A RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED, PHASE 2 STUDY OF SAFETY, TOLERABILITY, AND EFFICACY OF PIRFENIDONE IN PATIENTS WITH RHEUMATOID ARTHRITIS INTERSTITIAL LUNG DISEASE

ABSTRACT

TYPE Late Breaking TOPIC Diffuse Lung Disease PURPOSE: The TRAIL1 trial was a randomized, double-blinded, placebo-controlled, phase 2 study of safety, tolerability and efficacy of pirfenidone in patients with RA-ILD. METHODS: The TRAIL1 trial recruited patients aged 18 to 85 years with established RA-ILD at 33 sites in 4 countries. The primary endpoint was the incidence of the composite of decline from baseline in percent predicted forced vital capacity (FVC%) of 10% or greater or death during the 52-week treatment period. Safety was reflected by differences between the treatment arms for the rate of adverse events, serious adverse events, acute exacerbations, hospitalizations, and all-cause mortality. RESULTS: With a randomization target of 270 participants, the study was stopped due to slow recruitment exacerbated by the COVID-19 pandemic. A total of 231 subjects provided consent and 123 were randomized. The proportions who met the primary endpoint were 11% on pirfenidone vs. 15% on placebo [OR=0.67 (0.22, 2.03), p=0.48]. Subjects on pirfenidone had a slower rate of decline in lung function as measured by estimated annual change in FVC(ml)(-66 vs. -146, p=0.0082) and FVC% (-1.02 vs. -3.21, p=0.0028) (Table and Figure 1). There was no significant difference in the rate of treatment-emergent serious adverse events. CONCLUSIONS: Although TRAIL1 was underpowered to detect a difference in the composite primary endpoint, pirfenidone was found to be safe and slowed decline of FVC over time in subjects with RA-ILD. CLINICAL IMPLICATIONS This trial shows that prifenidone is safe in patients with rheumatoid arthritis-associated interstitial lung disease and slows the decline of forced vital capacity over time. DISCLOSURE Nothing to declare. KEYWORD Interstitial lung disease