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espanolEl registro de lupus de la Sociedad Espanola de Reumatologia (RELESSER) es un registro multicentrico de pacientes con lupus eritematoso sistemico seguidos en servicios de reumatologia espanoles, que contiene cuantiosa informacion sobre 4.024 pacientes. Hasta la fecha han sido publicados 14 analisis sobre la fase transversal del registro. Se describen los resultados mas relevantes, a criterio de los autores, concernientes a las caracteristicas clinicas acumuladas, nivel de actividad, tratamientos, refractariedad, dano y mortalidad. Se revisan asimismo los resultados de analisis especificos sobre el lupus incompleto, la nefritis lupica, las manifestaciones respiratorias, los eventos cardiovasculares, las infecciones graves, las neoplasias, la fibromialgia, el lupus en varones, el lupus en latinoamericanos y el lupus de inicio juvenil, comparando los diferentes subgrupos con el total de la cohorte. RELESSER se ha constituido como uno de los registros clinicos de lupus eritematoso sistemico mas importantes del mundo, resultando altamente productivo en terminos de generacion de conocimiento de la enfermedad en pacientes espanoles, util tambien para toda la comunidad cientifica. EnglishThe lupus register of the Spanish Society of Rheumatology (RELESSER) is a multicentre register of patients with systemic lupus erythematosus (SLE) under follow-up by Spanish Rheumatology Services. It contains data on a total of 4024 patients with SLE. So far, 14 studies have been published from the transversal phase of RELESSER. Here we report the more relevant contributions of those studies, according to the authors’ perspective, concerning cumulative clinical characteristics, level of activity, treatments, refractory disease, damage and mortality. We also review the main results of the analysis regarding incomplete SLE, lupus nephritis, respiratory manifestations, cardiovascular disease, serious infection, malignancies, fibromyalgia, SLE in males, SLE in Hispanics and juvenile-onset SLE, comparing the main characteristics of each subgroup to the global cohort. RELESSER has become one of the most important clinical SLE registers around the world, with a high yield in terms of knowledge generation about the disease in Spain, also useful for the entire scientific community.

The lupus register of the Spanish Society of Rheumatology (RELESSER) is a multicentre register of patients with systemic lupus erythematosus (SLE) under follow-up by Spanish Rheumatology Services. It contains data on a total of 4024 patients with SLE. So far, 14 studies have been published from the transversal phase of RELESSER. Here we report the more relevant contributions of those studies, according to the authors' perspective, concerning cumulative clinical characteristics, level of activity, treatments, refractory disease, damage and mortality. We also review the main results of the analysis regarding incomplete SLE, lupus nephritis, respiratory manifestations, cardiovascular disease, serious infection, malignancies, fibromyalgia, SLE in males, SLE in Hispanics and juvenile-onset SLE, comparing the main characteristics of each subgroup to the global cohort. RELESSER has become one of the most important clinical SLE registers around the world, with a high yield in terms of knowledge generation about the disease in Spain, also useful for the entire scientific community.

In the interest of digital security, 2-Factor Authentication (2FA), has been widely used throughout different sites and applications to secure and authenticate a user’s identity, Time-Based One-Time Password (TOTP) algorithm is one of the most utilized algorithms when it comes to 2FA due to its reliability when it comes to securing user access through generating a code that has a limited validity, usually for 30 seconds or less. TOTP generates a code with the use of current time and a secret key. Despite the security TOTP provides, the delivery of the code through SMS is still vulnerable to interception by a third party since the connection between the client and the server can be insecure. This paper proposes an enhancement to the TOTP algorithm by applying AES encryption to the generated code before delivering it to the client. This paper shows that the implementation of AES to the TOTP algorithm has helped generate a stronger OTP and has made it harder for hackers to crack

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministerio de Ciencia e Innovación (MCIN), through the Carlos III Institute of Health (ISCIII)-Fondo de Investigación Sanitaria (PI19/00545) Background Increasing evidences advocate for an important function of T cells in controlling immune homeostasis and pathogenesis after myocardial infarction (MI), although the molecular mechanisms remain elusive. Result and Methods In this study, a broad analysis of immune markers in 283 patients show a significant CD69 overexpression on Treg cells after MI. Our results in mice demonstrate that CD69 expression on Treg cells increases survival after left-anterior-descending coronary artery (LAD)-ligation. Cd69-/- mice develop strong IL17A+ gdT cell responses after ischemia that increase myocardial inflammation and, consequently, worsen cardiac function. CD69+ Treg cells induce apoptosis and decrease IL-17A production in gdT cells by a CD39-dependent mechanism. Adoptive transfer of CD69+ Treg cells to Cd69-/- mice after LAD-ligation reduces IL17A+ gdT cell recruitment increasing survival. Consistently, clinical data from two independent cohorts of patients indicate that increased CD69 expression in peripheral blood cells after acute MI is associated with a lower risk of re-hospitalization for chronic heart failure (CHF) after 2.5 years of follow-up. This result remained significant after adjustment for age, sex and traditional cardiac damage biomarkers (OR 0.929, 95% CI, 0.838-0.980; p Conclusion Our data highlight CD69 expression on T cells as a therapeutic and prognostic target to prevent CHF after MI.

The Deep Feature Synthesis (DFS) algorithm automates feature engineering and is capable of extracting and applying complicated featuresto a variety of processes. Due to the novelty of DFS as a method for feature engineering, critical ways for dealing with missing values and unwanted data in a dataset have yet to be established. This paper discusses the usage of mean, median, and mode imputation to preprocess data before analyzing it.However, it is only limited to displaying the differences between nonimputed and imputed datasets. This strategy enables users to obtain more precise results by eliminating biased estimations. This study demonstrates that there is a distinct difference between the two datasets. This paper is concluded by proving that imputing datasets will cause distinctness in the results compared to the results of the datasets with missing and unwanted values.

During recent decades, a tick-borne rickettsial syndrome, characterized by eschar and painful lymphadenopathy after Dermacentor marginatus-bite, has been described as an emerging rickettsiosis in Europe. Our group named it DEBONEL (Dermacentor-borne-necrosis-erythema-lymphadenopathy), regarding the vector and the main infection signs. Other groups called it TIBOLA (tick-borne-lymphadenophathy) and, later, SENLAT (scalp-eschar-and-neck-lymphadenopathy-after-tick-bite), expanding, in the latter, the etiological spectrum to other pathogens. Objective: To investigate the etiology of DEBONEL agents in our area, and to compare their epidemiological/clinical/microbiological characteristics. During 2001–2020, 216 patients clinically diagnosed of DEBONEL (the largest series from one center) in La Rioja (northern Spain) were examined. Rickettsia spp. were amplified in 14/104 (13.46%) blood samples, 69/142 (48.59%) eschar swabs, 7/7 (100%) biopsies, and 71/71 (100%) D. marginatus from patients. For samples in which Rickettsia was undetected, no other microorganisms were found. ‘Candidatus Rickettsia rioja’, Rickettsia slovaca, Rickettsia raoultii, and Rickettsia DmS1 genotype were detected in 91, 66, 4, and 3 patients, respectively. DEBONEL should be considered in patients with clinical manifestations herein described in areas associated to Dermacentor. The most frequently involved agent in our environment is ‘Ca. R. rioja’. The finding of Rickettsia sp. DmS1 in ticks attached to DEBONEL patients suggests the implication of other rickettsia genotypes.

Although thousands of long non-coding RNAs (lncRNAs) are encoded in mammalian genomes, their mechanisms of action are poorly understood, in part because they are often expressed at lower levels than their proposed targets. One such lncRNA is Xist, which mediates chromosome-wide gene silencing on one of the two X chromosomes (X) to achieve gene expression balance between males and females. How a limited number of Xist molecules can mediate robust silencing of a much larger number of target genes while maintaining specificity exclusively to genes on the X within each cell is not well understood. Here, we show that Xist drives non-stoichiometric recruitment of the essential silencing protein SHARP (also known as SPEN) to amplify its abundance across the inactive X, including at regions not directly occupied by Xist. This amplification is achieved through concentration-dependent homotypic assemblies of SHARP on the X and is required for chromosome-wide silencing. Expression of Xist at higher levels leads to increased localization at autosomal regions, demonstrating that low levels of Xist are critical for ensuring its specificity to the X. We show that Xist (through SHARP) acts to suppress production of its own RNA which may act to constrain overall RNA levels and restrict its ability to spread beyond the X. Together, our results demonstrate a spatial amplification mechanism that allows Xist to achieve two essential but countervailing regulatory objectives: chromosome-wide gene silencing and specificity to the X. This suggests a more general mechanism by which other low-abundance lncRNAs could balance specificity to, and robust control of, their regulatory targets.

Objetivo: Evaluar los casos de neumonía intrahospitalaria a pacientes con ventilación mecánica (NAVM), del hospital regional de alta especialidad Gustavo Adolfo Rovirosa Pérez en el área de urgencias, periodo enero 2016 a diciembre 2017. Métodos: Se realizó un estudio cuantitativo, observacional, retrospectivo y transversal. Se tomaron las variables de interés de pacientes críticos ingresados en el servicio de urgencias, con requerimientos de ventilación mecánica que desarrollaron neumonía 48 horas posteriores al inicio del apoyo ventilatorio. Se revisaron 97 expedientes clínicos, 30 cumplieron con los criterios de inclusión, se elaboró un formato para la recolección y elaboración de la base de datos, para el análisis de las variables se utilizó el software estadístico Spss versión 22. Resultados: La distribución del NAVM por género fue mayor en hombres (62.9%) que en mujeres (37.1%) y las edades oscilaron entre 18 y 86 años. Como diagnósticos de ingreso la causa principal fue el TCE severo (71.4%), seguido de trauma cráneo-facial (20%) y TCE moderado con mal manejo de secreciones (8.6%). Del total de expedientes analizados, 35 correspondieron a NAVM, con un promedio de evolución de 2 a 5 días y hasta más de 20 días. El 88.6% presentaron fiebre y la totalidad de las pacientes leucocitosis con un valor mínimo de 15,000. En las radiografías de tórax se observaron infiltrados y zonas de condensación en el 48.6% de los casos; en el caso del hemitórax afectado el más frecuente fue el derecho (62.9%), seguidos de daño bilateral (22.9%) y del izquierdo (14.3%). Conclusiones: El desarrollo de NAVM, está relacionado con el tiempo de exposición a la orointubación. Los signos clínicos y los cambios radiográficos, son relacionados a la sospecha de este tipo de neumonía y prácticamente en la totalidad de los casos, presentaron diagnósticos de ingreso relacionados a algún tipo de traumatismo., Objective: To evaluate the cases of nosocomial pneumonia in patients with mechanical ventilation (NAVM), from the regional hospital of high specialty Gustavo Adolfo Rovirosa Pérez in the emergency area, from January 2016 to December 2017. Methods: A quantitative, observational, retrospective and transversal study was carried out. The variables of interest were taken from critical patients admitted to the emergency department, with mechanical ventilation requirements that developed pneumonia 48 hours after the start of ventilatory support. 97 clinical files were reviewed, 30 met the inclusion criteria, a format for the collection and elaboration of the database was elaborated, for the analysis of the variables, the statistical software Spss version 22 was used. Results: The distribution of VAP by gender was higher in men (62.9%) than in women (37.1%) and the ages ranged between 18 and 86 years. The main cause of admission diagnoses was severe TBI (71.4%), followed by cranial-facial trauma (20%) and moderate TBI with poor secretion management (8.6%). Of the total of analyzed files, 35 corresponded to NAVM, with an average evolution of 2 to 5 days and up to more than 20 days. 88.6% presented fever and all patients with leukocytosis with a minimum value of 15,000. On chest radiographs, infiltrates and condensation zones were observed in 48.6% of the cases; in the case of the affected hemithorax, the most frequent was the right (62.9%), followed by bilateral (22.9%) and left (14.3%) injuries. Conclusions: The development of VAP, is related to the time of exposure to orointubation. Clinical signs and radiographic changes are related to the suspicion of this type of pneumonia and practically in all cases, they presented admission diagnoses related to some type of trauma.

Theranostic strategies involve select radionuclides that allow diagnostic imaging and tailored radionuclide therapy in the same patient. An example of a Food and Drug Administration-approved theranostic pair is the 68Ga- and 177Lu-labeled DOTATATE peptides, which are used to image neuroendocrine tumors, predict treatment response, and treat disease. However, when using radionuclides of 2 different elements, differences in the pharmacokinetic and pharmacodynamic profile of the agent can occur. Theranostic agents that incorporate the matched-pair radionuclides of scandium-43Sc/47Sc or 44Sc/47Sc-would guarantee identical chemistries and pharmacologic profiles. The aim of this study was to investigate production of 43,44,47Sc via proton-induced nuclear reactions on titanium nuclei using a 24-MeV cyclotron. Methods: Aluminum, niobium, and tantalum target holders were used with titanium foils and pressed TiO2 to produce scandium radionuclides with proton energies of up to 24 MeV. Irradiated targets were digested using NH4HF2 and HCl in a closed perfluoroalkoxy alkane vessel in 90 min. Scandium radionuclides were purified via ion-exchange chromatography using branched N,N,N',N'-tetra-2-ethylhexyldiglycolamide. The titanium target material was recovered via alkali precipitation with ammonia solution. Results: Titanium foil and TiO2 were digested with an average efficiency of 98% ± 3% and 95% ± 1%, respectively. The typical digestion time was 45 min for titanium foil and 75 min for TiO2 The average scandium recovery was 94% ± 3%, and the average titanium recoveries from digested titanium foil and TiO2 after precipitation as TiO2 were 108% ± 8% and 104% ± 5% of initial mass, respectively. Conclusion: This work demonstrated a robust method for the cyclotron production of scandium radionuclides that could be used with natural or enriched TiO2 target material.

A giant coronary artery aneurysm is an infrequent anomaly encountered as an incidental finding. An even more rare condition is its association with a coronary artery fistula. We report the case of a 61-year-old woman that combines two of the rarest coronary anomalies: a 70-mm giant circumflex aneurysm with an arteriovenous fistula tract draining to the superior vena cava. Considering the unique display of anatomy, the surgery was guided with 3-dimensional printing technology. Direct fistula occlusion near its outflow union, orifice source closure, aneurysmal sac exclusion, and two coronary artery bypass grafts were surgically performed. The postoperative course was satisfactory.

Resumen Las nuevas tecnologías y las redes sociales hoy en día forman parte de la formación médica en diversos ámbitos. Los cambios que veremos en la cirugía y el cambio generacional de los futuros cirujanos influirán en la manera en que la revolución tecnológica forme parte de la cirugía. En este artículo se revisan las nuevas condiciones de futuro que se afrontarán desde el mundo quirúrgico, la generación que será la base de dichos cambios, y las contribuciones, limitaciones y beneficios que las nuevas tecnologías pueden aportar.

This study aimed to identify species of Astyanax bimaculatus group from four Itaipu Reservoir tributaries (Paraná River Basin) by cytogenetics and molecular markers (COI) to investigate the possible occurrence of cryptic diversity in part of this basin. The four populations showed only one karyotype formula and simple AgNORs. FISH with 18S rDNA probe showed a high variation, and 5S rDNA probes evidenced simple sites in most of the specimens, although multiple sites are present in two specimens. The variations of 5S and 18S cistrons generated 13 cytotypes. The molecular data did not reveal cryptic diversity in the populations; however, its grouping with 82 sequences from other stretches of the Paraná River Basin originated three haplogroups (distances of 3.12% and 8.82%) and 33 haplotypes were identified. DNA Barcode suggests that cytogenetic variations represent a high polymorphism degree, and it identified the analyzed specimens as Astyanax lacustris, which confirms the morphological identification. Our data suggest that the cryptic diversity of this group in the tributaries of the Paraná River Basin is different than the proposed by the synonymizations of A. altiparanae and A. asuncionensis to A. lacustris. This study reinforces the importance of integrative cytogenetics and molecular methods for taxonomy. Resumo Este trabalho teve como objetivo identificar espécies do complexo Astyanax bimaculatus de quatro afluentes do reservatório de Itaipu (bacia do Rio Paraná) por métodos citogenéticos e moleculares (COI), investigando a possibilidade de ocorrência de diversidade críptica em parte desta bacia. As quatro populações apresentaram apenas uma fórmula cariotípica e AgNORs simples. A FISH com rDNA 18S apresentou alto grau de variação e as sondas de rDNA 5S evidenciaram sítios simples na maioria dos exemplares, embora sítios múltiplos tenham sido evidenciados em dois espécimes. As variações dos cistrons 5S e 18S geraram 13 citótipos. Os dados moleculares não revelaram diversidade críptica nas populações, entretanto, seu agrupamento com 82 sequências de outros trechos da mesma bacia formou três haplogrupos (distâncias de 3,12% e 8,82%) e gerou 33 haplótipos. O DNA Barcode sugere que as variações citogenéticas representam um alto grau de polimorfismo e identificou os espécimes analisados como Astyanax lacustris, confirmando a identificação por caracteres morfológicos. Nossos dados sugerem que a diversidade críptica do grupo nos afluentes da bacia do Rio Paraná é diferente do proposto pelas sinonimizações de A. altiparanae e A. asuncionensis para A. lacustris, reforçando a importância da integração de métodos citogenéticos e moleculares para a taxonomia.

Background: The CovidSurg-Cancer Consortium aimed to explore the impact of COVID-19 in surgical patients and services for solid cancers at the start of the pandemic. The CovidSurg-Gynecologic Oncology Cancer subgroup was particularly concerned about the magnitude of adverse outcomes caused by the disrupted surgical gynecologic cancer care during the COVID-19 pandemic, which are currently unclear. Objective: This study aimed to evaluate the changes in care and short-term outcomes of surgical patients with gynecologic cancers during the COVID-19 pandemic. We hypothesized that the COVID-19 pandemic had led to a delay in surgical cancer care, especially in patients who required more extensive surgery, and such delay had an impact on cancer outcomes. Study design: This was a multicenter, international, prospective cohort study. Consecutive patients with gynecologic cancers who were initially planned for nonpalliative surgery, were recruited from the date of first COVID-19- related admission in each participating center for 3 months. The follow-up period was 3 months from the time of the multidisciplinary tumor board decision to operate. The primary outcome of this analysis is the incidence of pandemic-related changes in care. The secondary outcomes included 30-day perioperative mortality and morbidity and a composite outcome of unresectable disease or disease progression, emergency surgery, and death. Results: We included 3973 patients (3784 operated and 189 nonoperated) from 227 centers in 52 countries and 7 world regions who were initially planned to have cancer surgery. In 20.7% (823/3973) of the patients, the standard of care was adjusted. A significant delay (>8 weeks) was observed in 11.2% (424/3784) of patients, particularly in those with ovarian cancer (213/1355 ; 15.7% ; P

BackgroundPatients with Rheumatoid Arthritis (RA) have an increased risk of infections. This may belinked to disease-related, the immunosuppressive therapy and the co-morbidities.Objectivesin an unselected group of RA patients, our aim was to assess the a)incidence b)features of disease and c)predictive factors of serious infections-related hospitalization.MethodsObservational study of all patients diagnosed with RA that were included in the vaccination program of our university hospital between October2011 and October 2016.The minimum follow-up was of 12 months; therefore, it was made until December 2020.Patients with serious infections-related hospitalization were a) compared with those not requiring hospital admission and, b)identified predictive factors (multivariate analysis adjusted by age and sex).Vaccination program in our hospital includes vaccination for Influenza, Streptococcus pneumoniae and Haemophilus influenzae.Information on patients, infections and hospitalizations was retrieved from the hospital and general physician records.ResultsWe studied 392RApatients (309women/83men); mean age 63.1±13.7 years.After a mean follow-up of 71.8±20.6 months, in 88 of 392patients (22.4%) (60 women) 187serious infections-related hospitalizations were required. The median [IQR] number of hospitalizations were 1.5 [1-2]. The main serious infections were respiratory (44 patients; 78 hospitalizations), urinary (33 patients; 48 hospitalization), cutaneous (19 patients; 28 hospitalizations), abdominal (17 patients, 20 hospitalizations), septic arthritis (7 patients; 8 hospitalizations), maxillofacial(2 patients, 2 hospitalizations), bacterial endocarditis (2 patients, 2 hospitalizations) and genital (1 patient, 1 hospitalization).Patients with serious infections-related hospitalization were older, with a longer RA, with more co-morbidities (hypertension, hypercholesterolemia diabetes mellitus, and Interstitial lung disease) and with more conventional and biological DMARDS (Table 1).Table 1.Comparative study of different groupsPatientswithserious infections-related hospitalization N=88Patients without serious infections-related hospitalization N=304pDemographic features and comorbiditiesAge (years),mean±SD69.7±11.259.2±12.60.005Women, n (%)60 (68.2)249 (81.9)0.33Active smokers, n (%)41 (46.6)114 (7.5)0.32Hypertension, n (%)56 (63.6)109 (35.8)0.004Hypercholesterolemia, n(%)47 (53.4)101 (33.2)0.02Diebetes Mellitus, n(%)25 (28.4)30 (9.9)0.0002RA featuresDuration of RA (months) mean±SD165.8±130.1128.6±102.60.005Positive RF, n (%)52(59.1)171(56.2)0.80Positive ACPA, n (%)48 (54.5)158 (52.6)0.81Erosive disease, n (%)32 (36.4)113 (51.9)0.89Associated Sjögren Syndrome, n (%)4 (4.5)16 (5.3)0.79Interstitial lung disease n (%)11 (12.5)9 (2.9)0.0008Subcutaneousnodules n (%)6 (6.8)16 (5.3)0.57Prednisone (or equivalent) dose mg/day, mean±SD5.3±4.53.3±3.80.001Number of convencional DMARDs, mean±SD1.9±1.41.5±1.30.05Number of biologic DMARDs, mean±SD0.1±0.20.1±0.40.03Number of JAK inhibitors, mean±SD69.7±11.259.2±12.60.1The predictive factors for hospitalization were hypertension and Diabetes Mellitus, RA related interstitial lung disease and treatment with biologic DMARDs. (Figure 1)Figure 1.Predictive factors for serious infections-related hospitalizationConclusionDespite to be included in a vaccination program up to 22% of patients required hospitalization due to serious infection. The main predictive factors were co-morbidities, interstitial lung disease and treatment with biologic DMARDs. Serious infections in RA remain to be an unmet need.Disclosure of InterestsNone declared

BackgroundTocilizumab (TCZ) is the only biologic drug approved in giant cell arteritis (GCA), based in two clinical trials (CT) (1,2). CT included selected patients who may differ from those of clinical practice (CP). A high proportion of GCA patients treated with TCZ in CT had a newly diagnosed GCA, whereas in CP, most of them are refractory/recurrent GCA (3,4). Although in CT the efficacy of TCZ seems to be similar in patients with newly diagnosed GCA and in patients with refractory/recurrent GCA, in CP it is not documented.ObjectivesTo compare in CP, the effectiveness and safety of TCZ in newly diagnosed vs refractory/recurrent GCA.MethodsMulticentre observational study on 471 GCA patients treated with TCZ. GCA was diagnosed by: a) ACR criteria, and/or b) temporal artery biopsy, and/or c) imaging techniques. A comparative study between patients with newly diagnosed GCA (6 weeks) (according to GiACTA study definitions) (2). Sustained remission was based on EULAR definitions (5).ResultsThe 471 GCA patients were divided into 2 subgroups: a) newly diagnosed GCA (n=91) and b) refractory/recurrent GCA (n=380) (Table 1).Table 1.Main features of patients with newly diagnosed GCA and refractory/recurrent GCA treated with tocilizumab.Newly diagnosed GCA (n=91)Refractory/recurrent GCA (n=380)pBaseline characteristics at TCZ onset Age(years), mean±SD74.3±8.573.3±9.10.35 Sex, female/male (% female)60/31 (66)282/98 (74)0.11 Time from GCA diagnosis to TCZ onset (months), median [IQR]1 [0.5-1]10 [4-24]0.0001 ESR, mm 1st hour, median [IQR]46 [17.5-80.5]27 [10-50]0.02 CRP, mg/dL, median [IQR]2.1 [0.7-8.5]1.3 [0.4-2.8]0.13 Haemoglobin, g/dL, mean±SD12.3±1.512.7±1.50.03 Prednisone dose, mg/day, median [IQR]40 [21.2-50]15 [10-30]Effectiveness and Safety after TCZ onsetFollow-up, (months), median [IQR]15 [6-27.5]22 [11-37]0.004Relevant adverse events, n (%)23 (25)102 (27)0.54Relevant adverse events per 100 patients-year2015NSSerious infections, n (%)13 (14)53 (14)0.49Serious infections per 100 patients-year11.28NSMACES, n (%)0 (0)1 (0.3)-MACES per 100 patients-year00.2-Malignancies n (%)2 (2)3 (0.8)0.99Malignancies per 100 patients-year1.60.5NSAbbreviations: CRP: C-reactive protein;ESR: erythrocyte sedimentation rate;GCA: giant cell arteritis; IQR: interquartile range; IV: intravenous; MACEs: major adverse cardiovascular events; NS: non significant; SC: subcutaneous; SD: standard deviationNo significant differences were observed between both groups in sustained remission, although a greater tendency towards sustained remission is observed in newly diagnosed than in refractory/recurrent GCA patients (Figure 1). The decrease in glucocorticoids dose was faster in the first three months in the newly diagnosed GCA group, but thereafter, was similar in both groups, as well as the appearance of relevant adverse events and serious infections.Figure 1.A) Sustained remission, and B) median prednisone dose required in patients with newly diagnosed GCA and in patients with refractory/recurrent GCA treated with tocilizumab.ConclusionThe effectiveness and safety of TCZ seems to be similar in patients with newly diagnosed GCA and in patients with refractory/recurrent GCA.References[1]Villiger PM, et al. Lancet. 2016; 387:1921-1927. PMID: 26952547[2]Stone JH, et al. N Engl J Med. 2017; 377:317-328. PMID: 28745999[3]Calderón-Goercke M, et al. Semin Arthritis Rheum. 2019; 49: 126-135. PMID: 30655091[4]Calderón-Goercke M, et al. Clin Exp Rheumatol. 2020; 124: S112-119. PMID: 32441643[5]Hellmich B, et al. Ann Rheum Dis. 2020; 79: 19-30. PMID: 31270110AcknowledgementsTocilizumab in Giant Cell Arteritis Spanish Collaborative Group: Juan C. González Nieto (H. Gregorio Marañón), Juan R. de Dios (H.U. Araba), Esther Fernández (H. Clínico Universitario Virgen de la Arrixaca), Isabel de la Morena (H. Clínico Universitario de Valencia), Patricia Moya (H. Sant Pau), Roser Solans i Laqué (H. Valle de Hebrón), Eva Pérez Pampín (H.U. de Santiago), José L. Andréu (H.U. Puerta de Hierro), Marcelino Revenga (H. Ramón y Cajal), Juan P. Baldivieso Achá (H. U. de La Princesa), Eztizen Labrador (H. San Pedro), Andrea García-Valle (Complejo Asistencial Universitario de Palencia), Adela Gallego (Complejo Hospitalario Universitario de Badajoz), Carlota Iñíguez (H.U. Lucus Augusti), Cristina Hidalgo (Complejo Asistencial Universitario de Salamanca), Noemí Garrido-Puñal (H. Virgen del Rocío), Ruth López-González (Complejo Hospitalario de Zamora), José A. Román-Ivorra (H.U. y Politécnico La Fe), Sara Manrique (H. Regional de Málaga), Paz Collado (H.U. Severo Ochoa), Enrique Raya (H. San Cecilio), Valvanera Pinillos (H. San Pedro), Francisco Navarro (H. General Universitario de Elche), Alejandro Olivé-Marqués (H. Trías i Pujol), Francisco J. Toyos (H.U. Virgen Macarena), María L. Marena Rojas (H. La Mancha Centro), Antoni Juan Más (H.U. Son Llàtzer), Beatriz Arca (H.U. San Agustín), Carmen Ordás-Calvo (H. Cabueñes), María D. Boquet (H. Arnau de Vilanova), Noelia Álvarez-Rivas (H.U. Lucus Augusti), María L. Velloso-Feijoo (H.U. de Valme), Cristina Campos (H. General Universitario de Valencia), Íñigo Rúa-Figueroa (H. Doctor Negrín), Antonio García (H. Virgen de las Nieves), Carlos Vázquez (H. Miguel Servet), Pau Lluch (H. Mateu Orfila), Carmen Torres (Complejo Asistencial de Ávila), Cristina Luna (H.U. Nuestra Señora de la Candelaria), Elena Becerra (H.U. de Torrevieja), Nagore Fernández-Llanio (H. Arnáu de Vilanova), Arantxa Conesa (H.U. de Castellón), Eva Salgado (Complejo Hospitalario Universitario de Ourense).Disclosure of InterestsJulio Sanchez-Martin: None declared, Javier Loricera: None declared, Clara Moriano: None declared, Santos Castañeda: None declared, J. Narváez: None declared, Vicente Aldasoro: None declared, Olga Maiz: None declared, Rafael Melero: None declared, Ignacio Villa-Blanco: None declared, Paloma Vela-Casasempere: None declared, Susana Romero-Yuste: None declared, Jose Luis Callejas-Rubio: None declared, Eugenio de Miguel: None declared, E. Galíndez-Agirregoikoa: None declared, Francisca Sivera: None declared, Carlos Fernández-López: None declared, Carles Galisteo: None declared, Iván Ferraz-Amaro: None declared, Lara Sanchez-Bilbao: None declared, Monica Calderón-Goercke: None declared, Jose Luis Hernández Hernández: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Grant/research support from: Abbvie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Grant/research support from: Abbvie, MSD and Roche

BackgroundLarge vessel involvement in Giant Cell Arteritis (GCA), especially the aorta and/or its main branches, is frequent. Tocilizumab (TCZ) has shown efficacy and safety in GCA and other large-vessel vasculitis (1-4).ObjectivesTo assess the efficacy and safety of TCZ in GCA patients with involvement of the aorta and/or its main branches.MethodsMulticenter observational study of 196 patients with GCA and involvement of the aorta and/or its major branches treated with TCZ. GCA was diagnosed by: a) ACR criteria, and/or b) temporal artery biopsy, and/or c) imaging techniques. The presence of aortitis was performed by imaging techniques, mainly PET, and A-MRI.Maintained remission was considered according to EULAR definitions (5).ResultsThe main features of the 196 patients are showed in Table 1. Polymyalgia rheumatica, constitutional syndrome and headache were the most frequent clinical manifestations at TCZ onset. At 6 months after starting TCZ, 20% of the patients reached a sustained remission, that was progressively increasing. (Figure 1). A corticosteroid-sparing effect was observed from month 1 of TCZ onset (Figure 1). Relevant adverse events were observed in 12 per 100 patients-year, documenting serious infections in 4.8 per 100 patients-year (Table 1).Table 1.Main features of 196 GCA patients with involvement of the aorta and/or its main branches treated with TCZ.GCA (n=196)Features at TCZ onsetAge(years), mean±SD71.3±9.5Sex, female/male (% female)148/48 (75)Time from GCA diagnosis to TCZ onset (months), median [IQR]7 [2-18.25]Systemic manifestations, n (%)Fever, n (%)24 (12)Constitutional syndrome, n (%)87 (44)PmR, n (%)131 (67)Ischaemic manifestations, n (%)Visual involvement, n (%)16 (8)Headache, n (%)74 (38)Jaw claudication, n (%)27 (14)Laboratory dataESR, mm 1st hour, median [IQR]32 [14-54]CRP, mg/dL, median [IQR]1.5 [0.6-3.2]Prednisone dose, mg/day, median [IQR]15 [10-30]Safety after TCZ onsetRelevant adverse events, per 100 patients-year12Serious infections, per 100 patients-year4.8Figure 1.A) Sustained remission, and B) median prednisone dose required in GCA patients with aortitis treated with tocilizumabConclusionTCZ seems to be effective and relatively safe in GCA patients with involvement of the aorta and/or its main branches.References[1]Calderón-Goercke M, et al. Semin Arthritis Rheum. 2019; 49: 126-135. PMID: 30655091[2]Loricera J, et al. Clin Exp Rheumatol. 2016; 34: S44-53. PMID: 27050507[3]Loricera J, et al. Clin Exp Rheumatol. 2015; 33: S19-31. PMID: 25437450[4]Prieto-Peña D, et al. Ther Adv Musculoskelet Dis. 2021; 13: 1759720X211020917. PMID: 34211589[5]Hellmich B, et al. Ann Rheum Dis. 2020; 79: 19-30. PMID: 31270110Disclosure of InterestsLara Sanchez-Bilbao: None declared, Javier Loricera Speakers bureau: from Roche, Novartis, UCB Pharma, Celgene, and Grünenthal., Rafael Melero: None declared, Santos Castañeda Speakers bureau: UAM-Roche, EPID- Future chair, Department of Medicine, Universidad Autónoma de Madrid, Madrid, Spain., Clara Moriano: None declared, Iván Ferraz-Amaro: None declared, J. Narváez: None declared, Vicente Aldasoro: None declared, Olga Maiz: None declared, Ignacio Villa-Blanco: None declared, Paloma Vela-Casasempere: None declared, Susana Romero-Yuste: None declared, Jose Luis Callejas-Rubio: None declared, Eugenio de Miguel: None declared, E. Galíndez-Agirregoikoa: None declared, Francisca Sivera: None declared, Carlos Fernández-López: None declared, Carles Galisteo: None declared, Julio Sanchez-Martin: None declared, Monica Calderón-Goercke: None declared, J. Luis Hernández: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, and MSD., Grant/research support from: AbbVie, MSD, Jansen, and Roche,, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD., Grant/research support from: Abbvie, MSD, and Roche

BackgroundTocilizumab (TCZ) has shown to be effective for large vessel vasculitis including giant cell arteritis (GCA) and Takayasu arteritis (TAK) (1-5). However, LVV-GCA and TAK show different demographic and clinical features that may influence on TCZ therapeutic response.ObjectivesTo compare the effectiveness of TCZ in patients with LVV-GCA and patients with TAK.MethodsObservational multicenter study of patients with LVV-GCA and TAK who received TCZ. Outcome variables were: a) proportion of patients who achieved complete clinical improvement along with normalization of laboratory markers (CRP ≤0.5mg/dL and/or ESR ≤ 20 mm/1st hour) at 12 months b) complete improvement in imaging techniques. A comparative study between patients with LVV-GCA and TAK was performed.ResultsWe evaluated 70 LVV-GCA and 57 TAK patients who received TCZ. Main clinical and demographic characteristic are described in Table 1. Patients with TAK were younger, had longer disease duration, had received more commonly previous biologic therapy and were receiving higher doses of prednisone at baseline. TCZ intravenous administration was more common in TAK patients (80.7% vs 48.6%; pTable 1.LVV-GCA (n=70)TAK (n=57)pGeneral featuresAge (years), mean ± SD67.2 ± 10.540.5 ± 16.3< 0.01Sex (female), n (%)51 (72.9)49 (86)0.07Disease evolution before TCZ onset (months), median [IQR]5 [2-15]12 [3-37]Baseline laboratory parametersESR (mm/1st hour), median [IQR]32 [12.5-54.7]31 [10-52]0.82CRP (mg/dL), median [IQR]1.4 [0.5-2.4]1.4 [0.5-3.5]0.41Baseline prednisone dose (mg/day), median [IQR]15 [10-20]30 [15-50]< 0.01Previous therapyConventional DMARDs, n(%)45 (64.3)44(77.2)0.51Biologic therapy, n (%)0(0)12 (21.1)TCZ therapyIntravenous, n (%)34 (48.6)46 (80.7)< 0.01Combined with MTX, n(%)24 (34.3)24 (42.1)0.37Follow-up time after TCZ onset, median [IQR]20 [10-36]18 [7-41]0.73Complete clinical improvement and ESR/CRP normalization at 12 months, n/N (%)35/47 (74.4)30/39 (76.9)0.79Complete improvement in imaging techniques, n/N(%)7/37 (18.9)8/38 (21.1)0.85CRP: C-reactive protein; DMARDs: Disease-modifying anti-rheumatic drugs ESR: erythrocyte sedimentation rate; GCA: giant cell arteritis; IQR: interquartile range; LVV: large vessel; MTX: methotrexate; n: Number of patients; N: total number of patients: TCZ: tocilizumab; TAK:takayasuFigure 1.ConclusionThe effectiveness of TCZ was similar in patients with LVV-GCA and TAK, despite a more refractory disease in TAK patients. A discordance between clinical and imaging activity improvement was observed in both LVV-GCA and TAK, as reported in previous studies (3).References[1]Calderón-Goercke M, et al. Semin Arthritis Rheum 2019; 49:126-35. https://doi.org/10.1016/j.semarthrit.2019.01.003[2]Prieto-Peña D et al. Ther Adv Musculoskelet Dis. 2021;13:175. PMID: 34211589.[3]Prieto Peña D et al. Clin Exp Rheumatol. 2021;39 Suppl 129:69-75. PMID: 33253103.[4]González-Gay MA, et al. Expert Opin Biol Ther. 2019;19:65-72. doi: 10.1080/14712598.2019.1556256.[5]Prieto-Peña D, et al. Semin Arthritis Rheum. 2019;48(4):720-727. doi: 10.1016/j.semarthrit.2018.05.007Disclosure of InterestsNone declared

BackgroundEpidemiological information on Giant Cell Arteritis (GCA) comes mainly from the Scandinavian countries of northern Europe, which show a higher incidence than the countries of southern Europe. GCA clinical manifestations can be divided into cranial, extracranial, and general syndrome.ObjectivesIn a large series of GCA from Spain, we studied a) the incidence of GCA, b) clinical manifestations, and c) comorbidities at the time of disease diagnosis.MethodsARTESER is a retrospective epidemiological observational study of GCA promoted by the Spanish Society of Rheumatology in which 26 hospitals participate. The inclusion criteria were: all new patients diagnosed with GCA by a) ACR criteria, b) positive diagnostic test (temporal artery biopsy, temporal artery ultrasound or other relevant imaging techniques) and/or c) investigator’s clinical judgment. The patient recruitment period ranged from June 1, 2013 to March 29, 2019. The overall incidence of GCA per 100,000 people ≥50 years for the whole period and the mean annual incidence were evaluated. The clinical variables were collected by reviewing the patient’s medical history.Results1675 patients were included. The average annual incidence rate was 7.42 (95% CI: 6.57-8.27). All the cases were older than 50 years, and the age group with the highest annual incidence was that of 80 to 84 years, where it reached a value of 22.63 (95% CI: 22.04 -23.22). The mean annual incidence is higher in women than in men 10.07 (95% CI: 8.74-11.55) vs 4.81 (95% CI 3.84-5.93) (Table 1).Table 1.General characteristics, comorbidities and clinical manifestationsEpidemiologic, demographic and diagnosisMenWomenTotalGender, n (%)497 (29.7)1178 (70.3)1675Incidence annual rate (95% CI)4.81 (3.84-5.93)10.07 (8.74-11.55)7.42 (6.57-8.27)Age at diagnosis, years, mean (SD)76.9 (8.3)76.9 (8.0)76.9 (8.1)Diagnosis only by ACR Criteria89 (17.91)266 (22.58)355 (21.19)Diagnosis only with objective tests73 (14.69)140 (11.88)213 (12.72)Diagnosis ACR criteria + diagnosis objective tests311 (62.58)734 (62.31)1045 (62.39)Diagnosis by clinical judgment24 (4.8)38 (3.2)62 (3.7)Comorbidities at diagnosisArterial hypertension, n (%)330 (66.8)749 (63.7)1079 (64.6)Dyslipidemia, n (%)238 (48.3)563 (47.9)801 (48.0)Cranial clinical manifestationsNew-onset headache, n (%)382 (76.9)955 (81.1)1337 (79.9)Visual Clinic, n (%)194 (39.0)411 (34.9)605 (36.1)Extracranial manifestations and general syndromePolymyalgia rheumatica, n (%)178 (35.8)521 (44.3)699 (41.8)Asthenia, n (%)239 (48.1)634 (53.9)873 (52.2)Analysis at diagnosisErythrocyte sedimentation rate mm/h, mean (SD)72.3 (34.7)77.4 (33.0)75.9 (33.6)The principal clinical characteristics of the population is shown in Table 1, the mean age at diagnosis was 76.9±8.1 years, 1178 (70.3%) were women. 1045 patients (62.39%) had ACR criteria and some positive objective test, 355 patients (21.9%) presented only ACR criteria and 213 (12.72%) only had a positive diagnostic test; 62 (3.7%) of the patients underwent diagnosis based on clinical judgment. The more frequent comorbidity was arterial hypertension (n=1079; 64.6%), followed by dyslipidemia (n=801, 48%). The predominant cranial manifestation was headache (n= 1337; 79.9%) and 605 patients experienced visual symptoms (36.1%). Polymyalgia rheumatica (n=699; 41.8%) and asthenia (n=837; 52.2%) were the most frequent extracranial and general syndrome manifestation, respectively. Regarding laboratory parameters, the most characteristic data was the increase of ESR (75.9±33.6 mm/1st h).ConclusionThe mean annual incidence of GCA in Spain, 7.42 (95% CI: 6.57-8.27), is lower than that of the Scandinavian countries. It is higher in people older than 80 years. More than 60% of the patients met the ACR criteria and had a positive diagnostic test. Cranial manifestations constituted the most clinical features. The most frequent clinical manifestations are cranial. Up to a third of patients had visual manifestations.AcknowledgementsThis study has been funded by ROCHE Farma. The funder has not participated in the design, analysis, or interpretation of the resultsDisclosure of InterestsNone declared

BackgroundAxial spondyloarthritis (axSpA) is characterised by inflammation of the sacroiliac joints (SIJ) and the spine. Secukinumab (SEC) treatment was clinically efficacious and reduced SIJ bone marrow oedema as detected by magnetic resonance imaging (MRI) in patients (pts) with non-radiographic (nr)-axSpA through 52 weeks in the PREVENT (NCT02696031) study.1ObjectivesTo report radiographic progression and the course of inflammation as assessed by X-ray and MRI of SIJ and spine over 2 years in the PREVENT study.MethodsStudy design and key endpoints have been reported earlier.1 In total, 555 pts were randomised (1:1:1) to receive SEC 150 mg, with (LD) or without loading (NL) doses, or placebo (PBO). Switch to open-label (OL) SEC or standard of care (SoC) was permitted after Week (Wk) 20. All pts (except those who switched to SoC) received OL SEC from Wk 52. Radiographs of the spine and SIJ were collected at baseline (BL) and Wk 104; MR images of the spine and SIJ were collected at BL, Wk 16, 52, and 104. Spinal radiographs were scored using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and SIJ radiographs according to modified New York criteria (mNYC). Pts whose screening SI joint radiographs fulfilled mNY criteria during the eligibility reading session were excluded from the study. Spinal MR images were assessed for signs of inflammation with the Berlin score. SIJ bone marrow oedema was assessed according to the Berlin Active Inflammatory Lesions Scoring. All images were evaluated in blinded fashion independently by 2 central readers. All data are reported from the Wk 104 reading session and are presented as observed.ResultsThe vast majority (98%) of pts treated with SEC 150 mg (pooled LD and NL) showed no structural progression, defined as change in total mSASSS score ≤ smallest detectable change (SDC) of 0.76 (80% agreement level) over 2 years. At BL, 62 pts (43 in SEC, 19 in PBO) presented with ≥1 syndesmophyte (≥1 vertebral unit scored by ≥1 reader). Among these pts, 9 in SEC (20.9%) and 7 in PBO (36.8%) groups had developed ≥1 new syndesmophyte by Wk 104. Among 237 SEC and 117 PBO pts without syndesmophytes at BL, only 4 pts on SEC (1.7%) and 4 pts on PBO (3.4%) developed ≥1 new syndesmophyte by Wk 104. SIJ radiographs showed that 88% of pts on SEC and 86% on PBO had no progression in SIJ (defined as change ≤ SDC (0.46) in total mNYC score) by Wk 104. No patient had an increase in total mNYC score of 2 or more. When screening radiographs of eligible pts were scored alongside post-BL images in the final reading campaign, approximately 25% of pts (68/277 and 34/139 pts in the SEC and PBO groups, respectively) were evaluated as mNY-positive at screening (pts were considered mNY-positive if ≥1 reader evaluated them as mNY-positive). Of these, 11/68 pts in the SEC (16.2%) and 5/34 in the PBO (14.7%) groups were evaluated as mNY-negative at Wk 104. In the SEC and PBO groups, 202 (96.7%) and 102 (97.1%) pts who were mNY-negative at screening stayed negative through Wk 104, respectively. Only 7 pts in the SEC (3.3%) and 3 in the PBO (2.9%) groups who were mNY-negative at BL were scored as mNY-positive at Wk 104. In both groups, fewer pts progressed from mNY-negative to mNY-positive than had a change in the opposite direction (from positive to negative), resulting in an overall negative net progression. Spinal inflammation on MRI (Berlin score) was low at BL with a mean of 0.82 in SEC and 1.07 in PBO groups with no meaningful change up to Wk 104 (mean of 0.56, SEC). SEC reduced SIJ bone marrow oedema score versus PBO at Wk 16 and Wk 52 with sustained reduction through Wk 104 in the overall patient population, with greater reduction in pts with BL score >2 (Figure 1).ConclusionMost pts initially randomised to SEC or PBO showed no radiographic progression through 2 years. There was some discrepancy between SIJ eligibility and efficacy reads. SEC reduced SIJ inflammation (bone marrow oedema) on MRI in pts with active nr-axSpA.References[1]Deodhar A, et al. Arthritis Rheumatol. 2021;73:110–20.Disclosure of InterestsJuergen Braun Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Medac, MSD (Schering-Plough), Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB pharma, Eli Lilly, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB, Eli Lilly, Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB, Eli Lilly, Ricardo Blanco Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, UCB pharma, MSD, Eli Lilly, Consultant of: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, UCB pharma, MSD, Grant/research support from: AbbVie, MSD, Roche, Helena Marzo-Ortega Speakers bureau: AbbVie, Celgene, Janssen, Eli Lilly and Company, Novartis, Pfizer, Takeda, UCB, Consultant of: AbbVie, Celgene, Janssen, Eli Lilly and Company, Novartis, Pfizer, Takeda, UCB, Grant/research support from: Janssen, Novartis, UCB, Lianne S. Gensler Consultant of: Gilead, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Grant/research support from: UCB, Pfizer, Filip van den Bosch Speakers bureau: AbbVie, BMS, Celgene, Galapagos, Janssen, Eli Lilly, Merck, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Celgene, Galapagos, Janssen, Eli Lilly, Merck, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, BMS, Celgene, Galapagos, Janssen, Eli Lilly, Merck, Novartis, Pfizer, UCB, Stephen Hall Speakers bureau: Novartis, Merck, Janssen, Pfizer, Eli Lilly, UCB, Consultant of: Novartis, Merck, Janssen, Pfizer, Eli Lilly, UCB, Grant/research support from: AbbVie, UCB, Janssen, Merck, Hideto Kameda Speakers bureau: Abbvie, Asahi-Kasei, Astellas, BMS, Chugai, Eisai, Eli Lilly, Gilead Sciences, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Consultant of: Abbvie, Astellas, Boehringer, Eli Lilly, Gilead Sciences, Janssen, Novartis, Sanofi, UCB, Grant/research support from: Abbvie, Asahi-Kasei, Boehringer, Chugai, Eisai, Mitsubishi-Tanabe, Denis Poddubnyy Speakers bureau: AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, Biocad, BMS, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Samsung Bioepis, UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, Marleen G.H. van de Sande Speakers bureau: Novartis, MSD, Consultant of: Abbvie, Novartis, Eli Lily, Grant/research support from: Novartis, Eli Lilly, Janssen, UCB, Désirée van der Heijde Paid instructor for: Novartis, AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Pfizer, UCB Pharma, and Director of Imaging Rheumatology BV, Tingting Zhuang Shareholder of: Novartis, Employee of: Novartis, Anna Stefanska Shareholder of: Novartis, Employee of: Novartis, Aimee Readie Shareholder of: Novartis, Employee of: Novartis, Hanno Richards Shareholder of: Novartis, Employee of: Novartis, Atul Deodhar Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB

BackgroundPatients (pts) with axial spondyloarthritis (axSpA) often experience delayed diagnosis, which can lead to treatment delay1. However, earlier diagnosis and treatment of axSpA pts can lead to a greater clinical response2. Secukinumab (SEC) 150 mg has demonstrated sustained improvement in signs and symptoms over 2 years in non-radiographic (nr)-axSpA pts3.ObjectivesTo assess the efficacy of SEC in pts with nr-axSpA [tumour necrosis factor (TNF) naïve] by subgroups of younger versus (vs) older pts and early vs late symptom duration of back pain.MethodsPREVENT (NCT02696031) is a phase 3, randomised study in pts with nr-axSpA and detailed study design is reported previously4. In this post hoc analysis, efficacy outcomes including Assessment of SpondyloArthritis international Society 40 (ASAS40), ASAS partial remission (ASAS PR), Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) inactive disease (ID) and low disease activity (LDA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the proportion of pts meeting the minimal clinically important difference criteria for total back pain (improvement of ≥50%) were assessed in the TNF naïve population. Age categories included 4 approximately equally distributed age groups (18 to 33, 34 to 42, 43 to 51 and ≥52 years). The categories for time since onset of back pain as a surrogate of disease symptoms and sign, was based on patients’ distribution and the hypothesis that patients with shorter disease duration will present better results (≤2, >2 to 5, >5 to 10 and >10 years). Missing responses were imputed as non-response up to Week (Wk) 16 and reported as observed at Wks 52 and 104. Data is presented here for categories 18-33 vs ≥52 years and patients with symptom duration ≤2 vs >10 years.ResultsAt Wk 104, greater improvements in ASAS40 scores were reported in younger (18-33 years) vs older age categories (>52 years) treated with SEC and also in patients with shorter disease duration (≤2 years) when compared to long term disease (Figure 1 and Table 1).Table 1.Efficacy responses with SEC up to Week 104 based on age and symptom durationAge 18-33 yearsAge >52 years≤2 years of back pain>10 years of back painSEC 150 mg LD (N=61)SEC 150 mg NL (N=59)PBO (N=61)SEC 150 mg LD (N=25)SEC 150 mg NL (N=33)PBO (N=28)SEC 150mg LD (N=51)SEC 150 mg NL (N=33)PBO (N=47)SEC 150 mg LD (N=50)SEC 150 mg NL (N=46)PBO (N=49)ASDAS-CRP ID and LDA50.8*55.9*34.4*36.0*39.4*21.4*51.0*48.5*40.4*44.0*30.4*26.5*77.4#81.1#72.2#45.8#46.7#33.3#77.3#60.0#77.3#53.3#48.7#37.2#71.7†70.2†77.6†50.0†57.1†60.9†74.4†69.2†82.1†55.3†53.3†53.8†BASDAI 5045.9*47.5*27.9*28.0*36.4*17.9*45.1*51.5*29.8*34.0*23.9*20.4*77.8#71.7#72.2#37.5#53.3#37.0#75.6#60.0#75.0#46.7#46.2#43.2#73.5†72.3†77.6†47.6†60.9†52.2†78.0†65.4†76.9†53.8†53.1†51.3†ASAS PR29.5*32.2*8.2*12.0*12.1*7.1*27.5*24.2*8.5*18.0*10.9*12.2*41.5#50.9#38.9#12.5#20.0#22.2#45.5#40.0#38.6#22.2#23.1#20.5#46.9†44.7†59.2†23.8†31.8†21.7†56.1†34.6†46.2†25.6†25.8†23.1†Total back pain50.8*50.8*27.9*24.0*30.3*32.1*51.0*48.5*36.2*32.0*23.9*32.7*74.1#75.5#72.2#58.3#46.7#44.4#73.3#63.3#72.7#53.3#48.7#47.7#71.4†68.1†79.6†61.9†52.2†52.2†75.6†69.2†74.4†61.5†50.0†59.0†Data is presented as % of responders. Symbols are used to denote the Weeks. *Week 16; #Week 52; †Week 104. All patients received open-label SEC 150 mg treatment after Week 52 up to Week 104. ASDAS-CRP ID and LDA (ASDAS-CRP . LD, loading dose; NL, without loading; PBO, placeboConclusionEfficacy responses were numerically higher with SEC in patients with nr-axSpA with shorter symptom duration and in younger age. These data suggest that earlier treatment improves patient outcomes in nr-axSpA.References[1]Lapane KL, et al. BMC Fam Pract. 2021;22(1):251[2]Poddubnyy D, Sieper J. Curr Rheumatol Rep. 2020;22(9):47[3]Poddubnyy D, et al. Ann Rheum Dis. 2021;80 (suppl1):707[4]Deodhar A et al. Arthritis Rheumatol. 2021;73(1):110-120Disclosure of InterestsAtul Deodhar Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly, Glaxo Smith & Kline, Novartis, Pfizer, UCB, Denis Poddubnyy Speakers bureau: AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, UCB, Roche, Consultant of: AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, UCB, Roche, Grant/research support from: AbbVie, MSD, Novartis, Pfizer, Ricardo Blanco Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, UCB pharma, MSD and Lilly, Consultant of: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, UCB pharma and MSD, Grant/research support from: AbbVie, MSD, and Roche, Stephen Hall Speakers bureau: Novartis, Merck, Janssen, Pfizer, Eli Lilly, and UCB, Consultant of: Novartis, Merck, Janssen, Pfizer, Eli Lilly, and UCB, Grant/research support from: AbbVie, UCB, Janssen, and Merck, Marina Magrey Consultant of: Eli Lily, Novartis, Grant/research support from: AbbVie, UCB and Amgen, Erhard Quebe-Fehling Shareholder of: Shareholder of Novartis, Employee of: Novartis, Renato Calheiros Shareholder of: Shareholder of Novartis, Employee of: Novartis, Patricia Pertel Shareholder of: Shareholder of Novartis, Employee of: Novartis, Helena Marzo-Ortega Speakers bureau: AbbVie, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Takeda and UCB, Consultant of: AbbVie, Celgene, Janssen, Moonlake, Lilly, Novartis, Pfizer and UCB, Grant/research support from: Janssen, Novartis and UCB

BackgroundAnkylosing spondylitis (AS) is a chronic, inflammatory disease resulting in debilitating clinical symptoms such as pain (70–83%), stiffness (54–90%) and fatigue (53–62%).1-3 Secukinumab (SEC 150 mg) has demonstrated long-term efficacy across multiple indications and is approved for the treatment of active AS in adults who have had an inadequate response to NSAIDs.4,5ObjectivesThe Phase 3 MEASURE 2 trial (NCT01649375) assessed long-term efficacy, safety and tolerability of SEC in patients (pts) with active AS. This post-hoc analysis was conducted specifically to evaluate long-term efficacy of SEC 150 mg on key clinical symptoms of pain, morning stiffness, physical function and fatigue in TNFi-naïve pts over 5 years.MethodsThe MEASURE 2 study design has been reported previously.5 This post-hoc analysis evaluated key clinical symptoms at baseline through Wk 260. Assessments included total and nocturnal back pain (visual analogue scale [0–100 mm]), overall spinal pain (neck, back, or hip) from BASDAI, and morning stiffness (average BASDAI). Physical function (SF-36 PCS, BASFI), fatigue (BASDAI, FACIT) and disease activity (ASDAS-CRP) are also reported. Data are presented as LS mean change (± SE) using mixed model repeated measures from Wks 4–16 and observed data (mean ± SD) from Wks 24–260.ResultsOf TNFi-naïve pts randomised to SEC 150 mg, 89 were included (SEC, n=44, placebo [PBO], n=45) in this analysis. Of these pts randomised to SEC 150 mg, 84% completed 5 years of treatment. Significantly greater improvements were observed in pts treated with SEC 150 mg vs PBO at Wk 16 and were sustained through 5 years (Figure 1; Table 1).Table 1.Pain, physical function and fatigue scoresEndpointTreatmentBL mean ± SD*Wk 16 LS mean, SE (p-value)Wk 52 ± SDWk 104 ± SDWk 156 ± SDWk 208 ± SDWk 260 ± SDBACK PAINTotal back painSEC66.86 ± 15.42-33.99, 3.42 (p=0.0000)-40.56 ± 24.35-37.74 ± 26.09-39.03 ± 26.65-37.77 ± 28.40-36.78 ± 29.76PBO67.69 ± 17.71-12.75, 3.46NANANANANANocturnal back painSEC66.84 ± 14.17-36.25, 3.50 (p=0.0000)-45.13 ± 23.92-40.54 ± 25.23-43.92 ± 25.10-41.13 ± 24.87-38.95 ± 28.91PBO63.87 ± 18.78-14.41, 3.54NANANANANAPHYSICAL FUNCTIONSF-36 PCSSEC34.87 ± 6.587.90, 0.98 (p=0.0012)8.44 ± 7.488.95 ± 7.878.98 ± 8.179.39 ± 8.398.55 ± 9.32PBO35.45 ± 6.513.23, 0.98NANANANANABASFISEC6.42 ± 1.95-2.89, 0.31 (p=0.0002)-3.38 ± 2.38-3.23 ± 2.39-3.10 ± 2.49-3.10 ± 2.47-2.86 ± 2.61PBO6.34 ± 1.99-1.18, 0.32NANANANANAFATIGUEOverall level (BASDAI)SEC7.00 ± 1.26-2.39, 0.34 (p=0.0095)-3.44 ± 2.32-3.30 ± 2.45-3.16 ± 2.61-3.12 ± 2.34-2.92 ± 2.71PBO7.18 ± 1.49-1.12, 0.34NANANANANAFACITSEC22.27 ± 8.0210.62, 1.26 (p=0.0052)12.14 ± 9.7611.00 ± 9.3710.79 ± 8.9112.39 ± 9.0910.64 ± 10.66PBO23.22 ± 7.945.48, 1.26NANANANANADISEASE ACTIVITYASDAS-CRPSEC3.73 ± 0.82-1.47, 0.14 (p=0.0000)-1.80 ± 1.16-1.66 ± 1.21-1.63 ± 1.35-1.69 ± 1.24-1.58 ± 1.36PBO3.89 ± 0.76-0.51, 0.14NANANANANA*Baseline refers to mean ± SD of observed values. LS mean change using MMRM for Wk 16 and observed data (mean ± SD) from Wks 24–260. SEC 150 mg, N=44 and PBO, N=45. ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score - C-reactive protein; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; BL, baseline; FACIT, Functional Assessment of Chronic Illness Therapy; LS, least square; MMRM, mixed-effects model repeated measures; NA, not available; PBO, placebo; SD, standard deviation; SEC, secukinumab; SF-36 PCS, Short Form-36 Physical Component Summary; Wk, week.ConclusionTNFi-naïve pts with active AS treated with SEC 150 mg experienced rapid improvements across a range of key clinical symptoms including pain, physical function and fatigue measures, that were sustained through 5 years.References[1]Deodhar A et al. 2020 BMC Rheumatol 2020;4:19[2]Ward M et al. Arth Care Res 1999;12:247–55[3]van Tubergen A et al. Arth Rheum 2002;47:8–16[4]Cosentyx SmPC (2020) [Accessed: 24 Jan 22][5]Baeten D et al. N Eng J Med 2015;373:2534–48AcknowledgementsThis study was sponsored by Novartis Pharma. Medical writing support for the development of this abstract, under the direction of the authors, was provided by Laura Crocker (BMedSci, Hons) of Ashfield MedComms, an Ashfield Health company, and funded by Novartis PharmaDisclosure of InterestsKarel Pavelka Speakers bureau: AbbVie, Pfizer, Roche, Eli Lilly, BMS, MSD, USB, Alan Kivitz Shareholder of: Amgen, Novartis, Gilead, Pfizer, Glaxosmithkline, Sanofi, Speakers bureau: AbbVie, Merck, Celgene, Novartis, Flexion, Pfizer, Gilead, Sanofi, UCB, Horizon, Consultant of: AbbVie, Celgene, Janssen, Boehringer Ingelheim, Pfizer, Flexion, Regeneron, Gilead, Sanofi, Sun Pharma Advanced Research, UCB, Merck, Novartis, Horizon, Renato Calheiros Employee of: I am currently an employee for Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, Erhard Quebe-Fehling Shareholder of: Novartis, Employee of: Novartis, Patricia Pertel Shareholder of: Novartis, Employee of: Novartis, Ricardo Blanco Speakers bureau: AbbVie, Amgen, Bristol-Myers, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and Sanofi, Consultant of: Astra-Zeneca, Galapagos, Janssen, Novartis, Pfizer, Grant/research support from: AbbVie, and Roche

BackgroundCOVID19 may present different degrees of severity. It is generally thought that viral infections in patients with rheumatic inflammatory diseases (R-IMID) or receiving immunosuppressive treatment tend to present more severe disease. However, data comparing the severity of the disease between R-IMID and the general population are scarce.ObjectivesTo assess the predisposing factors, clinical-analytical features and severity of COVID-19 infection in R-IMID compare to patients without R-IMID.MethodsCase-control study in a single University Hospital. We included all consecutive patients with a diagnosis of a R-IMID and a positive test for COVID-19 up to March 31st, 2021.A total of 274 controls were selected for each case, and matched by sex, age (± 5 years), and without previous diagnosis of R-IMID or use of immunosuppresive therapy.Confirmed infection was defined if the patient had a positive nasopharyngeal swab for SARS-CoV-2.COVID-19 case severity was divided into mild, moderate, severe and critical according to the United States National Institute of Health (NIH) COVID-19 guidelines (1). Mild/moderate COVID19 was compared with critical.ResultsWe included 274 patients (185 women/89 men), mean age 59.1 18 years.More frequent R-IMID were: Rheumatoid arthritis (RA) (n=87, 31.8%), Axial spondyloarthritis/ Psoriatic arthritis (SpA/PsA) (n=90, 32.8%), Polymyalgia Rheumatica (PMR) (n=22, 8%) and Systemic Lupus Erythematosus (SLE) (n=22, 8%)We also included 274 age and matched controls. Main characteristics of patients with R-IMID and controls are shown in Table 1.Table 1.Main clinical and analytical features of patients with R-IMID and matched controlsR-IMID patients (n=274)Controls (n=274)PAge59.1±1858.8±17.30.842Sex F/M, n, (%)185/89 (67.5/32.5)185/89 (67.5/32.5)1Comorbidities (n,%)Hypertension119 (43.4)84 (30.7)0.0026*Dyslipidemia119 (43.4)79 (28.8)0.0005*Diabetes mellitus36 (13.1)37 (13.5)1Pulmonary disease29 (10.6)32 (11.7)0.79Cardiovascular disease45 (16.4)33 (12)0.18Severity of the disease (n, %)Mild209 (76.3)204 (74.5)0.69Moderate35 (12.8)47 (17.2)0.19Severe9 (3.3)14 (5.1)0.39Critical21 (7.7)9 (3.3)0.04*Deaths17 (6.2)7 (2.6)0.0076*Analytical values, median [25-75th IQR]CRP4.7 [2-9.3]3.9 [1-7.3]0.176Lymphocytes (x103 /µL)1 [0.6-1.5]1.1 [0.8-2.5]0.711Platelets (x103 /µL)179 [141-237]174 [155-211]0.722D-Dimer (ng/mL)999 [342-1417]548 [336-997]0.032*CRP: C-reactive protein.Concerning comorbidities, hypertension and dyslipidemia were more frequent in patients with R-IMID (p< 0.05).COVID-19 symptoms’ distribution is shown in Figure 1.Figure 1.Symptoms in R-IMID patients and matched controls*: p < 0.05Cough and dyspnoea were more frequent and headache, odynophagia and diarrhea were less frequent in the R-IMID group.The only analytical difference was D-Dimer that was significantly higher in patients with R-IMID.Although most of the cases were mild, critical cases and deaths were more frequent in R-IMID (p ConclusionMost of the patients present a mild COVID-19. However, a more severe syndrome was observed in R-IMIDReferences[1]COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/. Accessed [insert date].Disclosure of InterestsDavid Martínez-López: None declared, Diana Prieto-Peña: None declared, Fabricio Benavides-Villanueva: None declared, Lara Sanchez-Bilbao: None declared, Cristina Corrales-Selaya: None declared, Alba Herrero-Morant: None declared, Carmen Álvarez-Reguera: None declared, Martin Trigueros-Vazquez: None declared, Reinhard Wallman: None declared, Miguel A González-Gay Speakers bureau: Consultation fees/participation in company-sponsored speaker´s bureau from Abbvie, Pfizer, Roche, and MSD., Grant/research support from: Dr. Miguel A. Gonzalez-Gay received grants/research supports from Abbvie, MSD, and Roche., Ricardo Blanco Speakers bureau: Consultation fees/participation in company-sponsored speaker´s bureau from Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, and MSD., Grant/research support from: Dr. Ricardo Blanco received grants/research supports from Abbvie, MSD, and Roche

BackgroundLarge-vessel vasculitis are characterized by the wall inflammation of the involved vessels, which can be detected by imaging tools (1-3). Ultrasound (US) is one of the most commonly used tools for the diagnosis of giant cell arteritis (GCA), especially in patients with a cranial phenotype. Tocilizumab (TCZ) has shown efficacy in large-vessel vasculitis (LVV) including GCA (4,5). However, the improvement objectified by imaging techniques such as US after TCZ therapy is poorly documented.ObjectivesTo assess the effectiveness of TCZ improving the wall vessel inflammation by US.MethodsObservational, multicenter study of 26 GCA patients treated with TCZ. GCA was diagnosed according to: a) ACR criteria, and/or b) biopsy of temporal artery, and/or c) presence of signs of vessel wall inflammation by US, defined by the presence of halo sign. In all the cases a baseline US and in the follow-up was mandatory.Patients were divided into two subgroups: a) with, and b) without signs of improvement (partial or total) in the follow-up US.ResultsWe studied 26 patients (19 women/7 men; mean age, 76.3±9.7 years). Main clinical features of GCA with and without US improvement are shown in Table 1. We found no significant differences in any of the variables studied between the two groups.Table 1.Main features of 27 GCA patients treated with tocilizumab followed by Ultrasound (US).With US improvement (n=21)Without US improvement (n=5)pBaseline characteristics at TCZ onsetGeneral characteristicsAge(years), mean±SD77.3±8.972.2±12.90.270Sex, female/male (% female)17/4 (80,95)2/3 (40)0.101Time from GCA diagnosis to TCZ onset (months), median [IQR]6 [3-9]3 [1-6]0.452Systemic manifestations, n (%)Fever, n (%)1/21 (4.76)1/5 (20)0.354Constitutional syndrome, n (%)10/21 (47.62)2/5 (40)0.999PmR, n (%)11/21 (52.38)1/5 (20)0.330Ischaemic manifestations, n (%)Visual involvement, n (%)1/21 (4.76)1/5 (20)0.354Headache, n (%)15/21 (71.43)5/5 (100)0.298Jaw claudication, n (%)4/15 (26.67)¼ (25)0.999Laboratory dataESR, mm 1st hour, median [IQR]33 [22-49]55 [54-80]0.216CRP, mg/dL, median [IQR]1.5 [0.7-6.7]3.8 [1-4.2]0.948Prednisone dose, mg/day, median [IQR]13.7 [10-30]30 [12.5-30]0.505Time from TCZ onset and follow-up US (months)3.9±3.63.1±2.10.456After TCZ onset, 21 of 26 patients (80.7%) showed US signs of improvement (12 complete, 9 partial). In 4 out of 5 patients in whom there was no improvement in US findings, clinical improvement was observed at first month after starting TCZ.ConclusionTCZ seems to be effective controlling GCA including vascular involvement detected by US. This improvement can be seen by follow-up US, especially when performed at least 3 months after TCZ onset.References[1]Loricera J, et al. Rev Esp Med Nucl Imagen Mol. 2015; 34: 372-7. PMID: 26272121[2]Loricera J, et al. Clin Exp Rheumatol. 2015; 33: S19-31. PMID: 25437450[3]Prieto-Peña D, et al. Ther Adv Musculoskelet Dis. 2021; 13: 1759720X211020917. PMID: 34211589[4]Martínez-Rodríguez I, et al. Semin Arthritis Rheum. 2018; 47: 530-537. PMID: 28967430[5]Prieto-Peña D, et al. Semin Arthritis Rheum. 2019; 48: 720-727. PMID: 29903537AcknowledgementsTocilizumab in Giant Cell Arteritis Spanish Collaborative Group: Juan C. González Nieto (H. Gregorio Marañón), Juan R. de Dios (H.U. Araba), Esther Fernández (H. Clínico Universitario Virgen de la Arrixaca), Isabel de la Morena (H. Clínico Universitario de Valencia), Patricia Moya (H. Sant Pau), Roser Solans i Laqué (H. Valle de Hebrón), Eva Pérez Pampín (H.U. de Santiago), José L. Andréu (H.U. Puerta de Hierro), Marcelino Revenga (H. Ramón y Cajal), Juan P. Baldivieso Achá (H. U. de La Princesa), Eztizen Labrador (H. San Pedro), Andrea García-Valle (Complejo Asistencial Universitario de Palencia), Adela Gallego (Complejo Hospitalario Universitario de Badajoz), Carlota Iñíguez (H.U. Lucus Augusti), Cristina Hidalgo (Complejo Asistencial Universitario de Salamanca), Noemí Garrido-Puñal (H. Virgen del Rocío), Ruth López-González (Complejo Hospitalario de Zamora), José A. Román-Ivorra (H.U. y Politécnico La Fe), Sara Manrique (H. Regional de Málaga), Paz Collado (H.U. Severo Ochoa), Enrique Raya (H. San Cecilio), Valvanera Pinillos (H. San Pedro), Francisco Navarro (H. General Universitario de Elche), Alejandro Olivé-Marqués (H. Trías i Pujol), Francisco J. Toyos (H.U. Virgen Macarena), María L. Marena Rojas (H. La Mancha Centro), Antoni Juan Más (H.U. Son Llàtzer), Beatriz Arca (H.U. San Agustín), Carmen Ordás-Calvo (H. Cabueñes), María D. Boquet (H. Arnau de Vilanova), Noelia Álvarez-Rivas (H.U. Lucus Augusti), María L. Velloso-Feijoo (H.U. de Valme), Cristina Campos (H. General Universitario de Valencia), Íñigo Rúa-Figueroa (H. Doctor Negrín), Antonio García (H. Virgen de las Nieves), Carlos Vázquez (H. Miguel Servet), Pau Lluch (H. Mateu Orfila), Carmen Torres (Complejo Asistencial de Ávila), Cristina Luna (H.U. Nuestra Señora de la Candelaria), Elena Becerra (H.U. de Torrevieja), Nagore Fernández-Llanio (H. Arnáu de Vilanova), Arantxa Conesa (H.U. de Castellón), Eva Salgado (Complejo Hospitalario Universitario de Ourense).Disclosure of InterestsJulio Sanchez-Martin: None declared, Javier Loricera: None declared, Lara Sanchez-Bilbao: None declared, Eugenio de Miguel: None declared, Rafael Melero: None declared, E. Galíndez-Agirregoikoa: None declared, J. Narváez: None declared, Carles Galisteo: None declared, Juan Carlos Nieto González: None declared, Patricia Moya: None declared, Eztizen Labrador-Sánchez: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Grant/research support from: Abbvie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Grant/research support from: Abbvie, MSD and Roche

BackgroundIsoniazid (INH) is used to treat latent tuberculosis infection (LTBI), and hepatotoxicity is one of the most frequent adverse effect. Several Disease-modifying drugs (DMARDs) can also cause hepatotoxicity. Many patients with rheumatic immune mediated diseases (R-IMID) receive INH prior to DMARDs for prophylaxis of LTBI. This risk of hepatotoxicity with DMARDs after hepatotoxicity with INH is unknown.ObjectivesTo assess the risk of hepatotoxicity with DMARDs in patients who have presented hepatotoxicity with INH.MethodsStudy of all consecutive R-IMID patients evaluated in the last five years (2016-2020) in a University Hospital, who presented hepatotoxicity after INH and later received DMARDs. We study if they also presented hepatotoxicity with DMARDs.Hepatotoxicity was defined as an elevation of liver enzymes (ALT and/or AST) upper the high limit after the introduction of the treatment.ResultsINH was used in 232 of 7218 patients with R-IMID. We finally included 64 patients (45 women; 70.3%; mean age 53.4±10.5 years), who had hepatotoxicity due to INH (Table 1).Table 1.Main characteristics of 64 patients with rheumatic immune-mediated diseases (R-IMID) that presented hepatotoxicity after receiving isoniazid (INH).VariablesPatients (n=64)Age (years), mean ±SD53.4±10.5Sex (women), n (%)45 (70.3)R-IMID- SpA / PsA36 (56.3%)- RA21 (32.8%)- SSc3 (4.7%)- Conectivopathies3 (4.7%)- Other2 (3.2%)Liver enzyme elevation over baseline (INH)*- x264 (100)- x322 (34.4)- x4 or higher13 (20.3)csDMARDs- MTX34 (53.1%)- HCQ15 (23.4)- LFN13 (20.3)- SSZ10 (15.6)bDMARDs47 (73.4%)Targeted synthetic DMARDs (Jakinib)8 (12.5)ABA: Abatacept; AZA: Azathioprine, HCQ: Hydroxychloroquine; INH: Isoniazid; LFN: Leflunomide; MMF: Mycophenolate mofetil, MTX: Methotrexate; PsA: Psoriatic arthritis, RA: Rheumatoid arthritis, RTX: Rituximab; SpA: Axial spondyloarthritis; SSc: Systemic sclerosis; TCZ: Tocilizumab; TNFi: TNF inhibitors* Patients with higher liver enzyme elevation are included in the previous groups.The most frequent R-IMIDs were rheumatoid arthritis, axial spondyloarthritis and psoriatic arthritis. Methotrexate (MTX) (n=34, 53.1%) and TNF inhibitors (n=27, 42.2%) were the conventional and biologic-DMARD more frequently used, respectively.Hepatotoxicity was higher with MTX (14 of 34, 41.2%), and lower with the other DMARDs (Figure 1). Hepatotoxicity was not observed with hydroxychloroquine, azathioprine, mycophenolate mofetil, secukinumab, abatacept or rituximab.Figure 1.Hepatotoxicity with different DMARDs in 64 patients with previous hepatotoxicity with INH* Patients with higher liver enzyme elevation are included in the previous groups.ConclusionIn patients with previous hepatotoxicity with INH, we observed an increased risk with different DMARDs, especially with MTX.Disclosure of InterestsDavid Martínez-López: None declared, Joy Osorio-Chavez: None declared, Virginia Portilla: None declared, Carmen Álvarez-Reguera: None declared, Alba Herrero-Morant: None declared, Lara Sanchez-Bilbao: None declared, Iñigo Gonzalez-Mazon: None declared, Miguel A González-Gay Speakers bureau: Consultation fees/participation in company-sponsored speaker´s bureau from Abbvie, Pfizer, Roche, and MSD, Grant/research support from: Dr. Miguel A. Gonzalez-Gay received grants/research supports from Abbvie, MSD, and Roche, Ricardo Blanco Speakers bureau: Consultation fees/participation in company-sponsored speaker´s bureau from Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, and MSD., Grant/research support from: Dr. Ricardo Blanco received grants/research supports from Abbvie, MSD, and Roche

BackgroundPositron emission tomography (PET) is one of the tools available for the diagnosis of extracranial large-vessel vasculitis (1-5). Tocilizumab (TCZ) has shown efficacy in large-vessel vasculitis (LVV) including GCA. However, the improvement objectified by imaging techniques after TCZ therapy in extracranial GCA patients is controversial.ObjectivesTo assess the effectiveness of TCZ improving the wall vessel inflammation by PET in GCA patients with large-vessel involvement.MethodsObservational, multicenter study of 101 GCA patients treated with TCZ. GCA was diagnosed according to: a) ACR criteria, and/or b) biopsy of temporal artery, and/or c) presence of signs of vessel wall inflammation by PET, defined by the presence of vascular wall uptake of Fluorodeoxyglucose (FDG). Patients were divided into two subgroups: a) with, and b) without signs of improvement (partial or total) in the follow-up PET.ResultsWe studied 101 patients (74 women/27 men; mean age 69.7±9.3 years). Main clinical features of GCA with and without PET improvement are shown in Table 1. The group of patients which experienced PET improvement was older and was receiving higher doses of corticosteroids at TCZ onset.Table 1.Main features of 101 GCA patients treated with tocilizumab and with presence of signs of vessel wall inflammation by PET.With PET improvement (n=88)Without PET improvement (n=13)pBaseline characteristics at TCZ onsetGeneral characteristicsAge(years), mean±SD70.6±9.163.8±9.20.014Sex, female/male (% female)67/21(76)7/6 (54)0.103Time from GCA diagnosis to TCZ onset (months), median [IQR]11 [4-24.2]4 [2-6]0.102Systemic manifestations, n (%)Fever, n (%)5 (6)2 (15)0.225Constitutional syndrome, n (%)36 (41)4 (31)0.466PmR, n (%)53 (60)9 (10)0.761Ischaemic manifestations, n (%)Visual involvement, n (%)2 (2)1 (1)0.342Headache, n (%)30 (34)3 (23)0.538Jaw claudication, n (%)8 (9)0 (0)0.592Laboratory dataESR, mm 1st hour, median [IQR]38.0 ± 26.213.54 ± 9.90.001CRP, mg/dL, median [IQR]1.5 [0.7-2.4]1 [0.5-1.7]0.179Prednisone dose, mg/day, median [IQR]40.3 ± 19.421.9 ± 12.70.001Time from TCZ onset and follow-up PET (months)13.1±8.010.1±5.30.446ConclusionTCZ seems to be effective controlling GCA including vascular involvement detected by PET. However, the improvement observed by PET is most often partial, and rarely complete.Figure 1.Improvement by PET according to the time of the test.References[1]Loricera J, et al. Rev Esp Med Nucl Imagen Mol. 2015; 34: 372-7. PMID: 26272121[2]Loricera J, et al. Clin Exp Rheumatol. 2015; 33: S19-31. PMID: 25437450[3]Prieto-Peña D, et al. Ther Adv Musculoskelet Dis. 2021; 13: 1759720X211020917. PMID: 34211589[4]Martínez-Rodríguez I, et al. Semin Arthritis Rheum. 2018; 47: 530-537. PMID: 28967430[5]Prieto-Peña D, et al. Semin Arthritis Rheum. 2019; 48: 720-727. PMID: 29903537AcknowledgementsTocilizumab in Giant Cell Arteritis Spanish Collaborative Group: Juan C. González Nieto (H. Gregorio Marañón), Juan R. de Dios (H.U. Araba), Esther Fernández (H. Clínico Universitario Virgen de la Arrixaca), Isabel de la Morena (H. Clínico Universitario de Valencia), Patricia Moya (H. Sant Pau), Roser Solans i Laqué (H. Valle de Hebrón), Eva Pérez Pampín (H.U. de Santiago), José L. Andréu (H.U. Puerta de Hierro), Marcelino Revenga (H. Ramón y Cajal), Juan P. Baldivieso Achá (H. U. de La Princesa), Eztizen Labrador (H. San Pedro), Andrea García-Valle (Complejo Asistencial Universitario de Palencia), Adela Gallego (Complejo Hospitalario Universitario de Badajoz), Carlota Iñíguez (H.U. Lucus Augusti), Cristina Hidalgo (Complejo Asistencial Universitario de Salamanca), Noemí Garrido-Puñal (H. Virgen del Rocío), Ruth López-González (Complejo Hospitalario de Zamora), José A. Román-Ivorra (H.U. y Politécnico La Fe), Sara Manrique (H. Regional de Málaga), Paz Collado (H.U. Severo Ochoa), Enrique Raya (H. San Cecilio), Valvanera Pinillos (H. San Pedro), Francisco Navarro (H. General Universitario de Elche), Alejandro Olivé-Marqués (H. Trías i Pujol), Francisco J. Toyos (H.U. Virgen Macarena), María L. Marena Rojas (H. La Mancha Centro), Antoni Juan Más (H.U. Son Llàtzer), Beatriz Arca (H.U. San Agustín), Carmen Ordás-Calvo (H. Cabueñes), María D. Boquet (H. Arnau de Vilanova), Noelia Álvarez-Rivas (H.U. Lucus Augusti), María L. Velloso-Feijoo (H.U. de Valme), Cristina Campos (H. General Universitario de Valencia), Íñigo Rúa-Figueroa (H. Doctor Negrín), Antonio García (H. Virgen de las Nieves), Carlos Vázquez (H. Miguel Servet), Pau Lluch (H. Mateu Orfila), Carmen Torres (Complejo Asistencial de Ávila), Cristina Luna (H.U. Nuestra Señora de la Candelaria), Elena Becerra (H.U. de Torrevieja), Nagore Fernández-Llanio (H. Arnáu de Vilanova), Arantxa Conesa (H.U. de Castellón), Eva Salgado (Complejo Hospitalario Universitario de Ourense).Disclosure of InterestsJulio Sanchez-Martin: None declared, Javier Loricera: None declared, Santos Castañeda: None declared, Clara Moriano: None declared, J. Narváez: None declared, Vicente Aldasoro: None declared, Olga Maiz: None declared, Rafael Melero: None declared, Ignacio Villa-Blanco: None declared, Paloma Vela-Casasempere: None declared, Susana Romero-Yuste: None declared, Jose Luis Callejas-Rubio: None declared, Eugenio de Miguel: None declared, E. Galíndez-Agirregoikoa: None declared, Francisca Sivera: None declared, Carlos Fernández-López: None declared, Carles Galisteo: None declared, Iván Ferraz-Amaro: None declared, Lara Sanchez-Bilbao: None declared, Monica Calderón-Goercke: None declared, Jose Luis Hernández Hernández: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Grant/research support from: Abbvie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Grant/research support from: Abbvie, MSD and Roche

BackgroundIgA vasculitis (IgAV) and IgA nephropathy (IgAN) are inflammatory conditions [1, 2], that share pathogenic mechanisms [1], in which B-lymphocytes are described as key cells implicated in these processes. BAFF, APRIL and BAFF-R are cytokines implicated in the development of B-lymphocytes [3, 4] and in autoimmune processes [5, 6]. In this regard, an influence of BAFF, APRIL and BAFFR polymorphisms was observed on several immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion variant for inflammatory conditions [7, 8].ObjectivesTo determine whether BAFF, APRIL and BAFFR could be used as differential biomarkers between IgAV and IgAN.MethodsBAFF rs374039502 (which colocalizes with BAFF GCTGT>A), two tag variants within APRIL (rs11552708 and rs6608) and two tag variants within BAFFR (rs7290134 and rs77874543) were genotyped in 394 Caucasian IgAV patients, 95 patients with IgAN and 832 matched healthy controls.ResultsSimilar genotype and allele frequencies were observed in the whole cohort of patients with IgAV when compared to those with IgAN when BAFF, APRIL and BAFFR variants were analyzed independently (Table 1). In accordance with that, no BAFF, APRIL and BAFFR genotype or allele differences were detected between IgAV patients who developed nephritis and patients with IgAN (Table 1). Additionally, no statistically significant differences were observed between the whole cohort of patients with IgAV and healthy controls as well as between patients with IgAN and healthy controls when each when BAFF, APRIL and BAFFR genetic variant was also analyzed independently (Table 1). Similar results were disclosed when haplotype frequencies of APRIL and BAFFR were compared between the different comparative groups above mentioned (data not shown).Table 1.Genotype and allele frequencies of BAFF, APRIL and BAFFR in the whole cohort of patients with IgAV, patients with IgAV who developed nephritis, patients with IgAN and healthy controls.PolymorphismChangeData setGenotypes, % (n)Alleles, % (n)1/21/11/22/212BAFF rs374039502T/AIgAV92.1 (363)7.9 (31)0.096.1 (757)3.9 (31)IgAV with nephritis90.1 (128)9.9 (14)0.095.1 (270)4.9 (14)IgAN91.6 (87)8.4 (8)0.095.8 (182)4.2 (8)Controls91.8 (764)7.8 (65)0.4 (3)95.7 (1593)4.3 (71)APRIL rs11552708G/AIgAV78.7 (310)20.1 (79)1.3 (5)88.7 (699)11.3 (89)IgAV with nephritis81.1 (116)18.9 (27)0.090.6 (259)9.4 (27)IgAN75.8 (72)23.2 (22)1.1 (1)87.4 (166)12.6 (24)Controls78.7 (655)19.7 (164)1.6 (13)88.6 (1474)11.4 (190)APRIL rs6608C/TIgAV72.6 (286)25.4 (100)2.0 (8)85.3 (672)14.7 (116)IgAV with nephritis75.5 (108)23.1 (33)1.4 (2)87.1 (249)12.9 (37)IgAN65.3 (62)30.5 (29)4.2 (4)80.5 (153)19.5 (37)Controls71.0 (591)26.6 (221)2.4 (20)84.3 (1403)15.7 (261)BAFFR rs7290134A/GIgAV58.9 (232)35.5 (140)5.6 (22)76.6 (604)23.4 (184)IgAV with nephritis60.1 (86)32.2 (46)7.7 (11)76.2 (218)23.8 (68)IgAN57.9 (55)38.9 (37)3.2 (3)77.4 (147)22.6 (43)Controls58.7 (488)35.1 (292)6.3 (52)76.2 (1268)23.8 (396)BAFFR rs77874543G/CIgAV83.2 (328)15.5 (61)1.3 (5)91.0 (717)9.0 (71)IgAV with nephritis83.1 (118)16.9 (24)0.091.5 (260)8.5 (24)IgAN86.3 (82)13.7 (13)0.093.2 (167)6.8 (13)Controls83.7 (696)16.0 (133)0.4 (3)91.6 (1525)8.4 (139)IgAV: IgA vasculitis; IgAN: IgA nephropathy.ConclusionOur results reveal a similar BAFF, APRIL and BAFFR genetic distribution in IgAV and IgAN, suggesting that these genes could not be used as differential biomarkers between these pathologies.References[1]N Engl J Med 2013;368:2402-14;[2]Am J Kidney Dis 1988;12:373-7;[3]J Exp Med 1999;189:1747-56;[4]Nat Genet 2005;37:793-4;[5]Arthritis Res Ther 2018;20:158;[6]Arthritis Res Ther 2020;22:157;[7]Engl J Med 2017;376:1615-26;[8]Sci Rep 2018;8:8195.AcknowledgementsThis study was supported by the European Regional Development Fund (ERDF) and “Fondo de Investigaciones Sanitarias” (grant PI18/00042 and PI21/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) [grant number CM20/00006]; SR-M is supported by funds of the RETICS Program co-funded by ERDF [grant number RD16/0012/0009]; VP-C is supported by a pre-doctoral grant from IDIVAL [grant number PREVAL 18/01]; RL-M is a recipient of a Miguel Servet type II programme fellowship from the ISCIII, co-funded by ESF `Investing in your future´ [grant number CPII21/00004].Disclosure of InterestsDiana Prieto-Peña: None declared, Fernanda Genre: None declared, Sara Remuzgo Martinez: None declared, Verónica Pulito-Cueto: None declared, Belén Atienza-Mateo: None declared, Belén Sevilla: None declared, Javier Llorca: None declared, Norberto Ortego: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda Fillloy: None declared, J. Narváez: None declared, LUIS CAMINAL MONTERO: None declared, PAZ COLLADO: None declared, Antonio Fernandez-Nebro: None declared, Gisela Díaz-Cordoves: None declared, Secundino Cigarrán: None declared, Jesús Calviño: None declared, Carmen Cobelo: None declared, Diego de Argila: None declared, Esther F. Vicente-Rabaneda: None declared, Esteban Rubio-Romero: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galíndez-Agirregoikoa: None declared, Oreste Gualillo: None declared, Javier Martin Ibanez: None declared, Santos Castañeda: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Miguel A González-Gay Speakers bureau: Abbvie, MSD, Jansen, and Roche, Grant/research support from: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD and GSK, Raquel López-Mejías: None declared