A recent clinical trial published in Alternative Therapies in Health and Medicines has highlighted the potential benefits of pirfenidone for treating nonspecific interstitial pneumonia (NSIP) in patients with primary Sjögren’s syndrome (pSS).
The trial involved 120 patients with primary Sjögren’s syndrome (pSS)-associated nonspecific interstitial pneumonia (NSIP), divided equally into two groups. The control group received hydroxychloroquine and prednisone, while the observation group also received pirfenidone. Baseline lung function was similar in both groups, but post-treatment results showed significant improvements in pulmonary function for both. The pirfenidone group demonstrated a notably greater increase in forced vital capacity percentage (FVC%) and diffusing capacity of the lung for carbon monoxide (DLCO%). High-resolution computed tomography (HRCT) scans revealed reduced lung fibrosis in both groups, with the pirfenidone group showing a more significant reduction in Warrick scores. Patient-reported outcomes from the Leicester Cough Questionnaire (LCQ) showed greater improvements in cough-related quality of life in the pirfenidone group. While both groups experienced significant post-treatment gains, the pirfenidone group consistently scored higher, highlighting its impact on symptom relief. However, concerns regarding pirfenidone’s safety arose, as there was a slightly higher incidence of mild adverse events, including neurosensory issues and drowsiness, requiring careful risk-benefit assessment.
Pirfenidone is a synthetic non-peptide compound that inhibits the production of several key factors involved in fibrosis, including transforming growth factor-beta 1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), platelet-derived growth factor (PDGF), interleukin 1 beta (IL-1β), and collagen 1 (COL1A1). These factors contribute to preventing or reducing excessive scar tissue formation in various organs. Pirfenidone has been shown to decrease apoptosis, downregulate angiotensin-converting enzyme (ACE) receptor expression, reduce inflammation through multiple pathways, and alleviate oxidative stress in pneumocytes and other cells. As an anti-fibrotic drug, pirfenidone targets multiple fibrogenic pathways to reduce fibrosis in idiopathic pulmonary fibrosis (IPF), suppressing growth factor production, inhibiting fibroblast proliferation, and preventing TGF-β-mediated differentiation of fibroblasts into myofibroblasts.
A retrospective cohort study examined the effectiveness of pirfenidone in patients with interstitial pneumonia with autoimmune features (IPAF). The study compared 81 patients treated with pirfenidone to 103 who did not receive the drug. At baseline, the pirfenidone group had lower FVC% and DLCO%, but after treatment, they showed significant improvements in FVC% at 6, 12, and 24 months. Even after adjusting for variables such as age, sex, and usual interstitial pneumonia pattern, pirfenidone-treated patients maintained superior FVC% gains. Higher doses (>600 mg/day) and longer treatment courses (>12 months) were associated with better outcomes. Additionally, the pirfenidone group required lower prednisone doses after 12 months. Though some side effects were reported, including one case of anaphylactic shock, pirfenidone demonstrated an overall favorable safety profile.
This study suggests that adding pirfenidone to standard therapy improves pulmonary function, reduces fibrosis on HRCT, and enhances the quality of life in pSS-associated NSIP. Future research should assess its efficacy in more severe cases and across other ILD subtypes. For rheumatologists, pirfenidone may be a valuable option for mild to moderate NSIP in Sjögren’s syndrome, though close monitoring of side effects is advised.
References
- Wei W, Zou W, Han W, Liu J. Clinical Observational Study on the Therapeutic Efficacy of Pirfenidone in Sjögren’s Syndrome Complicated with Nonspecific Interstitial Pneumonia. Altern Ther Health Med. 2024 Sep;30(9):307-311.
- Aimo A, Spitaleri G, Nieri D, Tavanti LM, Meschi C, Panichella G, Lupón J, Pistelli F, Carrozzi L, Bayes-Genis A, Emdin M. Pirfenidone for Idiopathic Pulmonary Fibrosis and Beyond. Card Fail Rev. 2022 Apr 14;8:e12.
- Antar SA, Saleh MA, Al-Karmalawy AA. Investigating the possible mechanisms of pirfenidone to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and/or anti-SARS-CoV-2. Life Sci. 2022 Nov 15;309:121048.
- Shah PV, Balani P, Lopez AR, Nobleza CMN, Siddiqui M, Khan S. A Review of Pirfenidone as an Anti-Fibrotic in Idiopathic Pulmonary Fibrosis and Its Probable Role in Other Diseases. Cureus. 2021 Jan 4;13(1):e12482.
- Chen T, Li QH, Zhang Y, Yin CS, Weng D, Zhou Y, Hu Y, Shi JY, Chen YN, Ye S, Wang XD, Wu CY, Huang Y, Zhang AH, Li HP. The role of pirfenidone in the treatment of interstitial pneumonia with autoimmune features. Clin Exp Rheumatol. 2022 Mar;40(3):560-567.