IPF drug extends benefit in post-COVID-19 lung injuries

A meta-analysis has shown the efficacy of the antifibrotic agent pirfenidone in preventing the onset and/or progression of interstitial lung abnormalities (ILAs) caused by COVID-19.

“[The effect was evident] during early- and late-stage disease,” said the researchers. “Hence, pirfenidone therapy may mitigate ILAs and preserve pulmonary function among survivors of COVID-19 pneumonia. Furthermore, pirfenidone exhibited an acceptable safety and tolerability profile.”

The eight studies (five randomized controlled trials and three cohort studies) included in the analysis comprised 637 participants (n=335 and 302 in the investigational and control groups, respectively). [Can Respir J 2026;doi:10.1155/carj/8812779]

In seven studies reporting mean chest high-resolution computed tomography (HRCT) scores pre- and post-treatment, the scores significantly dropped in the pirfenidone vs the control arm (standard mean difference [SMD], –0.86; p=0.001). The effect was consistent in the subgroup analyses (early stage: SMD, –0.46; p=0.04; late stage: SMD, –1.24; p<0.001).

Pirfenidone also outperformed control regimens in improving FEV₁ (SMD, 0.94; p<0.001), absolute changes in FEV₁ (SMD, 0.82; p=0.002), and FVC (SMD, 0.58; p=0.04). These effects were consistently observed in late-stage COVID-19 (SMD, 1.04; p<0.001, SMD, 0.93; p=0.008, and SMD, 0.50; p=0.008, respectively).

Pirfenidone treatment also led to a significant reduction in TNF-α level compared with controls (SMD, –1.13; p=0.007), and a trend toward reduced all-cause mortality (risk ratio [RR], 0.62; p=0.07).

According to the investigators, the reduction in TNF-α level underlines the experimental agent’s anti-inflammatory potential in the treatment of COVID-19. “Mitigation of hyperinflammation and fibrosis during acute-phase COVID-19 may facilitate the resolution of pneumonitis, lower the risk of developing pulmonary fibrosis, and reduce the severity of post-COVID-19 chronic lung disease.”

Compared with the control group, the experimental group had higher incidences of gastrointestinal adverse events (AEs; RR, 1.82; p=0.01) and discontinuation due to AEs (RR, 3.5; p=0.008). Nonetheless, the AEs were mild to moderate in severity and may be mitigated by dose reduction or therapy interruption.

Moreover, there were no serious or fatal AEs, thus confirming the safety and tolerability of pirfenidone in this setting, the researchers noted.

Excessive collagen deposition

Some patients with post-COVID-19 ILAs have partial or complete disease resolution, but most patients experience a chronic disease course. [Radiology 2021;299:E177-E186; Radiology 2021;301:E438-E440] These lung injuries complicating COVID-19 are attributed to viral infection and consequent hyperinflammation. [J Med Virol 2021;93:250-256]

The proinflammatory cytokine storm and fibroblast overactivity in COVID-19 may stimulate excessive collagen deposition in the interstitial spaces, leading to interstitial lung disease (ILD) and the subsequent radiographic signs of ILA. [Cells 2023;12:2238]

“Considering the global scale of the COVID-19 pandemic, the mitigation of COVID-19–induced ILD represents a significant issue for all populations,” the investigators noted.

Pirfenidone, an effective treatment for idiopathic pulmonary fibrosis (IPF), may mitigate post-COVID-19 ILAs by inhibiting collagen and extracellular matrix deposition, reducing oxidative stress, and attenuating fibrosis. [Life Sciences 2022;309:121048]

“The present study demonstrated that pirfenidone significantly reduced chest HRCT scores in patients with post-COVID-19 ILAs at both early and late disease stages, and significantly improved FEV₁ and the absolute standard of FVC, which are the key lung function parameters,” the researchers said.

Despite certain limitations, such as limited studies, heterogeneity across some studies, and the use of various therapeutic regimens in the control groups, the findings suggest that pirfenidone treatment may mitigate COVID-19–associated lung injury, potentially alleviating symptoms and improving quality of life, they continued.