OBJECTIVES: To compare long-term safety and efficacy outcomes of centanafadine vs lisdexamfetamine, methylphenidate, and atomoxetine, respectively, in adults with attention-deficit/hyperactivity disorder (ADHD) using matching-adjusted indirect comparison (MAIC).

METHODS: This MAIC of treatments for adult ADHD included patient-level data from the centanafadine trial NCT03605849 and published aggregate data from the lisdexamfetamine trial NCT00337285, the methylphenidate trial NCT00326300, and the atomoxetine trial NCT00190736. Propensity score weighting was used to match the patient characteristics in each comparison. Study outcomes were assessed up to 52 weeks (26 weeks for comparison with atomoxetine) and included safety (rates of adverse events [AEs] reported by ≥5% of patients in any treatment group in trials of a given comparison) and efficacy (mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale [AISRS] score or ADHD Rating Scale [ADHD-RS]).

RESULTS: In all comparisons of balanced populations, risks of AEs were statistically significantly lower with centanafadine or non-different between centanafadine and comparator; the largest differences in AE rates included upper respiratory tract infection (risk difference in percentage points: 18.75), insomnia (12.47), dry mouth (12.33), and headache (11.34) versus lisdexamfetamine; decreased appetite (20.25), headache (18.53), insomnia (12.65), and dry mouth (10.76) versus methylphenidate; nausea (26.18), dry mouth (25.07), fatigue (13.95), and headache (11.04) versus atomoxetine (all p<0.05). Compared with lisdexamfetamine, centanafadine had a smaller reduction in the AISRS/ADHD-RS score (6.15-point difference; p<0.05). There was no statistically significant difference in the change from baseline in AISRS score between centanafadine and methylphenidate (1.75-point difference; p=0.13) and between centanafadine and atomoxetine (1.60-point difference; p=0.21).

CONCLUSIONS: At up to 52 weeks, centanafadine showed significantly lower incidence of several AEs than lisdexamfetamine, methylphenidate, and atomoxetine; efficacy was lower than lisdexamfetamine and non-different from methylphenidate and atomoxetine. Future studies should evaluate patients’ and physicians’ valuations on treatment attributes and how tradeoff between safety and efficacy affects ADHD management.