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

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.