Solriamfetol for Excessive Sleepiness in Narcolepsy and Obstructive Sleep Apnea: Effect Sizes and Numbers Needed to Treat or Harm
Craig Chepke1, Andrew Cutler2, Samantha Floam3, Gregory Parks3, Russell Rosenberg4
1Excel Psychiatric Associates, 2Atrium Health, 3Axsome Therapeutics, 4Neurotrials Research
Objective:
To calculate effect size (ES), number-needed-to-treat (NNT), and number-needed-to-harm (NNH), statistical representations of efficacy and tolerability that may assist clinicians’ treatment decisions, from two solriamfetol registrational studies in excessive daytime sleepiness (EDS) in adults with narcolepsy or obstructive sleep apnea (OSA).
Background:
Solriamfetol, a dopamine/norepinephrine reuptake inhibitor (DNRI) and TAAR1 activator, is approved to treat EDS in adults with narcolepsy or OSA.
Design/Methods:
Data (including published endpoints, post-hoc analyses, and AEs) from phase 3 trials in EDS associated with narcolepsy (TONES 2) or OSA (TONES 3) were used to calculate ES, NNT, and NNH.
Results:
On the maintenance of wakefulness test (MWT), ES versus placebo (Cohen’s d) were 0.29, 0.82, and 1.13 for 75mg, 150mg, and 300mg solriamfetol (TONES 2) and 0.46, 0.89, 1.08, and 1.28 for 37.5mg, 75mg, 150mg, and 300mg (TONES 3). On the Epworth sleepiness scale (ESS), Cohen’s d values were 0.47, 0.80, and 1.02 for 75mg, 150mg, and 300mg solriamfetol (TONES 2), and 0.42, 0.37, 0.99, and 1.04 for 37.5mg, 75mg, 150mg, and 300mg (TONES 3). NNT (patients with ESS ≤10) were 7, 5, and 3 for 75mg, 150mg, and 300mg (TONES 2) and 8, 6, 4, and 3 for 37.5mg, 75mg, 150mg, and 300mg (TONES 3). For patient global impression of change (PGIc) scores, NNT was 4, 3, and 3 for 75mg, 150mg, and 300mg solriamfetol (TONES 2) and 16, 5, 3, and 3 for 37.5, 75mg, 150mg, and 300mg (TONES 3). Clinician global impression of change (CGIc) NNT results were similar to those for PGIc. NNH pooled across doses for AEs (≥5% patients) in TONES 2 and TONES 3, were greater than placebo and <10%, except headache in TONES 2 (NNH=6).
Conclusions:
In this post-hoc analysis ES, NNT, and NNH were favorable for solriamfetol treatment of EDS associated with narcolepsy and OSA.