系统性红斑狼疮患者处方 I 型干扰素抑制剂 anifrolumab 的画像

T. Reshetnyak, E. Aseeva, A. Shumilova, N. Nikishina, S. Shkireeva, A. Lila
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引用次数: 0

摘要

近年来,使用阻断I型干扰素(IFN)或其受体活性的单克隆抗体已成为系统性红斑狼疮(SLE)药物治疗的新方法。目的:研究接受I型IFN受体抑制剂阿尼夫单抗(AFM,Saphnelo®)治疗的系统性红斑狼疮患者的特征。这项为期 12 个月的前瞻性研究纳入了 21 名符合 2012 SLICC 标准的系统性红斑狼疮患者。对所有患者进行了系统性红斑狼疮标准实验室和免疫学指标检查。SLEDAI-2K指数用于确定系统性红斑狼疮的活动度,CLASI指数用于确定皮肤黏膜综合征的严重程度。器官损伤采用SLICC/ACR损伤指数(DI)进行评估。狼疮问卷(LupusQol)和疲劳问卷(FACIT-Fatigue)用于分析与健康相关的生活质量(HRQoL)。研究中女性患者居多,男女比例为 17 (81%)/4 (19%),年龄中位数为 31 [27; 46]岁,病程为 9 [6.0; 11.0]年。根据SLEDAI-2K指数,大多数患者(86%)具有中度或高度疾病活动性。在系统性红斑狼疮的临床表现中,以皮肤和黏膜病变为主(81%)。66%的病例出现不同程度的非侵蚀性多关节炎。24%的患者有血清炎(胸膜炎、心包炎),43%的患者有血液异常(溶血性贫血、白细胞减少症、淋巴细胞减少症),14%的患者有泌尿系统综合征(每日蛋白尿达0.5克/升和/或尿沉渣--视野中白细胞/红细胞/柱状体达5个,但无尿路感染)。所有患者都患有免疫性疾病。所有患者都服用了羟氯喹,95%的患者服用了糖皮质激素(GC),剂量为5至60毫克/天,66%的患者服用了免疫抑制剂(环磷酰胺、霉酚酸酯、硫唑嘌呤、甲氨蝶呤)。33%的患者曾接受过生物疾病修饰抗风湿药物(利妥昔单抗、贝利木单抗、双抗 B 细胞疗法)和 Janus 激酶抑制剂巴利替尼的治疗。所有患者的 HRQoL 均显著恶化。为21名系统性红斑狼疮患者开具AFM处方的适应症是:根据SLEDAI-2K和/或CLASI标准,活动性系统性红斑狼疮主要累及皮肤及其附属器官,出现多关节炎并伴有免疫功能紊乱,对之前的标准疗法不耐受/无效,无法达到口服GCs的低日均剂量。一些患者的其他临床表现包括:血清炎、轻度血液病(库姆斯阳性贫血、白细胞减少)、泌尿系统综合征。对于合并有系统性红斑狼疮和继发性APS、斯约格伦综合征以及高DI SLICC的患者,可以处方AFM。
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Portrait of a patient with systemic lupus erythematosus for the prescription of the type I interferon inhibitor anifrolumab
In recent years the use of monoclonal antibodies that block activity of type I interferon (IFN) or its receptors has become the new approach in the pharmacotherapy of systemic lupus erythematosus (SLE).Objective: to characterize patients with SLE treated with the type I IFN receptor inhibitor anifrolumab (AFM, Saphnelo®).Material and methods. The prospective 12-month study included 21 patients with SLE who met the 2012 SLICC criteria. Standard laboratory and immunological markers for SLE were examined in all patients. The SLEDAI-2K index was used to determine the activity of SLE and the CLASI index was used to determine the severity of the mucocutaneous syndrome. Organ damage was assessed using the SLICC/ACR Damage Index (DI). The LupusQol and FACIT-Fatigue questionnaires were used to analyze health-related quality of life (HRQoL).Results and discussion. Female patients prevailed in the study, female/male ratio – 17 (81%)/4 (19%), median age – 31 [27; 46] years, disease duration – 9 [6.0; 11.0] years. The majority of patients (86%) had moderate or high disease activity according to the SLEDAI-2K index. Among the clinical manifestations of SLE, skin and mucous membranes lesions predominated (81%). Non-erosive polyarthritis of varying severity was observed in 66% of cases. Serositis showed 24% of patients (pleurisy, pericarditis), 43% had hematological abnormalities (hemolytic anemia, leukopenia, lymphopenia) and 14% - urinary syndrome (daily proteinuria up to 0.5 g/l and/or urinary sediment – leukocytes/erythrocytes/cylinders up to 5 in the field of view in the absence of urinary tract infection). All patients had immunological disorders. 14% of them were diagnosed with antiphospholipid syndrome (APS) and 43% with Sjögren's syndrome.All patients received hydroxychloroquine, 95% received glucocorticoids (GC) from 5 to 60 mg/day, 66% received immunosuppressants (cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate). 33% of patients had anamnesis of treatment with biologic disease modifying antirheumatic drugs (rituximab, belimumab, dual anti-B-cell therapy) and Janus kinase inhibitor baricitinib. All patients experienced a significant deterioration in HRQoL.Conclusion. The indications for prescribing AFM to 21 patients with SLE were: active SLE according to SLEDAI-2K and/or CLASI with predominant involvement of skin, its appendages and development of polyarthritis with immunological disorders, intolerance/ineffectiveness of previous standard therapy and inability to achieve low average daily doses of oral GCs. Other clinical manifestations in some patients were: serositis, mild hematological disorders (Coombs-positive anemia, leukopenia), urinary syndrome. AFM could be prescribed for a combination of SLE with secondary APS and Sjögren's syndrome as well as for a high DI SLICC.
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