Pos0886 efficacy and Safety of Rituximab in Autoimmune Disease–associated Interstitial Lung Disease: A Prospective Cohort Study.

Abstract

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

CAR-T-Zell-Therapie bei autoimmunen Erkrankungen

“…Weitere Zulassungen für andere Autoimmunerkrankungen, wie den ANCA-assoziierten Vaskulitiden oder dem Pemphigus vulgaris, folgten. Darüber hinaus hat es auch einen hohen Stellenwert in der Therapie der Kollagenosen, insbesondere bei schweren Manifestationen und interstitieller Lungenerkrankung 17 . Allerdings profitieren nicht alle Patienten gleichermaßen, wie nicht zuletzt die hinter den Erwartungen zurückbleibenden Phase-II/III-Studien zu Rituximab und SLE demonstrierten 18 , 19 .…”

Rate of severe and fatal infections in a cohort of patients with interstitial lung disease associated with rheumatoid arthritis: a multicenter prospective study

“…Kim et al (2) found infection to be the cause of death in more than half of patients with RA-ILD, compared with only 16% in RA patients without ILD. Moreover, infections are the main cause of hospitalization in patients with RA-ILD treated with biologics or immunosuppressants, and superinfections are often associated with death resulting from disease progression (9,12).…”