elderly, affecting 25%-50% of those dwelling in the community and up to 80% of those institutionalized.² The reciprocal relationship between poor sleep and pain has been well established.³ Insomnia increases pain sensitivity and pain can interfere with sleep, thus impacting quality of life.⁴ Therefore, it is of critical clinical importance to evaluate whether a sleep-promoting drug such as lemborexant (LEM) can improve sleep in older patients, with both insomnia and ongoing pain. LEM is a dual orexin receptor antagonist approved in the United States, Japan, Canada, Australia and several Asian countries to treat adults with insomnia.  We report here, the effects of LEM in older subjects with insomnia and comorbid pain.

Methods:

Study E2006-G000-304 (Study 304; SUNRISE-1; NCT02783729) was a 1-month, double-blind, placebo (PBO)- and active-controlled study in subjects age ≥55y with insomnia disorder (full analysis set [FAS] = 1006). Subjects from the FAS who also endorsed some or extreme pain at baseline on the pain/discomfort dimension (subjects endorse one of the choices: no problems/some problems/extreme problems) of the EuroQual-5 Dimension-3 Level scale (EQ-5D-3L)⁵ were eligible for inclusion in these post-hoc analyses. Medical history of pain conditions and/or ongoing therapy for pain were not required for eligibility in Study 304 or these post-hoc analyses. Exclusion criteria for Study 304 included chronic pain that, in the opinion of the investigator, could have affected the subject’s safety or interfered with the study assessments. Subjects were randomized to bedtime doses of PBO, LEM 5mg (LEM5), 10mg (LEM10) or zolpidem tartrate extended release 6.25 mg (not reported here). Changes from baseline (CFB) in objective sleep parameters as assessed by polysomnography (latency to persistent sleep [LPS]; wake after sleep onset [WASO]) were analyzed by mixed-effect repeated measures analyses with adjustments for relevant factors.

Results:

Some or extreme pain at baseline was reported on the EQ-5D-3L by 183/1006 or approximately 18% of subjects in the FAS (PBO = 55/1006 [5.5%]; LEM5 = 78/1006 [7.8%]; LEM10 = 50/1006 [5.0%]). For LPS, baseline median values (minutes) were 31.0, 29.4 and 42.1 for PBO, LEM5 and LEM10, respectively. Decreases (improvement) in median CFB for LPS were significantly different and larger for both LEM doses compared with PBO at the beginning of treatment (mean of Nights 1/2: +2.5; -8.4, -15.8; both P < 0.005); and at the end of treatment (mean of Nights 29/30: -7.1,-9.9, -9.0; LEM5 P = 0.031, LEM10

P = 0.054). For WASO, baseline median values (minutes) were 101.0, 103.6 and 111.1 for PBO, LEM5 and LEM10, respectively. Decreases (improvement) in median CFB for WASO were significantly different and larger (P < 0.001) for both LEM doses compared with PBO at the beginning (mean of Nights 1/2; -1.5; −41.5, -64.4) and end of treatment (mean of Nights 29/30; -1.1, -37.9, -52.5). LEM was generally well tolerated with mild/moderate treatment-related adverse events.

Conclusion:

LEM treatment improved objective measures of sleep onset (LPS) and sleep maintenance (WASO) compared with PBO among older adults with insomnia and comorbid pain. The improvements from baseline in LPS were smaller compared to findings in the overall clinical trial population for Study 304 reported previously,⁶ but improvement for WASO was comparable. LEM was well tolerated in subjects with comorbid pain, with safety findings similar to the overall population. These data suggest LEM may effectively treat insomnia in older adults with concomitant painful conditions

This study was supported by Eisai Inc.

References: 1. Gulia KK, Kumar VM. Psychogeriatrics. 2018;18(3):155-65.
2. Cravello L, et al. Pain Ther. 2019;8(1):53-65.
3. Craner JR, Flegge LG. Pain Pract. 2022 Feb;22(2):171-181.
4. Finan PH, Goodin BR, Smith MT. J Pain. 2013 Dec;14(12).
5. EuroQol Research Foundation EQ-5D-3L User Guide. [(accessed on 3 March 2022)];2018 Available online: https://euroqol.org/wp-content/uploads/2021/01/EQ-5D-3LUserguide-14-0421.pdf.
6. Rosenberg R, et al. JAMA NetwOpen. 2019;2:e1918254.