Antifibrotic therapy may slow down FVC decline in RAILD 

The TRAIL1 study examining pirfenidone in patients with rheumatoid arthritis-associated interstitial lung disease (RAILD) did not meet its primary endpoint. Nonetheless, a trend was observed towards a beneficial effect for the agent under investigation, especially for patients with RAILD who displayed a pattern of usual interstitial pneumonia (UIP) on CT imaging.

Rheumatoid arthritis (RA) is the most common connective tissue disease, with a prevalence of 0.75% in the USA [1]. In addition, interstitial lung disease (ILD) can occur in up to 60% of the patients with RA [1]. To target RAILD, Prof. Ivan Rosas (Baylor College of Medicine, TX, USA) and colleagues designed the phase 2 TRAIL1 study (NCT02808871), which randomised 123 patients with RAILD to the antifibrotic agent pirfenidone or placebo [2]. The primary endpoint was a decline in percent predicted forced vital capacity (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; see Figure). 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 rates were comparable for the experimental and placebo group (15% vs 13%), with nausea being more common in the intervention arm (53% vs 18%).

Figure: Estimated change in FVC for pirfenidone versus placebo [2]



FVC, forced vital capacity; SD, standard deviation.

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  ALERT 3, RCT 2886, ERS International Congress 2022, Barcelona, Spain, 4–6 September.

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Posted on 30 October, 202229 February, 2024