OP0243 EFFICACY OF PIRFENIDONE IN SYSTEMIC SCLEROSIS RELATED INTERSTITIAL LUNG DISEASE – A RANDOMISED CONTROLLED TRIAL

Abstract

Background Interstitial lung disease (ILD) is a major cause of morbidity and mortality in systemic sclerosis(SSc).(1) Lung fibrosis in systemic sclerosis shares similar pathogenesis as idiopathic pulmonary fibrosis.(2) Pirfenidone slows the decline in lung functions in idiopathic pulmonary fibrosis.(3) Therefore, pirfenidone may be efficacious in SSc-ILD. Objectives To compare the efficacy and safety of pirfenidone with placebo in SSc-ILD. Methods This was a double-blind, randomised, placebo controlled trial. We enrolled 34 consecutive subjects of SSc-ILD with forced vital capacity (FVC) >50% of predicted value and diffusing capacity of lung for carbon monoxide > 30% of predicted value. Subjects were randomly assigned in a ratio of 1:1 to receive either pirfenidone (n = 17) or placebo (n = 17) and followed up for 6 months. Pirfenidone was started at 600 mg/day and increased to 2400 mg/day over one month and continued for the trial period. Primary outcome was to compare the proportion of patients with stabilisation or improvement in lung functions (FVC). Secondary outcome was to compare the change in FVC, Mahler’s dyspnea index, 6 minute walk distance (6MWD), modified Rodnan skin score (MRSS) and change in serum levels of tumour necrosis factor α (TNF-α) and tissue growth factor β (TGF-β) at the end of 6 months. Trial was registered with clinical trials registry of India (CTRI/2018/01/011449). Results By intention-to-treat analysis, 16 (94.1%) patients in treatment group showed stabilisation of lung function compared to 13 (76.5%) in control group (p = 0.335). The median change in FVC was -0.55% (IQR = -4.75% to 1.75%) and 1.0% (IQR = -8.5% to 5%) in the treatment and control groups respectively (p = 0.654). The median change in 6MWD was -15 (IQR = -42.5 – 13.75) meters and 0.0 (IQR = -50 – 30) meters in treatment and control groups respectively (p = 0.601). The median of focal scores for transitional dyspnea index in both the treatment and control groups were 3.0 (IQR = 0 – 3) (p = 0.838). Median change in MRSS was 0.0 (IQR = -2.0 – 1.0) and -1.0 (IQR = -4.0 – 0.0) in treatment and control groups (p = 0.828). Difference in TNF-α levels were -5.14 (IQR = -14.6 – 0.29) pg/ml in the treatment and -2.94 (IQR = -5.51 – -2.35) pg/ml control group (p = 0.918). Difference in TGF-β levels in the treatment and control groups were -186.73 (IQR = -731.43 – -64.6) pg/ml and 24.29 (IQR = -233.21 – 362.0) pg/ml respectively (p = 0.093). The mean tolerated dose of pirfenidone was 1700 ±644 mg/day. Adverse events were mild, most common among them were gastrointestinal followed by skin rashes. Only one serious gastrointestinal adverse effect was documented. Conclusion We failed to demonstrate a beneficial effect of pirfenidone over placebo in stabilising FVC, functional status, or skin disease after 6 months of therapy. A larger study with longer follow up period may be further required.