Efficacy and safety of pirfenidone in systemic sclerosis-related interstitial lung disease—a randomised controlled trial

• Published in: Rheumatology international Vol. 40; no. 5; pp. 703 - 710
• Main Authors: Acharya, Nupoor, Sharma, Shefali Khanna, Mishra, Debashish, Dhooria, Sahajal, Dhir, Varun, Jain, Sanjay
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2020; Springer Nature B.V
• Subjects: Adult; Clinical Trials; Double-Blind Method; Dyspnea; Female; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Lung diseases; Lung Diseases, Interstitial - drug therapy; Lung Diseases, Interstitial - etiology; Male; Medicine; Medicine & Public Health; Middle Aged; Pilot Projects; Pyridones - administration & dosage; Pyridones - adverse effects; Rheumatology; Scleroderma; Scleroderma, Systemic - complications; Treatment Outcome; Tumor necrosis factor-TNF; Vital Capacity - drug effects; Diffuse parenchymal lung disease; Connective tissue disease; Autoimmune; Scleroderma; Interstitial lung disease; Systemic sclerosis
• ISSN: 0172-8172; 1437-160X; 1437-160X
• DOI: 10.1007/s00296-020-04565-w

To assess the efficacy and safety of pirfenidone in systemic sclerosis-related interstitial lung disease (SSc-ILD). This was a double-blind, randomised, placebo-controlled, pilot study. Subjects with SSc-ILD and forced vital capacity (FVC) between 50 and 80% of the predicted (%pred) value were randomised in 1:1 ratio to receive either pirfenidone (2400 mg/day) or placebo for 6 months. Primary outcome was the proportion of subjects with either stabilisation or improvement in FVC at 6 months. Secondary outcomes were the absolute change in the %pred FVC, Mahler’s dyspnoea index, 6-min walk distance (6MWD), modified Rodnan skin score (MRSS) and serum levels of tumour necrosis factor α (TNF-α) and transforming growth factor β (TGF-β). Thirty-four subjects with median (range) age of 41 (20–63) years (91.2% women) and median (range) %pred FVC of 65 (51–78) were enrolled. Stabilisation/improvement in FVC was seen in 16 (94.1%) and 13 (76.5%) subjects in the pirfenidone and placebo groups, respectively ( p  = 0.33). The median (range) absolute change in %pred FVC was − 0.55 (− 9 to 7%) and 1.0 (− 42 to 11.5%) in the treatment and control groups, respectively ( p  = 0.51). The changes in 6MWD, dyspnoea scores, MRSS, and levels of TNF-α and TGF-β were not significantly different between groups. Common adverse events were gastrointestinal disturbances and skin rash. We failed to find a significant beneficial effect of pirfenidone over placebo in improving/stabilising FVC, exercise capacity, symptoms, or skin disease. Study is underpowered to provide conclusive evidence. Larger studies with longer follow-up periods are required.