Daridorexant in Patients With Insomnia Disorder: Number Needed to Treat, Number Needed to Harm & Likelihood to Be Helped or Harmed
Author Type(s)
Faculty
Document Type
Abstract
Publication Date
5-1-2023
DOI
10.1093/sleep/zsad077.0350
Journal Title
Sleep
Department
Psychiatry and Behavioral Sciences
Abstract
Introduction
Patients with insomnia disorder have difficulty initiating or maintaining sleep and have impaired daytime functioning. Daridorexant is a dual orexin receptor antagonist approved for the treatment of insomnia. This analysis reports the number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH) with daridorexant 25 mg or 50 mg versus placebo over 3 months. Methods
Phase 3 data from one of two pivotal trials (N=930: randomized 1:1:1 to daridorexant 25 mg, 50 mg, or placebo) were used to calculate NNT, NNH, and LHH. For the NNT analysis, wakefulness after sleep onset, latency to persistent sleep, self-reported total sleep time, the Insomnia Daytime Symptoms and Impacts Questionnaire, and the Insomnia Severity Index were explored. NNT was assessed using a range of clinically meaningful thresholds (CMTs), from minimal clinical improvement (MiCI) to marked clinical improvement. NNH analysis was performed on adverse events (AEs) occurring in >1% of participants in any treatment arm. LHH values were calculated for all NNT outcomes using the NNH estimates for somnolence and fatigue AEs. Results
At Month 1 and 3, NNT values at MiCI thresholds for daridorexant 50 mg ranged from 5–9 and 6–12, respectively, and were all statistically significantly different versus placebo, indicating a good therapeutic response. Daridorexant 50 mg had at least one NNT < 10 for CMTs across all outcomes. NNTs at MiCI thresholds for daridorexant 25 mg ranged between 7–328 and 8–1666. NNH values for daridorexant 25 and 50 mg were negative or not significantly different from placebo, confirming a good tolerability profile. For a somnolence AE, LHH values ranged from 83.3–200 for daridorexant 50 mg versus placebo. For a fatigue AE, LHH ranged from 4.3–10.2. Conclusion
Daridorexant 25 mg and 50 mg both have a positive benefit-risk ratio compared with placebo over 3 months. Furthermore, daridorexant 50 mg showed ‘good’ NNT values (i.e. NNT < 10) over all efficacy endpoints in relation to the CMTs. NNH results confirmed the good tolerability profile of both doses.
Recommended Citation
Chalet, F. X., Luyet, P. P., Rabasa, C., Vaillant, C., Saskin, P., Ahuja, A., & Citrome, L. (2023). Daridorexant in Patients With Insomnia Disorder: Number Needed to Treat, Number Needed to Harm & Likelihood to Be Helped or Harmed. Sleep, 46 (Suppl. 1), A155. https://doi.org/10.1093/sleep/zsad077.0350