A Matching-Adjusted Indirect Comparison (MAIC) of Centanafadine versus Methylphenidate Hydrochloride in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD): Short-Term Safety and Efficacy Outcomes: Comparaison indirecte ajustée par appariement (MAIC) entre centanafadine et le chlorhydrate de méthylphénidate chez les adultes atteints d'un trouble déficitaire de l'attention avec ou sans hyperactivité (TDAH) : Résultats en matière d'innocuité et d'efficacité à court terme.

Abstract

ObjectivesTo compare the short-term safety and efficacy of centanafadine, an investigational treatment, versus long-acting controlled-release methylphenidate hydrochloride (methylphenidate, Foquest^®) among adult patients with attention-deficit/hyperactivity disorder (ADHD), using matching-adjusted indirect comparison (MAIC).MethodsThis anchored MAIC used pooled individual patient data (IPD) from two centanafadine trials (NCT03605680, NCT03605836) and published aggregate data from one methylphenidate trial (NCT02139124). Using propensity scores, IPD from the centanafadine trials were reweighted to match the aggregate baseline characteristics of the methylphenidate trial. Safety and efficacy outcomes were compared at Week 4. Safety outcomes were the rates of adverse events reported by ≥5% of patients in any treatment group in either trial with an incidence twice that of the placebo. The efficacy outcome was the mean change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS)/ADHD Rating Scale-5 (ADHD-RS-5) score at Week 4.ResultsAfter matching, no significant differences in baseline characteristics were observed across trials. Relative to methylphenidate, centanafadine exhibited a better safety profile, with a significantly lower risk of insomnia (risk difference in percentage points: -9.46 points) and initial insomnia (-4.68 points). There was no significant difference in efficacy across treatments as measured by the mean change from baseline in AISRS/ADHD-RS-5 score.ConclusionsIn this MAIC, centanafadine was associated with a lower risk of insomnia and comparable (i.e., nondifferent) efficacy compared to methylphenidate at Week 4. Information on the comparative safety and efficacy of ADHD treatments in the adult population will help inform personalized treatment decisions given the range of treatment options with varying attributes.