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Abstract：
UNASSIGNED: Head-to-head trials comparing centanafadine, an investigational therapy for adults with attention-deficit/hyperactivity disorder (ADHD), with other treatment options are lacking.
UNASSIGNED: To compare safety and efficacy outcomes of centanafadine sustained-release vs lisdexamfetamine dimesylate (lisdexamfetamine), atomoxetine hydrochloride (atomoxetine), and viloxazine extended-release (viloxazine ER), respectively, using matching-adjusted indirect comparison (MAIC).
UNASSIGNED: This MAIC included patient-level data pooled from 2 centanafadine trials (NCT03605680 and NCT03605836) and published aggregate data from comparable trials of 3 comparators-lisdexamfetamine (NCT00334880), atomoxetine (NCT00190736), and viloxazine ER (NCT04016779)-in adult patients with ADHD. Propensity score weighting was used to match characteristics of individual patients from the centanafadine trials to aggregate baseline characteristics from the respective comparator trials. Safety outcomes were rates of adverse events for which information was available in the centanafadine and respective comparator trials. Efficacy outcome was mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) score (ADHD Rating Scale [ADHD-RS] was used as proxy in the comparison with lisdexamfetamine). Anchored indirect comparisons were conducted across matched populations of the centanafadine and respective comparator trials.
UNASSIGNED: After matching, baseline characteristics in the centanafadine trials were the same as those in the respective comparator trials. Compared with lisdexamfetamine, centanafadine was associated with a significantly lower risk of lack of appetite (risk difference [RD] in percentage points: 23.42), dry mouth (19.27), insomnia (15.35), anxiety (5.21), nausea (4.90), feeling jittery (3.70), and diarrhea (3.47) (all P < 0.05) but a smaller reduction in the AISRS/ADHD-RS score (6.58-point difference; P < 0.05). Compared with atomoxetine, centanafadine was associated with a significantly lower risk of nausea (RD in percentage points: 18.64), dry mouth (17.44), fatigue (9.21), erectile dysfunction (6.76), lack of appetite (6.71), and urinary hesitation (5.84) (all P < 0.05) and no statistically significant difference in the change in AISRS score. Compared with viloxazine ER, centanafadine was associated with a significantly lower risk of fatigue (RD in percentage points: 11.07), insomnia (10.67), nausea (7.57), and constipation (4.63) (all P < 0.05) and no statistically significant difference in the change in AISRS score.
UNASSIGNED: In an anchored MAIC, centanafadine showed a significantly better short-term safety profile than lisdexamfetamine, atomoxetine, and viloxazine ER; efficacy was lower than with lisdexamfetamine and comparable (ie, nondifferent) with atomoxetine and viloxazine ER. This MAIC provides important insights on the relative safety and efficacy of common treatment options to help inform treatment decisions in adults with ADHD. Safety assessment was limited to rates of adverse events reported in both trials of a given comparison.
UNASSIGNED: NCT03605680, NCT03605836, NCT00334880, NCT00190736, and NCT04016779.
UNASSIGNED: To compare safety and efficacy outcomes of centanafadine sustained-release vs lisdexamfetamine dimesylate (lisdexamfetamine), atomoxetine hydrochloride (atomoxetine), and viloxazine extended-release (viloxazine ER), respectively, using matching-adjusted indirect comparison (MAIC).
UNASSIGNED: This MAIC included patient-level data pooled from 2 centanafadine trials (NCT03605680 and NCT03605836) and published aggregate data from comparable trials of 3 comparators-lisdexamfetamine (NCT00334880), atomoxetine (NCT00190736), and viloxazine ER (NCT04016779)-in adult patients with ADHD. Propensity score weighting was used to match characteristics of individual patients from the centanafadine trials to aggregate baseline characteristics from the respective comparator trials. Safety outcomes were rates of adverse events for which information was available in the centanafadine and respective comparator trials. Efficacy outcome was mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) score (ADHD Rating Scale [ADHD-RS] was used as proxy in the comparison with lisdexamfetamine). Anchored indirect comparisons were conducted across matched populations of the centanafadine and respective comparator trials.
UNASSIGNED: After matching, baseline characteristics in the centanafadine trials were the same as those in the respective comparator trials. Compared with lisdexamfetamine, centanafadine was associated with a significantly lower risk of lack of appetite (risk difference [RD] in percentage points: 23.42), dry mouth (19.27), insomnia (15.35), anxiety (5.21), nausea (4.90), feeling jittery (3.70), and diarrhea (3.47) (all P < 0.05) but a smaller reduction in the AISRS/ADHD-RS score (6.58-point difference; P < 0.05). Compared with atomoxetine, centanafadine was associated with a significantly lower risk of nausea (RD in percentage points: 18.64), dry mouth (17.44), fatigue (9.21), erectile dysfunction (6.76), lack of appetite (6.71), and urinary hesitation (5.84) (all P < 0.05) and no statistically significant difference in the change in AISRS score. Compared with viloxazine ER, centanafadine was associated with a significantly lower risk of fatigue (RD in percentage points: 11.07), insomnia (10.67), nausea (7.57), and constipation (4.63) (all P < 0.05) and no statistically significant difference in the change in AISRS score.
UNASSIGNED: In an anchored MAIC, centanafadine showed a significantly better short-term safety profile than lisdexamfetamine, atomoxetine, and viloxazine ER; efficacy was lower than with lisdexamfetamine and comparable (ie, nondifferent) with atomoxetine and viloxazine ER. This MAIC provides important insights on the relative safety and efficacy of common treatment options to help inform treatment decisions in adults with ADHD. Safety assessment was limited to rates of adverse events reported in both trials of a given comparison.
UNASSIGNED: NCT03605680, NCT03605836, NCT00334880, NCT00190736, and NCT04016779.
摘要：
■头对头试验比较centanafadine，针对患有注意力缺陷/多动障碍（ADHD）的成年人的研究性治疗，缺乏其他治疗选择。
为了比较centanafadine缓释剂与二甲磺酸盐（lisdexamfetamine）的安全性和有效性结果，盐酸托莫西汀（托莫西汀），和维洛嗪延长释放（维洛嗪ER），分别,使用匹配调整间接比较(MAIC)。
■该MAIC包括来自2项centanafadine试验（NCT03605680和NCT03605836）的患者水平数据，以及来自3项比较剂-利德西非他明（NCT00334880）的可比试验的已发表汇总数据，托莫西汀(NCT00190736),和维洛嗪ER（NCT04016779）-在成年ADHD患者中。倾向评分加权用于匹配centanafadine试验中个体患者的特征，以汇总各自比较试验的基线特征。安全性结果是不良事件的发生率，其信息在centanafadine和各自的比较试验中可用。疗效结果是成人ADHD研究者症状评定量表（AISRS）评分（ADHD评定量表[ADHD-RS]用作与lisdexamfetamine比较的代理）中相对于基线的平均变化。在centanafadine和各自的比较试验的匹配人群中进行了锚定间接比较。
■匹配后，centanafadine试验中的基线特征与各自的比较试验中的基线特征相同.与lisdexamfetamine相比，centanafadine与食欲不振的风险显着降低相关（风险差异[RD]为23.42个百分点），口干（19.27），失眠（15.35），焦虑（5.21），恶心（4.90），感到紧张不安（3.70），和腹泻（3.47）（均P<0.05），但AISRS/ADHD-RS评分降低较小（6.58分差异；P<0.05）。与托莫西汀相比，centanafadine与恶心风险显着降低相关（RD的百分比：18.64），口干（17.44），疲劳(9.21)，勃起功能障碍（6.76），缺乏食欲（6.71），和尿迟疑(5.84)(均P<0.05),AISRS评分变化无统计学差异。与维洛嗪ER相比，centanafadine与疲劳风险显着降低相关（RD的百分比：11.07），失眠（10.67），恶心（7.57），与便秘(4.63)比较(均P<0.05),AISRS评分变化无统计学差异。
■在锚定的MAIC中，centanafadine显示出明显优于lisdexamfetamine的短期安全性，托莫西汀,和维洛沙嗪ER；疗效低于利德西非他明和可比（即，无差异)与托莫西汀和维洛嗪ER。该MAIC提供了有关常见治疗方案的相对安全性和有效性的重要见解，以帮助告知ADHD成人的治疗决策。安全性评估仅限于给定比较的两个试验中报告的不良事件发生率。
■NCT03605680、NCT03605836、NCT00334880、NCT00190736和NCT04016779。
为了比较centanafadine缓释剂与二甲磺酸盐（lisdexamfetamine）的安全性和有效性结果，盐酸托莫西汀（托莫西汀），和维洛嗪延长释放（维洛嗪ER），分别,使用匹配调整间接比较(MAIC)。
■该MAIC包括来自2项centanafadine试验（NCT03605680和NCT03605836）的患者水平数据，以及来自3项比较剂-利德西非他明（NCT00334880）的可比试验的已发表汇总数据，托莫西汀(NCT00190736),和维洛嗪ER（NCT04016779）-在成年ADHD患者中。倾向评分加权用于匹配centanafadine试验中个体患者的特征，以汇总各自比较试验的基线特征。安全性结果是不良事件的发生率，其信息在centanafadine和各自的比较试验中可用。疗效结果是成人ADHD研究者症状评定量表（AISRS）评分（ADHD评定量表[ADHD-RS]用作与lisdexamfetamine比较的代理）中相对于基线的平均变化。在centanafadine和各自的比较试验的匹配人群中进行了锚定间接比较。
■匹配后，centanafadine试验中的基线特征与各自的比较试验中的基线特征相同.与lisdexamfetamine相比，centanafadine与食欲不振的风险显着降低相关（风险差异[RD]为23.42个百分点），口干（19.27），失眠（15.35），焦虑（5.21），恶心（4.90），感到紧张不安（3.70），和腹泻（3.47）（均P<0.05），但AISRS/ADHD-RS评分降低较小（6.58分差异；P<0.05）。与托莫西汀相比，centanafadine与恶心风险显着降低相关（RD的百分比：18.64），口干（17.44），疲劳(9.21)，勃起功能障碍（6.76），缺乏食欲（6.71），和尿迟疑(5.84)(均P<0.05),AISRS评分变化无统计学差异。与维洛嗪ER相比，centanafadine与疲劳风险显着降低相关（RD的百分比：11.07），失眠（10.67），恶心（7.57），与便秘(4.63)比较(均P<0.05),AISRS评分变化无统计学差异。
■在锚定的MAIC中，centanafadine显示出明显优于lisdexamfetamine的短期安全性，托莫西汀,和维洛沙嗪ER；疗效低于利德西非他明和可比（即，无差异)与托莫西汀和维洛嗪ER。该MAIC提供了有关常见治疗方案的相对安全性和有效性的重要见解，以帮助告知ADHD成人的治疗决策。安全性评估仅限于给定比较的两个试验中报告的不良事件发生率。
■NCT03605680、NCT03605836、NCT00334880、NCT00190736和NCT04016779。
