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接受利妥昔单抗治疗的炎症性风湿和肌肉骨骼疾病患者的COVID-19结局:一项队列研究。

COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study.

作者信息

Avouac Jérôme, Drumez Elodie, Hachulla Eric, Seror Raphaèle, Georgin-Lavialle Sophie, El Mahou Soumaya, Pertuiset Edouard, Pham Thao, Marotte Hubert, Servettaz Amélie, Domont Fanny, Chazerain Pascal, Devaux Mathilde, Claudepierre Pascal, Langlois Vincent, Mekinian Arsène, Maria Alexandre Thibault Jacques, Banneville Béatrice, Fautrel Bruno, Pouchot Jacques, Thomas Thierry, Flipo René-Marc, Richez Christophe

机构信息

Université de Paris, Service de Rhumatologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre Université de Paris, Paris, France.

ULR 2694-METRICS: Évaluation des Technologies de Santé et des Pratiques Médicales, Université de Lille, CHU Lille, Lille, France.

出版信息

Lancet Rheumatol. 2021 Jun;3(6):e419-e426. doi: 10.1016/S2665-9913(21)00059-X. Epub 2021 Mar 25.

Abstract

BACKGROUND

Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases.

METHODS

In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609.

FINDINGS

Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66-6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46-0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55-3·19, p=0·53).

INTERPRETATION

Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases.

FUNDING

None.

摘要

背景

各种观察结果表明,与未接受利妥昔单抗治疗的患者相比,接受利妥昔单抗治疗的炎症性风湿和肌肉骨骼疾病患者的新冠病毒病(COVID-19)病程可能更不利。我们旨在研究利妥昔单抗治疗是否与炎症性风湿和肌肉骨骼疾病患者的严重COVID-19结局相关。

方法

在这项队列研究中,我们分析了来自法国RMD COVID-19队列的数据,该队列包括18岁及以上患有炎症性风湿和肌肉骨骼疾病且高度怀疑或确诊为COVID-19的患者。主要终点是接受利妥昔单抗治疗的患者(利妥昔单抗组)与未接受利妥昔单抗治疗的患者(非利妥昔单抗组)的COVID-19严重程度。严重疾病定义为需要入住重症监护病房或导致死亡。次要目标是分析死亡情况和住院时间。采用治疗权重倾向评分法的逆概率来调整潜在的混杂因素(年龄、性别、动脉高血压、糖尿病、吸烟状况、体重指数、间质性肺疾病、心血管疾病、癌症、皮质类固醇使用、慢性肾衰竭以及基础疾病[类风湿关节炎等])。通过将两个人口平均差异除以其标准差,计算比值比和风险比及其95%置信区间作为效应量。本研究已在ClinicalTrials.gov注册,注册号为NCT04353609。

结果

在2020年4月15日至2020年11月20日期间,收集了1090例患者的数据(平均年龄55.2岁[标准差16.4]);734例(67%)为女性,356例(33%)为男性。在这1090例患者中,137例(13%)发生了严重COVID-19,89例(8%)死亡。在调整潜在混杂因素后,利妥昔单抗组的63例患者中严重疾病的发生率更高(效应量3.26,95%置信区间1.66 - 6.40,p = 0.0006),住院时间明显更长(0.62,0.46 - 0.85,p = 0.0024),而非利妥昔单抗组的1027例患者中则不然。利妥昔单抗组的63例患者中有13例(21%)死亡,而非利妥昔单抗组的1027例患者中有76例(7%)死亡,但利妥昔单抗组调整后的死亡风险没有显著增加(效应量1.32,95%置信区间0.55 - 3.19,p = 0.53)。

解读

利妥昔单抗治疗与更严重的COVID-19相关。对于炎症性风湿和肌肉骨骼疾病患者,必须特别谨慎地使用利妥昔单抗。

资金来源

无。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045c/7993930/2d81f91d675f/gr1_lrg.jpg

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