Abstract：
Diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN) are challenging and often intractable complex medical conditions, with a substantial impact on the quality of life. Mirogabalin, a novel voltage-gated Ca2+ channel α2δ ligand, was approved for the indication of DPNP and PHN. However, the time course of effects has not yet been clarified.We aimed to establish pharmacodynamic and placebo effect models of mirogabalin and pregabalin in DPNP and PHN, and to quantitatively compare the efficacy characteristics (maximum efficacy, onset time, and other pharmacodynamic parameters) and safety of mirogabalin and pregabalin. Public databases were comprehensively searched for randomized placebo-controlled clinical trials. A model-based meta-analysis (MBMA) was developed to describe the time course of drug efficacy and placebo effects. Adverse events were compared using a fixed-effects meta-analysis. Sixteen studies including 5,147 participants were eligible for this study. The placebo effect was relatively high and gradually increased with time, and it required at least eight weeks to reach a plateau. The pharmacodynamic model revealed that the maximum pure efficacy for mirogabalin and pregabalin was approximately -7.85 % and -8.86 %, respectively; the efficacy of mirogabalin to relieve DPNP and PHN was not superior to that of pregabalin, and both drugs had similar safety. While the rate constant of the onset rate of pregabalin was approximately thrice as high as that of mirogabalin. In addition, the baseline level of pain was an important factor affecting pregabalin efficacy. These findings are helpful in evaluating the clinical extension value of mirogabalin. They suggest that the high placebo effect and the baseline level of pain should be considered when grouping patients in future research and development of voltage-gated Ca2+ channel neuroanalgesic.
摘要：
糖尿病周围神经性疼痛（DPNP）和带状疱疹后神经痛（PHN）是具有挑战性且通常难以治疗的复杂医学疾病，对生活质量有重大影响。米罗加巴林,一种新型的电压门控Ca2+通道α2δ配体，被批准用于DPNP和PHN的适应症。然而,影响的时间进程尚未明确。我们旨在建立米罗加巴林和普瑞巴林在DPNP和PHN中的药效学和安慰剂效应模型。并定量比较疗效特征(最大疗效，发病时间,和其他药效学参数）和米罗加巴林和普瑞巴林的安全性。全面搜索公共数据库中的随机安慰剂对照临床试验。开发了基于模型的荟萃分析（MBMA）来描述药物疗效和安慰剂作用的时程。使用固定效应荟萃分析比较不良事件。包括5,147名参与者在内的16项研究符合这项研究的条件。安慰剂效应相对较高，并随时间逐渐增强，它需要至少八周才能达到平稳状态。药效学模型显示，米罗加巴林和普瑞巴林的最大纯药效约为-7.85%和-8.86%，米罗加巴林缓解DPNP和PHN的疗效均不优于普瑞巴林，两种药物具有相似的安全性。而普瑞巴林的起效率的速率常数大约是米加巴林的三倍。此外,基线疼痛水平是影响普瑞巴林疗效的重要因素.这些发现有助于评估米罗加巴林的临床推广价值。他们建议，在未来的电压门控Ca2通道神经镇痛药的研究和开发中，对患者进行分组时应考虑高安慰剂效应和疼痛的基线水平。
