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BackgroundInterstitial lung disease (ILD) is a common condition in patients with connective tissue disease (CTD). It is associated with increased morbidity and mortality. Rituximab (RTX) has been approved for treatment of RA and some recent retrospective studies suggest that it could be an alternative treatment for patients with CTD-ILD, even in cases that prove refractory to conventional immunosuppressants.ObjectivesTo analyze the efficacy and safety of RTX in connective tissue disease associated with interstitial lung disease (CTD-ILD).MethodsWe performed a multicenter, prospective, observational study of patients with CTD-ILD receiving RTX between 2015 and 2020. Patients who had worsening of respiratory symptoms or decline in the pulmonary function tests (PFT) compared to the time of ILD diagnosis were treated with rituximab. The patients were assessed using high-resolution computed tomography and PFT baseline, at 12 months, and at the end of follow-up. The main outcome measure at the end of follow-up was forced vital capacity (FVC)>10% or diffusing capacity of the lungs for carbon monoxide (DLCO)>15% and radiological progression or death. We recorded clinical characteristics, time to initiation of RTX, concomitant treatment, infections, and hospitalization. A Cox regression analysis was performed to identify factors associated with worsening of ILD.ResultsWe included 37 patients with CTD-ILD treated with RTX for a median (IQR) of 38.2 (17.7-69.0) months (Table 1). At the end of the follow-up, disease had improved or stabilized in 23 patients (62.1%) and worsened in 7 (18.9%); 7 patients (18.9%) died. Mean PFT values decreased significantly at the start of RTX compared to the date of ILD diagnosis in FVC (72.2[21.3]vs 73.5 [16.9] mg/l;p=0.040) and DLCO-SB (55.9 [15.7] vs 58.3 [16.1] mg/l; p=0.041). No significant decline was observed in median FVC (72.2 vs 70.8; p=0.530) or DLCO (55.9 vs 52.2; p=0.100). The multivariate analysis showed the independent predictors for worsening of CTD-ILD to be baseline DLCO (OR [95% CI], 0.904 [0.8-0.9]; p=0.015), time to initiation of RTX (1.01 [1.001-1.02]; p=0.029), and mycophenolate (0.202 [0.04-0.8]; p=0.034). The infection incidence rate was 0.21 patient-years.Table 1.Baseline demographic and clinical characteristics of 37 patients with CTD-ILD receiving rituximab.VariableTotal n=37RAn=19SSn=14IMn=4p ValueFemale sex, n (%)27 (73.0)13 (68.4)11 (78.6)3 (75.0)0.806Age in years, mean (SD)62.8 (9.9)67.7 (9.7)57.9 (7.9)56.6 (5.5)0.001Smoking0.147Never smoked, n (%)20 (54.1)9 (47.4)7 (50.0)4 (100.0)Smoked at some time, n (%)17 (45.9)10 (52.6)7 (50.0)0 (0.0)Duration of CTD, months, median (IQR)107.8 (49.5-188.8)151.0 (8.,0-240.5)89.6 (51.3-184.4)35.1 (25.1-49.0)0.017Duration of ILD, months, median (IQR)65.4 (31.1-110.3)82.2 (37.4-120.1)64.5 (35.5-107.1)25.9 (25.0-36.0)0.136Time to initiation of RTX, median (IRQ)12.0 (6.5-48.2)25.1 (7.0-57.6)11.4 (3.9-43.6)7.4 (7.0-10.4)0.455Duration of treatment with RTX, median (IQR)38.2 (23.4-69.9)45.3 (22.2-79.9)52.5 (24.7-63.3)22.8 (17.7-36.2)0.291Combined with csDMARDs, n (%)15 (40.5)9 (47.4)5 (35.7)1 (25.0)0.637Methotrexate, n (%)5 (13.5)2 (10.5)3 (21.4)0 (0.0)0.468Leflunomide, n (%)2 (5.4)2 (10.5)0 (0.0)0 (0.0)0.367Sulfasalazine, n (%)1 (2.7)1 (5.3)0 (0.0)0 (0.0)0.615Hydroxychloroquine, n (%)7 (18.9)4 (21.1)2 (14.3)1 (25.0)0.840Combination with immunosuppressants, n (%)20 (54.1)7 (36.8)9 (64.3)4 (100.0)0.044Mycophenolate, n (%)19 (51.4)6 (31.6)9 (64.3)4 (100.0)0.021Azathioprine, n (%)1 (2.7)1 (5.3)0 (0.0)0 (0.0)0.615Corticosteroids, n (%)25 (67.6)14 (73.7)7 (50.0)4 (100.0)0.121Doses of corticosteroids, median (IQR)5.0 (0.0-10.0)5.0 (0.0-10.0)2.5 (0.0-7.5)10.0 (8.1-10.5)0.519ConclusionLung function improved or stabilized in more than half of patients with CTD-ILD treated with RTX. No significant increase in infection rates was observed. Early treatment and combination with mycophenolate could reduce the risk of progression of ILD.Disclosure of InterestsNone declared

Background:Interstitial Lung Disease (ILD) is a severe extraarticular manifestation of rheumatoid arthritis (RA). In this line, several radiological patterns of RA-ILD have been described: i) usual interstitial pneumonia (UIP), ii) nonspecific interstitial pneumonia (NSIP), iii) obliterating bronchiolitis, iv) organized pneumonia and mixed patterns. Abatacept (ABA) could be an effective and safe option for patients with RA-ILD, although the response in the different radiological patterns is not well defined.Objectives:Our aim was to assess the response to ABA in different radiological patterns of ILD.Methods:Observational retrospective multicenter study of RA-ILD treated with ABA. ILD was diagnosed by HRCT and classified by radiological patterns in 3 different subgroups of RA-ILD: a) UIP, b) NSIP and c) “other”. ABA was used sc. or iv. at standard dose. We assessed: a) Dyspnoea (MMRC scale; significant variation ≥1); b) Respiratory function tests (significant changes ≥10% in FVC and DLCO); c) HRCT imaging; d) DAS28 e)prednisone dose.Variables were collected at months 0, 3, 6, 12 months and subsequently every 12 months until a maximum of 60 months.Results:We included 263 patients: 106 UIP, 84 NSIP and 73 others (150 women / 113 men), mean age 64.64±10 years. Total patients positive for RF or CCPA were 235 (89.4%) and 233 (88.6%), respectively. In 26 out of 263 patients, the development of ILD was closely related to the administration of sDMARDs (MTX n = 11 and LFN n = 1) or bDMARDs (ETN n = 5, ADA n = 4, CZP n = 2 and IFX n = 3). Patient characteristics are shown in table 1. Figure 1 shows the evolution of the cases with available data after a mean follow-up of 22.7±19.7 months. Mean DLCO and FVC remained stable in the 3 groups without statistically significant changes, and all the groups showed a statistically significant reduction in DAS28 and prednisone dose.Conclusion:ABA could be a good choice of treatment in patients with RA-ILD independently of the radiological pattern of ILD.Disclosure of Interests:Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Santos Castañeda: None declared, Rafael Melero: None declared, J. Loricera: None declared, Francisco Ortiz-Sanjuán: None declared, A. Juan-Mas: None declared, Carmen Carrasco-Cubero Speakers bureau: Janssen, MSD, AbbVie, Novartis, Bristol Myers Squibb, and Celgene, S, Rodriguéz-Muguruza: None declared, S. Rodrigez -Garcia: None declared, R. Castellanos-Moreira: None declared, RAQUEL ALMODOVAR Speakers bureau: Abbvie, Celgene, Janssen, Lilly, Novartis, Pfizer., CLARA AGUILERA CROS: None declared, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Sergi Ordoñez: None declared, Susana Romero-Yuste: None declared, C. Ojeda-Garcia: None declared, Manuel Moreno: None declared, Gemma Bonilla: None declared, I. Hernández-Rodriguez: None declared, Mireia Lopez Corbeto: None declared, José Luis Andréu Sánchez: None declared, Trinidad Pérez Sandoval: None declared, Alejandra López Robles: None declared, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Natalia Mena-Vázquez: None declared, C. Peralta-Ginés: None declared, ANA URRUTICOECHEA-ARANA: None declared, Luis Marcelino Arboleya Rodríguez: None declared, J. Narváez: None declared, DESEADA PALMA SANCHEZ: None declared, Olga Maiz-Alonso: None declared, J. Fernández-Leroy: None declared, I. Cabezas-Rodriguez: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, A. Ruibal-Escribano: None declared, JR De Dios-Jiménez Aberásturi: None declared, Paloma Vela-Casasempere: None declared, C. González-Montagut Gómez: None declared, J M Blanco: None declared, Noelia Alvarez-Rivas: None declared, N. Del-Val: None declared, M. Rodíguez-Gómez: None declared, Eva Salgado-Pérez: None declared, Carlos Fernández-López: None declared, E.C. Cervantes Pérez: None declared, A. Devicente-DelMas: None declared, Blanca Garcia-Magallon Consultant of: MSD, Speakers bureau: Pfizer, Amgen, Celgene, MSD, Cristina Hidalgo: None declared, Sabela Fernández: None declared, R. López-Sánchez: None declared, Edilia García-Fernández: None declared, S. Castro: None declared, P. Morales-Garrido: None declared, Andrea García-Valle: None declared, Rosa Expósito: None declared, L. Exposito-Perez: None declared, Lorena Pérez Albaladejo: None declared, Ángel García-Aparicio: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

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