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

BackgroundInterstitial Lung Disease (ILD) is the most common lung involvement in rheumatoid arthritis (RA) and leads to increased morbidity and mortality. Some retrospective observational studies suggest that abatacept (ABT) could be effective and safety, although there are no clinical trials and prospectively collected data are scarce.ObjectivesTo evaluate prospective the effectiveness and safety of ABT in patients with ILD associated RA (ILD-RA).MethodsDesign and Protocol: We performed a multicenter, prospective, observational study of patients with interstitial lung disease secondary to rheumatoid arthritis (ILD-RA) receiving ABT between 2015 and 2021. The patients were assessed using high-resolution computed tomography and lung function tests at the beginning of treatment (V0), at 12 months (V12), and at the end of follow-up in 2021 (fV). The study was approved by the Ethics Committee (Code 1719-N-15). Main variable: effectiveness of ABT according to evolution of ILD at the end of follow-up: (1) improvement (ie improvement of FVC ≥10% or DLCO ≥15% and no radiological progression), (2) no progression (stabilization or improvement in FVC ≤ 10% or DLCO <15% and no radiological progression), (3) progression (worsening of FVC >10% or DLCO >15% and radiological progression) or (4) death. Other variables: clinical and analytical characteristics, treatments and safety (infections, hospitalization and mortality). Statistical analysis: Cox regression analysis to identify factors associated with worsening of ILD-RA treated with ABT.ResultsThirty-eight ILD-RA patients started ABT treatment during prospective follow-up. A total of 22/38 (57.9%) were men and the mean (SD) age was 66.1 (9.1) years. The mean (SD) evolution of ILD was 43.9 (30.0) months and the median (IQR) time with ABT was 17.0 (12.1-34.8) months. The baseline clinical-epidemiological characteristics and pulmonary progression of the patients are shown in Table 1. At the end of follow-up (fV) 28/38 (73.6%) had improvement/stabilization and 7/38 (18.4%) progressed and 3/38 (7.8%) of them died (COVID-19 pneumonia, respiratory infection and ILD progression, respectively). There were no significant differences in FVC (75.3 [8.7] vs 77.7 [14.6]; p=0.775) or in FEV1 (83.9 [10.7] vs 84.7 [13.2]; p=0.416) nor in the DLCO (61.0 [17.4] vs 60.7 [15.2]; p=0.789) at the end of follow-up. There was a greater numberwith improvement/stabilization among the patients who were in combination with Methotrexate compared to those who were in monotherapy (83.3% vs 39.1%; p=0.046). The baseline variables that were independently associated with progression-mortality of ILD-RA in fV were: baseline FVC (OR [95% CI], 0.895 [0.805-0.996]; p=0.042) and duration of ILD-RA (OR [95% CI], 1.204 [1.148-2.112; p=0.046]). Two patients discontinued ABT during follow-up due to insufficient joint and pulmonary response.Table 1.Characteristics of patients with ILD-RA treated with Abatacept.VariableILD-RA n=38Baseline clinical-epidemiological characteristics Sex, man, n (%)22 (57.9) Age in years, mean (SD)66.1 (9.1) Race, caucasian, n (%)38 (100.0) Smoking history  No smoker, n (%)23 (60.5)  Smoker, n (%)15 (39.5) Time of evolution RA, months, median (IQR)139.1 (68.1-218.7) RF, n (%)36 (94.7) Anti-CCP, n (%)32 (84.2) ANA, n (%)8 (22.9) Radiological pattern  UPI, n (%)26 (68.0)  NSIP, n (%)12 (32.0)Treatment DMARDs, n (%)33 (86.8) Methotrexate, n (%)19 (50.0) Leflunomide n (%)11 (22.9) Sulfasalazine, n (%)2 (5.3) Hydroxychloroquine, n (%)6 (15.7)Immunosuppressants, n (%)11 (297)Antifibrotic, n (%)1 (2.6)Corticosteroids, n (%)32 (84.2)Corticosteroids, median (IQR)5.0 (2.5-10.0)Pulmonary progression (fv) Improvement-Stabilization, n (%)22 (73.6) Progression-Mortality, n (%)10 (26.4)ConclusionMore than half of the patients with ILD-RA treated with ABT manage to stabilize or improve their lung disease after a median follow-up of 17 months. Patients who worsen or die have lower baseline FVC values ​​and ILD-RA with a longer evolution time.Disclosure of InterestsNone declared