P153 Rituximab and tocilizumab and their effect on lung disease progression in scleroderma: a retrospective cohort study at a single centre
P153 Rituximab and tocilizumab and their effect on lung disease progression in scleroderma: a retrospective cohort study at a single centre
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P153 利妥昔单抗和托珠单抗及其对硬皮病肺部疾病进展的影响：单中心回顾性队列研究
DOI：
10.1093/rheumatology/kead104.194
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发表时间：
2023
期刊：
影响因子：
5.5
通讯作者：
Goldman N
中科院分区：
文献类型：
--
作者：
Goldman N
间质性肺病（ILD）是系统性硬化症（SSc）的主要死亡原因之一。来自随机对照试验的证据表明托珠单抗和利妥昔单抗对保护肺功能有有益作用。然而，临床试验竞技场之外的比较数据仍然有限。决定何时和谁治疗与特定treatments.MethodsWe进行了回顾性分析，所有SSc患者参加一个单一的专家中心谁收到利妥昔单抗或托珠单抗。收集人口统计学、临床和实验室数据沿着连续肺功能。如果治疗前和/或治疗后肺功能不可用，则排除患者。根据抗拓扑异构酶I抗体（ATA）状态以及其他临床、实验室和放射学特征分析数据。结果共纳入129例患者，其中87例接受利妥昔单抗治疗，32例接受托珠单抗治疗，10例接受两种治疗。接受两种治疗的10例患者中有8例（80%）在托珠单抗治疗前接受利妥昔单抗治疗。76例（58.9%）患者患有弥漫性SSc，102例（79%）患者患有ILD。利妥昔单抗组52例（53.6%）患者和托珠单抗组17例（40.5%）患者同时使用霉酚酸酯（MMF）。利妥昔单抗和托珠单抗的中位治疗前肺功能用力肺活量百分比（%FVC）和转移因子百分比（%DLCO）分别为67.9%和42.5%以及85.5%和59.8%。利妥昔单抗治疗前后%FVC和%DLCO的中位变化分别为+0.35%和-0.8%，托珠单抗治疗前后分别为-0.9%和+0.2%。使用SSc中%FVC变化的最小临床重要差异，大多数患者在两种治疗中改善或保持稳定（69.3%利妥昔单抗，64.1%托珠单抗）。与托珠单抗相比，利妥昔单抗组FVC下降的患者百分比较小。利妥昔单抗的作用不受ATA状态的影响。相比之下，ATA阳性患者更可能对托珠单抗产生应答（p = 0.0073）（中位FVC变化：托珠单抗，+60 ml ATA阳性vs-110 ml ATA阴性;利妥昔单抗，0 ml ATA阳性vs 0 ml ATA阴性）。疾病持续时间和CRP没有影响治疗反应任一therapy.ConclusionOur回顾性队列提供了现实生活中的数据，支持使用利妥昔单抗和托珠单抗，以稳定间质性肺病在SSc。基于自身抗体特异性和临床参数的差异反应可能有助于优化SSc-ILD生物治疗的患者选择。需要进一步研究以了解驱动这些患者组中差异反应的确切作用机制，以更好地了解SSc-ILD的发病机制。Goldman：赠款/研究支持; MRC/SRUK临床研究培训奖学金[赠款编号MR/V030108/1]。泰南：没有。比斯利：没有。马吉德：没有。丹顿：咨询; CD一直是Roche. V. H.的顾问。王：没有。
Background/AimsInterstitial lung disease (ILD) is one of the leading causes of death in systemic sclerosis (SSc). Evidence from randomised controlled trials suggests a beneficial effect of tocilizumab and rituximab on preserving lung function. However, comparative data outside the arena of clinical trials remains limited. Deciding when and who to treat with specific treatments remains challenging.MethodsWe performed a retrospective analysis of all SSc patients attending a single specialist centre who had received rituximab or tocilizumab. Demographic, clinical and laboratory data was collected along with serial lung function. Patients were excluded if lung function pre- and/or post-therapy was not available. Data were analysed based on anti-topoisomerase I antibody (ATA) status and other clinical, laboratory and radiological features. Wilcoxon T test and Fisher’s exact test were used.Results129 patients were included, of which 87 received rituximab, 32 tocilizumab and 10 both therapies. 8 of 10 (80%) patients who had received both therapies received rituximab prior to tocilizumab. 76 (58.9%) patients had diffuse SSc and 102 (79%) had ILD. Concurrent mycophenolate mofetil (MMF) was prescribed for 52 (53.6%) patients with rituximab and 17 (40.5%) patients with tocilizumab. Median pre-treatment lung function percentage forced vital capacity (%FVC) and percentage transfer factor (%DLCO) were 67.9% and 42.5% and 85.5% and 59.8% for rituximab and tocilizumab respectively. Median change %FVC and %DLCO pre- and post-treatment were +0.35% and -0.8% for rituximab and -0.9% and +0.2% for tocilizumab. Using minimally clinically important difference for change in %FVC in SSc, the majority of patients improved or remained stable (69.3% rituximab, 64.1% tocilizumab) with both treatments. A smaller percentage of patients on rituximab demonstrated FVC decline compared with tocilizumab. The effect from rituximab was not impacted by ATA status. In contrast, ATA positive patients were more likely to respond to tocilizumab (p = 0.0073) (median FVC change: tocilizumab, + 60ml ATA positive vs -110ml ATA negative; rituximab, 0ml ATA positive vs 0ml ATA negative). Disease duration and CRP had no effect on treatment response for either therapy.ConclusionOur retrospective cohort provides real-life data supporting the use of both rituximab and tocilizumab to stabilise ILD in SSc. Differential response based on autoantibody specificity and clinical parameters may help optimise patient selection for biological therapy in SSc-ILD. Further research to understand the exact mechanism of action driving the differential response in these patient groups is needed to greater understand the pathogenesis of SSc-ILD.DisclosureN.R. Goldman:Grants/research support; MRC/SRUK Clinical Research Training Fellowship [grant number MR/V030108/1].A. Tynan:None.C. Beesley:None.R. Mageed:None.C. Denton:Consultancies; CD has been a consultant to Roche.V.H. Ong:None.