Antifibrotic therapy may slow down FVC decline in RAILD

Pirfenidone in rheumatoid arthritis-associated interstitial lung disease failed its primary endpoint, but may benefit RAILD patients with usual interstitial pneumonia.

The safety analysis did not show unexpected issues

Rheumatoid arthritis (RA) is the most common connective tissue disease, with a prevalence of 0.75% in the USA1. In addition, interstitial lung disease (ILD) occurs in 19–63% of the patients with RA1. To target RAILD, Prof. Ivan Rosas (Baylor College of Medicine, TX, USA) and colleagues designed the phase 2 TRAIL1 study (NCT02808871), in which 123 patients with RAILD were randomised to the antifibrotic agent pirfenidone or placebo2. The primary endpoint was a decline in percent predicted FVC by 10% or more or death.

Although Prof. Rosas mentioned that the primary endpoint was not met, a positive effect of pirfenidone on the estimated annual change in FVC was reported (pirfenidone -66 mL vs placebo -146 mL; P=0.0082). When the investigators looked at estimated annual change in FVC by high resolution CT pattern, it was noted that those with UIP benefitted from pirfenidone compared with placebo (-43 mL vs -169 mL; P=0.0014), whereas those without UIP may not (-85 mL vs -68 mL; P=0.57). The safety analysis did not show unexpected issues. The serious adverse event (AE) rates were comparable for the experimental and placebo group (15% vs 13%), with nausea being more common in the intervention arm (53% vs 18%). 

Prof Rosas emphasised that although the trial was underpowered due to recruitment issues, the use of pirfenidone was associated with clinically relevant improvements of FVC decline compared with placebo. “Our study adds to the emerging evidence that patients with ILD with progressive disease may benefit from antifibrotic therapy. A phase 3 trial is needed to support the findings of the current phase 2 trial.”

  1. Salomon JJ, et al. Adv Ther. 2019;36(11):3279–3287.
  2. Salomon JJ, et al. Randomized, Double Blinded, Placebo-Controlled, Phase 2 Study of Safety, Tolerability and Efficacy of Pirfenidone in Patients with Rheumatoid Arthritis Interstitial Lung Disease I. ALERT 3, RCT 2886, ERS International Congress 2022, Barcelona, Spain, 4–6 September.