利妥昔单抗在系统性硬化症中的生物仿制药“Acellbia”的使用

L. Ananyeva, L. Garzanova, O. Desinova, R. Shayakhmetova, M. Starovoytova, O. Koneva, O. Ovsyannikova, S. Glukhova, E. Nasonov
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Complicated and expensive methods for obtaining genetically engineered biological preparations have contributed to the emergence of more accessible biosimilars, one of which is the RTX biosimilar, Acellbia (Biocad, Russian Federation). The “biosimilar” versions of RTX might reduce the cost of therapy and increase patients accessibility to this treatment option. The RTX biosimilar Acellbia (ACB) has received approval in Russian Federation in 2014 for all indications held by reference RTX (including rheumatoid arthritis and ANCA-associated vasculitis).The aim of this study was to investigate the efficacy and safety of Acellbia in patients with systemic sclerosis.Material and methods. Our prospective uncontrolled study included 20 patients (14 women) aged 50±14 years, with a disease duration of 3.5±2.7 years. Indications for the prescribing of ACB were high disease activity and the presence of risk factors for progression. All patients had radiological signs of interstitial lung disease, 13 (65%) were positive for antibodies to topoisomerase 1. None of the patients had previously been treated with biological therapy. All patients received glucocorticoids in low doses and 15 (75%) patients were not on concomitant immunosuppressants during the study. ACB was administered in doses of 2 g (two doses of 1 g with a weekly interval) at inclusion of the study and after 6–8 months according to the same scheme, cumulative dose – 4 g. An assessment of basic measurements was obtained at baseline (Point 0), before the second course (after 7.2±1.7 mo, Point 1) and at the end of follow-up (13.4±1.6 mo, Point 2). The results are presented in the form of mean values and standard deviations.Results. There was a positive effect on the main manifestations of the disease, which accompanied by stable depletion of CD19+ B lymphocytes in the peripheral blood. At the intermediate assessment (between points 0–1), no significant changes were observed, with the exception of the skin score. At the end of the study, most of the parameters showed a significant improvement between points 0–2. The activity of the disease (EScSG-AI) decreased, and the skin score decreased from 12.8±11 to 6.2±5.6 (p=0.002). The forced vital capacity (% of predicted) increased from 89±18.2 to 98.26±16.13% (p=0.0002), and the diffusion capacity of the lungs (% of predicted) increased from 56.8±15.7 to 61.9±17.2% (p<0.019). A significant decrease in CRP, antitopoisomerase-1 antibodies, as well as IgG (from 12.6±2.6 to 10.2±2.2 g/l) was noted. Repopulation to normal level of B lymphocytes did not occur in any case, and complete depletion of B lymphocytes at the end of the study was maintained in 83% of patients (15 of 18). The quality of life questionnaire SHAQ improved (p=0.0001), and the average dose of prednisolone was reduced from 11.0±2.7 to 9.4±2.3 mg/day (p=0.03). Positive changes according to HRCT was evident in 9 (45%) patients due to a decrease in ground glass opacity. The frequency and spectrum of adverse events (AEs) corresponded to those already known for RTX. Of the 20 patients who received 2 courses of ACB, two withdrew from the evaluation at Point 2 due to pregnancy (1) and lung cancer (1). A total of 11 (55%) AEs were reported in 9 (45%) patients, most of them were classified as mild. Infectious complications developed in 7 (35%) patients: respiratory infections of the upper respiratory tract (4), positivity in the TB skin test (2), otitis (1), cystitis (1) and cholecystitis (1). One patient developed calf vein thrombosis and lung cancer was diagnosed in one case.Conclusion. Our data suggest that Acellbia could be used for the treatment of SSc. A short-term, prospective, uncontrolled study showed good efficacy and acceptable safety of the ACB biosimilar in SSc. A significant decrease of skin fibrosis and improvement of lung functions have been proven. The clinical effect of ACB manifested by the 6th month from the start of therapy and reached its maximum one year after its initiation. Due to the positive efficacy of ACB, it can be prescribed for the patients with SSc with ineffectiveness and/or intolerance to immunosuppressants, and could be considered as a first-line therapy. Our data should be confirmed by the results of controlled clinical trials.","PeriodicalId":21518,"journal":{"name":"Rheumatology Science and Practice","volume":"17 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The use of “Acellbia” – a biosimilar of rituximab in systemic sclerosis\",\"authors\":\"L. Ananyeva, L. Garzanova, O. Desinova, R. Shayakhmetova, M. Starovoytova, O. Koneva, O. Ovsyannikova, S. 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引用次数: 0

摘要

介绍。现代治疗系统性硬化症(SSc)的可能性仍然有限,因为大多数使用的药物没有改善疾病的作用。这鼓励了对潜在影响疾病基本病理过程的新方法的研究。一个例子是抗b细胞治疗,特别是利妥昔单抗(RTX)。到目前为止,RTX还没有注册用于治疗SSc,但在最近的荟萃分析和临床建议中反映了其使用的大量积极经验。获得基因工程生物制剂的复杂和昂贵的方法促成了更容易获得的生物类似药的出现,其中之一是RTX生物类似药Acellbia (Biocad,俄罗斯联邦)。RTX的“生物仿制药”版本可能会降低治疗成本,并增加患者对这种治疗选择的可及性。RTX生物仿制药Acellbia (ACB)已于2014年在俄罗斯联邦获得批准,用于参考RTX持有的所有适应症(包括类风湿性关节炎和anca相关血管炎)。本研究的目的是探讨Acellbia对系统性硬化症患者的疗效和安全性。材料和方法。本前瞻性非对照研究纳入20例患者(14例女性),年龄50±14岁,病程3.5±2.7年。ACB的适应症是疾病活动性高和存在进展危险因素。所有患者均有肺间质性疾病的影像学征象,13例(65%)拓扑异构酶1抗体阳性。这些患者之前都没有接受过生物疗法。所有患者均接受低剂量糖皮质激素治疗,15例(75%)患者在研究期间未同时使用免疫抑制剂。ACB在纳入研究时和6-8个月后按照相同的方案以2g剂量(两次剂量为1g,每周间隔一次)给予,累积剂量- 4g。在基线(0点)、第二疗程前(7.2±1.7个月,1点)和随访结束时(13.4±1.6个月,2点)对基本测量进行评估。结果以平均值和标准差的形式呈现。对本病主要表现有积极作用,伴外周血CD19+ B淋巴细胞稳定耗竭。在中间评估(0-1分之间),除皮肤评分外,未观察到显著变化。在研究结束时,大多数参数在0-2分之间显示出显著的改善。疾病活动性(EScSG-AI)下降,皮肤评分从12.8±11降至6.2±5.6 (p=0.002)。用力肺活量(预测的%)由89±18.2%提高到98.26±16.13% (p=0.0002),肺弥散量(预测的%)由56.8±15.7%提高到61.9±17.2% (p<0.019)。CRP、抗拓扑异构酶-1抗体和IgG显著下降(从12.6±2.6 g/l降至10.2±2.2 g/l)。在任何情况下,B淋巴细胞都没有恢复到正常水平,在研究结束时,83%的患者(18人中有15人)保持了B淋巴细胞的完全耗尽。生活质量问卷SHAQ改善(p=0.0001),泼尼松龙平均剂量由11.0±2.7 mg/d降至9.4±2.3 mg/d (p=0.03)。9例(45%)患者由于磨玻璃混浊减少,HRCT显示明显阳性变化。不良事件(ae)的频率和频谱与已知的RTX相关。在接受2个疗程ACB治疗的20例患者中,2例因妊娠(1例)和肺癌(1例)在第2点退出评估。9例(45%)患者共报告11例(55%)ae,其中大多数为轻度ae。感染并发症7例(35%),上呼吸道感染4例,TB皮肤试验阳性2例,中耳炎1例,膀胱炎1例,胆囊炎1例,小腿静脉血栓形成1例,肺癌1例。我们的数据表明,Acellbia可以用于治疗SSc。一项短期、前瞻性、非对照研究表明,ACB生物类似药在SSc中具有良好的疗效和可接受的安全性。皮肤纤维化的显著减少和肺功能的改善已被证实。ACB的临床疗效在开始治疗后6个月表现出来,在开始治疗后1年达到顶峰。由于ACB的阳性疗效,可用于对免疫抑制剂无效和/或不耐受的SSc患者,可考虑作为一线治疗。我们的数据应该得到对照临床试验结果的证实。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The use of “Acellbia” – a biosimilar of rituximab in systemic sclerosis
Introduction. The possibilities of modern therapy for systemic sclerosis (SSc) remains limited, since most of the used drugs do not have a diseasemodifying effect. This encourages the study of new approaches that potentially affect the fundamental pathological processes underlying the disease. One example is anti-B cell therapy, in particular rituximab (RTX). Until now RTX do not have a registration for the treatment of SSc, but there is a large positive experience of its use, which is reflected in recent meta-analyses and clinical recommendations. Complicated and expensive methods for obtaining genetically engineered biological preparations have contributed to the emergence of more accessible biosimilars, one of which is the RTX biosimilar, Acellbia (Biocad, Russian Federation). The “biosimilar” versions of RTX might reduce the cost of therapy and increase patients accessibility to this treatment option. The RTX biosimilar Acellbia (ACB) has received approval in Russian Federation in 2014 for all indications held by reference RTX (including rheumatoid arthritis and ANCA-associated vasculitis).The aim of this study was to investigate the efficacy and safety of Acellbia in patients with systemic sclerosis.Material and methods. Our prospective uncontrolled study included 20 patients (14 women) aged 50±14 years, with a disease duration of 3.5±2.7 years. Indications for the prescribing of ACB were high disease activity and the presence of risk factors for progression. All patients had radiological signs of interstitial lung disease, 13 (65%) were positive for antibodies to topoisomerase 1. None of the patients had previously been treated with biological therapy. All patients received glucocorticoids in low doses and 15 (75%) patients were not on concomitant immunosuppressants during the study. ACB was administered in doses of 2 g (two doses of 1 g with a weekly interval) at inclusion of the study and after 6–8 months according to the same scheme, cumulative dose – 4 g. An assessment of basic measurements was obtained at baseline (Point 0), before the second course (after 7.2±1.7 mo, Point 1) and at the end of follow-up (13.4±1.6 mo, Point 2). The results are presented in the form of mean values and standard deviations.Results. There was a positive effect on the main manifestations of the disease, which accompanied by stable depletion of CD19+ B lymphocytes in the peripheral blood. At the intermediate assessment (between points 0–1), no significant changes were observed, with the exception of the skin score. At the end of the study, most of the parameters showed a significant improvement between points 0–2. The activity of the disease (EScSG-AI) decreased, and the skin score decreased from 12.8±11 to 6.2±5.6 (p=0.002). The forced vital capacity (% of predicted) increased from 89±18.2 to 98.26±16.13% (p=0.0002), and the diffusion capacity of the lungs (% of predicted) increased from 56.8±15.7 to 61.9±17.2% (p<0.019). A significant decrease in CRP, antitopoisomerase-1 antibodies, as well as IgG (from 12.6±2.6 to 10.2±2.2 g/l) was noted. Repopulation to normal level of B lymphocytes did not occur in any case, and complete depletion of B lymphocytes at the end of the study was maintained in 83% of patients (15 of 18). The quality of life questionnaire SHAQ improved (p=0.0001), and the average dose of prednisolone was reduced from 11.0±2.7 to 9.4±2.3 mg/day (p=0.03). Positive changes according to HRCT was evident in 9 (45%) patients due to a decrease in ground glass opacity. The frequency and spectrum of adverse events (AEs) corresponded to those already known for RTX. Of the 20 patients who received 2 courses of ACB, two withdrew from the evaluation at Point 2 due to pregnancy (1) and lung cancer (1). A total of 11 (55%) AEs were reported in 9 (45%) patients, most of them were classified as mild. Infectious complications developed in 7 (35%) patients: respiratory infections of the upper respiratory tract (4), positivity in the TB skin test (2), otitis (1), cystitis (1) and cholecystitis (1). One patient developed calf vein thrombosis and lung cancer was diagnosed in one case.Conclusion. Our data suggest that Acellbia could be used for the treatment of SSc. A short-term, prospective, uncontrolled study showed good efficacy and acceptable safety of the ACB biosimilar in SSc. A significant decrease of skin fibrosis and improvement of lung functions have been proven. The clinical effect of ACB manifested by the 6th month from the start of therapy and reached its maximum one year after its initiation. Due to the positive efficacy of ACB, it can be prescribed for the patients with SSc with ineffectiveness and/or intolerance to immunosuppressants, and could be considered as a first-line therapy. Our data should be confirmed by the results of controlled clinical trials.
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