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贝林单抗联合较高剂量泼尼松龙起始治疗可有效加快糖皮质激素减量:一项 96 周的回顾性研究。

Initiation of belimumab with higher daily prednisolone is effective for rapid glucocorticoid reduction: A 96-week retrospective study.

机构信息

Department of Rheumatology, Kakogawa Central City Hospital, Kakogawa, Japan.

Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan.

出版信息

Lupus. 2024 May;33(6):598-607. doi: 10.1177/09612033241240859. Epub 2024 Mar 21.

Abstract

OBJECTIVES

For appropriate glucocorticoid (GC) reduction, we investigated the optimal strategy including baseline factors that could reduce GC more than 50% with 96 weeks of belimumab.

METHODS

This is a retrospective cohort study of Kakogawa Central City hospital from 2019 to 2023. We identified SLE patients who were receiving 200 mg of belimumab weekly by subcutaneous injection for 96 weeks. The background at baseline, trends in clinical indicators, and factors involved in GC reduction were statistically analyzed. Finally, univariate and multivariate logistic analyses were carried out to identify baseline factors associated ≥50% GC reduction at 96 weeks.

RESULTS

Forty-seven patients were enrolled, with a median daily prednisolone of 5 mg. Almost 90% of them received concomitant immunosuppressants and/or hydroxychloroquine. Serological indices, daily GC dose, and SLEDAI-2K scores showed significant improvement in 96 weeks. At baseline, a significant negative correlation has been shown between the daily dose of GC and the duration from onset or last flare, as well as C4 levels. At 96 weeks, GC reduction rate and SLEDAI-2K scores were negatively correlated with duration from onset or last flare to initiation of belimumab. Mycophenolate mofetil use was significantly frequent in patients with lupus nephritis (LN), which also correlated with the frequency of past flares. In addition, LN presence was associated with higher SLEDAI-2K scores at 96 weeks, and baseline SLEDAI-2K ≥10 was associated with significantly higher GC dose at 96 weeks. Univariate analysis of the factor contributing to achieving ≥50% GC reduction at 96 weeks has pointed shorter disease duration and higher daily GC dose at baseline as significant variables. Finally, we performed a multivariate analysis by combining above two items with age, which extracted the higher daily GC dose at baseline as a significant variable (OR (95% CI) 1.25 (1.00 to 1.56), = .047).

CONCLUSIONS

Our study showed that a delay in belimumab initiation led to higher SLEDAI-2K score and difficulty in achieving a 50% GC reduction at 96 weeks. Since GC-related adverse events increase with long-term administration of GC though with small daily doses, we proposed here that belimumab should be started in combination with higher daily prednisolone.

摘要

目的

为了适当减少糖皮质激素(GC)的用量,我们研究了基线因素,这些因素可以使 96 周内接受贝利尤单抗治疗的患者的 GC 减少 50%以上。

方法

这是一项回顾性队列研究,纳入了 2019 年至 2023 年兵库县加古川市中心医院的系统性红斑狼疮(SLE)患者。患者每周接受 200mg 贝利尤单抗皮下注射,共 96 周。对基线时的背景、临床指标的趋势以及与 GC 减少相关的因素进行统计学分析。最后,进行单因素和多因素逻辑分析,以确定 96 周时与 GC 减少≥50%相关的基线因素。

结果

共纳入 47 例患者,中位泼尼松龙日剂量为 5mg。他们中几乎 90%的患者同时接受免疫抑制剂和/或羟氯喹治疗。96 周时血清学指标、GC 日剂量和 SLEDAI-2K 评分均有显著改善。基线时,GC 日剂量与发病或上次 flares 至贝利尤单抗起始时间以及 C4 水平呈显著负相关。96 周时,GC 减少率和 SLEDAI-2K 评分与发病或上次 flares 至贝利尤单抗起始时间呈负相关。狼疮肾炎(LN)患者更常使用霉酚酸酯,这也与过去 flares 的频率相关。此外,LN 存在与 96 周时更高的 SLEDAI-2K 评分相关,而基线时 SLEDAI-2K≥10 与 96 周时更高的 GC 剂量相关。单因素分析显示,96 周时达到 GC 减少≥50%的相关因素包括基线时较短的病程和较高的 GC 日剂量。最后,我们将上述两项与年龄相结合进行多因素分析,结果显示基线时较高的 GC 日剂量是一个显著变量(比值比(95%置信区间)1.25(1.00 至 1.56), =.047)。

结论

我们的研究表明,贝利尤单抗起始延迟导致 SLEDAI-2K 评分升高,难以在 96 周时达到 GC 减少 50%。由于长期小剂量应用 GC 会导致与 GC 相关的不良反应增加,我们建议在此基础上加用较高剂量的泼尼松龙。

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