PMID- 38056314 OWN - NLM STAT- MEDLINE DCOM- 20240112 LR - 20240206 IS - 1532-866X (Electronic) IS - 0049-0172 (Print) IS - 0049-0172 (Linking) VI - 64 DP - 2024 Feb TI - Effectiveness and tolerability of antifibrotics in rheumatoid arthritis-associated interstitial lung disease. PG - 152312 LID - S0049-0172(23)00154-3 [pii] LID - 10.1016/j.semarthrit.2023.152312 [doi] AB - OBJECTIVE: Our aim was to investigate the effectiveness and tolerability of antifibrotics in a real-world cohort of patients with rheumatoid arthritis-associated interstitial lung diseases (RA-ILD). METHODS: In this retrospective cohort study, we identified RA-ILD patients initiating antifibrotics at Mass General Brigham Integrated Health Care System, a large multi-hospital healthcare system in Boston, MA, USA. We used electronic query to identify all patients with at least 2 RA diagnosis codes and a prescription for either nintedanib or pirfenidone (2014-2023). All analyzed patients met 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for RA and had definite RA-ILD according to Bongartz criteria. Data regarding pulmonary function test (PFT) results, adverse events (AEs), tolerability, and clinical data were collected. A linear mixed model with random intercept was used to compare the within-patient trajectory of the percent predicted forced vital capacity (FVCpp) within 18-months before to 18-months after antifibrotic initiation among those with these PFT data. Lung transplant-free survival and drug retention was estimated in a Kaplan-Meier analysis and a Cox regression analysis was performed to identify independent baseline factors associated with lung transplant or mortality. RESULTS: We analyzed 74 patients with RA-ILD that initiated antifibrotics (mean age 67.8 years, 53 % male); 40 patients initiated nintedanib and 34 initiated pirfenidone. Median follow-up was 89 weeks (min 4, max 387). There was a significant improvement in the estimated slope of FVCpp after antifibrotic initiation (-0.3 % per year after initiation compared to -6.2 % per year before antifibrotic initiation, p = 0.03). Nintedanib and pirfenidone had similar FVCpp trajectory. Twenty-six patients (35 %) died and 4 (5 %) had undergone lung transplantation during follow-up. Male sex and heavy smoking were each associated with the composite outcome of lung transplant or mortality. AEs were reported in 41 (55 %) patients, with gastrointestinal (GI) AEs being most common (n = 30). The initial antifibrotic was discontinued in 34 (46 %) patients mostly due to GI AEs (n = 19). The median drug retention time was 142 weeks (95 %CI 56, 262) with no difference between nintedanib and pirfenidone (p = 0.68). CONCLUSION: In this first real-world study of antifibrotic use dedicated to RA-ILD, antifibrotic initiation was associated with a modestly improved trajectory of FVCpp. AEs were frequently reported, particularly GI, and discontinuation was common. However, lung transplant and mortality rates were still high, emphasizing the need for further therapeutic strategies in patients with severe RA-ILD. These real-world data complement previous trial data that investigated efficacy and safety. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Juge, Pierre-Antoine AU - Juge PA AD - Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. FAU - Hayashi, Keigo AU - Hayashi K AD - Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. FAU - McDermott, Gregory C AU - McDermott GC AD - Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. FAU - Vanni, Kathleen M M AU - Vanni KMM AD - Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. FAU - Kowalski, Emily AU - Kowalski E AD - Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. FAU - Qian, Grace AU - Qian G AD - Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. FAU - Bade, Katarina AU - Bade K AD - Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. FAU - Saavedra, Alene AU - Saavedra A AD - Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. FAU - Dieude, Philippe AU - Dieude P AD - Universite de Paris Cite, INSERM UMR 1152, F-75018, Paris, France; Service de Rhumatologie, Hopital Bichat-Claude Bernard, AP-HP, F-75018, Paris, France. FAU - Dellaripa, Paul F AU - Dellaripa PF AD - Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. FAU - Doyle, Tracy J AU - Doyle TJ AD - Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. FAU - Sparks, Jeffrey A AU - Sparks JA AD - Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. Electronic address: jsparks@bwh.harvard.edu. LA - eng GR - R01 AR077607/AR/NIAMS NIH HHS/United States GR - P30 AR070253/AR/NIAMS NIH HHS/United States GR - R01 AR080659/AR/NIAMS NIH HHS/United States GR - T32 AR007530/AR/NIAMS NIH HHS/United States GR - T32 AR055885/AR/NIAMS NIH HHS/United States GR - P30 AR072577/AR/NIAMS NIH HHS/United States GR - R01 HL155522/HL/NHLBI NIH HHS/United States PT - Journal Article DEP - 20231124 PL - United States TA - Semin Arthritis Rheum JT - Seminars in arthritis and rheumatism JID - 1306053 SB - IM MH - Humans MH - Male MH - Aged MH - Female MH - Retrospective Studies MH - *Lung Diseases, Interstitial/complications/drug therapy MH - *Arthritis, Rheumatoid/complications/drug therapy MH - Lung MH - *Lung Transplantation PMC - PMC10841613 MID - NIHMS1949549 OTO - NOTNLM OT - Antifibrotics OT - Interstitial lung diseases OT - Rheumatoid arthritis COIS- Declaration of Competing Interest Dr. Juge has received honoraria from Bristol Myers Squibb, Boehringer Ingelheim and AstraZeneca, and a grant from Novartis. Dr. Doyle has received support from Bayer and Bristol Myers Squibb, consulting fees from Boehringer Ingelheim and L.E.K. consulting, and has been part of a clinical trial funded by Genentech. Dr. Sparks has received research support from Bristol Myers Squibb and performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer, and ReCor unrelated to this work. Other authors report no financial disclosures. EDAT- 2023/12/07 00:42 MHDA- 2024/01/12 06:42 PMCR- 2025/02/01 CRDT- 2023/12/06 18:12 PHST- 2023/07/25 00:00 [received] PHST- 2023/10/13 00:00 [revised] PHST- 2023/11/09 00:00 [accepted] PHST- 2025/02/01 00:00 [pmc-release] PHST- 2024/01/12 06:42 [medline] PHST- 2023/12/07 00:42 [pubmed] PHST- 2023/12/06 18:12 [entrez] AID - S0049-0172(23)00154-3 [pii] AID - 10.1016/j.semarthrit.2023.152312 [doi] PST - ppublish SO - Semin Arthritis Rheum. 2024 Feb;64:152312. doi: 10.1016/j.semarthrit.2023.152312. Epub 2023 Nov 24.