Otten Brady, Weinberg Danielle, Gregoski Mathew J, James W Ennis
Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, SC, USA.
Internal Medicine, Medical University of South Carolina, Charleston, SC, USA.
Respir Med. 2025 Oct;247:108301. doi: 10.1016/j.rmed.2025.108301. Epub 2025 Aug 7.
Tumor necrosis factor inhibitors (TNFi) infliximab and adalimumab are commonly used third-line treatments for chronic or refractory sarcoidosis. The utility of monitoring TNFi levels and anti-drug antibody (ADA) formation in sarcoidosis is unclear. This study aimed to identify factors associated with TNFi trough levels and ADA prevalence in real-world sarcoidosis patients.
We included sarcoidosis patients treated with TNFi for ≥3 months at an academic specialty clinic who had trough drug and ADA levels assessed due to suboptimal therapeutic response. Associations between TNFi levels and dosing, patient characteristics, concomitant medications, and presence of ADAs were analyzed by univariate analysis.
90 patients (median age 51 years, 66 % female, 60 % Black) met inclusion criteria (64 infliximab, 26 adalimumab). 66 % of patients were on at least 1 additional anti-sarcoidosis medication. The most common infliximab dose was 5 mg/kg every 6 weeks and adalimumab 40 mg weekly. Mean trough levels were 14.6ug/ml and 13.1ug/ml, respectively. ADAs were more prevalent in those on adalimumab (30.8 % vs 19.0 %). ADA presence was significantly associated with low infliximab (p < 0.001) and adalimumab levels (p < 0.001). For infliximab, concurrent use of second-line medications was associated with reduced prevalence of ADAs (8 % vs 38.9 %, p = 0.013) compared to patients on no additional immunosuppression.
This is the largest reported cohort assessing TNFi drug and ADA levels in sarcoidosis to date. Prevalence of ADAs was high, particularly against adalimumab. Second-line therapy may reduce ADA formation. Monitoring TNFi drug and ADA levels may aid clinicians in managing patients with a suboptimal response to therapy.
肿瘤坏死因子抑制剂（TNFi）英夫利昔单抗和阿达木单抗是治疗慢性或难治性结节病常用的三线治疗药物。在结节病中监测TNFi水平和抗药物抗体（ADA）形成的效用尚不清楚。本研究旨在确定在真实世界的结节病患者中与TNFi谷浓度和ADA患病率相关的因素。
我们纳入了在一家学术专科诊所接受TNFi治疗≥3个月的结节病患者，这些患者因治疗反应欠佳而进行了药物谷浓度和ADA水平评估。通过单因素分析分析TNFi水平与给药剂量、患者特征、合并用药以及ADA存在情况之间的关联。
90例患者（中位年龄51岁，66%为女性，60%为黑人）符合纳入标准（64例使用英夫利昔单抗，26例使用阿达木单抗）。66%的患者至少使用了1种额外的抗结节病药物。英夫利昔单抗最常用的剂量是每6周5mg/kg，阿达木单抗是每周40mg。平均谷浓度分别为14.6μg/ml和13.1μg/ml。ADA在使用阿达木单抗的患者中更为普遍（30.8%对19.0%）。ADA的存在与英夫利昔单抗（p<0.001）和阿达木单抗水平低（p<0.001）显著相关。对于英夫利昔单抗，与未使用额外免疫抑制剂的患者相比，同时使用二线药物与ADA患病率降低相关（8%对38.9%，p=0.013）。
这是迄今为止报道的评估结节病中TNFi药物和ADA水平的最大队列。ADA的患病率很高，尤其是针对阿达木单抗。二线治疗可能会减少ADA的形成。监测TNFi药物和ADA水平可能有助于临床医生管理对治疗反应欠佳的患者。
