A matching-adjusted indirect comparison of centanafadine versus lisdexamfetamine, methylphenidate and atomoxetine in adults with attention-deficit/hyperactivity disorder: long-term safety and efficacy
Journal of Comparative Effectiveness Research, 2024
Aim
To compare long-term safety and efficacy outcomes of centanafadine versus lisdexamfetamine dimesylate (lisdexamfetamine), methylphenidate hydrochloride (methylphenidate) and atomoxetine hydrochloride (atomoxetine), respectively, in adults with attention-deficit/hyperactivity disorder (ADHD) using matching-adjusted indirect comparisons (MAICs).
Patients & methods
Patient-level data from a centanafadine trial (NCT03605849) and published aggregate data from a lisdexamfetamine trial (NCT00337285), a methylphenidate trial (NCT00326300) and an atomoxetine trial (NCT00190736) were used. Patient characteristics were matched in each comparison using propensity score weighting. Study outcomes were assessed up to 52 weeks and included safety (rates of adverse events [AEs]) and efficacy (mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale [AISRS] or ADHD Rating Scale [ADHD-RS] score).
Results
In all comparisons of matched 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) and dry mouth (12.33) versus lisdexamfetamine; decreased appetite (20.25), headache (18.53) and insomnia (12.65) versus methylphenidate; and nausea (26.18), dry mouth (25.07) and fatigue (13.95) versus atomoxetine (all p < 0.05). Centanafadine had a smaller reduction in the AISRS/ADHD-RS score versus lisdexamfetamine (6.15-point difference; p < 0.05) and no statistically significant difference in the change in AISRS score versus methylphenidate (1.75-point difference; p = 0.13) and versus atomoxetine (1.60-point difference; p = 0.21).
Conclusion
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.
Authors
Schein J, Cloutier M, Gauthier-Loiselle M, Catillon M, Xu C, Qu A, Lee F, Childress A