Lemborexant and suvorexant for treating insomnia: An indirect comparison using number needed to treat, number needed to harm, and likelihood to be helped or harmed

Introduction: Lemborexant is approved in the US for treating insomnia in adults. We evaluated the evidence-base for lemborexant and suvorexant, both dual orexin receptor antagonists (DORAs), for number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH; defined as NNH/NNT).

Methods: Data from randomized placebo-controlled trials for lemborexant (1mo duration and 6mo duration) and suvorexant (both 3mo duration) were evaluated. Efficacy outcomes and adverse event rates were contrasted with placebo and compared. Efficacy was assessed at 1mo and 3mo using different definitions of treatment response: ‚â•15% improvement for subjective sleep onset latency (sSOL) and subjective wake after sleep onset (sWASO), respectively; or ‚â•6-point improvement on the Insomnia Severity Index (ISI). Somnolence was a key tolerability outcome. Data for each drug were pooled: lemborexant 5mg, 10mg; suvorexant 15mg, 20mg.

Results: NNT(95%CI) vs. placebo at 1mo and 3mo for sSOL response was 5(4-6) / 6(4-8) for lemborexant and 12(7-34) / 26(ns) for suvorexant; sWASO response, 8(6-14) / 10(6-26) and 12(8-37) / 16(9-102), respectively; and ISI response, 7(5-11) / 5(4-8) and 10(7-19) / 8(6-14), respectively. NNH(95%CI) vs. placebo for somnolence was 19(14-28) / 12(9-17) for lemborexant at 1mo and 3mo and 28(17-82) for suvorexant at 3mo. All LHH values for lemborexant and suvorexant were >1, suggesting a favorable benefit/risk ratio.

Conclusions: Lemborexant demonstrated a numerically larger effect size (lower NNT) vs. placebo than suvorexant on sleep measures. These findings help assess the evidence-base for evaluating benefit-risk profiles and making treatment decisions for adult insomnia patients.