Lai Pei-Hsinq, Lu Cheng-Hsun, Cheng Chiao-Feng, Chang Ting-Wei, Lan Ting-Yuan, Hsieh Song-Chou
Department of Internal Medicine, Taipei City Hospital Zhongxiao Branch, Taipei , Taiwan.
Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Clin Rheumatol. 2025 Jul 31. doi: 10.1007/s10067-025-07598-3.
To identify factors associated with COVID-19 outcomes in patients with immune-mediated inflammatory diseases (IMID) treated with rituximab (RTX) and determine candidates for RTX administration/maintenance.
We conducted a case-control study of RTX-treated IMID patients with COVID-19 (May 2021-April 2023), including 32 hospitalized cases and 64 non-hospitalized controls matched by age, sex, IMID diagnosis. Logistic regression was used to analyze pre-COVID biochemical markers within 3-months and RTX-specific factors. Secondary outcomes in hospitalized cases included COVID-19 severity, viral shedding, and all-cause mortality.
Higher RTX exposure was associated with reduced glucocorticoid dependence and higher pre-COVID albumin levels while correlated with lower IgG levels. However, lower pre-COVID albumin (OR: 0.231, p = 0.012) and higher maintenance glucocorticoid use (OR: 1.170, p = 0.007) were independently associated with hospitalization, regardless of IgG levels or RTX exposure. Among hospitalized cases, lower admission albumin (albumin_D; OR: 0.029, p = 0.014) predicted severe COVID-19. Patients with albumin_D < 3.45 g/dL had higher mortality, regardless of IgG_D or RTX timing, and experienced prolonged viral shedding despite antiviral mono-therapy. Albumin_D ≥ 3.45 g/dL and IgG_D ≥ 687 mg/dL were associated with the lowest mortality risk. Timing of the last RTX dose did not influence secondary outcomes.
Pre-COVID albumin and glucocorticoid dependence are independently associated with hospitalization regardless of RTX-specific factors. Admission albumin predicts secondary outcomes. Risk of rituximab on COVID-19 outcomes is not universal. Albumin ≥ 3.45 g/dL and IgG ≥ 687 mg/dL identify lower-risk patients, providing guidance for safer RTX administration. Key Points • Risk of rituximab on COVID-19 outcomes in immune-mediated inflammatory diseases is not universal. Serum albumin and IgG levels are critical to determine the COVID-19 outcomes. • Patients with serum albumin ≥ 3.45 g/dL and IgG ≥ 687 mg/dL demonstrate a lower risk associated with rituximab, providing guidance for its safer administration in the post-COVID-19 era amidst potential challenges from emerging infections. • Serum albumin serves as a significant prognostic marker for COVID-19 outcomes in patients receiving rituximab treatment. • The timing of the most recent rituximab infusion does not affect COVID-19 outcomes in these patients.
确定接受利妥昔单抗（RTX）治疗的免疫介导性炎症性疾病（IMID）患者中与新冠病毒疾病（COVID-19）转归相关的因素，并确定RTX给药/维持治疗的候选对象。
我们对2021年5月至2023年4月期间接受RTX治疗的IMID合并COVID-19患者进行了一项病例对照研究，包括32例住院病例和64例非住院对照，根据年龄、性别、IMID诊断进行匹配。采用逻辑回归分析3个月内COVID-19前的生化指标和RTX特异性因素。住院病例的次要转归包括COVID-19严重程度、病毒清除和全因死亡率。
较高的RTX暴露与糖皮质激素依赖性降低和COVID-19前较高的白蛋白水平相关，而与较低的IgG水平相关。然而，无论IgG水平或RTX暴露情况如何，COVID-19前较低的白蛋白（比值比：0.231，p = 0.012）和较高的维持糖皮质激素使用量（比值比：1.170，p = 0.007）与住院独立相关。在住院病例中，较低的入院白蛋白（白蛋白_D；比值比：0.029，p = 0.014）预示着严重的COVID-19。白蛋白_D < 3.45 g/dL的患者死亡率较高，无论IgG_D或RTX给药时间如何，且尽管接受抗病毒单药治疗，病毒清除时间仍延长。白蛋白_D≥3.45 g/dL和IgG_D≥687 mg/dL与最低死亡风险相关。最后一剂RTX的给药时间不影响次要转归。
无论RTX特异性因素如何，COVID-19前的白蛋白和糖皮质激素依赖性与住院独立相关。入院白蛋白可预测次要转归。利妥昔单抗对COVID-19转归的影响并非普遍存在。白蛋白≥3.45 g/dL和IgG≥687 mg/dL可识别低风险患者，为更安全地使用RTX提供指导。要点：• 利妥昔单抗对免疫介导性炎症性疾病中COVID-19转归的影响并非普遍存在。血清白蛋白和IgG水平对确定COVID-19转归至关重要。• 血清白蛋白≥3.45 g/dL且IgG≥687 mg/dL的患者与利妥昔单抗相关的风险较低，为在COVID-19后时代面对新出现感染的潜在挑战时更安全地使用利妥昔单抗提供了指导。• 血清白蛋白是接受利妥昔单抗治疗患者中COVID-19转归的重要预后标志物。• 最近一次利妥昔单抗输注的时间不影响这些患者的COVID-19转归。
