Yıldırım Reşit, Cansu Döndü Üsküdar, Dinler Mustafa, Korkmaz Cengiz
Department of Internal Medicine, Division of Rheumatology, Eskişehir Osmangazi University, Eskişehir, Turkey.
Rheumatol Int. 2024 Dec;44(12):2927-2934. doi: 10.1007/s00296-024-05714-1. Epub 2024 Sep 12.
Tocilizumab (TCZ) which is a humanized interleukin (IL)-6 receptor antibody has been increasingly widespread used in rheumatology practice. TCZ-related hypofibrinogenemia is a not well-described side effect, but awareness seems to be incresing as publications on this topic are also becoming more frequent. Our aim in this study was to determine the frequency, timing, and approach to TCZ-related hypofibrinogenemia in rheumatic diseases. We retrospectively screened our patients who received TCZ for inflammatory rheumatic diseases and studied serum fibrinogen at least once before and/or after drug administration. We recorded and analyzed demographic features (age, gender, diagnosis), comorbidities, laboratory parameters, management, and outcome data. 30 patients who received TCZ due to rheumatological diseases and had at least one fibrinogen level were included in this study. 73.3% were female and median age was found to be 65 (42-82) years, with median disease duration of 148 (36-500) months. 90% of the patients received TCZ for RA and 10% for GCA. We examined the fibrogen levels at an average of 24 months (min 1 max 108) following the start of TCZ treatment. The study group was divided into those with normal fibrinogen levels (normal fibrinogen group) and those with low fibrinogen levels (lowfibrinogen group). In total, hypofibrinogenemia was found in 14 (46.6%) patients. Median serum fibrinogen level in the low fibrinogen group after TCZ was calculated to be 151.5 mg/dl (min 92 max 171). Most patients were asymptomatic (71.4%). Ecchymoses were in seen 4 (28,6%) patients. No major bleeding were seen. TCZ was discontinued in 5 out of 14 patients (35.7%), while 9 out of 14 patients (64.3%) were closely followed. Outcomes regarding fibrinogen levels (11 out of 14) were as follows: increase in 4 and not checked in one after cessation of the drug, 3 spontaneous increases under the drug, and 3 persistently low levels on TCZ treatment. We found no difference in terms of gender (p = 0.417), platelets (p = 0.343), ESR (p = 0.448), and CRP (p = 0.660) at the time of TCZ initiation between groups. TCZ-related hypofibrinogenemia is more frequent than expected with occurence in both the early and late stages of treatment. Further research is required to determine whether to regularly measure fibrinogen levels in patients using TCZ and how to treat patients with hypofibrinogenemia.
托珠单抗（TCZ）是一种人源化白细胞介素（IL）-6受体抗体，已在风湿病治疗中越来越广泛地应用。与TCZ相关的低纤维蛋白原血症是一种描述不多的副作用，但随着关于该主题的出版物越来越频繁，人们对此的认识似乎也在提高。我们在本研究中的目的是确定风湿病中与TCZ相关的低纤维蛋白原血症的发生率、发生时间及处理方法。我们回顾性筛查了接受TCZ治疗炎性风湿病的患者，并在给药前和/或给药后至少测量一次血清纤维蛋白原。我们记录并分析了人口统计学特征（年龄、性别、诊断）、合并症、实验室参数、处理措施及结局数据。本研究纳入了30例因风湿病接受TCZ治疗且至少有一次纤维蛋白原水平检测结果的患者。其中73.3%为女性，中位年龄为65（42 - 82）岁，中位病程为148（36 - 500）个月。90%的患者因类风湿关节炎接受TCZ治疗，10%因巨细胞动脉炎接受治疗。我们在开始TCZ治疗后平均24个月（最短1个月，最长108个月）检测纤维蛋白原水平。研究组分为纤维蛋白原水平正常组（正常纤维蛋白原组）和纤维蛋白原水平低组（低纤维蛋白原组）。总共14例（46.6%）患者出现低纤维蛋白原血症。TCZ治疗后低纤维蛋白原组的中位血清纤维蛋白原水平经计算为151.5mg/dl（最低92，最高171）。大多数患者无症状（71.4%），4例（28.6%）患者出现瘀斑，未观察到严重出血情况。14例患者中有5例（35.7%）停用了TCZ，14例患者中有9例（64.3%）接受密切随访。关于纤维蛋白原水平的结局（14例中的11例）如下：停药后4例升高，1例未复查，3例在用药期间自发升高，3例在TCZ治疗期间纤维蛋白原水平持续较低。我们发现两组在开始使用TCZ时，在性别（p = 0.417）、血小板（p = 0.343）、血沉（p = 0.448）和C反应蛋白（p = 0.660）方面无差异。与TCZ相关的低纤维蛋白原血症比预期更常见，在治疗的早期和晚期均可发生。需要进一步研究以确定是否应定期检测使用TCZ患者的纤维蛋白原水平，以及如何治疗低纤维蛋白原血症患者。
