Yavropoulou Maria P, Kasdagli Maria-Iosifina, Makras Polyzois, Diomatari Konstantina-Maria, Anastasilakis Athanasios D, Mitsikostas Dimos D, Kassi Eva, Sfikakis Petros P, Kravvariti Evrydiki
Endocrinology Unit, 1st Department of Propaedeutic and Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Laikon University Hospital of Athens, 11527 Athens, Greece.
Department of Hygiene and Epidemiology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Maturitas. 2024 Jan;179:107874. doi: 10.1016/j.maturitas.2023.107874. Epub 2023 Oct 31.
Nocebo is a concept of therapeutics referring to unpleasant symptoms attributed by a patient to a drug, due to negative anticipation. Patients receiving oral anti-osteoporotic drugs in randomized controlled trials (RCT) can experience adverse events leading to dropout, implying that nocebo contributes to treatment discontinuation for these drugs. In this study we aim to investigate the nocebo effect of subcutaneous anti-osteoporotic drugs with a higher compliance rate than orally administered drugs.
We searched MEDLINE, EMBASE, SCOPUS, and Cochrane databases for double-blind trials investigating subcutaneous anti-osteoporotic drugs for osteoporosis (namely, denosumab, teriparatide, abaloparatide and romosozumab) published up to May 2023.
Dropouts due to reported adverse events in the placebo arms ("nocebo dropouts").
Data from 17 trials were extracted. Among 10,529 placebo-treated patients the pooled nocebo-dropout percentage was 3 % for denosumab (average: 0.03; 95 % CI: 0.01-0.05), 1 % for romosozumab (average: 0.01; 95 % CI: 0.00-0.03) and 6 % for teriparatide and abaloparatide (average: 0.06; 95 % CI: 0.05-0.07). Nocebo-dropouts were significantly higher in men than women (6 % vs. 3 %, respectively, p = 0.012), in older (mean age >68 years) than in younger patients (5 % vs. 1 %, respectively, p = 0.017) and in those with more severe osteoporosis (based on the percentage of participants with prior fragility-related fractures in the study cohort) compared with patients with no prior fracture history (4 % vs. 1 %, respectively, p = 0.046).
Nocebo responses may contribute to treatment discontinuation with subcutaneous anti-osteoporotic drugs in clinical practice. Higher nocebo-related dropout rates in the higher-risk RCT population (older patients, males, those with prior fractures) show that nocebo mechanisms have the potential to hinder therapeutic efforts to specific populations who would benefit most. Prospero registration number CRD42020212843.
反安慰剂效应是一种治疗学概念，指患者因负面预期将不愉快症状归因于某种药物。在随机对照试验（RCT）中接受口服抗骨质疏松药物治疗的患者可能会经历不良事件而导致退出试验，这意味着反安慰剂效应会导致这些药物的治疗中断。在本研究中，我们旨在调查皮下注射抗骨质疏松药物的反安慰剂效应，其依从率高于口服药物。
我们检索了MEDLINE、EMBASE、SCOPUS和Cochrane数据库，以查找截至2023年5月发表的关于皮下注射抗骨质疏松药物治疗骨质疏松症（即地诺单抗、特立帕肽、阿巴洛帕肽和罗莫佐单抗）的双盲试验。
安慰剂组中因报告的不良事件导致的退出者（“反安慰剂退出者”）。
提取了17项试验的数据。在10529名接受安慰剂治疗的患者中，地诺单抗的合并反安慰剂退出率为3%（平均值：0.03；95%CI：0.01 - 0.05），罗莫佐单抗为1%（平均值：0.01；95%CI：0.00 - 0.03），特立帕肽和阿巴洛帕肽为6%（平均值：0.06；95%CI：0.05 - 0.07）。男性的反安慰剂退出率显著高于女性（分别为6%和3%，p = 0.012），年龄较大者（平均年龄>68岁）高于年龄较小者（分别为5%和1%，p = 0.017），骨质疏松更严重者（基于研究队列中既往有脆性骨折的参与者百分比）高于无既往骨折史的患者（分别为4%和1%，p = 0.046）。
在临床实践中，反安慰剂反应可能导致皮下注射抗骨质疏松药物的治疗中断。在高风险RCT人群（老年患者、男性、既往有骨折者）中较高的反安慰剂相关退出率表明，反安慰剂机制有可能阻碍对最能从中受益的特定人群的治疗努力。Prospero注册号CRD42020212843。
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