利妥昔单抗与天疱疮患者长期心血管和代谢结局风险的关联。
Association of Rituximab With Risk of Long-term Cardiovascular and Metabolic Outcomes in Patients With Pemphigus.
机构信息
Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
出版信息
JAMA Dermatol. 2023 Jan 1;159(1):56-61. doi: 10.1001/jamadermatol.2022.5182.
IMPORTANCE
The association of different therapeutic approaches with long-term cardiovascular and metabolic outcomes in patients with pemphigus remains to be precisely evaluated.
OBJECTIVE
To assess the risk of long-term cardiovascular and metabolic outcomes and all-cause mortality in patients with pemphigus managed by rituximab compared with those receiving treatment with first-line corticosteroid-sparing agents (azathioprine and mycophenolate mofetil [MMF]).
DESIGN, SETTING, AND PARTICIPANTS: A global population-based retrospective cohort study compared 961 patients with pemphigus that was managed with rituximab with those treated with azathioprine or MMF (n = 961) regarding the risk of several cardiovascular and metabolic outcomes. Propensity score matching was performed to optimize comparability. Patients were enrolled from the Global Collaborative Network of TriNetX platform.
MAIN OUTCOMES AND MEASURES
Risk of myocardial infarction, stroke, peripheral vascular disease, pulmonary embolism, hypertension, hyperlipidemia, type 2 diabetes, obesity, osteoporosis, and avascular bone necrosis.
RESULTS
Of 1602 participants, 855 (53.4%) were women and 747 (46.6%) were men; the mean (SD) age was 54.8 (16.6) years for those treated with rituximab and 54.4 (18.2) years for those treated with azathioprine or MMF. Compared with those treated by azathioprine/MMF, patients treated with rituximab experienced a lower risk of myocardial infarction (relative risk [RR], 0.45; 95% CI, 0.24-0.86; P = .01), stroke (RR, 0.42; 95% CI, 0.26-0.69; P < .001), peripheral vascular disease (RR, 0.47; 95% CI, 0.28-0.79; P = .003), hypertension (RR, 0.48; 95% CI, 0.38-0.63; P < .001), hyperlipidemia (RR, 0.45; 95% CI, 0.32-0.64; P < .001), type 2 diabetes (RR, 0.63; 95% CI, 0.51-0.77; P < .001), obesity (RR, 0.49; 95% CI, 0.34-0.72; P < .001), and osteoporosis (RR, 0.46; 95% CI, 0.30-0.71; P < .001). The all-cause mortality was comparable between patients in both groups (hazard ratio, 0.94; 95% CI, 0.62-1.43; log-rank P = .77).
CONCLUSIONS AND RELEVANCE
The results of this cohort study suggest that rituximab was associated with protection against long-term cardiovascular and metabolic outcomes compared with conventional immunosuppressants. This agent might be particularly preferred in individuals with preexisting cardiovascular and metabolic risk factors.
重要性：不同治疗方法与天疱疮患者长期心血管和代谢结局的关联仍需准确评估。
目的：评估与接受一线皮质类固醇节约剂（硫唑嘌呤和吗替麦考酚酯[MMF]）治疗的患者相比，接受利妥昔单抗治疗的天疱疮患者的长期心血管和代谢结局以及全因死亡率的风险。
设计、设置和参与者：这是一项全球基于人群的回顾性队列研究，比较了接受利妥昔单抗治疗的 961 例天疱疮患者与接受硫唑嘌呤或 MMF 治疗的患者（n=961）的几种心血管和代谢结局的风险。为了优化可比性，进行了倾向评分匹配。患者从全球协作网络的 TriNetX 平台招募。
主要结局和测量：心肌梗死、中风、外周血管疾病、肺栓塞、高血压、高血脂、2 型糖尿病、肥胖症、骨质疏松症和无菌性骨坏死的风险。
结果：在 1602 名参与者中，855 名（53.4%）为女性，747 名（46.6%）为男性；接受利妥昔单抗治疗的患者的平均（SD）年龄为 54.8（16.6）岁，接受硫唑嘌呤/MMF 治疗的患者为 54.4（18.2）岁。与接受硫唑嘌呤/MMF 治疗的患者相比，接受利妥昔单抗治疗的患者发生心肌梗死的风险较低（相对风险[RR]，0.45；95%CI，0.24-0.86；P=0.01）、中风（RR，0.42；95%CI，0.26-0.69；P<0.001）、外周血管疾病（RR，0.47；95%CI，0.28-0.79；P=0.003）、高血压（RR，0.48；95%CI，0.38-0.63；P<0.001）、高血脂（RR，0.45；95%CI，0.32-0.64；P<0.001）、2 型糖尿病（RR，0.63；95%CI，0.51-0.77；P<0.001）、肥胖症（RR，0.49；95%CI，0.34-0.72；P<0.001）和骨质疏松症（RR，0.46；95%CI，0.30-0.71；P<0.001）。两组患者的全因死亡率无差异（风险比，0.94；95%CI，0.62-1.43；对数秩 P=0.77）。
结论和相关性：该队列研究的结果表明，与传统免疫抑制剂相比，利妥昔单抗与长期心血管和代谢结局的保护作用相关。该药物在存在心血管和代谢危险因素的个体中可能特别受欢迎。
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