SPANISH NATIONAL REGISTRY OF BELIMUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

BackgroundBelimumab (BLM) is a monoclonal antibody that inhibits B-lymphocyte stimulating factor (BlyS) approved as a specific treatment for systemic lupus erythematosus (SLE) in 2011. We present the experience with BLM in a Spanish cohort with more than 460 patients.ObjectivesTo describe demographic characteristics, efficacy and safety of BLM in patients with SLE in Spanish population since its approval.MethodsDescriptive, retrospective, multicenter study in patients diagnosed with SLE according to EULAR/ACR 2019, SLICC and/or ACR 1997 diagnostic criteria. Data regarding SLE patients treated with BLM were collected from medical records (2011-2022). Demographic features, efficacy, laboratory variables, SLEDAI, renal involvement, steroid dose, administration routes and safety were assessed. To see whether a trend in BLM prescription had changed or not over time, two periods of time were analyzed: 2011-2016 (period1) and 2017-2022 (period2).ResultsBaseline characteristics of patients are summarized in Table 1.A total of 462 patients (36 hospitals) were included, 50.9% were on intravenous (IV), 34% on subcutaneous (SC) and 15.1% switched from IV to SC route. The median number of pre-BLM csDMARD use was 2.0 (2.0-3.0), being hydroxychloroquine (HCQ) the most frequently used (94.5%). Fifty-two patients were treated with IV cyclophosphamide with a median of 6 bolus received. At the time of BLM start, 443 patients were on prednisone with a median dose of 6.2 mg (5.0-10.0). Significant decreases in prednisone dose, SLEDAI and anti-DNA antibodies were observed from baseline until the last visit, whereas complement C3 and C4 values raised (Figure 1). A total of 118 patients (27.4%) had renal involvement with a median proteinuria of 1.0 g/day (0.5-2.4). Renal biopsy was done in 102 out of 118 patients, being class IV (33%), class III (21%) and class V (16%) the most frequently reported. After BLM, 73.3% of these patients improved (median proteinuria of 0.2 g/day (0.1-0.7).In period1, 100 patients started BLM compared to 362 in period2. The median time from SLE diagnosis to BLM begin was 7.1 (4.0-13.7) and 6.2 (2.1 -14.4) years in period1 and period2, respectively (p=0.454). We found a trend to use more csDMARD before BLM treatment in period1: 2.5 (2-3) vs. 2 (2-3) (p=0.088).A total of 143 (30.5%) patients discontinued treatment mostly due to inefficacy (55.9%) and infections (11.9%). In fact, 116 patients developed infections, mostly mild;2 patients died, 16 had COVID-19 and 4 patients developed tumors requiring discontinuation of the drug.ConclusionIn our cohort of SLE patients in a real-world setting, BLM has been effective, safe and seems to be a good choice to treat renal involvement.References[1]Navarra SV, Guzmán RM, Gallacher AE, et al. Lancet. 2011;377(9767):721-31.[2]Stohl W, Hiepe;rt al. Arthritis Rheum. 2012;64(7):2328-37.[3]Furie R, Rovin BH, Houssiau F, et al. N Engl J Med. 2020;383(12):1117-1128.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

RELATION BETWEEN COVID-19 AND ANCA VASCULITIS. STUDY IN A SINGLE UNIVERSITY HOSPITAL

BackgroundAnti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) is a small vessel vasculitis. Hallmarked by the presence of antibodies against antigens in cytoplasmic granules of neutrophils. Different microbiological agents and vaccines can trigger an AAV, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and Coronavirus disease 2019 (COVID-19) vaccine.ObjectivesTo compare: a) proportion of positive ANCA (+ANCA) test in 2019 (COVID-19 pre-pandemic) vs 2021 (COVID-19 pandemic), b) clinical features and c) vasculitis activity between vasculitis related to COVID 19 vaccination vs non-related.MethodsAll ANCA tests performed in 2019 and 2021 in a referral hospital were reviewed. Additionally, we studied 18 +ANCA patients diagnosed in 2021 and accepted to participate in present study. The patients were divided in two groups: a) +ANCA after SARS-CoV-2 mRNA vaccine (COVID-related) and +ANCA before COVID-19 vaccine (COVID-nonrelated). Diagnosis of underlying AAV was based on ACR/EULAR 2022 criteria. Disease activity was assessed with Birmingham Vasculitis Activity Score (BVAS). ANCA testing was done by chemiluminescence assay using IO-FLASH (Inova, San Diego, CA) according to the instructions of the manufacturer.ResultsANCA tests were positive in 14 of 1287 cases (1.1%) and in 32 of 1434 (2.2%) cases in 2019 and 2021, respectively (figure 1, the differences were statistically significant (p=0.020). The main features of 18 ANCA+ patients diagnosed in 2021 are summarized in table 1. COVID-19 related patients showed a median of 7 points on BVAS score compared of the median of 5 points on BVAS score on not related patients.ConclusionThere seems to be an increase of +ANCA at the expense of anti-PR3 antibodies following the COVID-19 vaccine. In patients with +ANCA following vaccination there seems to be an increased disease activity according to BVAS score without reaching statistical significance.References[1]Damoiseaux, J., et al Autoimmunity Reviews.2021. PMID 34896650.[2]Irure-Ventura, et al. IScience.2022. PMID 35937087.Table 1.Main general features of 18 patients with ANCA+ test diagnosed in 2021.FEATURESAll cases n= 18Related n= 13Non-related n= 5p*Age (years), mean±SD62±1767±15.352±16.50.167Male/ Female n, (% male)10/8 (55.6)9/4 (69.2%)1/4(20)0.067ANCA-test specificity, n (%)MPO-ANCA9 (50)7 (53.8)2(40)0.609PR3-ANCA8 (44.4)5 (38.5)3(60)0.423Both1 (5.6)1 (7.7)0-CRP (mg/dL), median [IQR]2,4 [0.4-10.7]3.8 [0.4-10.1]1 [0.4-10.9]0.802ESR, mm/1st hours, median [IQR]50 [25-104]47 [25.3-71.8]50 [25-120]0.634BVAS, median [IQR]6.5 [4.2-8]7 [4-8]5 [5-8]0.842FFS, n (%)03 (16.7)2 (15.4)1 (20)0.819≥115 (83.3)11 (84.6)4 (80)0.819ENT involvement, n (%)12(66.7)10 (76.9)2 (40)0.148MSK involvement, n (%)11(61.1)7(53.8)4 (80)0.322CNS/PNS involvement, n (%)10 (55.6)7 (53.8)3 (60)0.819Lung involvement, n (%)9 (50)6 (46.2)3 (60)0.609Kidney involvement, n (%)8 (44.4)7 (53.8)1 (40)0.208Ocular involvement, n (%)2 (11.1)2 (15.4)00.366Cutaneous involvement, n (%)2 (11.1)02 (40)0.019*p values according to Man Whitney test.Abbreviations (in alphabetical order):AAV: anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis;ACR: American college of Rheumatology;ANCA: Antineutrophil cytoplasmic antibody;BVAS: Birmingham Vasculitis Activity Score;CNS: central nervous system;CRP: C-Reactive protein;dL: deciliter;ENT: ear, nose, throat;ESR: erythrocyte sedimentation rate;FFS: Five-Factors Score;g;IQR: Interquartile range;mg: milligram;MSK: musculoskeletal;MPO-ANCA= ANCA specific for myeloperoxidase;n=Number;PNS: peripheral nervous system;PR3-ANCA= ANCA specific for proteinase 3;SD: Standard DeviationFigure 1.Comparison of ANCA test in 2019 and 2021.[Figure omitted. See PDF]Acknowledgements:NIL.Disclosure of InterestsFabricio Benavides-Villanueva: None declared, Vanesa Calvo-Río Speakers bureau: Dra V. Calvo had participation in company-sponsored speaker´s bureau from Roche, Novartis, Galápagos, UCB Pharma, MSD, Celgene, and Grünenthal and received support for attending m etings and/or travel from Janssen, Abbvie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer, Galápagos., J. Loricera Speakers bureau: Dr. J. Loricera had participation in company-sponsored speaker´s bureau from Roche, Novartis, Galápagos, UCB Pharma, MSD, Celgene, and Grünenthal., Consultant of: Dr. J. Loricera had consultation fees in company-sponsored speaker´s bureau from Roche, Novartis, Galápagos, UCB Pharma, MSD, Celgene, and Grünenthal and received support for attending meetings and/or travel from Janssen, Abbvie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer, Galápagos., Juan Irure-Ventura: None declared, Marcos Lopez-Hoyos: None declared, Ricardo Blanco Speakers bureau: Dr. R. Blanco had participation in company sponsored speaker´s bureau from Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Consultant of: Dr. R. Blanco had consultation from Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Grant/research support from: Dr. R. Blanco received grants/research supports from Abbvie, MSD and Roche.