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美泊利单抗具有临床益处,包括减少口服糖皮质激素用量,且与基线嗜酸性肉芽肿性多血管炎(EGPA)特征无关。

Mepolizumab has clinical benefits including oral corticosteroid sparing irrespective of baseline EGPA characteristics.

作者信息

Jayne David R W, Terrier Benjamin, Hellmich Bernhard, Khoury Paneez, Baylis Lee, Bentley Jane H, Steinfeld Jonathan, Yancey Steven W, Kwon Namhee, Wechsler Michael E, Akuthota Praveen

机构信息

Department of Medicine, University of Cambridge, Cambridge, UK.

Service de Médecine Interne, Hôpital Cochin, Paris, France.

出版信息

ERJ Open Res. 2024 Jan 8;10(1). doi: 10.1183/23120541.00509-2023. eCollection 2024 Jan.

Abstract

BACKGROUND

The Mepolizumab in Relapsing or Refractory EGPA (MIRRA) trial (GSK ID: 115921/NCT02020889) demonstrated that mepolizumab increased remission time and reduced oral corticosteroid (OCS) use compared with placebo in patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA). The present analysis investigated the impact of baseline characteristics on clinical outcomes and characterised the OCS-sparing effect of mepolizumab.

METHODS

In a phase 3, randomised controlled trial for patients with EGPA (MIRRA), patients received standard of care plus mepolizumab 300 mg or placebo every 4 weeks for 52 weeks. The accrued duration of remission, the proportion of patients in remission at weeks 36 and 48, and the proportion of patients with clinical benefit (remission, OCS or relapse-related) were assessed according to baseline EGPA characteristic subgroups (). Mepolizumab-related OCS-sparing benefits were also quantified.

RESULTS

Accrued duration of remission and the proportion of patients in remission at weeks 36 and 48 were greater with mepolizumab than placebo across the baseline subgroups of refractory disease, immunosuppressant use, EGPA duration, relapse number and OCS use ≤20 mg·day. The proportion of patients with clinical benefit was greater with mepolizumab placebo (range 76-81% 25-39%), irrespective of immunosuppressant use or EGPA duration. Patients treated with mepolizumab placebo accrued significantly more weeks on OCS ≤4 mg·day (OR 5.06, 95% CI 2.47-10.38) and had a mean of 1423.1 mg less per-patient OCS exposure over 52 weeks.

CONCLUSIONS

Mepolizumab treatment provided benefits to patients with EGPA across varying baseline clinical characteristics and can be considered an OCS-sparing treatment in EGPA.

摘要

背景

美泊利珠单抗治疗复发或难治性嗜酸性肉芽肿性多血管炎(EGPA)试验(MIRRA,GSK ID:115921/NCT02020889)表明,与安慰剂相比,美泊利珠单抗可延长复发或难治性EGPA患者的缓解时间并减少口服糖皮质激素(OCS)的使用。本分析研究了基线特征对临床结局的影响,并对美泊利珠单抗的糖皮质激素节省效应进行了特征描述。

方法

在一项针对EGPA患者的3期随机对照试验(MIRRA)中,患者接受标准治疗加美泊利珠单抗300mg或安慰剂,每4周一次,共52周。根据基线EGPA特征亚组评估缓解累积持续时间、第36周和第48周缓解患者的比例以及具有临床获益(缓解、OCS或复发相关)患者的比例。还对美泊利珠单抗相关的糖皮质激素节省效益进行了量化。

结果

在难治性疾病、免疫抑制剂使用、EGPA病程、复发次数和OCS使用≤20mg·天的基线亚组中,美泊利珠单抗组的缓解累积持续时间以及第36周和第48周缓解患者的比例均高于安慰剂组。无论免疫抑制剂使用情况或EGPA病程如何,美泊利珠单抗组具有临床获益的患者比例均高于安慰剂组(范围为76 - 81%对25 - 39%)。接受美泊利珠单抗治疗的患者与接受安慰剂治疗的患者相比,接受≤4mg·天OCS治疗的累积周数显著更多(OR 5.06,95%CI 2.47 - 10.38),并且在52周内每位患者的OCS暴露量平均少1423.1mg。

结论

美泊利珠单抗治疗为具有不同基线临床特征的EGPA患者带来了益处,可被视为EGPA的一种糖皮质激素节省治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86f7/10772899/7f99bec4541b/00509-2023.01.jpg

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