TNF-α inhibitors

TNF - α 抑制剂
  • 文章类型: Editorial
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  • 文章类型: Journal Article
    类风湿性关节炎(RA)与明显的全身和局部骨丢失有关。这项研究的目的是评估15个月的肿瘤坏死因子α抑制剂(TNFαI)与甲氨蝶呤(MTX)联合治疗是否会影响女性RA患者的硬化素(SOST)循环水平。使用免疫测定试剂盒测量SOST的血浆水平。基线SOST水平在RA患者和对照参与者之间没有显着差异。绝经后RA妇女的硬化蛋白水平往往高于绝经前RA妇女。用TNFαI治疗15个月后,血浆SOST水平降低。在开始生物治疗之前,循环SOST水平与患者的年龄(P<0.05)和炎症标志物显著相关,如ESR(p<0.05)。多因素回归分析显示年龄是RA患者SOST基线水平的唯一显著预测因子(β=0.008,p=0.028,R2模型=0.293)。此外,SOST水平与基于红细胞沉降率(DAS28-ESR)的28关节疾病活动评分值之间呈正相关(P<0.05),以及经过15个月的生物治疗(p<0.05)。因此,血浆SOST水平可能有助于监测RA患者TNFαI治疗的疗效。根据我们的结果,TNFαI,结合MTX,对骨代谢标志物SOST的显著降低具有对骨转换的有益作用。
    Rheumatoid arthritis (RA) is associated with significant systemic and local bone loss. The aim of this study was to assess whether or not 15-month tumor necrosis factor α inhibitor (TNFαI) therapy in combination with methotrexate (MTX) affects circulating levels of sclerostin (SOST) in female RA patients. Plasma levels of SOST were measured using immunoassays kits. Baseline SOST levels showed no significant differences between RA patients and control participants. Postmenopausal women with RA tended to have higher sclerostin levels than premenopausal woman with RA. After 15 months of treatment with TNFαI, plasma levels of SOST were decreased. Before starting biological therapy, circulating levels of SOST significantly correlated with the patient\'s age (p < 0.05) and the marker of inflammation, such as ESR (p < 0.05). Multivariate regression analysis showed that age was the only significant predictor for baseline SOST levels in women with RA (β = 0.008, p = 0.028, R2 model = 0.293). Moreover, a positive correlation between SOST levels and the 28 joint disease activity score value based on the erythrocyte sedimentation rate (DAS28-ESR) was found at baseline (p < 0.05), as well as after 15 months of biological therapy (p < 0.05). Thus, plasma SOST levels may be helpful for monitoring the efficacy of TNFαI treatment in RA patients. According to our results, TNFαI, in combination with MTX, has a beneficial effect on bone turnover with a significant reduction in bone metabolism marker SOST.
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  • 文章类型: Journal Article
    化脓性汗腺炎(HS)是一种炎症性皮肤疾病,具有潜在的炎症过程。由于现有治疗方法的疗效有限,HS仍然是一个治疗挑战。肿瘤坏死因子-α(TNF-α)抑制剂的安全性和有效性,阿达木单抗,英夫利昔单抗,和依那西普,在这个患者群体中进行了很好的研究,在某些情况下,HS对他们没有反应。近年来,关于其他反TNF的应用的证据越来越多,包括塞托珠单抗(CPZ)和戈利木单抗。我们试图评估戈利木单抗和CPZ在HS管理中的总体安全性和有效性。在PubMed上进行了全面搜索,Scopus,WebofScience,和OvidEmbase数据库,以及谷歌学者搜索引擎从启动到2023年8月31日。共有9项和4项研究使用CPZ和戈利木单抗治疗HS,分别。伴随炎性免疫介导疾病的个体,怀孕的女性,对先前治疗无效的患者在CPZ给药后实现了化脓性汗腺炎临床反应。此外,戈利木单抗在其他治疗失败后治疗顽固性HS方面显示出希望,如阿达木单抗和抗白细胞介素-1。CPZ和戈利木单抗可以是中重度HS的有效治疗选择,尤其是对其他TNF抑制剂无反应的患者,例如阿达木单抗。
    Hidradenitis suppurativa (HS) is an inflammatory skin condition with an underlying inflammatory process. Due to the limited efficacy of available treatments, HS remains a therapeutic challenge. The safety and efficacy of tumor necrosis factor-α (TNF-α) inhibitors, adalimumab, infliximab, and etanercept, are well studied in this patient population, and in some cases, HS was unresponsive to them. In recent years, evidence has been growing regarding the application of other anti-TNFs, including certolizumab pegol (CPZ) and golimumab. We sought to evaluate the overall safety and efficacy of golimumab and CPZ in the management of HS. A comprehensive search was performed on the PubMed, Scopus, Web of Science, and Ovid Embase databases, as well as the Google Scholar search engine from initiation to 31 August 2023. A total of nine and four studies used CPZ and golimumab to treat HS, respectively. Individuals with concomitant inflammatory immune-mediated diseases, pregnant females, and patients who were refractory to previous treatments achieved a Hidradenitis Suppurativa Clinical Response following CPZ administration. Also, golimumab showed promise in treating recalcitrant HS after the failure of other treatments, such as adalimumab and anti-interleukin-1. CPZ and golimumab can be efficacious treatment options for moderate-to-severe HS, especially in patients who are unresponsive to other TNF inhibitors, such as adalimumab.
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  • 文章类型: Case Reports
    继发于荚膜组织胞浆的噬血细胞淋巴组织细胞增多症(HLH)很少见,全球影响<1%,死亡率高达31%。在这里,我们提出了一个罕见的HLH继发于H囊膜,影响一名57岁女性类风湿关节炎患者.广泛的调查没有揭示,尽管广谱抗生素,她的病情恶化了,导致呼吸衰竭,需要体外膜氧合(ECMO)支持,需要多种血管加压药的休克,和需要血液透析的急性肾损伤(AKI)。诊断证实播散性组织胞浆菌病(DHP),提示两性霉素B和甲基强的松龙治疗,导致泊沙康唑治疗的显着改善和出院。继发性HLH,主要由DHP等严重感染引起,正在讨论。在人类免疫缺陷病毒(HIV)血清阴性个体中,对这种情况的研究有限。诊断涉及HLH-2004和HScore标准。由于多器官衰竭风险和治疗复杂性,管理组织胞浆菌病相关的HLH仍然具有挑战性,需要进一步研究。
    Hemophagocytic lymphohistiocytosis (HLH) secondary to Histoplasma capsulatum is rare, impacting <1% globally, with a mortality rate of up to 31%. Herein, we present a rare case of HLH secondary to H capsulatum, affecting a 57-year-old female with rheumatoid arthritis. Extensive investigations were unrevealing and despite broad-spectrum antibiotics, her condition worsened, leading to respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support, shock requiring multiple vasopressors, and acute kidney injury (AKI) requiring hemodialysis. Diagnosis confirmed disseminated histoplasmosis (DHP), prompting Amphotericin B and methylprednisolone treatment, resulting in significant improvement and discharge with posaconazole therapy. Secondary HLH, primarily arising from severe infections like DHP, is discussed. Limited research exists on this condition in human immunodeficiency virus (HIV)-seronegative individuals. Diagnosis involves HLH-2004 and HScore criteria. Managing histoplasmosis-associated HLH remains challenging due to multiorgan failure risks and treatment complexities and needs further research.
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  • 文章类型: Journal Article
    背景:生物仿制药是生物药物,具有提高医疗支出效率和抑制药物相关成本上涨的潜力。然而,必须精心安排通过非医疗转换等举措将其引入医院处方集,以免导致治疗中断或导致卫生资源利用率提高,例如额外的访问或实验室测试,在其他人中。这项回顾性队列研究旨在评估CT-P13的引入对使用鼻祖英夫利昔单抗或CT-P13治疗的患者的医疗支出的影响。
    方法:胃肠病学,纳入了2017年9月至2020年12月在瑞士西部一所大学医院接受治疗的免疫变态反应学和风湿病患者,并分为七个队列,基于他们的治疗途径(即,使用和停用CT-P13和/或原药英夫利昔单抗)。从医院的成本核算部门获得瑞士法郎的费用,并从住院记录中提取住院时间。通过自举计算队列之间的成本和住院时间的比较。
    结果:60种免疫变态反应学,包括84例风湿病和114例胃肠病患者。住院和门诊费用平均(sd)每住院日1,611瑞士法郎(1,020),每次输液4,991瑞士法郎(6,931),分别。平均(sd)住院时间为20(28)天。尽管免疫变态反应和风湿病患者的平均费用高于消化内科患者,治疗途径并未正式解释费用和住院时间的差异.卫生资源利用的差异很小。
    结论:CT-P13的引入和患者治疗管理的中断与平均门诊和住院费用以及住院时间的差异无关。与其他文献报道的结果相反。未来的研究应集中在非医疗转换政策的成本效益和患者的潜在利益。
    BACKGROUND: Biosimilars are biologic drugs that have the potential to increase the efficiency of healthcare spending and curb drug-related cost increases. However, their introduction into hospital formularies through initiatives such as non-medical switching must be carefully orchestrated so as not to cause treatment discontinuation or result in increased health resource utilization, such as additional visits or laboratory tests, among others. This retrospective cohort study aims to assess the impact of the introduction of CT-P13 on the healthcare expenditures of patients who were treated with originator infliximab or CT-P13.
    METHODS: Gastroenterology, immunoallergology and rheumatology patients treated between September 2017 and December 2020 at a university hospital in Western Switzerland were included and divided into seven cohorts, based on their treatment pathway (i.e., use and discontinuation of CT-P13 and/or originator infliximab). Costs in Swiss francs were obtained from the hospital\'s cost accounting department and length of stay was extracted from inpatient records. Comparisons of costs and length of stay between cohorts were calculated by bootstrapping.
    RESULTS: Sixty immunoallergology, 84 rheumatology and 114 gastroenterology patients were included. Inpatient and outpatient costs averaged (sd) CHF 1,611 (1,020) per hospital day and CHF 4,991 (6,931) per infusion, respectively. The mean (sd) length of stay was 20 (28) days. Although immunoallergology and rheumatology patients had higher average costs than gastroenterology patients, differences in costs and length of stay were not formally explained by treatment pathway. Differences in health resource utilization were marginal.
    CONCLUSIONS: The introduction of CT-P13 and the disruption of patient treatment management were not associated with differences in average outpatient and inpatient costs and length of stay, in contrast to the results reported in the rest of the literature. Future research should focus on the cost-effectiveness of non-medical switching policies and the potential benefits for patients.
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  • 文章类型: Systematic Review
    背景:越来越多的随机对照试验(RCT)证明了肿瘤坏死因子-α(TNF-α)抑制剂在治疗非影像学轴性脊柱关节炎(nr-axSpA)中的有效性。本研究旨在评价TNF-α抑制剂治疗nr-axSpA的疗效。
    方法:PubMed,EMBASE,WebofScience,和Cochrane图书馆数据库在2023年6月之前使用特定关键词系统地搜索相关RCT。主要结果是在国际脊柱关节炎协会(ASAS40)中获得评估的患者比例为40%。次要结局包括ASAS20,巴斯强直性脊柱炎疾病活动指数50%(BASDAI50),ASAS部分缓解,ASAS5/6。
    结果:共纳入8个RCT,涉及1,376例患者。接受抗TNF治疗的患者表现出更高的ASAS40发生率(合并RR=2.36;95%CI:1.63-3.42;p<0.001)。此外,TNF-α抑制剂组显示出更高的BASDAI50率(合并RR=2.06;95%CI:1.48-2.89),ASAS20率(合并RR=1.48;95%CI:1.31-1.67),ASAS部分缓解率(合并RR=2.33;95%CI:1.58-3.43),和ASAS5/6率(RR=3.46;95%CI:2.05-5.83)高于安慰剂组。
    结论:TNF-α抑制剂治疗nr-axSpA有效。
    BACKGROUND: A growing number of randomized controlled trials (RCTs) have demonstrated the effectiveness of tumor necrosis factor-α (TNF-α) inhibitors in treating non-radiographic axial spondyloarthritis (nr-axSpA). This study aimed to evaluate the efficacy of TNF-α inhibitors in the treatment of nr-axSpA.
    METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were systematically searched for relevant RCTs using specific keywords up to June 2023. The primary outcome was the proportion of patients who achieved Assessment in SpondyloArthritis international Society 40% (ASAS40). Secondary outcomes included ASAS20, Bath Ankylosing Spondylitis Disease Activity Index 50% (BASDAI50), ASAS partial remission, and ASAS5/6.
    RESULTS: A total of eight RCTs involving 1,376 patients were included. Patients receiving anti-TNF therapy exhibited a higher rate of ASAS40 (pooled RR = 2.36; 95% CI: 1.63-3.42; p < 0.001). In addition, the TNF-α inhibitor group showed higher BASDAI50 rates (pooled RR = 2.06; 95% CI: 1.48-2.89), ASAS20 rates (pooled RR = 1.48; 95% CI: 1.31-1.67), ASAS partial remission rates (pooled RR = 2.33; 95% CI: 1.58-3.43), and ASAS5/6 rates (RR = 3.46; 95% CI: 2.05-5.83) than the placebo group.
    CONCLUSIONS: The TNF-α inhibitors were effective in treating nr-axSpA.
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  • 文章类型: Journal Article
    眼睑炎是一种影响眼睑边缘的常见慢性炎症性疾病;眼睑炎的病理生理学很复杂,尚未完全了解。该疾病在解剖学上分为前(睫毛炎症)和后(睑板腺功能障碍)类型。诊断依赖于临床检查,揭示了像皮屑这样的特征,血管变化,睑板腺功能障碍.眼睑炎治疗的主要目标是缓解症状,预防复发,和并发症风险最小化。治疗选择包括盖子卫生,局部和全身抗生素,外用皮质类固醇,和omega-3补充剂。然而,重要的是要强调报告的眼睑炎病例是系统治疗的副作用,特别是在化疗的背景下,硼替佐米,西妥昔单抗,TNFα抑制剂,还有dupilumab.至关重要的是,定期和认真地监测接受此类治疗的患者,以便及时建立适当的支持治疗。更重要的是未来对导致这些眼部副作用发生的病理生理机制的研究,以便找到解决该问题的方法。
    Blepharitis is a common chronic inflammatory condition affecting the eyelid margins; the pathophysiology of blepharitis is complex and not fully understood. The disease is anatomically divided into anterior (inflammation of eyelashes) and posterior (meibomian gland dysfunction) types. Diagnosis relies on clinical examination, revealing characteristic features like scurf, vascular changes, and meibomian gland dysfunction. The main goals of blepharitis treatment are symptom relief, recurrence prevention, and complication risk minimization. Treatment options include lid hygiene, topical and systemic antibiotics, topical corticosteroids, and omega-3 supplements. However, it is important to highlight reported cases of blepharitis as side effects of systemic therapies, particularly in the context of chemotherapy, bortezomib, cetuximab, TNFα inhibitors, and dupilumab. It is crucial to monitor patients undergoing such treatments regularly and attentively in order to promptly set up adequate supportive therapy. Of even more importance is future research on the pathophysiological mechanisms responsible for the occurrence of these ocular side effects in order to find a nosological cure for the issue.
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  • 文章类型: Journal Article
    银屑病发病机制涉及TNF-α,IL-23和IL17,生物制剂对其非常有效。在五种可用于银屑病的TNF-α抑制剂中,即英夫利昔单抗,阿达木单抗,依那西普,戈利木单抗和塞妥珠单抗(CZP),CZP由于其结构而具有独特的作用机制。由于CZP缺乏Fc区,它不会穿过胎盘,可以安全地用于孕妇。它的聚乙二醇化性质允许在组织中更长的分布时间,与其他TNF-α抑制剂相比,可能导致更持久的作用。在临床试验中,CZP对银屑病皮肤症状和关节症状的疗效与其他TNF-α抑制剂相当,在安全性方面没有明显的差异。
    牛皮癣是一种影响皮肤并导致关节问题的皮肤病。有一些叫做TNF-α抑制剂的药物效果很好,尤其是联合问题。目前有五种TNF-α抑制剂可用于治疗牛皮癣。其中一个,赛托珠单抗pegol,与其他人不同。它缺少一个特定的部分,这使得它不太可能通过胎盘。这意味着它对孕妇和哺乳期妇女更安全。临床试验表明,塞托珠单抗pegol与其他TNF-α抑制剂一样有效治疗牛皮癣的皮肤和关节症状。它也同样安全。
    Psoriasis pathogenesis involves TNF-α, IL-23 and IL17, against which biologics have been highly effective. Among the five TNF-α inhibitors available for psoriasis, namely infliximab, adalimumab, etanercept, golimumab and certolizumab pegol (CZP), CZP has a unique mechanism of action due to its structure. As CZP lacks the Fc region, it does not cross the placenta and can be safely used in pregnant women. Its PEGylated nature allows for longer distribution time in tissues, potentially leading to a longer-lasting effect compared with other TNF-α inhibitors. In clinical trials, the efficacy of CZP on psoriasis skin symptoms and joint symptoms was comparable to other TNF-α inhibitors, with no discernible differences in safety profiles.
    Psoriasis is a skin condition that affects the skin and causes joint problems. There are some medicines called TNF-α inhibitors that work well, especially for the joint issues. There are currently five TNF-α inhibitors available for treating psoriasis. One of these, certolizumab pegol, is different from the others. It lacks a specific part, which makes it less likely to pass through the placenta. This means it\'s safer for pregnant and breastfeeding women. Clinical trials have shown that certolizumab pegol is just as effective as other TNF-α inhibitors for treating the skin and joint symptoms of psoriasis. It\'s also equally safe.
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  • 文章类型: Journal Article
    在怀孕期间,过多的因素导致母体免疫力的变化。葡萄膜炎发作在妊娠早期和治疗不足的患者中更为频繁。怀孕期间非感染性葡萄膜炎的管理仍未得到充分研究。由多学科的眼科医生小组进行了书目审查,以巩固现有证据,妇科医生和风湿病学家。我们小组建议使用最低剂量的皮质类固醇进行初始管理,最好是在当地,治疗眼内炎症,同时确保良好的新生儿结局。如果无效,临床医生应考虑添加环孢菌素,硫唑嘌呤或塞托珠单抗,在怀孕期间似乎是安全的。其他疗法(如甲氨蝶呤,霉酚酸酯和烷化剂)是致畸的或对胎儿有不利影响。此外,建议进行仔细的多学科前概念讨论和密切跟进,监测突然发作并积极减少药物剂量,主要终点集中在保护眼组织免受炎症,同时给予最小的不良妊娠和胎儿结局的风险。
    In pregnancy, a plethora of factors causes changes in maternal immunity. Uveitis flare-ups are more frequent in the first trimester and in undertreated patients. Management of non-infectious uveitis during pregnancy remains understudied. A bibliographic review to consolidate existing evidence was performed by a multidisciplinary group of Ophthalmologists, Gynaecologists and Rheumatologists. Our group recommends initial management with minimum-required doses of corticosteroids, preferably locally, to treat intraocular inflammation whilst ensuring good neonatal outcomes. If ineffective, clinicians should consider addition of Cyclosporine, Azathioprine or Certolizumab pegol, which are seemingly safe in pregnancy. Other therapies (such as Methotrexate, Mycophenolate Mofetil and alkylating agents) are teratogenic or have a detrimental effect on the foetus. Furthermore, careful multidisciplinary preconception discussions and close follow-up are recommended, monitoring for flare-ups and actively tapering medication doses, with a primary endpoint focused on protecting ocular tissues from inflammation, whilst giving minimal risk of poor pregnancy and foetal outcomes.
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  • 文章类型: Journal Article
    组织胞浆菌病是使用肿瘤坏死因子(TNF)-α抑制剂治疗的患者中第二常见的肉芽肿疾病,仅次于肺结核。然而,关于开始免疫生物学治疗的患者的治疗前筛查程序和预防性治疗需求的信息有限.
    这是一项队列研究,通过检测尿液样本中的组织胞浆菌抗原,在开始使用TNF-α抑制剂之前,评估无症状HIV阴性患者的组织胞浆菌病患病率。在生物制剂开始后,患者完成了180天的随访,以评估提示组织胞浆菌病的症状发作。
    从2021年1月到2022年12月,在巴西南部的中心接受了治疗自身免疫性疾病的TNF-α抑制剂的54名患者。在治疗前的筛查中,尿组织胞浆抗原检测阳性的患病率为14.8%.免疫生物学治疗6个月后,54例患者均未出现组织胞浆菌病,包括8名检测呈阳性的病人.
    慢性患者的荚膜组织支原体感染的患病率可能高于预期,但潜伏感染对无症状患者的影响仍不确定,包括用免疫生物学药物如TNF-α抑制剂开始治疗的那些。我们的研究没有确定该组中播散性组织胞浆菌病诊断的危险因素,包括免疫生物学治疗前进行的抗原测试的阳性结果。迄今为止,在开始使用TNF-α抑制剂之前,没有证据推荐组织胞浆菌病的常规抗原筛查或预防性治疗.
    使用尿液检测真菌感染来筛查即将开始服用免疫生物学药物的无症状人群。这项研究观察了组织胞浆菌病的患病率,真菌感染,在即将开始使用TNF-α抑制剂治疗的无症状患者中,这是用于自身免疫性疾病的药物。研究人员在患者开始治疗之前对尿液样本进行了组织胞浆抗原检测,并在开始用药后随访180天,看看他们是否出现了组织胞浆菌病的症状。该研究包括巴西南部的54名患者,他们发现14.8%的患者在开始治疗前组织胞浆抗原检测呈阳性。然而,没有病人,包括那些测试呈阳性的人,在6个月的随访期间发生了组织胞浆菌病。研究人员得出结论,组织胞浆菌病感染在这些患者中可能比以前认为的更常见,但目前尚不清楚抗原检测阳性的无症状患者在开始TNF-α抑制剂治疗时是否会出现感染。该研究没有发现该组患者发生组织胞浆菌病的任何具体危险因素,根据他们的发现,他们不建议在开始TNF-α抑制剂治疗前对组织胞浆菌病进行常规筛查或预防性治疗.
    UNASSIGNED: Histoplasmosis is the second most frequent granulomatous disease in patients treated with tumor necrosis factor (TNF)-α inhibitors, second only to tuberculosis. However, there is limited information about pre-therapy screening procedures and the need for preventive treatments for patients who will start immunobiologicals.
    UNASSIGNED: This is a cohort study that evaluated the prevalence of histoplasmosis in asymptomatic HIV-negative patients before initiation of TNF-α inhibitors by testing for Histoplasma antigen in urine samples. The patients included completed a 180-day follow-up after the initiation of the biologics to assess the onset of symptoms suggestive of histoplasmosis.
    UNASSIGNED: From January 2021 to December 2022, 54 patients who were prescribed a TNF-α inhibitor agent for treating autoimmune diseases in centers in southern Brazil were included. In the screening before therapy, the prevalence of a positive urinary Histoplasma antigen test was 14.8%. None of the 54 patients developed histoplasmosis after 6 months of immunobiological therapy, including the eight patients who tested positive.
    UNASSIGNED: The prevalence of Histoplasma capsulatum infection in chronic patients may be higher than expected, but the impact of latent infection in asymptomatic patients is still uncertain, including those starting treatment with immunobiological drugs such as TNF-α inhibitors. Our study did not identify risk factors for the diagnosis of disseminated histoplasmosis in this group, including a positive result in an antigen test performed before immunobiological therapy. To date, there is no evidence to recommend routine antigen-based screening or preventive therapy for histoplasmosis before initiating a TNF-α inhibitor.
    Using a urine test for fungal infection to screen people without symptoms who are about to start taking immunobiologic medications This study looked at the prevalence of histoplasmosis, a fungal infection, in asymptomatic patients who were about to start treatment with TNF-α inhibitors, which are medications used for autoimmune diseases. The researchers tested urine samples for Histoplasma antigen before the patients started the treatment and followed them for 180 days after starting the medication to see if they developed any symptoms of histoplasmosis. The study included 54 patients in southern Brazil, and they found that 14.8% of the patients tested positive for the Histoplasma antigen before starting the treatment. However, none of the patients, including those who tested positive, developed histoplasmosis during the 6-month follow-up. The researchers concluded that histoplasmosis infection may be more common in these patients than previously thought, but it’s still not clear if asymptomatic patients with a positive antigen test will develop the infection when starting TNF-α inhibitor treatment. The study did not find any specific risk factors for developing histoplasmosis in this group of patients, and based on their findings, they did not recommend routine screening or preventive therapy for histoplasmosis before starting TNF-α inhibitor treatment.
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