Difference in background factors between responders to gabapentin enacarbil treatment and responders to placebo: pooled analyses of two randomized,double-blind,placebo-controlled studies in Japanese patients with restless legs syndrome

ObjectiveRestless legs syndrome (RLS) is a sensorimotor disorder that is characterized by uncomfortable and unpleasant sensations mainly in the legs. Two placebo-controlled studies (Phase II/III and post-marketing) in Japanese patients with RLS failed to demonstrate the efficacy of gabapentin enacarbil (GE) 600 mg in the change from baseline in International Restless Legs Syndrome Rating Scale (IRLS) score at the end of the treatment period. The high response to placebo is thought to be a possible reason why the post-marketing study failed. The objectives of these post hoc analyses were to determine potential predictive factors associated with improvement in IRLS score with GE treatment and to identify subgroups with higher placebo responses.MethodsWe combined data from the two Japanese studies and analyzed change from baseline in IRLS score in the pooled population and subgroups defined by several patient characteristics. Moreover, we calculated the variable importance of each factor and performed predictive enrichment analysis to identify an enrichable subpopulation with greater improvement by GE treatment.ResultsThe post hoc analyses suggested that higher baseline IRLS score (≥21) and higher body mass index (≥25 kg/m²) were associated with higher placebo responses. On the other hand, positive family history of RLS, prior use of dopaminergic receptor agonists, and higher baseline ferritin level (≥50 ng/mL) were associated with higher responses to GE.ConclusionsOur results suggest that patients with typical idiopathic RLS characteristics, including positive family history and no low ferritin level, would be expected to derive the greatest benefits from GE treatment.     

羟考酮联合加巴喷丁治疗中重度癌性疼痛的Meta-分析

目的 系统评价羟考酮联合加巴喷丁应用中重度癌性疼痛的有效性和安全性。方法 检索PubMed、Medline、中国期刊全文数据库（CNKI）、维普中文科技期刊全文数据库（VIP）、中国生物医学全文数据库（CBM）和万方数据库中关于羟考酮联合加巴喷丁治疗癌性疼痛的随机对照研究,检索时限为2000年1月至2017年8月。由2名研究者独立提取数据、评价质量,并交叉核对。采用RevMan 5.2软件进行Meta-分析。结果 共纳入10项研究,687例患者。Meta-分析结果显示：羟考酮联合加巴喷丁较羟考酮单用能显著提高疼痛缓解率[OR=3.85,95%CI（2.25~6.60）,P<0.000 01]和降低疼痛评分[MD=-0.83,95%CI（-0.95~-0.70）,P<0.000 01];能显著减少羟考酮的剂量[MD=-17.10,95%CI（-20.16~-14.04）,P<0.000 01];能显著减少便秘[OR=0.58,95%CI（0.42,0.82）,P=0.002]和恶心呕吐[OR=0.55,95%CI（0.37,0.82）,P=0.003]的发生率;能显著提高细胞免疫（CD4、CD8、CD4/CD8）和体液免疫（IgA、IgG、IgM）水平,差异均有统计学意义（P<0.01）。结论 羟考酮联合加巴喷丁能显著提高疼痛缓解率、降低疼痛评分,减少羟考酮平均日剂量,增强免疫功能,减少便秘和恶心呕吐等不良反应发生率,但两组头痛头晕、嗜睡和尿潴留的发生率无统计学差异。     

丹珍头痛胶囊治疗偏头痛疗效的Meta分析

目的 评价丹珍头痛胶囊治疗偏头痛的疗效及安全性。方法 检索中国生物医学文献数据库（CBM）、中国学术期刊全文数据库（CNKI）、维普中文科技期刊数据库（VIP）、万方数据库和Pubmed数据库有关丹珍头痛胶囊治疗偏头痛的随机对照试验（RCTs）,采用Modified Jadad评分量表对纳入文献进行质量评价,应用RevMan 5.3软件进行统计分析。结果 最终纳入9篇RCTs,共891例患者。Meta分析结果显示,丹珍头痛胶囊治疗偏头痛的总有效率高于西药组[RR=1.26,95%CI（1.19,1.35）],差异有统计学意义（P < 0.001）。亚组分析显示,单纯应用丹珍头痛胶囊比单纯使用常规西药总有效率更高[RR=1.28,95%CI（1.19,1.39）,P < 0.001],在常规西药基础上加用丹珍头痛胶囊可提高治疗的总有效率[RR=1.22,95%CI（1.10,1.36）,P=0.000 3],丹珍头痛胶囊治疗偏头痛总有效率高于盐酸氟桂利嗪[RR=1.26,95%CI（1.17,1.34）,P < 0.001]和加巴喷丁[RR=1.32,95%CI（1.10,1.57）,P=0.002],差异均有统计学意义（P < 0.05）。丹珍头痛胶囊组未见严重不良反应。结论 丹珍头痛胶囊治疗偏头痛的疗效可能优于常规西药,在常规西药基础上联合丹珍头痛胶囊可提高疗效。为提高结论的可靠性,尚需更多高质量、多中心、大样本的RCTs。     

加巴喷丁胶囊联合小计量泼尼松对带状疱疹神经痛患者免疫功能及疼痛物质的影响

目的 探讨加巴喷丁胶囊联合小剂量泼尼松治疗对带状疱疹患者清神经肽Y（NPY）、P物质（SP）及T细胞亚群的影响及近期临床疗效。方法 选择海南省人民医院2015年1月-2016年12月期间收治的带状疱疹患者128例,随机数表法分为对照组与观察组,每组各64例。其中对照组患者给予小剂量泼尼松治疗,观察组患者给予加巴喷丁胶囊联合小剂量泼尼松治疗。比较两组患者近期疗效,治疗前后患者视觉模拟尺评分（VAS）、T淋巴细胞亚群变化情况（CD3⁺和CD4⁺、CD8⁺、CD4⁺/CD8⁺）及NPY和SP水平。结果 经不同方案治疗后,观察组的总有效率为95.31%,对照组总有效率为85.94%,两组相比差异显著且具有统计意义（χ²=8.67,P < 0.05）。与治疗前相比,两组患者治疗后的VAS评分显著降低,同组治疗前后比较差异有统计学意义（P < 0.05）;治疗后,观察组VAS评分显著低于对照组,差异有统计学意义（P < 0.05）。与治疗前相比,两组患者治疗后T淋巴细胞亚群CD3⁺和CD4⁺、CD4⁺/CD8⁺明显增高,同组治疗前后比较差异有统计学意义（P < 0.05）;观察组治疗后T淋巴细胞亚群CD3⁺和CD4⁺、CD4⁺/CD8⁺较对照组增加更显著,差异有统计学意义（P < 0.05）。两组NPY和SP水平较治疗前均显著下降,同组治疗前后比较差异有统计学意义（P < 0.05）;治疗后,观察组NPY和SP水平均显著低于对照组,差异有统计学意义（P < 0.05）。结论 加巴喷丁胶囊联合小剂量泼尼松治疗对带状疱疹患者能够有效改善患者临床症状,缓轻患者的神经疼痛,改善患者机体免疫功能功能,降低外周血NPY、SP水平,值得临床推广和应用。     

Hemichorea associated with gabapentin therapy with hypoperfusion in contralateral basal ganglion - a case of a paraplegic patient with neuropathic pain

Functional imaging in patients with movement disorders has suggested abnormalities of regional cerebral blood flow (rCBF). We describe a patient with thoracic cord lesion with subsequent severe neuropathic pain. Right hemichorea developed and was related to adjunctive therapy with gabapentin. The patient's hemichorea decreased gradually after cessation of gabapentin. The study of rCBF revealed hypoperfusion in the contralateral basal ganglia compared with the previous study of rCBF. Our patient is the first patient with neuropathic pain, treated with gabapentin who developed hemichorea, in the absence of brain lesions. Imaging studies of rCBF showed a perfusion defect in the contralateral basal ganglion.     

加巴喷丁联合A型肉毒素治疗复发性三叉神经痛的疗效分析

目的 探讨加巴喷丁联合A型肉毒素治疗复发性三叉神经痛（TN）的疗效。方法 选取2018年1月—2020年8月华中科技大学协和江南医院收治的复发性TN患者110例作为研究对象。将患者分为试验组和对照组,各55例。对照组采用加巴喷丁治疗,试验组在对照组的基础上给予A型肉毒素治疗。对比两组患者的疗效及不良反应发生情况。结果 两组治疗前、治疗后2周、治疗后8周静息时VAS评分比较,经重复测量设计的方差分析,结果 ①不同时间点VAS评分有差异（F =9.046,P <0.05）;②两组VAS评分有差异（F =7.097,P <0.05）,试验组治疗后VAS评分较对照组低,相对镇痛效果较好;③两组VAS评分变化趋势有差异（F =10.002,P <0.05）。试验组总有效率高于对照组（P <0.05）。试验组治疗前与治疗后8周的S100β、神经元特异性烯醇化酶差值高于对照组（P <0.05）。两组药物总不良反应率比较,差异无统计学意义（P >0.05）。结论 加巴喷丁联合A型肉毒素治疗复发性TN可增强疗效,降低S100β、NSE水平,且安全性良好。