ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: L10

A Randomized, Double-Blinded, Placebo-Controlled, Phase 2 Study of Safety, Tolerability and Efficacy of Pirfenidone in Patients with Rheumatoid Arthritis Interstitial Lung Disease

joshua solomon1, Felix Woodhead2, Sonye Danoff3, Shana Haynes-Harp4, Tanvi Naik5, Cathie Spino5, Shelley Hurwitz6, Rie Maurer6, Daniel Chambers7, Martin Kolb8, Hiliary Goldberg6 and Ivan Rosas4, 1National Jewish Health, Denver, CO, 2University of Leicester, Leicester, United Kingdom, 3Johns Hopkins University, Baltimore, MD, 4Baylor College of Medicine, Houston, TX, 5University of Michigan, Ann Arbor, MI, 6Brigham and Womens Hospital, Boston, MA, 7University of Queensland, Brisbane, Australia, 8McMaster University, Hamilton, ON, Canada

Meeting: ACR Convergence 2021

Date of first publication: October 22, 2021

Keywords: , , ,

Session Information

Session Title: Late-Breaking Posters (L01 - L15)

Session Type: Poster Session D

Background/Purpose: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a prevalent and morbid condition leading to premature death in 10% of those affected. 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.  Key secondary endpoints included change in absolute and FVC% over 52 weeks.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).  This effect on decline was also seen when analyzed within participants with baseline usual interstitial pneumonia (UIP) pattern on high resolution computed tomography (HRCT) (FVC(ml)(-43 vs. -169, p=0.0014) and FVC% (-0.2 vs. -3.81, p=0.0002) (Table and Figure 2).  There was no significant difference in the rate of treatment-emergent serious adverse events.

Conclusion: 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.  This effect was more pronounced in those with a UIP pattern on baseline HRCT.

Table – Key Secondary Endpoints

Figure 1.jpeg”

Figure 1 – Change in FVC over 52 weeks

Figure 2.jpeg”

Figure 2 – Change in FVC by HRCT pattern over 52 weeks

j. solomon, None; F. Woodhead, Melius Pharma, 2, Boehringer Ingelheim, 6; S. Danoff, Genentech/Roche, 12, Subcontract of investigator initiated study, Boehringer Ingelheim, 5, Bristol Myer Squibb, 5; S. Haynes-Harp, None; T. Naik, None; C. Spino, None; S. Hurwitz, None; R. Maurer, None; D. Chambers, Roche, 5, 12, Clinical trial site; M. Kolb, Boehringer Ingelheim, 1, 2, 5, 6, Roche, 2, 5, Algernon, 1, 2, Pieris, 2, 5, Horizon, 1, United Therapeutics, 1, 5, Bellerophon, 1; H. Goldberg, genetech, Inc, 5; I. Rosas, None.

To cite this abstract in AMA style:

solomon j, Woodhead F, Danoff S, Haynes-Harp S, Naik T, Spino C, Hurwitz S, Maurer R, Chambers D, Kolb M, Goldberg H, Rosas I. 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]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/a-randomized-double-blinded-placebo-controlled-phase-2-study-of-safety-tolerability-and-efficacy-of-pirfenidone-in-patients-with-rheumatoid-arthritis-interstitial-lung-disease/. Accessed September 24, 2022.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomized-double-blinded-placebo-controlled-phase-2-study-of-safety-tolerability-and-efficacy-of-pirfenidone-in-patients-with-rheumatoid-arthritis-interstitial-lung-disease/