Supplementary materials: A matching-adjusted indirect comparison of centanafadine versus lisdexamfetamine, methylphenidate and atomoxetine in adults with attention-deficit/hyperactivity disorder: long-term safety and efficacy

These are peer-reviewed supplementary materials for the article 'A matching-adjusted indirect comparison of centanafadine versus lisdexamfetamine, methylphenidate and atomoxetine in adults with attention-deficit/hyperactivity disorder: long-term safety and efficacy' published in the Journal of Comparative Effectiveness Research.Supplementary Table S1: Identification of comparator trialsSupplementary Table S2: List of comparator trials considered with reasons for exclusionSupplementary Table S3: Characteristics of clinical trials included in the analysesSupplementary Figure S1: Arm-by-arm outcomes before and after matching: centanafadine vs lisdexamfetamineSupplementary Figure S2: Arm-by-arm outcomes before and after matching: centanafadine vs methylphenidateSupplementary Figure S3: Arm-by-arm outcomes before and after matching: centanafadine vs atomoxetineAim: 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.

本数据集为发表于《比较有效性研究杂志》的论文《针对成人注意力缺陷/多动障碍患者，对centanafadine与lisdexamfetamine、methylphenidate及atomoxetine的匹配调整间接比较：长期安全性与有效性》的同行评审补充材料。补充表S1：比较试验识别；补充表S2：考虑的比较试验列表及排除原因；补充表S3：纳入分析的临床试验特征；补充图S1：匹配前后按组别展示的centanafadine与lisdexamfetamine的结局；补充图S2：匹配前后按组别展示的centanafadine与methylphenidate的结局；补充图S3：匹配前后按组别展示的centanafadine与atomoxetine的结局。研究目的：旨在通过匹配调整的间接比较（MAICs），比较centanafadine与lisdexamfetamine dimesylate（lisdexamfetamine）、methylphenidate hydrochloride（methylphenidate）和atomoxetine hydrochloride（atomoxetine）在成人注意力缺陷/多动障碍（ADHD）患者中的长期安全性和有效性。研究方法：本研究使用了来自centanafadine试验（NCT03605849）的患者水平数据，以及lisdexamfetamine试验（NCT00337285）、methylphenidate试验（NCT00326300）和atomoxetine试验（NCT00190736）的已发表汇总数据。在每个比较中，使用倾向得分加权对患者的特征进行匹配。研究结局评估至52周，包括安全性（不良事件[AE]的发生率）和有效性（成人ADHD研究者症状评分量表[AISRS]或ADHD评分量表[ADHD-RS]评分的基线变化）。结果：在所有匹配人群的比较中，centanafadine组的不良事件风险显著降低，或与比较药物无显著差异；不良事件发生率最大差异包括与lisdexamfetamine相比，上呼吸道感染（风险差异：18.75个百分点）、失眠（12.47）和口干（12.33）；与methylphenidate相比，食欲下降（20.25）、头痛（18.53）和失眠（12.65）；与atomoxetine相比，恶心（26.18）、口干（25.07）和疲劳（13.95）（所有p < 0.05）。与lisdexamfetamine相比，centanafadine在AISRS/ADHD-RS评分上的降幅较小（6.15分之差；p < 0.05），与methylphenidate相比，AISRS评分的变化无统计学显著差异（1.75分之差；p = 0.13），与atomoxetine相比，变化也无统计学显著差异（1.60分之差；p = 0.21）。结论：在52周内，centanafadine显示出比lisdexamfetamine、methylphenidate和atomoxetine显著更低的不良事件发生率；其有效性低于lisdexamfetamine，但与methylphenidate和atomoxetine无统计学显著差异。