1319: Real World Data on Antifibrotics in Rheumatoid Arthritis-Interstitial Lung Disease. National Multicenter Study of 73 Patients

Belén Atienza-Mateo¹, Ana Serrano-Combarro², Maria Martin-Lopez³, Santos Castañeda⁴, Rafael Benito Melero-Gonzalez⁵, Jesus Loarce-Martos⁶, Natalia Mena Vazquez⁷, Carmen carrasco-Cubero⁸, Carolina Diez-Morrondo⁹, David Castro-Corredor¹⁰, Tomás Vazquez-Rodriguez¹¹, andrea Garcia-Valle¹², Gema Bonilla¹³, Marina Rodriguez-lopez¹⁴, Ignacio Brana Abascal¹⁵, SARA MARIA ROJAS HERRERA¹⁶, Juan Camilo Sarmiento-Monroy¹⁷, Pablo Andujar-Brazal¹⁸, Juan Ramon De Dios¹⁹, Carmen Gonzalez-Montagut Gomez²⁰, Sergio Ordonez-Palau²¹, Anahy Maria Brandy-Garcia²², Fernando Lozano²³, Maria Lopez-Lasanta²⁴, Cristina Campos Fernández²⁵, Marta Garijo Bufort²⁶, Ivette Casafont-Sole²⁷, Calderon Goercke²⁸, Carlota Laura Iñiguez²⁹, Francisco Ortiz-Sanjuán³⁰, Emilio Giner-Serret³¹, Bryan Josue Flores Robles³², Mireia Moreno³³, Evelin Cecilia Cervantes-Perez³⁴, Diego Ferrer³⁵, Ricardo Blanco³⁶ and On behalf of the Collaborative Group Members³⁷, ¹Rheumatology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain, ²Division of Rheumatology, Hospital Universitario Marqués de Valdecilla. IDIVAL, Immunopathology group, Santander, Spain, ³Hospital 12 de Octubre, Madrid, Spain, ⁴Hospital Universitario de la Princesa, Madrid, Spain, ⁵CHU Vigo, O Carballino, Spain, ⁶Ramón y Cajal University Hospital, Madrid, Spain, ⁷IBIMA, Málaga, Spain, ⁸Department of Rheumatology, Hospital Universitario de Badajoz, Badajoz, Spain, ⁹Division of Rheumatology, Hospital de León, León, Spain, ¹⁰General University Hospital of Ciudad Real, Santa Cruz de Mudela (Ciudad Real), Spain, ¹¹Rheumatology, Complejo Hospitalario Universitario de Ferrol, A Coruña, Spain, ¹²Division of Rheumatology, Complejo Asistencial Universitario de Palencia, Palencia, Spain, ¹³Department of Rheumatology, Hospital Clínico Universitario La Paz, Madrid, Spain, ¹⁴Division of Rheumatology, Hospital Clínico Universitario de Santiago, La Coruna, Spain, ¹⁵Division of Rheumatology, Hospital Universitario Central de Asturias, Oviedo, Spain, ¹⁶Division of Rheumatology, Hospital de Mérida, Mérida, Spain, ¹⁷Hospital Clínic, Barcelona, Spain, ¹⁸Division of Rheumatology, Hospital Universitario Doctor Peset, Valencia, Spain, ¹⁹Hospital Universitario Araba, Vitoria, Spain, ²⁰H. Clínico Universitario de Valladolid, Valladolid, Spain, ²¹H. Arnau de Vilanova, Lleida, Spain, ²²Hospital Germans Trias i Pujol, Badalona, Spain, ²³Hospital Universitario 12 de Octubre, Madrid, Spain, ²⁴Hospital Universitari Vall d'Hebron, Rheumatology, Barcelona, Spain, ²⁵Hospital General Universitario Valencia, Valencia, Spain, ²⁶H. de Sagunto, Valencia, Italy, ²⁷Hospital Universitari Germans Trias i Pujol, Badalona, Spain, ²⁸Hospital Universitario Marqués de Valdecilla, Santander, Spain, ²⁹Hospital Universitario Lucus Augusti, Lugo, Spain, ³⁰Hospital Universitario y Politécnico La Fe, Valencia, Spain, ³¹Hospital Royo Villanova, Teruel, Spain, ³²Hospital Universitario San Pedro, Logroño, Spain, ³³Parc Tauli Hospital Universitari, I3PT(UAB), Barcelona, Spain, ³⁴Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain, ³⁵Division of Pneumology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain, ³⁶Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain, ³⁷Spanish Collaborative Group of Interstitial Lung Disease Associated with Rheumatoid Arthritis, Spain, Spain

Background/Purpose: Interstitial lung disease (ILD) is a critical complication of rheumatoid arthritis (RA). Abatacept and rituximab are the preferred disease-modifying antirheumatic drugs (DMARDs) for RA-ILD. However, progression of ILD despite its use is not uncommon. A subgroup analysis of the INBUILD trial has shown a slower decline in forced vital capacity (FVC) in patients with progressive fibrosing autoimmune disease-related ILD with nintedanib (NINTE) [Arthritis Rheumatol 2022;74(6):1039-47]. However, data on antifibrotics use for RA-ILD in clinical practice (CP) are scarce. Our aim was: a) To assess the efficacy of antifibrotic drugs, NINTE and pirfenidone (PIRFE), in Spanish RA-ILD patients with a progressive phenotype in CP; b) To compare the profile of CP RA-ILD patients with those included in the INBUILD trial.

Methods: National multicenter study of RA-ILD patients to whom NINTE or PIRFE were added due to progressive fibrosing ILD. Demographic and clinical variables were collected from all patients. These features were compared with those of RA-ILD patients included in the INBUILD trial (n=89, 42 NINTE and 47 placebo). Forced vital capacity (FVC) evolution was the primary endpoint. Results are expressed as percentage, mean±SD or median [IQR].

Results: A total of 73 patients (24 women/49 men) from CP were collected, mean age of 69±9 years. The median [IQR] ILD duration up to antifibrotic initiation was of 56.5 [21.5-83] months. NINTE was the most widely used antifibrotic (n=66), combined with immunosuppressive treatment in all cases: corticosteroids in 44, cDMARD in 20 (mycophenolate mofetil=8, leflunomide=6, methotrexate=3, hydroxychloroquine=2, azathioprine=1), bDMARD in 43 (abatacept=31, rituximab=10, anti-IL6R=2) and/or JAKi in 4 (baricitinib=2, tofacitinib=1, filgotinib=1). Mean FVC one year before NINTE start was 80±21 (% pred.), whilst mean baseline FVC was 71±23 (% pred.). Table 1 shows the comparison of baseline characteristics of RA-ILD patients treated with NINTE in CP and in the INBUILD trial. The evolution of FVC and diffusing capacity of the lungs for carbon monoxide (DLCO) in our patients with NINTE from the previous year of antifibrotic initiation is shown in Figure 1. After a median follow-up of 15.5 [3.5-23.5] months, no significant decline in mean FVC or DLCO values was observed. In addition, 86% of the patients presented stabilization or improvement of dyspnea. NINTE was withdrawn in 14 patients due to: gastrointestinal adverse events (11), death (1), hemorrhage risk (1), and stabilization (1). PIRFE was administered to 7 patients (4 men), combined with abatacept in 3 patients, leflunomide in 1, and methotrexate in 1. Mean baseline FVC and DLCO were 69±22 and 49±14 (% pred.), respectively. As with NINTE, a stability in the evolution of lung function was observed. PIRFE was withdrawn in 4 patients due to: gastrointestinal adverse events (2), inefficacy (1), and stabilization (1).

Conclusion: Antifibrotics, especially NINTE, seem to slow ILD progression in patients with RA-ILD. In CP, our patients are treated belatedly in the evolution of the disease, but results are satisfactory. Combination of antifibrotics and DMARDs is feasible and safe.






B. Atienza-Mateo: None; A. Serrano-Combarro: None; M. Martin-Lopez: None; S. Castañeda: None; R. Melero-Gonzalez: None; J. Loarce-Martos: Boehringer-Ingelheim, 6, Bristol-Myers Squibb(BMS), 6, Galapagos, 6; N. Mena Vazquez: None; C. carrasco-Cubero: None; C. Diez-Morrondo: None; D. Castro-Corredor: None; T. Vazquez-Rodriguez: None; a. Garcia-Valle: None; G. Bonilla: None; M. Rodriguez-lopez: None; I. Brana Abascal: None; S. ROJAS HERRERA: None; J. Sarmiento-Monroy: None; P. Andujar-Brazal: None; J. De Dios: None; C. Gonzalez-Montagut Gomez: None; S. Ordonez-Palau: None; A. Brandy-Garcia: None; F. Lozano: None; M. Lopez-Lasanta: None; C. Campos Fernández: None; M. Garijo Bufort: None; I. Casafont-Sole: None; C. Goercke: None; C. Iñiguez: None; F. Ortiz-Sanjuán: Eli Lilly, 6, Grunenthal, 2, GSK, 2; E. Giner-Serret: None; B. Flores Robles: None; M. Moreno: None; E. Cervantes-Perez: None; D. Ferrer: None; R. Blanco: AbbVie, 5, 6, Amgen, 6, AstraZeneca, 2, BMS, 6, Eli Lilly, 6, Galapagos, 2, 6, Janssen, 2, 6, MSD, 6, Novartis, 2, 6, Pfizer, 2, 6, Roche, 5, 6, Sanofi, 6; O. Collaborative Group Members: None.