Janssen Scientific Affairs LLC, Titusville, NJ, USA.
Neuropsychiatr Dis Treat. 2012;8:375-85. doi: 10.2147/NDT.S32581. Epub 2012 Aug 27.
A post hoc analysis from a multiphase trial with open-label transition and maintenance phases, a double-blind relapse prevention phase, and an optional open-label extension examined the long-term tolerability with continuous once-monthly injectable paliperidone palmitate 39, 78, 117, or 156 mg (25, 50, 75, or 100 mg equivalents [mg eq] of paliperidone) in subjects with recently diagnosed (≤5 years; n = 216) versus chronic illness (>5 years; n = 429) schizophrenia.
Adverse events reported at a ≥2% margin between subgroups were identified. Relative risks (in the recently diagnosed compared with the chronically ill) and 95% confidence intervals (CI) were determined, and CI not including 1 were considered potentially significant.
In both subgroups, the mean monthly dose was 109 mg (69.9 mg eq). Continuous mean exposures were 333.9 ± 271.9 and 308.7 ± 278.3 days in the recently diagnosed and chronic illness subgroups, respectively. Using the criteria outlined in the methods, nasopharyngitis was a potentially significant event reported in more chronically ill than recently diagnosed subjects at months 6, 9, 12, and endpoint (7.2% versus 2.8%; relative risk 0.384; 95% CI 0.163-0.907). Influenza (2.8% versus 0.7%; relative risk 3.9; 95% CI 1.003-15.730) and amenorrhea (3.2% versus 0.9%; relative risk 3.476; 95% CI 1.029-11.744) at endpoint were potentially significant events in more recently diagnosed than chronically ill subjects. Mean weight changes, sedation/somnolence, any extrapyramidal symptom-related or glucose-related events were generally similar between the groups. The mean prolactin level increased in both sexes in both subgroups (changes from baseline of +41.8 ng/mL and +26.5 ng/mL in recently diagnosed and chronic illness females and +12.3 ng/mL and +15.1 ng/mL in recently diagnosed and chronic illness males, respectively), and were higher in females with recently diagnosed illness than in females who were chronically ill (P = 0.0002 at endpoint). Prolactin-related events were reported by 7.9% of recently diagnosed subjects with schizophrenia and 3.5% of those who were chronically ill.
The long-term tolerability of paliperidone palmitate was generally similar in recently diagnosed schizophrenia subjects and those with more chronic illness, with the exception of some prolactin-related measures.
一项多相试验的事后分析，该试验有开放标签转换和维持阶段、双盲复发预防阶段以及可选的开放标签扩展，检查了最近诊断（≤5 年；n=216）与慢性疾病（>5 年；n=429）精神分裂症患者连续每月注射一次帕利哌酮棕榈酸酯 39、78、117 或 156mg（帕利哌酮 25、50、75 或 100mg 等效物[mg eq]）的长期耐受性。
确定了在亚组之间有≥2%差异的不良事件报告。确定了相对风险（在最近诊断的患者与慢性疾病患者相比）和 95%置信区间（CI），并且不包括 1 的 CI 被认为具有潜在意义。
在两个亚组中，平均每月剂量为 109mg（69.9mg eq）。最近诊断和慢性疾病亚组的连续平均暴露分别为 333.9±271.9 和 308.7±278.3 天。使用方法中概述的标准，与最近诊断的患者相比，更多的慢性疾病患者在第 6、9、12 个月和终点报告了潜在的显著事件：鼻咽炎（7.2%比 2.8%；相对风险 0.384；95%CI 0.163-0.907）。流感（2.8%比 0.7%；相对风险 3.9；95%CI 1.003-15.730）和闭经（3.2%比 0.9%；相对风险 3.476；95%CI 1.029-11.744）在终点是最近诊断的患者比慢性疾病患者更常见的潜在显著事件。两组之间体重变化、镇静/嗜睡、任何锥体外系症状相关或血糖相关事件通常相似。两组中男性和女性的平均催乳素水平均升高（最近诊断的女性基线增加+41.8ng/mL 和+26.5ng/mL，慢性疾病女性增加+12.3ng/mL 和+15.1ng/mL；最近诊断的男性增加+12.3ng/mL 和+15.1ng/mL），并且最近诊断的疾病女性的催乳素水平高于慢性疾病女性（在终点时 P=0.0002）。7.9%的最近诊断的精神分裂症患者和 3.5%的慢性疾病患者报告了与催乳素相关的事件。
帕利哌酮棕榈酸酯的长期耐受性在最近诊断的精神分裂症患者和慢性疾病患者中通常相似，除了一些与催乳素相关的指标外。
