非肾性系统性红斑狼疮患者应用贝利尤单抗治疗的感染风险比传统口服免疫抑制剂更低

目的：该研究旨在比较贝利尤单抗与口服免疫抑制剂治疗系统性红斑狼疮（SLE）的感染风险。

方法：应用来自美国多中心电子健康记录数据库的观察数据，确定了2011-2021年期间启动贝利尤单抗、硫唑嘌呤、甲氨蝶呤或霉酚酸酯的非肾性狼疮患者。研究中设计并模拟了假设的目标试验，通过比较贝利尤单抗与每种口服免疫抑制剂以估计严重感染和因严重感染而住院的累积发生率和风险比（HRs）。应用倾向评分重叠加权来平衡基线协变量，并使用治疗加权的逆概率对治疗组的依从性进行调整。评估创伤性损伤的控制结局。

结果：在21481例患者中，该研究分别比较了2841例和6343例起始予贝利尤单抗和硫唑嘌呤治疗的患者，2642例和8242例贝利尤单抗和甲氨蝶呤治疗的患者，以及2813例和8407例贝利尤单抗和霉酚酸酯治疗的患者。在倾向得分重叠加权后，所有协变量在每次比较中进行平衡，平均年龄为45岁，94%为女性。与硫唑嘌呤和霉酚酸酯相比，贝利尤单抗与严重感染（HRs 0.82 [95% CI 0.72-0.92]和0.69 [0.61-0.78]）和感染住院（HRs 0.73 [95% CI 0.57-0.94]和0.56 [0.43-0.71]）的风险较低相关。与甲氨蝶呤相比，贝利单抗的感染风险也更低（HR 0.86 [95% CI 0.76-0.97]）。不同治疗组之间的创伤性损伤风险无差异。

结论：贝利尤单抗比口服免疫抑制剂的严重感染风险更低。这为SLE的治疗提供了风险/利益依据。

Objective: We investigated the comparative risk of infection with belimumab versus oral immunosuppressants for the treatment of systemic lupus erythematosus (SLE).

Methods: Using observational data from a U.S. multi-center electronic health record database, we identified patients with SLE but without lupus nephritis who initiated belimumab, azathioprine, methotrexate, or mycophenolate between 2011-2021. We designed and emulated hypothetical target trials to estimate the cumulative incidence and hazard ratios (HRs) of serious infection and hospitalization for serious infection comparing belimumab vs. each oral immunosuppressant. We used propensity score overlap weighting to balance baseline covariates and adjusted for adherence to treatment group using inverse probability of treatment weighting. We also assessed the control outcome of traumatic injury.

Results: Among 21,481 patients, we compared 2841 and 6343 initiators of belimumab and azathioprine, 2642 and 8242 initiators of belimumab and methotrexate, and 2813 and 8407 initiators of belimumab and mycophenolate, respectively. After propensity score overlap weighting, all covariates were balanced in each comparison, with mean age 45 years and 94% females. Compared to azathioprine and mycophenolate, belimumab was associated with lower risks of both serious infection (HRs 0.82 [95% CI 0.72-0.92] and 0.69 [0.61-0.78]), and hospitalization for infection (HRs 0.73 [95% CI 0.57-0.94] and 0.56 [0.43-0.71]). The risk of infection was also lower for belimumab compared with methotrexate (HR 0.86 [95% CI 0.76-0.97]). There were no differences in traumatic injury risks across treatment groups.

Conclusion: Belimumab was associated with lower risks of serious infection than oral immunosuppressants. This finding should inform risk/benefit considerations for SLE treatment.

引自：Materne E, Choi H, Zhou B, Costenbader KH, Zhang Y, Jorge A. Comparative Risks of Infection with Belimumab versus Oral Immunosuppressants in Patients with Non-Renal Systemic Lupus Erythematosus. Arthritis Rheumatol. 2023 Jun 1. doi: 10.1002/art.42620. Epub ahead of print. PMID: 37262382.