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Animal models unraveling the complexity of vitiligo pathogenesis 动物模型揭示白癜风发病机制的复杂性
IF 13.6 1区 医学 Q1 Medicine Pub Date : 2024-01-05 DOI: 10.1016/j.autrev.2024.103515
Prashant Giri , Dharm Desai , Mitesh Dwivedi

Vitiligo is a chronic skin condition marked by the gradual loss of pigmentation, leading to the emergence of white or depigmented patches on the skin. The exact cause of vitiligo remains not entirely understood, although it is thought to involve a blend of genetic, autoimmune, and environmental factors. While there is currently no definitive cure for vitiligo, diverse treatments exist that may assist in managing the condition and fostering repigmentation in specific instances. Animal models play a pivotal role in comprehending the intricate mechanisms that underlie vitiligo, providing valuable insights into the progression and onset of the disease, as well as potential therapeutic interventions. Although induced experimental models lack the nuanced characteristics observed in natural experimental models, relying solely on a single animal model might not fully capture the intricate pathogenesis of vitiligo. Different animal models simulate specific aspects of human vitiligo pathogenesis to varying degrees. This review extensively explores the array of animal models utilized in vitiligo research, shedding light on their respective advantages, disadvantages, and applications.

白癜风是一种慢性皮肤病,其特征是色素逐渐脱失,导致皮肤上出现白色或脱色斑块。白癜风的确切病因尚不完全清楚,但据认为涉及遗传、自身免疫和环境因素的综合作用。虽然目前还没有彻底治愈白癜风的方法,但有多种治疗方法可以帮助控制病情,并在特定情况下促进色素恢复。动物模型在理解导致白癜风的复杂机制方面发挥着关键作用,为了解疾病的进展和发病过程以及潜在的治疗干预措施提供了宝贵的见解。虽然诱导实验模型缺乏在自然实验模型中观察到的细微特征,但仅靠单一动物模型可能无法完全捕捉到白癜风错综复杂的发病机制。不同的动物模型能在不同程度上模拟人类白癜风发病机制的特定方面。本综述广泛探讨了白癜风研究中使用的一系列动物模型,阐明了它们各自的优缺点和应用。
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引用次数: 0
Idiopathic and connective tissue disease-associated pulmonary arterial hypertension (PAH): Similarities, differences and the role of autoimmunity 特发性和结缔组织病相关性肺动脉高压(PAH):相似之处、不同之处以及自身免疫的作用
IF 13.6 1区 医学 Q1 Medicine Pub Date : 2024-01-03 DOI: 10.1016/j.autrev.2024.103514
Elvira Favoino , Marcella Prete , Vasiliki Liakouli , Patrizia Leone , Adriana Sisto , Luca Navarini , Marta Vomero , Francesco Ciccia , Piero Ruscitti , Vito Racanelli , Roberto Giacomelli , Federico Perosa

Pre-capillary pulmonary arterial hypertension (PAH) is hemodynamically characterized by a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg, pulmonary capillary wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) > 2. PAH is classified in six clinical subgroups, including idiopathic PAH (IPAH) and PAH associated to connective tissue diseases (CTD-PAH), that will be the main object of this review. The aim is to compare these two PAH subgroups in terms of epidemiology, histological and pathogenic findings in an attempt to define disease-specific features, including autoimmunity, that may explain the heterogeneity of response to therapy between IPAH and CTD-PAH.

毛细血管前肺动脉高压(PAH)的血液动力学特征是平均肺动脉压(mPAP)≥20 mmHg,肺毛细血管楔压(PAWP)≤15 mmHg,肺血管阻力(PVR)≥2。PAH 可分为六个临床亚组,包括特发性 PAH(IPAH)和与结缔组织疾病相关的 PAH(CTD-PAH),这将是本综述的主要对象。本综述的主要目的是比较这两个 PAH 亚组在流行病学、组织学和病理学方面的发现,试图确定疾病的特异性特征(包括自身免疫),以解释 IPAH 和 CTD-PAH 对治疗反应的异质性。
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引用次数: 0
Is minor salivary gland biopsy still mandatory in Sjogren's syndrome? Does seronegative Sjogren's syndrome exist? 干燥综合征的小唾液腺活检仍然是强制性的吗?血清阴性干燥综合征是否存在?
IF 13.6 1区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.autrev.2023.103425
Chiara Baldini , Onorina Berardicurti , Roberto Giacomelli , Michele Bombardieri

Sjӧgren's disease (SjD) is a systemic autoimmune disorder characterized by the chronic inflammation and dysfunction of exocrine glands, mainly salivary glands, causing dryness of the eyes and of the mouth. The disease may affect different organs and tissues with complex and heterogeneous clinical presentation, usually with sicca symptoms, profound fatigue, chronic pain, major organ involvement, and lymphomas. SjD diagnosis is based on the combination of clinical, serological, and functional tests with histological biomarkers. Minor salivary gland biopsy (mSGB) represents the cornerstone for the diagnosis of SjD, allowing the study of the characteristic focal infiltration of B- and T lymphocytes. Besides, mSGB might also have a prognostic role, being the infiltrates more complex in patients with severe SjD. But biopsy, so far, is not mandatory for SjD and mSG ultrasound and peripheral biomarkers might replace its role in the future. Another important aspect of SjD is the presence of autoantibodies, although 20 to 30% of patients are “seronegative” for specific autoantibodies (ANA, antiRo/SSA, antiLa/SSB). The characteristics of this subset of patients are currently under evaluation and “new” autoantibodies and biomarkers might be necessary for better patient's stratification and follow-up.

干燥综合征(SjD)是一种全身性自身免疫性疾病,其特征是外分泌腺(主要是唾液腺)的慢性炎症和功能障碍,导致眼睛和口腔干燥。该疾病可能影响不同的器官和组织,具有复杂和异质的临床表现,通常伴有干燥症状、严重疲劳、慢性疼痛、主要器官受累和淋巴瘤。SjD的诊断是基于临床、血清学和功能测试与组织学生物标志物的结合。小唾液腺活检(mSGB)是诊断SjD的基石,可以研究B和T淋巴细胞的特征性局灶性浸润。此外,mSGB也可能具有预后作用,因为严重SjD患者的浸润更为复杂。但到目前为止,活检对SjD和mSG超声并不是强制性的,外周生物标志物可能会在未来取代它的作用。SjD的另一个重要方面是自身抗体的存在,尽管20%至30%的患者对特定的自身抗体(ANA、抗Ro/SSA、抗La/SSB)呈“血清阴性”。这部分患者的特征目前正在评估中,“新的”自身抗体和生物标志物可能是更好的患者分层和随访所必需的。
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引用次数: 0
Is fibromyalgia an autoimmune disorder? 纤维肌痛是一种自身免疫性疾病吗?
IF 13.6 1区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.autrev.2023.103424
Daniel Clauw , Piercarlo Sarzi-Puttini , Greta Pellegrino , Yehuda Shoenfeld

Fibromyalgia (FM) is a multifactorial syndrome which includes not only widespread pain and stiffness, now recognized as major symptoms, but also numerous other somatic, emotional, and neuropsychic manifestation. The lack of specific validated biological and instrumental biomarkers has made FM a condition of unexplained medical significance, and its pathophysiology remains controversial and subject to debate. The current hypothesis regarding the pathogenesis of FM proposes that its development is influenced by various mechanism, including genetic predisposition, stressful life events, inflammatory processes, and cognitive-emotional factors. However, despite the extensive research conducted to date, the available data do not provide a clear understanding of the pathogenesis of FM.

In this article, we report the opposing viewpoints of two leading experts who debate the question of whether FM is an autoimmune disease, based on scientific data regarding this condition. Both perspectives are discussed and the latest evidence on the pathophysiology of FM is reported to provide a comprehensive understanding of this complex syndrome.

纤维肌痛(FM)是一种多因素综合征,不仅包括广泛的疼痛和僵硬,现在被认为是主要症状,还包括许多其他身体、情绪和神经精神表现。由于缺乏特定的经验证的生物和仪器生物标志物,FM成为一种具有无法解释的医学意义的疾病,其病理生理学仍然存在争议和争论。目前关于FM发病机制的假说认为,FM的发展受到各种机制的影响,包括遗传易感性、压力性生活事件、炎症过程和认知情绪因素。然而,尽管迄今为止进行了广泛的研究,但现有数据并不能清楚地了解FM的发病机制。在这篇文章中,我们报道了两位主要专家的对立观点,他们根据有关FM是否是一种自身免疫性疾病的科学数据,就FM是否是这种疾病的问题进行了辩论。对这两种观点进行了讨论,并报道了FM病理生理学的最新证据,以全面了解这种复杂的综合征。
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引用次数: 0
Is it safe to withdraw low-dose glucocorticoids in SLE patients in remission? 处于缓解期的系统性红斑狼疮患者停用小剂量糖皮质激素安全吗?
IF 13.6 1区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.autrev.2023.103446
Alexis Mathian , Laurent Arnaud , Guillermo Ruiz-Irastorza

Glucocorticoids (GCs) remain a cornerstone of the treatment of Systemic Lupus Erythematosus (SLE). Numerous studies have emphasized the risk of damage accrual in SLE patient treated with GC, but currently, it is not possible to dissociate favorable and undesirable effects of GCs because their underlying mechanisms are entangled at the molecular level. Here, we review whether available data suggest that it is possible, feasible and desirable to taper and discontinue GC treatment in SLE. The main potential concern with GC withdrawal is the risk of SLE flare, which is strongly associated with increased organ damage, mortality, healthcare costs, decreased quality of life and work productivity. While most studies have assumed the cut off point for low doses (e.g. 7.5/mg/d) as the limit for safety, it is still controversial whether lower doses may influence damage accrual long-term. Also, a recent randomized trial has shown that a daily dose of 5 mg of prednisone in SLE patients in short-term remission can prevent up to 50–75% of flares, with an acceptable safety profile. However, this treatment is not mandatory for all patients. Yet, several observational studies highlight that discontinuation of GC is associated with lower damage accrual. Currently, we do not have a reliable method to identify patients who may require long-term low-dose GC. Therefore, further research is needed to identify a subgroup at high risk of relapse who would benefit from continuing prednisone. In the meantime, when considering the discontinuation of very low-dose prednisone, the decision must be individualized, as HCQ and conventional immunosuppressive agents are not without risk of side effects.

糖皮质激素(GCs)仍然是治疗系统性红斑狼疮(SLE)的基石。许多研究都强调了接受糖皮质激素治疗的系统性红斑狼疮患者损伤累积的风险,但目前还无法将糖皮质激素的有利和不利影响区分开来,因为它们的内在机制在分子水平上相互纠缠。在此,我们回顾了现有的数据是否表明,在系统性红斑狼疮患者中减量和停用 GCs 治疗是可能的、可行的和可取的。停用 GC 的主要潜在问题是系统性红斑狼疮复发的风险,这与器官损伤、死亡率、医疗费用、生活质量下降和工作效率提高密切相关。虽然大多数研究都将低剂量(如 7.5/mg/d)作为安全性的临界点,但低剂量是否会长期影响损害的累积仍存在争议。另外,最近的一项随机试验显示,对短期缓解的系统性红斑狼疮患者每天使用 5 毫克的泼尼松可以预防高达 50-75% 的复发,而且安全性也可以接受。然而,并非所有患者都必须接受这种治疗。然而,一些观察性研究强调,停用 GC 与较低的损伤累积有关。目前,我们还没有可靠的方法来确定哪些患者可能需要长期低剂量 GC。因此,我们需要进一步研究,以确定哪些高复发风险亚群可从继续使用泼尼松中获益。同时,在考虑停用极低剂量泼尼松时,必须因人而异,因为 HCQ 和常规免疫抑制剂并非没有副作用风险。
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引用次数: 0
Is cyclophosphamide still the gold standard in early severe rapidly progressive systemic sclerosis? 环磷酰胺仍然是早期严重快速进行性系统性硬化症的金标准吗?
IF 13.6 1区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.autrev.2023.103439
Corrado Campochiaro , Yannick Allanore , Yolanda Braun-Moscovici , Marco Matucci-Cerinic , Alexandra Balbir-Gurman

Cyclophosphamide (CYC) has been a gold standard of treatment for severe progressive Systemic Sclerosis (SSc), especially in patients with concomitant interstitial lung disease (ILD). This approach was based on results of several interventional studies, including randomized control trials, which mainly addressed SSc-ILD as a primary end point and skin involvement as a second one. The use of CYC is time-limited due to significant adverse events. More recently, other immunosuppressive and biological agents showed efficacy but better safety profile in patients with SSc and SSc-ILD. With regards to other end-points, post-hoc analyses, systematic reviews and metalysis showed that CYC had limited influence on patients' quality of life, event-free survival and mortality. Comprehensive patient's stratification according to a molecular, cellular and phenotypic pattern may help in choosing of personalized medicine with more ambitious treatment effect and should be the future direction. According to the above available data and even if scientific evidence may be missing, experts' opinion has changed the attitude to CYC as an anchor drug in the management of severe SSc. Indeed, CYC has been pushed to the second and even third treatment option after mycophenolate mofetil, tocilizumab or rituximab. This position became obvious during debate on this topic at CORA meeting 2023.

环磷酰胺(CYC)一直是治疗严重进行性系统性硬化症(SSc)的金标准,尤其是在伴有间质性肺病(ILD)的患者中。该方法基于几项干预研究的结果,包括随机对照试验,主要将SSc-ILD作为主要终点,将皮肤受累作为第二终点。由于严重的不良事件,CYC的使用是有时间限制的。最近,其他免疫抑制和生物制剂在SSc和SSc-ILD患者中显示出疗效,但安全性更好。关于其他终点,事后分析、系统回顾和金属分析表明,CYC对患者的生活质量、无事件生存率和死亡率的影响有限。根据分子、细胞和表型模式对患者进行全面分层可能有助于选择具有更高治疗效果的个性化药物,这应该是未来的方向。根据上述可用数据,即使可能缺乏科学证据,专家们的意见也改变了人们对CYC作为治疗严重SSc的锚定药物的态度。事实上,CYC已经被推到了霉酚酸酯、托西珠单抗或利妥昔单抗之后的第二甚至第三种治疗方案。这一立场在2023年CORA会议关于这一主题的辩论中变得显而易见。
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引用次数: 0
Subclinical giant cell arteritis in polymyalgia rheumatica: Concurrent conditions or a common spectrum of inflammatory diseases? 多发性风湿病的亚临床巨细胞动脉炎:并发症还是炎症性疾病的共同谱系?
IF 13.6 1区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.autrev.2023.103415
Carlo Salvarani , Roberto Padoan , Luca Iorio , Alessandro Tomelleri , Benjamin Terrier , Francesco Muratore , Bhaskar Dasgupta

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common conditions in older adults. Their clinical connection has been recognized over time, with many patients experiencing both conditions separately, simultaneously or in temporal sequence to each other. Early GCA detection is essential to prevent vascular damage, but identifying subclinical GCA in PMR patients remains a challenge and routine screening is not standard practice. Subclinical GCA prevalence in newly diagnosed PMR patients ranges from 23 to 29%, depending on the screening method. Vessel wall imaging and temporal artery biopsy can detect subclinical GCA. Epidemiology and trigger factors show similarities between the two conditions, but PMR is more common than GCA. Genetic and pathogenesis studies reveal shared inflammatory mechanisms involving dendritic cells, pro-inflammatory macrophages, and an IL-6 signature. However, the inflammatory infiltrates differ, with extensive T cell infiltrates seen in GCA while PMR shows an incomplete profile of T cell and macrophage-derived cytokines. Glucocorticoid treatment is effective for both conditions, but the steroid requirements vary. PMR overall mortality might be similar to the general population, while GCA patients with aortic inflammatory aneurysms face increased mortality risk. The GCA-PMR association warrants further research. Considering their kinship, recently the term GCA-PMR Spectrum Disease (GPSD) has been proposed.

巨细胞动脉炎(GCA)和多发性风湿痛(PMR)是老年人的常见病。随着时间的推移,人们逐渐认识到这两种疾病在临床上的联系,许多患者会分别、同时或依次出现这两种疾病。早期发现 GCA 对预防血管损伤至关重要,但在 PMR 患者中识别亚临床 GCA 仍是一项挑战,常规筛查也不是标准做法。在新诊断的 PMR 患者中,亚临床 GCA 的发病率为 23% 至 29%,具体取决于筛查方法。血管壁成像和颞动脉活检可发现亚临床GCA。流行病学和诱发因素显示这两种疾病有相似之处,但 PMR 比 GCA 更常见。遗传学和发病机制研究显示,树突状细胞、促炎性巨噬细胞和 IL-6 特征参与了共同的炎症机制。然而,炎症浸润有所不同,GCA 可见广泛的 T 细胞浸润,而 PMR 则显示出不完整的 T 细胞和巨噬细胞衍生细胞因子特征。糖皮质激素治疗对这两种疾病都有效,但对类固醇的需求各不相同。PMR 的总死亡率可能与普通人群相似,而患有主动脉炎症性动脉瘤的 GCA 患者则面临更高的死亡风险。GCA与PMR的关联值得进一步研究。考虑到它们之间的亲缘关系,最近有人提出了 GCA-PMR 光谱病(GPSD)这一术语。
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引用次数: 0
Deciphering the clinical significance of longitudinal antiphospholipid antibody titers 解读抗磷脂抗体滴度纵向变化的临床意义
IF 13.6 1区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.autrev.2023.103510
Cecilia B. Chighizola , Rohan Willis , Gabriella Maioli , Savino Sciascia , Laura Andreoli , Olga Amengual , Massimo Radin , Maria Gerosa , Tatsuya Atsumi , Guilherme de Jesus , Laura Trespidi , D. Ware Branch , Roberto Caporali , Danieli Andrade , Robert Roubey , Michelle Petri , Maria Laura Bertolaccini

In antiphospholipid syndrome (APS), the risk of clinical manifestations increases with higher titers of antiphospholipid antibodies (aPL). Despite the adoption of aPL titers in the classification approach to aPL-positive subjects, the value of longitudinal monitoring of those titers in the follow-up is still debated, being well studied only in systemic lupus erythematosus (SLE). The literature suggests that the rate of aPL positivity decreases during follow-up in primary APS, estimating that seroconversion occurs in between 8.9 and 59% of patients over time. Negativisation of aPL occurs more frequently in asymptomatic aPL carriers than in patients with full-blown APS as well as in subjects with single aPL positivity or low aPL antibody titers. In patients with SLE, aPL typically behave fluctuating from positive to negative and back again in the course of follow-up.

The few studies assessing the longitudinal course of aPL positivity with no associated systemic connective tissue disease reported a progressive decrement of aPL titers over time, in particular of antibodies against β2 glycoprotein I (antiβ2GPI) and cardiolipin (aCL) of IgG isotype. After a thrombotic event, aPL titers tend to decrease, as emerged from cohorts of both primary and secondary APS. Hydroxychloroquine has been identified as the most effective pharmacological agent to reduce aPL titers, with multiple studies demonstrating a parallel reduction in thrombosis rate. This review addresses available evidence on the significance of aPL titer fluctuation from clinical, therapeutic and pathogenic perspectives.

在抗磷脂综合征(APS)中,临床表现的风险随着抗磷脂抗体(aPL)滴度的升高而增加。尽管在对 aPL 阳性患者进行分类时采用了 aPL 滴度,但在随访中对这些滴度进行纵向监测的价值仍存在争议,只有对系统性红斑狼疮(SLE)进行了深入研究。文献表明,在原发性 APS 的随访过程中,aPL 阳性率会下降,据估计,随着时间的推移,8.9% 到 59% 的患者会发生血清转换。在无症状的 aPL 携带者中,aPL 阴性化的发生率要高于全面性 APS 患者以及单个 aPL 阳性或 aPL 抗体滴度较低的受试者。在系统性红斑狼疮患者中,aPL在随访过程中通常表现为从阳性到阴性再到阳性的波动。少数评估无相关系统性结缔组织疾病的aPL阳性的纵向过程的研究报告称,随着时间的推移,aPL滴度逐渐下降,尤其是IgG同型的β2糖蛋白I抗体(抗β2GPI)和心磷脂抗体(aCL)。血栓事件发生后,aPL 滴度往往会下降,这一点已在原发性和继发性 APS 的研究中得到证实。羟氯喹已被确定为降低 aPL 滴度最有效的药物,多项研究也证明羟氯喹可同时降低血栓形成率。本综述从临床、治疗和致病角度探讨了有关 aPL 滴度波动重要性的现有证据。
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引用次数: 0
When should targeted therapies be used in the treatment of lupus nephritis: Early in the disease course or in refractory patients? 在治疗狼疮性肾炎时应何时使用靶向疗法?病程早期还是难治性患者?
IF 13.6 1区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.autrev.2023.103418
Ioannis Parodis , Roberto Depascale , Andrea Doria , Hans-Joachim Anders

Although the prognosis of lupus nephritis (LN) has improved over the last few decades, 5–20% of patients still progress to kidney failure. Hence, there is an unmet need to improve the management of LN. Two novel drugs, belimumab and voclosporin, have been recently approved for LN and obinutuzumab is in the late stage of development. In randomised controlled trials (RCTs), all these drugs, added to the standard-of-care, were more effective than standard-of-care alone in achieving renal response. Now the question is: should these new drugs be used early in the disease course or just in refractory patients? The main reasons supporting the early use are based on the RCTs that demonstrated benefits when combinatory regimen was initiated early in incident and relapsing patients leading to a higher proportion of patients to achieve renal response, hence reducing nephron loss and the risk of kidney failure. The main reasons supporting the use of the combinatory regimens primarily in relapsing/refractory patients acknowledge that many patients responded well even without add-on medications, allowing a more economic use of innovative and costly drugs. However, good predictors of renal response to standard-of-care are lacking and, thus, the decision of adding new treatments early or just in refractory or relapsing patients has to consider drug access, risks of over or undertreatment, and preservation of kidney function in high-risk individuals.

尽管狼疮性肾炎(LN)的预后在过去几十年里有所改善,但仍有 5-20% 的患者会发展为肾衰竭。因此,改善狼疮肾炎治疗的需求尚未得到满足。最近,贝利木单抗和voclosporin这两种新型药物已被批准用于治疗LN,而obinutuzumab正处于后期开发阶段。在随机对照试验(RCT)中,所有这些药物在加入标准疗法后,在获得肾脏反应方面都比单独使用标准疗法更有效。现在的问题是:这些新药应该在病程早期使用,还是只用于难治性患者?支持早期用药的主要理由是,有研究表明,在发病和复发患者中尽早使用联合疗法可提高获得肾脏反应的患者比例,从而减少肾小球损失和肾衰竭风险。支持主要在复发/难治患者中使用联合治疗方案的主要原因是,许多患者即使不使用附加药物也能取得良好的疗效,从而可以更经济地使用昂贵的创新药物。然而,目前还缺乏对标准疗法肾脏反应的良好预测指标,因此,在决定早期或仅在难治或复发患者中添加新疗法时,必须考虑药物的可及性、过度治疗或治疗不足的风险以及高危人群肾功能的保护。
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引用次数: 0
Start RA treatment – Biologics or JAK-inhibitors? 开始 RA 治疗--生物制剂还是 JAK 抑制剂?
IF 13.6 1区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.1016/j.autrev.2023.103429
Roberto Caporali , Sabino Germinario , Dorottya Kacsándi , Ernest Choy , Zoltán Szekanecz

Janus Kinase inhibitors (JAKi) have been approved for the treatment of Rheumatoid Arthritis (RA) for several years. They are the first oral advanced treatment with efficacy similar to, if not greater than, biologic agents. Recently, concerns over their safety was raised by the results from Oral Surveillance trial suggesting that tofacitinib, one of the JAKi, was associated with higher cardiovascular adverse events and malignancies than TNF inhibitors (TNFi). Since then, regulatory authorities have added warnings to the labels of JAKi. On this purpose, whether rheumatologists should use JAKi as first line advance treatment has become a controversial topic. Some rheumatologists have argued that biologics should be first line advance treatment since there are extensive effectiveness and safety data. In addition, with the advent of biosimilar drugs, they are the most cost-effective treatment. On the other hand, JAKi are very efficacious and are generally safe apart from older and high-risk patients. When TNFi are contraindicated and in certain RA patients ,especially when an oral drug is preferable, JAKi have significant advantage providing patients are involved in the decision-making process.

Janus 激酶抑制剂(JAKi)获准用于治疗类风湿性关节炎(RA)已有数年。它们是第一种口服高级治疗药物,疗效与生物制剂相似,甚至更强。最近,口服监测试验结果表明,与 TNF 抑制剂(TNFi)相比,JAKi 药物之一托法替尼与更高的心血管不良事件和恶性肿瘤相关,这引起了人们对其安全性的担忧。此后,监管机构在JAKi的标签上增加了警告字样。为此,风湿病学家是否应将 JAKi 作为一线先期治疗药物已成为一个有争议的话题。一些风湿病学家认为,生物制剂应作为一线先期治疗药物,因为已有大量的有效性和安全性数据。此外,随着生物类似药的出现,它们是最具成本效益的治疗方法。另一方面,JAKi疗效显著,除了老年患者和高危患者外,一般都是安全的。在TNFi禁忌症和某些RA患者中,尤其是在口服药物更可取的情况下,只要患者参与决策过程,JAKi就有明显的优势。
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Autoimmunity reviews
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