Daridorexant for patients with chronic insomnia disorder: number needed to treat, number needed to harm, and likelihood to be helped or harmed.

OBJECTIVES: Appraise the evidence for daridorexant 50 mg and 25 mg versus placebo when treating chronic insomnia disorder in terms of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH). METHODS: NNT, NNH, and LHH were calculated from a 3-month pivotal Phase 3 study (N = 930; randomized 1:1:1 to daridorexant 50 mg, daridorexant 25 mg, or placebo once nightly). Wakefulness after sleep onset, latency to persistent sleep, self-reported total sleep time, Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), and Insomnia Severity Index were used for the NNT efficacy analysis. NNH safety analysis was performed using rates of adverse events (AEs) occurring in >1% of the participants in any arm. LHH was assessed for all NNT estimates, contrasting them with NNH estimates for somnolence, headache, and fatigue AEs. RESULTS: NNT estimates for daridorexant 50 mg versus placebo were <10 for clinically meaningful thresholds across all outcomes. NNT estimates for daridorexant 25 mg versus placebo were not as robust as those observed for daridorexant 50 mg, with many values exceeding 10. NNH estimates for daridorexant 50 mg and 25 mg versus placebo did not show a statistically significant treatment difference except for falls, where NNH was negative for the daridorexant 50 mg group (-44 [95% CI -328; -21]; rate of falls was greater with placebo than for daridorexant 50 mg). All LHH ratios at Months 1 and 3 were >1 (except for daridorexant 25 mg for the IDSIQ alert/cognition domain), indicating that patients were more likely to respond to daridorexant 50 mg and 25 mg than to experience an AE of somnolence, headache, or fatigue. CONCLUSION: Daridorexant 50 mg and 25 mg have a favorable benefit-risk ratio over 3 months. Daridorexant 50 mg demonstrated more robust (lower) NNT estimates versus placebo than daridorexant 25 mg.

Daridorexant, a dual orexin receptor antagonist, is a new treatment for chronic insomnia disorder. This analysis examined the effect and safety of daridorexant 50 and 25 mg, using data from a 3-month Phase 3 study (NCT03545191) to measure 'number needed to treat' (NNT) and 'number needed to harm' (NNH).NNT estimates how many patients need to be treated over a specific period to see one more beneficial response. Estimates versus placebo <10 indicate an effective treatment. Daridorexant 50 mg estimates were <10 for all objective and subjective measurements of insomnia assessed in this analysis, including evaluation of daytime functioning. NNT estimates for daridorexant 25 mg versus placebo were not as robust as daridorexant 50 mg, with values >10.NNH is calculated in the same way as NNT but estimates harmful outcomes rather than benefits. Estimates versus placebo >10 means the treatment is reasonably well tolerated.Using NNT and NNH, the 'likelihood to be helped or harmed' (LHH) ratio was calculated, determining how more likely a patient is to benefit versus experiencing harm from a treatment (LHH of >1 denotes a positive benefit­risk ratio). Both daridorexant doses had a favorable benefit­risk ratio over 3 months with LHH > 1.This analysis supports daridorexant 50 mg as the optimal dose to treat insomnia in adults, offering improved effectiveness compared with daridorexant 25 mg, with a similarly good safety profile.

The Associations between Insomnia Severity and Health Outcomes in the United States.

Little is known about the associations between insomnia severity, insomnia symptoms, and key health outcomes. Using 2020 United States National Health and Wellness Survey (NHWS) data, we conducted a retrospective, cross-sectional analysis to determine the associations between insomnia severity and a number of health outcomes germane to patients (health-related quality of life (HRQoL), employers and government (workplace productivity), and healthcare payers (healthcare resource utilization (HCRU)). The Insomnia Severity Index (ISI) questionnaire was used to evaluate overall insomnia severity. HRQoL was assessed using the physical and mental component summary scores of the Short Form-36v2 (SF-36v2) questionnaire, and health utility status was measured using the Short Form-6D (SF-6D) and EuroQoL-5D (EQ-5D) questionnaires. Workplace productivity was measured using the Work Productivity and Activity Impairment (WPAI) questionnaire. After adjusting for confounders, greater insomnia severity was significantly associated with worsened quality of life, decreased productivity, and increased HCRU in an apparent linear fashion. These findings have important implications for future research, including the need for specific assessment of insomnia symptoms and their impact on key health outcomes.