From University of Liverpool and The Walton Centre National Health Service (NHS) Foundation Trust, Liverpool; Institute of Psychiatry, Psychology and Neuroscience, Guy's and St Thomas' Hospital, and University College London, London; Modepharma Limited, Beckenham; Queen Elizabeth University Hospital, Glasgow; University West of England, Bristol; Swansea University, Swansea; Norfolk and Norwich University NHS Trust, Norwich; Cambridge University Hospitals, Cambridge; and University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
Ann Intern Med. 2017 Oct 3;167(7):476-483. doi: 10.7326/M17-0509. Epub 2017 Sep 12.
Two small trials suggest that low-dose intravenous immunoglobulin (IVIg) may improve the symptoms of complex regional pain syndrome (CRPS), a rare posttraumatic pain condition.
To confirm the efficacy of low-dose IVIg compared with placebo in reducing pain during a 6-week period in adult patients who had CRPS from 1 to 5 years.
1:1 parallel, randomized, placebo-controlled, multicenter trial for 6 weeks, with an optional 6-week open extension. Patients were randomly assigned to 1 of 2 study groups between 27 August 2013 and 28 October 2015; the last patient completed follow-up on 21 March 2016. Patients, providers, researchers, and outcome assessors were blinded to treatment assignment. (ISRCTN42179756).
7 secondary and tertiary care pain management centers in the United Kingdom.
111 patients with moderate or severe CRPS of 1 to 5 years' duration.
IVIg, 0.5 g/kg of body weight, or visually indistinguishable placebo of 0.1% albumin in saline on days 1 and 22 after randomization.
The primary outcome was 24-hour average pain intensity, measured daily between days 6 and 42, on an 11-point (0- to 10-point) rating scale. Secondary outcomes were pain interference and quality of life.
The primary analysis sample consisted of 108 eligible patients, 103 of whom had outcome data. Mean (average) pain scores were 6.9 points (SD, 1.5) for placebo and 7.2 points (SD, 1.3) for IVIg. The adjusted difference in means was 0.27 (95% CI, -0.25 to 0.80; P = 0.30), which excluded the prespecified, clinically important difference of -1.2. No statistically significant differences in secondary outcomes were found between the groups. In the open extension, 12 of the 67 patients (18%) who received 2 IVIg infusions had pain reduction of at least 2 points compared with their baseline score. Two patients in the blinded phase (1 in the placebo and 1 in the IVIg group) and 4 in the open IVIg phase had serious events.
Results do not apply to patients who have had CRPS for less than 1 year or more than 5 years and do not extend to full-dose treatment (for example, 2 g/kg). The study was inadequately powered to detect subgroup effects.
Low-dose immunoglobulin treatment for 6 weeks was not effective in relieving pain in patients with moderate to severe CRPS of 1 to 5 years' duration.
Medical Research Council/National Institute for Health Research Efficacy and Mechanism Evaluation Program, Pain Relief Foundation, and Biotest United Kingdom.
两项小型试验表明，低剂量静脉注射免疫球蛋白（IVIg）可能改善复杂性区域疼痛综合征（CRPS）的症状，CRPS 是一种罕见的创伤后疼痛病症。
确认低剂量 IVIg 与安慰剂相比，在减少 1 至 5 年 CRPS 成年患者 6 周内疼痛的疗效。
2013 年 8 月 27 日至 2015 年 10 月 28 日进行了为期 6 周的 1:1 平行、随机、安慰剂对照、多中心试验，可选 6 周开放延伸期。患者在 2013 年 8 月 27 日至 2015 年 10 月 28 日之间随机分配到 2 个研究组之一；最后一名患者于 2016 年 3 月 21 日完成随访。患者、提供者、研究人员和结果评估者对治疗分配均不知情。（ISRCTN42179756）。
英国 7 个二级和三级疼痛管理中心。
111 名患有 1 至 5 年中度或重度 CRPS 的患者。
IVIg，0.5 g/kg 体重，或随机分组后第 1 天和第 22 天使用 0.1%白蛋白生理盐水的视觉上不可区分的安慰剂，剂量为 0.5 g/kg 体重。
主要结局是 24 小时平均疼痛强度，在第 6 天至第 42 天之间每天测量，采用 11 分（0 至 10 分）评分量表。次要结局是疼痛干扰和生活质量。
主要分析样本包括 108 名符合条件的患者，其中 103 名患者有结局数据。安慰剂组的平均（平均）疼痛评分为 6.9 分（标准差，1.5），IVIg 组为 7.2 分（标准差，1.3）。平均差值为 0.27（95%CI，-0.25 至 0.80；P=0.30），排除了预先指定的 -1.2 的临床重要差异。两组间次要结局无统计学显著差异。在开放延伸期，接受 2 次 IVIg 输注的 67 名患者中有 12 名（18%）疼痛减轻至少 2 分，与基线评分相比。在盲法阶段有 2 名患者（安慰剂组 1 名，IVIg 组 1 名）和开放 IVIg 阶段有 4 名患者发生严重事件。
结果不适用于 CRPS 持续时间少于 1 年或超过 5 年的患者，也不适用于全剂量治疗（例如，2 g/kg）。该研究没有足够的能力来检测亚组效应。
6 周的低剂量免疫球蛋白治疗对 1 至 5 年中度至重度 CRPS 患者的疼痛缓解无效。
医学研究委员会/国家卫生研究院疗效和机制评估计划、疼痛缓解基金会和百特英国。
