Matching-adjusted Indirect Comparison of Treatments for Attention-Deficit/Hyperactivity Disorder in Pediatric Patients: A Focus on Short-Term Outcomes

Short-term safety and efficacy outcomes of centanafadine versus common attention-deficit/hyperactivity disorder (ADHD) treatments were evaluated in pediatric patients using matching-adjusted indirect comparisons (MAICs). Patient-level data from centanafadine trials (NCT05428033, NCT05257265) and published trial data from key comparators (lisdexamfetamine [NCT00556296, NCT01552902], atomoxetine [DOI: 10.1176/appi.ajp.159.11.1896], guanfacine extended-release [ER; NCT00152009], viloxazine ER [NCT03247530, NCT03247517], methylphenidate ER tablet [NCT01552902] and methylphenidate ER capsule [NCT02520388]) were used. Baseline characteristics of patients in each comparison were balanced using propensity score weighting. Safety was assessed using adverse event (AE) rates and included those with ≥5% and twice the placebo rate in any treatment arm in a given comparison. Efficacy was assessed using mean change in ADHD Rating Scale (ADHD-RS) score from baseline.

Across all comparisons, AE rates were lower or not statistically significantly different with centanafadine versus the respective comparator. Among AEs showing lower rates with centanafadine were insomnia (versus lisdexamfetamine, methylphenidate ER tablet and methylphenidate ER capsule), decreased weight (versus lisdexamfetamine and methylphenidate ER tablet), upper abdominal pain (versus atomoxetine and guanfacine ER), vomiting (versus atomoxetine and methylphenidate ER capsule), and irritability (versus lisdexamfetamine) (all p < 0.05). For efficacy, only lisdexamfetamine had a larger improvement in ADHD-RS score than centanafadine (p < 0.05). Differences across other comparisons were not statistically significant.

Altogether, MAICs showed that in pediatric patients with ADHD, centanafadine had lower or non-different AE rates than all comparators; efficacy was lower than lisdexamfetamine and non-different from other comparators. Future studies investigating the long-term comparative safety and efficacy of ADHD treatments in pediatric patients are warranted.