Respiratory Department, Hospital Médica Sur, Mexico City, Mexico.
Centro Respiratorio de México, Mexico City, Mexico; Tobacco and COPD Research Department, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
Respir Med. 2023 Oct;217:107362. doi: 10.1016/j.rmed.2023.107362. Epub 2023 Jul 13.
One of the major concerns with post-acute sequelae of COVID-19 (PASC) is the development of pulmonary fibrosis, for which no approved pharmacological treatment exists. Therefore, the primary aim of this open-label study was to evaluate the safety and the potential clinical efficacy of a prolonged-release pirfenidone formulation (PR-PFD) in patients having PASC-pulmonary fibrosis.
Patients with PASC-pulmonary fibrosis received PR-PFD 1800 mg/day (1200 mg in the morning after breakfast and 600 mg in the evening after dinner) for three months. Blood samples were taken to confirm the pharmacokinetics of PR-PFD, and adverse events (AEs) were evaluated monthly using a short questionnaire. Symptoms, dyspnea, and pulmonary function tests (spirometry, diffusing capacity for carbon monoxide, plethysmography, and 6-min walk test [6MWT]) were evaluated at baseline, and one and three months after having started the PR-PFD treatment.
Seventy subjects with mild to moderate lung restriction were included. The most common AEs were diarrhea (23%), heartburn (23%), and headache (16%), for which no modifications in the drug study were needed. Two patients died within the first 30 days of enrolment, and three opted not to continue the study, events which were not associate with PR-PFD. Pulmonary function testing, 6MWT, dyspnea, symptoms, and CT scan significantly improved after three months of treatment with PR-PFD.
In patients with PASC pulmonary fibrosis, three months' treatment with PR-PFD was safe and showed therapeutic efficacy. Still, it remains to be seen whether the pulmonary fibrotic process remains stable, becomes progressive or will improve.
新冠病毒感染后疾病（PASC）的主要关注点之一是肺纤维化的发展，目前尚无批准的药物治疗方法。因此，本开放性研究的主要目的是评估延长释放吡非尼酮制剂（PR-PFD）在患有 PASC-肺纤维化患者中的安全性和潜在临床疗效。
患有 PASC-肺纤维化的患者接受 PR-PFD 1800mg/天（早餐后 1200mg，晚餐后 600mg）治疗三个月。采集血样以确认 PR-PFD 的药代动力学，并用简短问卷每月评估不良事件（AE）。在基线时以及开始 PR-PFD 治疗后一个月和三个月评估症状、呼吸困难和肺功能测试（肺活量测定、一氧化碳弥散量、体积描记法和 6 分钟步行试验[6MWT]）。
共纳入 70 例有轻至中度肺限制的患者。最常见的 AE 是腹泻（23%）、烧心（23%）和头痛（16%），无需修改药物研究。两名患者在入组后的前 30 天内死亡，三名患者选择不继续该研究，这些事件与 PR-PFD 无关。PR-PFD 治疗三个月后，肺功能测试、6MWT、呼吸困难、症状和 CT 扫描均显著改善。
在患有 PASC 肺纤维化的患者中，PR-PFD 治疗三个月是安全的，并显示出治疗效果。然而，肺纤维化过程是否保持稳定、进展或改善仍有待观察。
