Evaluating the likelihood to be helped or harmed after treatment with viloxazine extended-release in children and adolescents with attention-deficit/hyperactivity disorder

Abstract

Aims: When clinicians evaluate potential medications for their patients, they must weigh the probability of a treatment's benefits against the possible risks. To this end, the present analyses evaluate the novel nonstimulant viloxazine extended-release (viloxazine ER) using measures of effect size to describe the potential benefits of its treatment in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) as well as the risk of discontinuation because of intolerable adverse events.

Methods: These post hoc analyses use pooled data from four pivotal Phase 3 trials in paediatric patients treated with viloxazine ER. The Likelihood to be Helped or Harmed (LHH) effect size measure was calculated to describe the probability of patients benefiting from treatment vs discontinuing. The Number Needed to Treat (NNT) was calculated from frequently used thresholds of response. The Number Needed to Harm (NNH) was calculated using discontinuations because of adverse events.

Results: LHH values for viloxazine ER ranged from 5 to 13, suggesting that subjects were 5-13 times more likely to benefit from, rather than discontinue, viloxazine ER treatment. Specifically, NNT values for viloxazine ER treatment ranged from 6 to 7. NNH values for viloxazine ER treatment ranged from 31 to 74. By convention, single-digit NNTs (<10) suggest the intervention is potentially useful, while NNH values ≥10 for adverse events suggest it is potentially safe or tolerable.

Conclusions: These results indicate that patients with ADHD are likely to benefit from treatment with viloxazine ER, and are unlikely to discontinue, as viloxazine ER treatment was associated with favourable LHH, NNT, and NNH values. Clinicaltrials.gov: NCT03247530, NCT03247543, NCT03247517, NCT03247556.

Conflict of interest statement

A Nasser, AR Kosheleff, T Liranso, P Qin, JT Hull, GD Busse, and J Rubin are employees of Supernus Pharmaceuticals, Inc For a list of M Fava's lifetime disclosures, please see this link. V Maletic is an employee of the University of South Carolina School of Medicine. He is a consultant for ACADIA Pharmaceuticals Inc; Alfasigma USA, Inc; Alkermes, Inc; Allergan; Eisai‐Purdue; Intra‐Cellular Therapies; Janssen; H. Lundbeck A/S; Otsuka America Pharmaceutical, Inc; Sage Pharmaceuticals; Sunovion Pharmaceuticals Inc; Supernus Pharmaceuticals, Inc; and Takeda Pharmaceutical Company Limited. He serves on the speakers’ bureau of ACADIA Pharmaceuticals Inc; Alkermes, Inc; Allergan; Ironshore; Intra‐Cellular; Janssen; H. Lundbeck A/S; Otsuka America Pharmaceutical, Inc; Sunovion Pharmaceuticals Inc; and Takeda Pharmaceutical Company Limited; and his spouse serves on the speakers’ bureau of Otsuka America Pharmaceutical, Inc F Lopez has served as a consultant to and received speaker fees and/or research support from Eli Lilly, GSK, Ironshore, Neos, Novartis, Noven, Pfizer, Shire, Sunovion, Supernus, and Tris.

© 2021 Supernus Pharmaceuticals Inc. International Journal of Clinical Practice published by John Wiley & Sons Ltd.

Figures

FIGURE 1

Likelihood to be helped or harmed. Likelihood to be Helped or Harmed (LHH) based on the rate of discontinuations because of adverse events and (A) ADHD‐RS‐5 criteria only or (B) either ADHD‐RS‐5 criteria or CGI‐I criteria. LHH values under each symbol represent the likelihood of responding to treatment vs discontinuing treatment because of adverse events. ADHD‐RS‐5, Attention‐Deficit Hyperactivity Disorder Rating Scale, Fifth Edition; CGI‐I, Clinical Global Impressions – Improvement

FIGURE 2

Number needed to treat. Number Needed to Treat (NNT; ± 95% confidence intervals) based on (A) ADHD‐RS‐5 criteria only or (B) either ADHD‐RS‐5 criteria or CGI‐I criteria. NNT values under each symbol represent the number of patients who need to be treated before one patient responds. ADHD‐RS‐5, Attention‐Deficit Hyperactivity Disorder Rating Scale, Fifth Edition; CGI‐I, Clinical Global Impressions – Improvement

FIGURE 3

Number needed to harm. Number Needed to Harm (NNH; ± 95% confidence intervals) based on the rate of discontinuations because of adverse events. NHH values represent the number of patients who need to be treated before one patient discontinues treatment because of adverse events. Confidence intervals for NNH values that are not statistically significant (ie, Children, blue square) contain two ranges of numbers: negative infinity to a negative value (ie, −infinity to −110), and a positive value to positive infinity (ie, +27 to +infinity), and suggest that there exists no difference in event rates between patients treated with viloxazine ER and placebo. NNH values are to the left of each symbol, 95% upper‐ and lower‐bound confidence intervals are to the right