Gravelin Misty, Nguyen Theophilus, Davies Madeleine, Richards Blair, Sexton Jonathan Z, Gregg Kevin, Weatherwax Kevin J
Michigan Institute for Clinical and Health Research (MICHR), Michigan Medicine, University of Michigan.
College of Pharmacy, University of Michigan.
medRxiv. 2023 Oct 30:2023.10.30.23297757. doi: 10.1101/2023.10.30.23297757.
Due to its indolent nature, nontuberculous mycobacteria (NTM) are increasing in global prevalence as a cause of pulmonary infections and are difficult to treat with traditional antibiotics. Here, we study the repurposing of clofazimine (CFZ) to treat NTM through expanded access in a single health system. Our main objectives are to describe the feasibility of accessing and analyzing expanded access data and to generate hypotheses regarding CFZ use in NTM treatment.
A retrospective chart review was performed on patients within a single health system who had been approved for expanded access of clofazimine or who received it through an outside hospital for NTM treatment. Data were collected on patients' baseline demographics, details of their NTM infection, concomitant therapies, and results as of 30 June 2021.
A total of 55 patients were identified upon initial review as potentially receiving CFZ for NTM infection. After excluding 19 patients who did not initiate CFZ, data from the remaining 36 patients were collected and summarized. The median age at which patients were diagnosed with NTM was 51.3 years old, with a median BMI of 21.2 kg/m. Patients were more likely to be female (64%), have a baseline lung disease (72%), and 52% were current or former smokers at the time of their diagnosis. The most common species isolated was complex (47%) followed by (36%), with the most common site of infection being the lung (78%). The majority of patients presented with productive cough with excess sputum production followed by pulmonary nodules and bronchiectasis present on radiograph.
This study demonstrated the difficulty of collecting retrospective real-world data via electronic healthcare records on symptoms, side effects, and radiography from patients who obtained a drug through expanded access. Based on the findings of this study, we recommend further research into the potential use of CFZ in patients with pulmonary infections.
由于非结核分枝杆菌（NTM）具有惰性，其作为肺部感染的病因在全球的患病率正在上升，并且难以用传统抗生素进行治疗。在此，我们通过在单一医疗系统中扩大药物可及范围，研究氯法齐明（CFZ）重新用于治疗NTM的情况。我们的主要目标是描述获取和分析扩大可及范围数据的可行性，并就CFZ在NTM治疗中的应用提出假设。
对单一医疗系统内已获批扩大使用氯法齐明或通过外部医院接受该药治疗NTM的患者进行回顾性病历审查。收集了患者的基线人口统计学数据、NTM感染细节、伴随治疗情况以及截至2021年6月30日的结果。
初步审查共确定了55例可能接受CFZ治疗NTM感染的患者。排除19例未开始使用CFZ的患者后，收集并汇总了其余36例患者的数据。患者被诊断为NTM的中位年龄为51.3岁，中位体重指数为21.2kg/m。患者更可能为女性（64%），有基线肺部疾病（72%），52%在诊断时为现吸烟者或既往吸烟者。分离出的最常见菌种是 复合体（47%），其次是 （36%），最常见的感染部位是肺部（78%）。大多数患者表现为咳痰增多的湿性咳嗽，其次是影像学上出现肺结节和支气管扩张。
本研究表明，通过电子医疗记录收集从扩大可及范围获得药物的患者的症状、副作用和影像学检查等回顾性真实世界数据存在困难。基于本研究结果，我们建议进一步研究CFZ在 肺部感染患者中的潜在应用。
