Schein Jeff, Catillon Maryaline, Xu Chunyi, Qu Alice, Lemyre Anaïs, Gauthier-Loiselle Marjolaine, Cloutier Martin, Childress Ann
Global Value & Real World Evidence, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA.
HEOR, Analysis Group, Inc., New York, NY, USA.
Can J Psychiatry. 2025 Jun 2:7067437251342279. doi: 10.1177/07067437251342279.
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.
目的
采用匹配调整间接比较（MAIC）方法，比较成人注意力缺陷多动障碍（ADHD）患者中，研究性治疗药物森他法定与长效缓释盐酸哌甲酯（哌甲酯，Foquest）的短期安全性和疗效。
方法
本锚定MAIC使用了两项森他法定试验（NCT03605680、NCT03605836）的汇总个体患者数据（IPD），以及一项哌甲酯试验（NCT02139124）已发表的汇总数据。利用倾向评分，对森他法定试验的IPD进行重新加权，以匹配哌甲酯试验的汇总基线特征。在第4周比较安全性和疗效结果。安全性结果是在任何一项试验中，任何治疗组中报告的不良事件发生率≥5%且发生率是安慰剂两倍的事件发生率。疗效结果是第4周时成人ADHD研究者症状评定量表（AISRS）/ADHD评定量表-5（ADHD-RS-5）评分相对于基线的平均变化。
结果
匹配后，各试验间基线特征未观察到显著差异。相对于哌甲酯，森他法定表现出更好的安全性，失眠风险（风险差异百分点：-9.46个百分点）和初始失眠风险（-4.68个百分点）显著更低。以AISRS/ADHD-RS-5评分相对于基线的平均变化衡量，各治疗组间疗效无显著差异。
结论
在本MAIC中，与哌甲酯相比，第4周时森他法定失眠风险更低，疗效相当（即无差异）。鉴于成人ADHD治疗选择具有不同属性，关于成人ADHD治疗药物比较安全性和疗效的信息将有助于指导个性化治疗决策。
