Safety and Tolerability of Rituximab in the Treatment of Systemic Sclerosis

IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Doklady Biochemistry and Biophysics Pub Date : 2024-06-10 DOI:10.1134/S1607672924700856
L. A. Garzanova, L. P. Ananyeva, O. A. Koneva, O. V. Desinova, M. N. Starovoytova, O. B. Ovsyannikova, R. U. Shayakhmetova, S. I. Glukhova
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Abstract

Rituximab (RTX) has been used for the treatment of systemic sclerosis (SSс) for a long time and has shown good efficacy for skin fibrosis and interstitial lung disease (ILD). However, data on tolerability and long-term adverse events (AEs) during RTX therapy in SSc are insufficient. The objective of this study was to assess the tolerability and safety of RTX in patients with SSс in a long-term prospective follow-up. Our open-label prospective study included 151 SSс patients who received at least one RTX infusion. The mean age of the patients was 47.9 ± 13.4 years; the majority of them were women (83%). The mean disease duration was 6.4 ± 5.8 years. The mean follow-up period after the first RTX infusion was 5.6 ± 2.6 years (845.6 patient-years (PY)). All patients received RTX in addition to ongoing therapy with prednisone and/or immunosuppressants. AEs were assessed and recorded by a doctor in the hospital immediately after RTX infusion and then by patient’s reported outcome during the observation period. All causes of death were considered, regardless of treatment. A total of 85 AEs (56%) were registered, the overall incidence of AEs was 10/100 PY (95% confidence interval (CI) 8–12). The highest frequency of all AEs was observed in the first 2–6 months after the first course of RTX, however, these were mainly mild and moderate AEs (71%). The most frequent AEs were infections, they were observed in 40% of cases, with no serious opportunistic infections reported. The overall incidence of all infections was 7.1/100 PY (95% CI 5.5–9), serious infections—1.5/100 PY (95% CI 0.9–2.6). Infusion reactions occurred in 8% of patients. Other AEs were noted in 3% (0.6/100 PY, 95% CI 0.3–1.4). The overall incidence of serious AEs was 18%—3.2/100 PY (95% CI 2.2–4.6). There was a significant decrease of the immunoglobulin G (Ig G) during follow-up; however, its average values remained within normal limits. There were 17 deaths (11%) (2/100 PY, 95% CI 1.3–3.2). In most cases, patients died from the progression of the major organ failure, which arose before RTX treatment. In our study, the safety profile of RTX in SSс was assessed as favorable. It was similar to the AE profile in other autoimmune diseases treated with RTX. With an increase in the cumulative dose of RTX, no increase in AEs was observed. The mortality is comparable to the other severe autoimmune diseases in observational studies. Monitoring of IgG may be useful for patients with SSс on RTX therapy for early detection of the risk of developing infectious complications. RTX could be considered as a relatively safe drug for the complex therapy of SSс when standard therapy is ineffective or impossible.

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利妥昔单抗治疗系统性硬化症的安全性和耐受性
利妥昔单抗(RTX)用于治疗系统性硬化症(SSс)已有很长一段时间,对皮肤纤维化和间质性肺病(ILD)显示出良好的疗效。然而,有关RTX治疗系统性硬化症期间的耐受性和长期不良事件(AEs)的数据尚不充分。本研究旨在通过长期前瞻性随访评估RTX在SSс患者中的耐受性和安全性。我们的开放标签前瞻性研究纳入了151名至少接受过一次RTX输注的SSс患者。患者的平均年龄为(47.9 ± 13.4)岁,其中大多数为女性(83%)。平均病程为(6.4 ± 5.8)年。首次输注 RTX 后的平均随访时间为 5.6 ± 2.6 年(845.6 患者年)。所有患者在接受泼尼松和/或免疫抑制剂治疗的同时还接受了RTX治疗。在输注 RTX 后,由医院的一名医生立即对 AEs 进行评估和记录,然后根据患者在观察期间报告的结果进行评估和记录。所有死亡原因均被考虑在内,与治疗无关。共登记了 85 例 AEs(56%),AEs 的总发生率为 10/100 PY(95% 置信区间 (CI):8-12)。在首个 RTX 疗程后的 2-6 个月内,所有 AE 的发生率最高,但主要是轻度和中度 AE(71%)。最常见的不良反应是感染,占 40%,没有严重机会性感染的报道。所有感染的总发生率为 7.1/100PY(95% CI 5.5-9),严重感染为 1.5/100PY(95% CI 0.9-2.6)。8%的患者发生了输液反应。其他 AE 为 3%(0.6/100 人,95% CI 0.3-1.4)。严重 AEs 的总发生率为 18%-3.2/100PY(95% CI 2.2-4.6)。随访期间,免疫球蛋白 G(Ig G)明显下降,但其平均值仍在正常范围内。共有 17 人死亡(11%)(2/100 PY,95% CI 1.3-3.2)。在大多数病例中,患者死于 RTX 治疗前出现的主要器官功能衰竭。在我们的研究中,RTX治疗SSс的安全性评价良好。它与其他接受RTX治疗的自身免疫性疾病的AE情况相似。随着RTX累积剂量的增加,未观察到AEs增加。死亡率与观察性研究中的其他严重自身免疫性疾病相当。对接受RTX治疗的SSс患者进行IgG监测可能有助于及早发现发生感染性并发症的风险。当标准疗法无效或无法使用时,RTX可被视为一种相对安全的药物,用于SSс的综合治疗。
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来源期刊
Doklady Biochemistry and Biophysics
Doklady Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
1.60
自引率
12.50%
发文量
68
审稿时长
6-12 weeks
期刊介绍: Doklady Biochemistry and Biophysics is a journal consisting of English translations of articles published in Russian in biochemistry and biophysics sections of the Russian-language journal Doklady Akademii Nauk. The journal''s goal is to publish the most significant new research in biochemistry and biophysics carried out in Russia today or in collaboration with Russian authors. The journal accepts only articles in the Russian language that are submitted or recommended by acting Russian or foreign members of the Russian Academy of Sciences. The journal does not accept direct submissions in English.
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