Background: Anifrolumab (ANI) is a human monoclonal antibody that binds to the type I interferon receptor subunit 1 (IFNAR1), thus blocking the biological activity of type I IFNs. ANI was approved by Spanish authorities on June 1, 2023. Its use is indicated in adults with moderately to severely active autoantibody-positive systemic lupus erythematosus (SLE) in combination with standard treatment. Objectives: To describe in Spanish clinical practice since its approval a) SLE profile of patients, b) effectiveness and c) safety. Methods: Descriptive, retrospective, multicenter study in patients diagnosed with SLE according to EULAR/ACR 2019, SLICC and/or ACR 1997 diagnostic criteria. Data regarding were collected from medical records (June 2023-January 2024). Demographic features, clinical and laboratory variables, previous and concomitant therapy, activity index (SLE-DAS, SLEDAI-2k, PGA), organic damage index (SLICC SDI) and safety were assessed. Results: Baseline characteristics of patients and therapy before ANI are summarized in Table 1. A total of 91 patients (82 women/9 men), mean age 32.7±11.5 years (range 15-59 years) (38 hospitals) were included.The main reason for starting ANI was: skin activity (n=60, 65.9%), joint activity (n=52, 57.1%), hematological activity (n=25, 27.5%), renal activity (n=2, 2.2%), corticosteroids dependence (n=5, 5.5%) and serious side effects with belimumab (BLM) (n=2, 2.2%).All patients received 300 mg/4 w of ANI except one patient who received a loading dose (900 mg/4 w x3 months and after 300 mg/4 w) due to renal involvement.Concomitant treatments with ANI were: corticosteroids (n=78), antimalarials (n=68), mycophenolate mofetil (MMF) (n=23), methotrexate (MTX) (n=13), azathioprine (AZA) (n=5), tacrolimus (n=5), leflunomide (LFN) (n=2), rituximab (RTX) (n=1), cyclophosphamide (CYM) (n=1), sulfones (n=2) and anakinra (n=1).A rapid and maintained significant decreases in SLE-DAS, SLEDAI-2k, PGA and anti-dsDNA antibodies were observed from 1 month until the last visit. Complement C3 and C4 levels also increased significantly (Figure 1). No increase in the chronicity index was observed.After a follow-up of 4.8±3.6 months the main side effects observed were: herpes zoster (n=3), arterial hypotension (n=2), headache (n=2), suppurative hidradenitis (n=1), influenza A pneumonia (n=1), skin reaction (n=1), herpes simplex virus infection and urinary infection (n=1). In follow-up, 7 patients discontinued treatment due to primary failure (n=3), secondary failure (n=2), severe pneumonia (n=1), arterial hypotension (n=1). Conclusion: In our cohort of SLE patients in a real-world setting, ANI has showed a rapid effectiveness, and a relatively good safety. Therefore, ANI seems to be a good choice to treat patients refractory to other therapies. ANI in severe and refractory patients even was used combined with other biologic therapy. REFERENCES: [1] Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019 Sep;78(9):1151-1159. Acknowledgements: NIL. Disclosure of Interests: Vanesa Calvo-Río Abbie, Lilly, Grünenthal, AMGEN, MSD, Novartis, Galápagos, Vifor, GSK, Otsuka, Janssen, M. Retuerto-Guerrero: None declared, Judit Font: None declared, Ivette Casafont-Solé: None declared, A. Mayo-Juanatey: None declared, Juan Jose Alegre Sancho: None declared, Dalifer Freites: None declared, Cristina Hormigos: None declared, Noemí Garrido-Puñal: None declared, Guillermo Gonzalez Arribas: None declared, Juan Roberto Miguelez Sanchez: None declared, Andrea García-Valle: None declared, Marta Ibañez: None declared, Fernando Lozano Morillo: None declared, Ángel García Manzanares: None declared, S. Sandoval-Moreno: None declared, Josefina Cortés-Hernández: None declared, Deseada Palma Sanchez: None declared, Leticia Lojo: None declared, Evelin Cecilia Cervantes Pérez: None declared, Paz Collado: None declared, Cristina Arciniega Larios: None declared, Luis Sala Icardo: None declared, Eztizen Labrador-Sánchez: None declared, Cilia Peralta-Ginés: None declared, Nahia Plaza-Aulestia: None declared, Miguel Medina Malone: None declared, Jose Rosas Gómez de Salazar: None declared, Montserrat Corteguera: None declared, Laura Cebrián-Méndez: None declared, Fred Antonio Anton Pages: None declared, Jose Ramón Lamúa Riazuelo: None declared, Maria Dolores Fábregas Canales: None declared, María José Alados Hernández: None declared, Marta Garijo Bufort: None declared, Anna Pàmies: None declared, Luis Sarabia De Ardanaz: None declared, Rodrigo Aguirre-del-Pino: None declared, Jose Angel Cabezas Lefler: None declared, Alvaro Seijas-Lopez: None declared, Maria del Carmen Carrasco Cubero: None declared, Ana Lopez-Ceron Cofiño: None declared, Vera Ortiz-Santamaria: None declared, Santos Castañeda: None declared, Carmen Bejerano: None declared, Ricardo Blanco Abbvie, Pfizer, Roche, Bristol-Myers-Squibb, Janssen, Lilly, Novartis, UCB, and MSD, Abbvie, MSD, Roche.Figure 1Evolution of C3, C4 and anti-dsDNA levels and activity and organ damage indices after starting anifrolumab. Table 1Clinical manifestations and treatments received before starting anifrolumabClinical manifestations before ANIN (%)Therapy before ANIN (%)Concomitant therapy with ANIN (%)articular87 (95.6%)oral steroids88 (96.7%)oral steroids78 (85.7%)cutaneous75 (82.4%)antimalarials88 (96.7%)antimalarials68 (74.7%)hematological57 (62.6%)BLM73 (80.2%)MMF23 (25.3%)oral ulcers47 (51.6%)MMF46 (50.5%)MTX13 (14.3%)alopecia46 (50.5%)AZA38 (41.7%)AZA5 (5.5%)renal30 (33%)RTX34 (37.3%)tacrolimus5 (5.5%)serositis28 (30.8%)MP boluses32 (35.1%)leflunomide2 (2.2%)neuropsychiatric12 (13.2%)CYM19 (20.9%)sulfones2 (2.2%)digestive6 (6.6%)tacrolimus9 (9.9%)RTX1 (1.1%)Abbreviations in alphabetical order: ANI: anifrolumab; AZA: azathioprine; BLM: belimumab; CYM: cyclophosphamide; MMF: mycophenolate mofetil; MP: methylprednisolone; MTX: Methotrexate; RTX: rituximabCYM1 (1.1%)anakinra1 (1.1%)

Background: Uveitis is a frequent extraarticular manifestation of axial Spondyloarthritis (axSpA), specifically anterior uveitis. Effects of biological therapy on uveitis associated to axSpA are poorly understood. Objectives: To assess in axSpA a) the frequency of uveitis and clinical features; b) its association with axSpA activity, c) effectiveness of synthetic disease-modifying drugs and biological therapy and, d) frequency of ocular surface pathology. Methods: A retrospective longitudinal study from a cohort of 309 unselected patients with axSpA classified according to the Assessment of SpondyloArthritis International Society criteria. All patients were diagnosed and managed uniformly in a single university centre. Uveitis was diagnosed by ophthalmologist. Sociodemographic data, clinical features, disease activity and treatments were collected. Incidence of uveitis was calculated before and after treatments initiation, reported as exposure adjusted incidence rate (EAIR) per 100 patient-years of biological drug exposure. Results: Uveitis was observed in 50 patients (21 women/29 men) out of 309 (16.2%) and ocular surface pathology in 8 (2.7%). Demographic and clinical features in patients who developed ocular pathology and specifically uveitis and those who did not are summarized in Table 1. Uveitis was acute in all cases, anterior (98%), unilateral (72%), unilateral alternate (28%) and recurrent (70%). Ocular surface pathology was episcleritis (75%), scleritis (12.5%) and corneal ulcer (12.5%). Patients with uveitis had a greater frequency of positive HLA-B27 (88% p<0.001) and severe sacroilitis (56% p=0.03) than patients without uveitis. Activity indexes (BASDAI, ASDAS) were similar regardless ocular involvement. Biological DMARDs were used in 24 (48%) patients with uveitis; 22(44%) of them received anti-TNFα monoclonal antibodies, etanercept (ETN) 4 (2%), secukinumab (SECU) 12 (24%) and JAK inhibitors (JAKi) 7 (14%). The EAIR of uveitis before treatment with sulfasalazine (SLZ) was 13.06 episodes/100 patients-year, with monoclonal anti-TNFα developed 1.76 episodes/100 patients-year, with SECU 1.35 episodes/100 patients/year and with JAKi 6.97 episodes/100 patients/year. After treatment, patients treated with SLZ, monoclonal anti-TNFα and JAKi developed 4.15, 1.47 and 2.35 episodes/100 patients/years, respectively, while in those treated with SECU was 3.15 episodes/100 patients/year. Conclusion: Uveitis was observed in 16.2% of axSpA, while ocular pathology surface in 2.7%. Most patients with uveitis had positive HLA-B27 and severe sacroilitis in x-ray was more frequent. The most frequent pattern of uveitis observed in axSpA was acute, anterior and unilateral. The uveitis exposure adjusted incidence rate decreased with SLZ, antiTNFα monoclonal antibodies and JAKi and increased with SECU. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.Figure 1Uveitis exposure adjusted incidence rate before and after biological therapy Table 1General features of 309 patients with axSpA and differences between patients with and without ocular involvement and uveitis.Overal (n=309)Ocular involvement (n=55)Non-ocular involvement (n=254)p valueUveitis (n=50)Non-uveitis (n=259)p valueAge (years), mean±SD53.17±11.6653.37±10.2453,12±11.980.7253.63±10.5153.07±11.900.56Sex (women/men), n (% of women)127/182 (41.1)24/31 (43.6)103/151 (40.6%)0.6721/29 (42)106/153 (40.9)0.88HLA-B27positive197 (64)46 (83.6)151 (59.7)0.00144 (88)153 (59.3)<0.001Inflamatory back pain291 (96.7)54 (98.2)237 (96.3)0.4949 (98)242 (96.4)0.56Peripheral arthritis106 (34.3)18 (32.7)88 (34.6)0.7816 (32)90 (34.7)0.70Psoriasis38 (12.3)6 (10.9)32 (12.6)0.726 (12)32 (12.4)0.94Inflammatory Bowel disease26 (8.4)5 (9.1)21 (8,3)0.844 (8)22 (8.5)0.90Ocular surface pathology8 (2.6)8 (14.5)0 (0)0.003 (6)5 (2)0.10BASDAI, mean±SD3.67±2.133.42±2.273.72±2.100.393.51±2.253.70±2.110.64ASDAS, mean±SD2.28±0.972.09±0.972.32±0.970.222.13±0.932.31±0.980.38Severe sacroiliitis (grade 3,4), n(%)132 (42.7)30 (54.5)102 (40.2)0.0528 (56)104 (40.2)0.03Sacroilitis on MRI (ASAS criteria) (n%)148 (47.9)23 (41.8)125 (51)0.2119 (38)129 (51.6)0.07

Background: Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) is a group of vasculitis that affect small vessels. Includes Granulomatosis with polyangiitis (GPA), Eosinophilic granulomatosis with polyangiitis (EGPA) and Microscopic polyangiitis (MPA). Precise estimation of the incidence has been difficult due to the absence of reliable diagnosis criteria and studies with heterogeneous population. Objectives: To estimate the incidence of AAV in a Northern Spanish region between 2000 and 2023. Compare our results with similar studies from other countries. Methods: Population-based study of 176 patients diagnosed with small vessel vasculitis between January 1st of 2000 to December 31st of 2023. Selected from a data base from clinical reports provided from different departments (Immunology, Dermatology, Nephrology, Internal Medicine, Pneumology and Rheumatology). The diagnosis of AAV was according to ACR/EULAR 2022 criteria. Patients that did not meet criteria were classified as Indeterminate Vasculitis. Incidence was reported annually (on December 31st of every year) per 1,000,000 (106) habitants per year and the incidence by diagnosis was calculated. We searched similar studies from the available bibliography. Results: A total of 176 (92 men/84 women) patients were included. The mean age at diagnosis was 69.5±13.6 years. The most frequent type of AAV was MPA with 67 (38.1%) followed by GPA, EGPA with 64 (36.4%) and 24 (13.6%) respectively. The Indeterminate group had 21 (11.9%) patients.Annual incidence of AAV in Cantabria area between 2000-2023 period was 15.5 (95% IC: 11.5-19.3) per 106 habitants. The incidence in male and female were 16.6 (95% IC: 11.8-21.2) and 14.1 (95% IC: 10-18.1) per 106 habitants, respectively. The incidence by diagnosis were 5.6 (95% IC:4-7.3) for GPA, 5.9 (95%IC: 4-7.8) for MPA and 2.2 (95% IC:0.9-3.3) for EGPA. FIGURE 1. A comparison between different geographical areas showed wide variations in annual incidence. The highest annual incidence was observed in Nordic countries, The United States and Central Europe. The lowest results were in Southern Europe. TABLE 1 Conclusion: There seems to be a progressive increase in incidence of AAV over the years in the studied population. Annual incidence in our region was like others. REFERENCES: [1] Mohammad A et al: https://doi.org/10.1093/rheumatology/keaa089. Acknowledgements: NIL. Disclosure of Interests: Fabricio Benavides-Villanueva: None declared, A. Herrero-Morant: None declared, Vanesa Calvo-Río: None declared, Diana Prieto-Peña: None declared, Salma Al Fazazi: None declared, Mónica Renuncio-García: None declared, Adrián Martín-Gutiérrez: None declared, Amparo Sánchez López: None declared, Claudia Poo-Fernandez: None declared, Clara Escagedo Cagigas: None declared, Maria Rodriguez Vidriales: None declared, Ricardo Blanco Abbvie, Pfizer, Roche, Bristol-Myers-Squibb, Janssen, Lilly, Novartis, UCB and MSD, Abbvie, Pfizer, Roche, Bristol-Myers-Squibb, Janssen, Lilly, Novartis, UCB and MSD.Figure 1A. Annual incidence of AAV in 176 patients between 2000-2023 B. Annual incidence by diagnosis. Table 1Epidemiological studies on AAV in other geographic regions. Incidence calculated by cases/106 per year (CI 95%)Author, year.CountryTime periodDiagnosis CriteriaN casesIncidenceIncidence GPAIncidence MPAIncidence EGPAPearce FA, 2016UK2007-2013EMA ACR9010723.1 (18.9-27.9)8.2 (5.8-11.3)13.4 (10.3-17.2)1.5 (0.6-3.1)Nilsen AT, 2020Norway1999-2013EMA ACR9014020.2 (17-23.8)12.7 (10.2-15.6)5.3 (3.7-7.3)2.2 (1.2-3.6)Mohammad AJ, 2009Sweden1997-2006EMA ACR9014021.8 (18.2-25.4)9.8 (7.4-12.2)10.1 (7.7-12.6)0.9 (0-0.17)Hellmich, B, 2021Germany2013-2016ND305446 (39-53)34 (28-40)13 (11-15)NDDadoniene, J, 2005Lithuania1990-1999ACR9020543.8 (38.1-50.3)2.1 (1.1-4.1)ND1.3 (0.5-2.9)Panagiotakis SH, 2009Greece1995-2003ACR906719.5 (15.7-23.4)6.6 (3.7-9.6)10.2 (5.8-14.6)NDRomero-Gomez C, 2015Spain1994-2010ACR90296.2 (3.9-8.4)2.1 (0.8-3.4)3.4 (1.7-5-.1)0.6 (0-1.3)Pamuk ÖN, 2016Turkey2004-2014ACR90508.1 (1-15.2)4.8 (0-10.3)2.4 (0-6.3)0.8 (0-4)Berti A,2017USA1996-2015EMA ACR905833 (24-41)13 (8-18)16 (10-22)4 (1-6)Fujimoto S, 2011Japan2005-2009EMA, ACR908622.6 (19.1-26.2)2.1 (0.6-3.7)18.2 (14.3-22)2.4 (0.3-4.4)Present studio, 2023Spain2000-2023ACR/EULAR2217615.5 (11.5-19.3)5.6 (4-7.3)5.9 (4-7.8)2.2 (0.9-3.3)Abbreviations (in alphabetical order):ACR: American college of Rheumatology; CI: Confidence interval; EGPA: Eosinophilic granulomatosis with polyangiitis; EMA: European Medicine Agency; EULAR: European Alliance of Associations for Rheumatology; GPA: Granulomatosis with polyangiitis; MPA: Microscopic polyangiitis; N: number; ND: No available data; UK: United Kingdom; USA: United States of America.

Background: Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are included in the group of small vessel vasculitis. They are often associated with ANCA specificity for myeloperoxidase (ANCA-MPO) or proteinase 3 (PR3-ANCA) and include three clinical entities: granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA). Their similarities in clinical features make the differential diagnosis a challenge for the physicians. In 1990 the American college of Rheumatology (ACR) developed classification criteria for AAV, including GPA and GEPA, but excluding MPA. In 2007 the European Medicine Agency (EMA) and in 2022 the ACR/EULAR) developed new classification criteria for the three subgroups of AAV (GPA, MPA and EGPA). Objectives: To compare the three different classification criteria in AAV. Methods: Study of patients diagnosed with AAV according to expert clinical rheumatologist opinion between January of 2000 and December of 2023 in a Northern Spanish region. Patients were reclassified based on the three set of criteria: ACR 1990, EMA 2007 algorithm and 2022 ACR/EULAR criteria. Patients not meeting the classification criteria were considered as undetermined vasculitis. Results: We included 176 (92 men/84 women) patients; mean age at diagnosis of 69.5±13.6 years. According to expert rheumatologists, patients had been diagnosed as MPA (n=44; 25%) GPA (n=53; 30%), EGPA (n=23; 13 %) and undetermined AAV (n=56;32%).With 1990 ACR criteria, 31(18%) patients were diagnosed with GPA, 14 (8%) patients were diagnosed with EGPA and 131 (74.4%) were classified like an indeterminate vasculitis. With the 2007 EMA algorithm 49 patients were diagnosis of GPA (28%) 16 (9%) with EGPA, 50 (28.4%) with MPA and 61(35%) like indeterminate. With the 2022 ACR/EULAR criteria, 67 (38 %) patients were diagnosed with MPA, 64 (36 %) with GPA, 24 (14 %) with EGPA and 21(12%) with undetermined AAV.When the ACR 1990, EMA 2007 and the 2022 ACR/EULAR criteria were compared, we found that 2022 ACR/EULAR criteria were better to reclassify the undetermined AVV into the other three entities (Figure 1). Conclusion: The ACR/EULAR 2022 showed the best correlation with the expert clinical rheumatologist opinion to classify AAV. REFERENCES: [1] Kuwata R, Evaluation of the Validity of the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Antineutrophil Cytoplasmic Antibody-associated Vasculitis for an Asian Population on the Basis of the Patterns of Organ Involvement [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). Acknowledgements: NIL. Disclosure of Interests: Fabricio Benavides-Villanueva: None declared, Diana Prieto-Peña: None declared, Vanesa Calvo-Río: None declared, Ricardo Blanco Abbvie, Pfizer, Roche, Bristol-Myers-Squibb, Janssen, Lilly, Novartis, UCB and MSD., Abbvie, MSD and Roche.Figure 1Differences between expert clinical opinion (EXP), ACR 1990, EMA 2007 and ACR/EULAR 2022 criteria.

Background: Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV), affects small and medium-sized vessels. The exact mechanisms leading to an excess production of ANCA are not clear. In healthy individuals, ANCA specific for proteinase (PR3-ANCA) and for myeloperoxidase (MPO-ANCA) are detected in circulation. These findings suggests that ANCA presence is not enough for developing AAV and that further steps are necessary for the onset of autoimmunity1. It has been shown that both Coronavirus disease 2019 (COVID-19) infection and vaccine may trigger AAV2. Objectives: To compare the presence of AAV in new onset ANCA positive tests (+ANCA) in 2019 (COVID-19 pre-pandemic) vs 2021 and 2022 (COVID-19 pandemic). Methods: All ANCA tests performed in 2019, 2021 and 2022 in a referral hospital were reviewed. Patients with new onset +ANCA tests during each year were studied and divided in two groups: +ANCA with AAV and +ANCA without AAV. Diagnosis of underlying AAV was based on ACR/EULAR 2022 criteria. Disease activity and prognosis at diagnosis were assessed with Birmingham Vasculitis Activity Score (BVAS) and Five Factor Score (FFS). ANCA testing was done by chemiluminescence assay using IO-FLASH (Inova, San Diego, CA). Results: We found new +ANCA tests in 46 of 1290 cases (3.6%), 45 of 1434 (3.1%) and 55 of 1687 (3.3%) in 2019, 2021 and 2022 respectively. They were diagnosed with AAV in 13 (28%), 22 (49%) and 14 (25%) cases in 2019, 2021, and 2022, respectively (Figure 1). The proportion was significantly higher in 2021 (p=0.031, Pearson Chi-Square test). The main features of AAV cases are summarized in Table 1. Mean age and sex were similar in pre-COVID (2019) and COVID (2021 and 2022) years. Although AAV severity (BVAS and FFS) were also similar, ANCA levels, proportion of PR3-ANCA, and granulomatosis with polyangiitis (GPA) were higher in AAV patients with new onset in COVID years (p=0.524, p=0.417 and p=0.480). In 2021 and 2022, 75 cases had +ANCA after vaccination or documented COVID-19 infection, with a median of 70 days [IQR95%C:28-168] and 134 days [IQR 95%CI: 74-202] until +ANCA test in AAV and no AAV cases respectively (p=0.012, Mann-Whitney U test). Conclusion: We observed similar rates of new onset +ANCA test in pre-COVID (2019) and during the COVID pandemic years (2021-2022). There was an increase of new AAV cases in 2021 probably coinciding in addition to COVID-19 pandemic with mass COVID-19 vaccination. No increased disease activity (BVAS) or worse prognosis (FFS) were observed. Also, may be a temporal relation of COVID-19 disease or vaccination with AAV cases during pandemic. REFERENCES: [1] Kronbichler A, et al. Int J Mol Sci. 2020. PMID: 33023023. [2] Irure-Ventura J, et al. iScience. 2022. PMID: 35937087. Acknowledgements: NIL. Disclosure of Interests: Ligia Gabrie: None declared, Fabricio Benavides-Villanueva: None declared, Hector Miguel Ulloa Alvarado: None declared, Mónica Renuncio-García: None declared, Diana Prieto-Peña: None declared, Vanesa Calvo-Río Abbvie, Lilly, Grünenthal, AMGEN, MSD, Novartis, Galápagos, Vifor, GSK and Otsuka, Ricardo Blanco Abbvie, Pfizer, Roche, Bristol-Myers-Squibb, Janssen, Lilly, Novartis, UCB and MSD, Abbvie, MSD and Roche.