1st Propaedeutic and Internal Medicine Clinic, Joint Academic Rheumatology Program, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527, Athens, Greece.
Postgraduate Medical Studies in the Physiology of Aging and Geriatric Syndromes, School of Medicine, National and Kapodistrian University of Athens, 11527, Athens, Greece.
Osteoporos Int. 2023 Mar;34(3):585-598. doi: 10.1007/s00198-022-06658-7. Epub 2023 Jan 4.
Dropout from placebo arms in randomized-controlled trials is a surrogate for nocebo responses, resulting from patients' negative expectations to treatment. Among 16,460 placebo-treated patients in oral anti-osteoporotic drug trials, nocebo dropouts were 8% on average, being higher in older patients. This implies that nocebo may contribute to the osteoporosis treatment gap in clinical practice.
Osteoporosis is a common disease requiring long-term treatment. Despite the availability of effective anti-osteoporotic drugs, adherence to treatment is low. Nocebo, a behavior mostly related to the negative expectations to a certain treatment, decreases adherence and negatively affects treatment outcomes and health-related care costs in chronic diseases. Since in double-blind placebo-controlled randomized trials any unfavorable outcome leading to discontinuation in placebo arms is considered as nocebo, we aimed to investigate the size of nocebo response in patients participating in osteoporosis trials.
We searched MEDLINE, EMBASE, SCOPUS, and Cochrane databases for dropouts due to reported adverse events in the placebo arms (nocebo dropouts) in all double-blind trials investigating anti-osteoporotic drugs published between January 1993 and March 2022. Only data on bisphosphonates and selective estrogen receptor modulators (SERMs) were analyzed (Prospero registration number CRD42020212843).
Data from 44 trials were extracted. In 16,460 placebo-treated patients, the pooled nocebo-dropout was 8% both for bisphosphonates (average: 0.08; range 0.01-0.27; 95%CI 0.06-0.10) and SERMs (average: 0.08; range 0.03-0.15; 95%CI 0.05-0.13). Nocebo-dropouts were higher in bisphosphonate trials enrolling individuals ≥ 65 years (11%) (n = 18) compared to trials enrolling younger individuals (6%) (n = 18) (average: 0.11; 95%CI 0.08-0.13 vs. average: 0.06; 95%CI 0.05-0.08, respectively, p = 0.001). Participants' sex, dosing-intervals, publication year, or severity of osteoporosis had no impact on the nocebo-dropouts.
Almost 1 in 10 osteoporosis patients receiving placebo in trials of bisphosphonates and SERMs experiences AEs leading to dropout, implying that nocebo contributes to treatment-discontinuation in clinical practice. Efforts to identify and minimize nocebo, especially in older patients, are warranted.
骨质疏松症是一种常见的需要长期治疗的疾病。尽管有有效的抗骨质疏松药物，但治疗的依从性很低。在慢性病中，与对某种治疗的负面预期相关的行为主要为“反安慰剂”，它会降低治疗的依从性，并对治疗结果和与健康相关的护理费用产生负面影响。由于在双盲安慰剂对照随机临床试验中，任何导致安慰剂组停药的不良事件（反安慰剂停药）都被认为是反安慰剂，因此，我们旨在研究参加骨质疏松症试验的患者中反安慰剂反应的大小。
我们检索了 MEDLINE、EMBASE、SCOPUS 和 Cochrane 数据库，以查找 1993 年 1 月至 2022 年 3 月期间发表的所有双盲研究中因报告的不良反应而导致安慰剂组停药（反安慰剂停药）的双盲试验数据。仅分析了双膦酸盐和选择性雌激素受体调节剂（SERMs）的数据（Prospecro 注册号 CRD42020212843）。
从 44 项试验中提取了数据。在 16460 名接受安慰剂治疗的患者中，双膦酸盐的反安慰剂停药率为 8%（平均：0.08；范围 0.01-0.27；95%CI 0.06-0.10），SERMs 的反安慰剂停药率为 8%（平均：0.08；范围 0.03-0.15；95%CI 0.05-0.13）。在纳入年龄≥65 岁的个体的双膦酸盐试验中，反安慰剂停药率较高（11%）（n=18），而纳入年轻个体的试验中反安慰剂停药率较低（6%）（n=18）（平均：0.11；95%CI 0.08-0.13 vs. 平均：0.06；95%CI 0.05-0.08，分别为 p=0.001）。参与者的性别、给药间隔、出版年份或骨质疏松症的严重程度对反安慰剂停药率没有影响。
在双膦酸盐和 SERMs 的临床试验中，每 10 名接受安慰剂治疗的骨质疏松症患者中就有近 1 人因出现导致停药的不良反应，这意味着反安慰剂导致了临床实践中的治疗中断。有必要努力识别和最小化反安慰剂，特别是在老年患者中。
Zotero 插件