Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea (Republic of).
Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Goryeodae-ro, Seongbuk-gu, 02841, Seoul, Korea (Republic of).
Z Rheumatol. 2022 Jun;81(5):430-437. doi: 10.1007/s00393-021-00969-6. Epub 2021 Mar 9.
The goal of this meta-analysis was to assess the frequency and magnitude of placebo and nocebo responses in placebo-controlled randomized controlled trials (RCTs) of Janus kinase (JAK) inhibitor monotherapy for rheumatoid arthritis (RA) METHODS: We performed a meta-analysis on the rates of placebo response, adverse effects (AEs), severe AEs (SAEs) and withdrawal due to AEs in placebo-controlled randomized clinical trials (RCTs) of JAK inhibitor therapy for RA.
Five RCTs contained a total of 1422 patients (746 trial participants and 676 controls). The pooled incidence of an American College of Rheumatology 20% (ACR20) response rate was 33.0% (95% CI 19.6-44.9%) in placebo-treated patients and 68.3% (95% CI 61.4-74.1%) in active drug-treated patients. A strong negative correlation was observed between drug efficacies (ACR20 response) and AE rates in the placebo arm, indicating that the stronger the placebo response, the weaker the nocebo response (r = -0.906, P = 0.034). The pooled estimate of at least one AE was 54.1% (95% CI 44.6-63.4%) in placebo-treated patients and 54.5% (95% CI 46.2-62.6%) in active drug-treated patients. The pooled SAE rate was 3.9% (95% CI 2.7-5.7%) in placebo-treated patients and 3.8% (95% CI 2.5-5.7%) in active comparator-treated patients. The pooled estimate of withdrawal owing to an AE was 4.1% (95% CI 1.4-11.3%) in placebo-treated patients and 2.1% (95% CI 0.8-5.4%) in active drug-treated patients. However, there were no differences in the pooled risk of AE, SAEs, or withdrawal owing to AEs between the active comparator and placebo groups. A strong positive correlation was observed in AE rates between the placebo and active arms, indicating that the stronger the nocebo response, the higher the AE rate in the active arm (r = 0.957, P = 0.012).
The frequency of placebo and nocebo responses was 33.0 and 54.1%, respectively, in JAK monotherapy trials for RA. The findings indicated that the strengths of placebo and nocebo responses are inversely proportional and that clinically significant differences were absent between AE, SAE, and dropout owing to AEs.
本荟萃分析旨在评估 Janus 激酶（JAK）抑制剂单药治疗类风湿关节炎（RA）的安慰剂对照随机对照试验（RCT）中安慰剂和反安慰剂反应的频率和程度。
我们对 JAK 抑制剂治疗 RA 的安慰剂对照 RCT 中安慰剂反应、不良反应（AE）、严重不良反应（SAE）和因 AE 停药的发生率进行了荟萃分析。
5 项 RCT 共纳入 1422 例患者（746 例试验参与者和 676 例对照）。安慰剂治疗组的美国风湿病学会 20%（ACR20）反应率为 33.0%（95%CI 19.6-44.9%），活性药物治疗组为 68.3%（95%CI 61.4-74.1%）。药物疗效（ACR20 反应）与安慰剂组的 AE 发生率之间存在强烈的负相关，表明安慰剂反应越强，反安慰剂反应越弱（r=-0.906，P=0.034）。安慰剂治疗组至少有一种 AE 的发生率为 54.1%（95%CI 44.6-63.4%），活性药物治疗组为 54.5%（95%CI 46.2-62.6%）。安慰剂治疗组 SAE 发生率为 3.9%（95%CI 2.7-5.7%），活性药物治疗组为 3.8%（95%CI 2.5-5.7%）。安慰剂治疗组因 AE 停药的发生率为 4.1%（95%CI 1.4-11.3%），活性药物治疗组为 2.1%（95%CI 0.8-5.4%）。然而，活性对照与安慰剂组之间 AE、SAE 或因 AE 停药的发生率无差异。安慰剂组和活性药物组的 AE 发生率之间存在强烈的正相关，表明反安慰剂反应越强，活性药物组的 AE 发生率越高（r=0.957，P=0.012）。
JAK 单药治疗 RA 的试验中安慰剂和反安慰剂反应的频率分别为 33.0%和 54.1%。研究结果表明，安慰剂和反安慰剂反应的强度呈反比关系，AE、SAE 和因 AE 停药之间不存在临床显著差异。
