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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.

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

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

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

The aim of this study was to translate and adapt the physical activity and leisure motivation scale (PALMS) into Spanish, and to analyse its validity and reliability. The sample comprised 867 adolescents, with a mean age of 14.04 ± 1.19 years, 53.9% of whom were male. During the translation process, some of the items in the instrument were modified slightly, improving its comprehensibility. On the other hand, the exploratory factor analysis did not present an adequate factor structure, so a more in-depth analysis was carried out, using item response theory and confirmatory factor analysis, the conclusion was that it would be appropriate to eliminate several items from the scale. From this, a final shortened version, consisting of 25 items, was produced, with adequate fit indices—CFI = 0.933, TLI = 0.918, SRMR = 0.042, RMSEA = 0.052 (90% CI 0.048, 0.056)—and good reliability for each of the dimensions, ranging from 0.625 to 0.835. It can be concluded that the abbreviated version of the PALMS instrument, adapted for Spanish adolescents (PALMS-e), is a valid and reliable instrument for assessing their motives for doing physical activity.

Crystal-storing histiocytosis (CSH) is a rare disorder characterized by the accumulation of nonneoplastic histiocytes containing intracytoplasmic crystallized immunoglobulins. In most cases, there is an associated underlying lymphoplasmacytic neoplasm expressing Ig kappa light chain. About 131 cases of CSH have been identified. There is a localized and a generalized form of CSH and it can involve several sites including bone marrow, lungs, lymph nodes, liver, spleen, gastrointestinal tract, and kidney. Generalized CSH is less frequent and involves multiple organs and tends to have a worst prognosis than localized CSH. Around 20 cases of renal involvement in CSH have been reported so far. Paraprotein-induced crystalline nephropathy can be divided into two categories based on whether the crystals in the kidney are intracellular (including light chain proximal tubulopathy with crystals and CSH) or extracellular (including the crystalline variant of myeloma cast nephropathy and crystalglobulin-induced nephropathy). The former tends to present with slowly worsening kidney dysfunction and generally has a good prognosis, whereas the latter usually presents with rapidly progressive renal failure and is associated with poor renal outcome. We present a case of generalized CSH associated with extracellular crystalline nephropathy with a fulminant and fatal clinical course. Kappa light-chain crystals were found exclusively extracellularly within the tubular lumen, not within the tubular epithelial cells nor the histiocytes, and the massive presence of those precipitates led to the acute renal failure. Consequently, we review the renal involvement in CSH in the literature and discuss the unique mechanism of renal injury in this case.

BackgroundUpadacitinib (UPA) is an inhibitor of JAK kinases recently approved by EMA for the treatment of psoriatic arthritis (PsA) in Europe (January 2021) 1. UPA has shown efficacy in refractory patients to anti-TNF 2.ObjectivesA) to assess efficacy and safety of UPA in the first cases in Spain in clinical practice. B) to compare the profile of clinical practice patients with clinical trial of UPA in PsA refractory to biologics 2.MethodsStudy of 39 patients of clinical practice with PsA treated with UPA in Spain. The diagnosis of PsA was made using CASPAR criteria. Patients who received at least one dose of UPA were included. Results are expressed as percentage, mean±SD or median [IRQ].Results39 patients (29♀/10♂), mean age of 51.5 ± 11.4 years (Table 1). Pattern joint involvement was as follows: peripheral (n=19), axial (3) and mixed (17) During the PsA evolution, patients also presented enthesitis (59%) nail involvement (28.2%) and dactylitis (35.9%).Table 1.CLINICAL PRACTICE N=39CLINICAL TRIAL N=211pBaseline demographic parametersAge, years (mean±SD)51.5±11.453.0 ± 12.00.4706Sex, n (%) female29 (74.4)113 (53.6)0.016Disease CharacteristicsDuration of psoriatic arthritis, year (mean±SD)12.41±8.689.5 ± 8.40.0499HAQ-DI1.10± 0.421.10 ± 0.61.000Swollen joint count, mean±SD6±7.2911.3 ± 8.2< 0.001Painful joint count, mean±SD7.48±7.5824.9 ± 17.3< 0.001Enthesitis, n (%)23 (59.0) MASES172 (81.5) SPARCCDactylitis, n (%)14 (35.9)55(26.1)0.217PASI score, mean±SD2.72±2.3210.1 ± 9.2< 0.001CRP (mg/L)11.1±18.8611.2 ± 18.51.000Oral glucocorticoid use, n (%)17 (43.6)22 (10.4)< 0.001Concomitant synthetic DMARDs, n (%)16(41)98 (46,4)0.532Previous use of biological DMARDs, n (%)39(100)195 (92.4)0.075Number of prior failed biologic DMARDs, n(%)13(7.7)135 (63.7)24(10.3)35 (16.5)0.383≥332(82)24 (11.3)UPA in monotherapy, n (%)23(59)113 (53.6)0.531HAQ-DI Health Assessment Questionnaire-Disability Index, PASI Psoriasis Area Severity Index, CRP C-reactive protein, DMARD disease-modifying antirheumatic drugPrior to UPA, most patients (59%) had received oral prednisone or equivalent (max 9.03±12.12mg/d), synthetic immunosuppressants (mean1.8±0.9) and biological therapy (TB) (4.5±2.1). TB were as follows: etanercept (25), adalimumab (28), infliximab (12), golimumab (16), certolizumab (15), secukinumab (29), ustekinumab (21) Abatacept (2), brodalumab (1) and ixekizumab (17). Apremilast was used in 13, Tofacitinib in 11 and filgotinib in 1.After a mean follow-up of 12.41± 8.68.3 years after the PsA diagnosis, UPA was started (15 mg/24 h), 43.6% associated prednisone (7.35±3.36 mg/d). In 16 (41%) UPA was started in combined therapy: methotrexate (9), salazopyrin (3) and leflunomide (4); in the remaining 23 (59%), monotherapy was prescribed. At UPA onset patients presented peripheral arthritis (76.9%), axial involvement (35.8%), skin involvement (25.6%), enthesitis (41%), and dactylitis (10.3%).Patients of clinical practice compared with clinical trial there were more women, have a longer duration of PsA, and received a higher proportion of previous TB (Table 1).After a median follow-up of 4.28 ± 2.6 months, patients showed prompt improvement in activity indexes (DAS28, DAPSA) (Figure 1) and laboratory test (CRP mg/L decreased from 4.00 [1.5;10.0] to 0.40 [0.30;4.00] (p 0.024) at the sixth month. Extra-articular manifestations also improved: dactylitis in 25% patients, enthesitis (43.8%), skin involvement (40%) and onychopathy (50%).Figure 1.No serious events were reported. Minor side effects were reported in 7 patients (17.9%), and UPA was discontinued in 9 due to inefficiency.ConclusionIn this preliminary study, first patients of clinical practice in Spain with UPA in PsA had a longer evolution and received a greater number of TB than those of clinical trial. As in the UPA clinical trial, it seems effective, rapid and relatively safe in daily clinical practice for refractory PsA.References[1]https://www.ema.europa.eu/en[2]Mease PJ, et al. Ann Rheum Dis 2021;80:312–320Disclosure of InterestsNone declared

BackgroundTocilizumab (TCZ) has shown efficacy in large-vessel vasculitis, including Giant Cell Arteritis (GCA) (1-3). Clinical trials with TCZ in GCA was performed with intravenous (iv) TCZ in a phase 2 trial (3), and with subcutaneous (sc) TCZ in the phase 3 GiACTA (4). However, in GCA there are no studies comparing IV vs SC TCZ.ObjectivesTo compare the efficacy of TCZ in GCA patients according to the route of administration IV-TCZ vs SC-TCZ.MethodsMulticentre study of 471 patients diagnosed with GCA and treated with TCZ. They were divided into 2 groups according to the route of administration: a) IV, and b) SC. GCA was diagnosed by: a) ACR criteria, and/or b) temporal artery biopsy, and/or c) imaging techniques. Sustained remission was established according to EULAR definitions (5).ResultsWe studied 471 patients (mean age, 74±9 years) treated with TCZ, 238 with IV-TCZ and 233 with SC-TCZ (Table 1). The time between diagnosis of GCA and TCZ onset was shorter in the SC TCZ group. Regarding acute phase reactants at the beginning of TCZ, no differences were found between both groups. There were no significant differences in sustained remission or in glucocorticoid-sparing effect of TCZ (Figure 1). Patients on IV TCZ treatment suffered more relevant adverse effects during follow-up.Table 1.Main characteristics of GCA patients treated with intravenous and subcutaneous tocilizumabIV TCZ (n= 238)SC TCZ (n=233)PBaseline characteristics at TCZ onsetAge(years), mean±SD73.3±8.773.7±9.30.63Sex, female/male (% female)175/63 (73)167/66 (72)0.65Time from GCA diagnosis to TCZ onset (months), median [IQR]8 [3-23.5]5 [2-15]0.016ESR, mm 1st hour, median [IQR]30.5 [12.5-53]28 [10-56.5]0.66CRP, mg/dL, median [IQR]1.4 [0.5-2.8]1.4 [0.4-4]0.92Prednisone dose, mg/day, median [IQR]20 [10-40]20 [10-36.2]0.69Safety after TCZ onsetFollow-up, (months), median [IQR]27 [16-44]14 [6-26.7]Relevant adverse events, n (%)80 (34)46 (19)Relevant adverse events per 100 patients-year12.715.2NSSerious infections, n (%)44 (18)21 (9)0.44Serious infections per 100 patients-year6.77.2NSMACEs, n (%)/1 (0.4)0 (0)-MACEs per 100 patients-year0.10NSMalignancies, n (%)4 (1.7)1 (0.4)0.20Malignancies per 100 patients-year0.60.3NSAbbreviations: 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 deviationConclusionIn GCA, TCZ seems equally effective and safe regardless of the route of administration IV or SC.References[1]Calderón-Goercke M, et al. Semin Arthritis Rheum. 2019; 49: 126-135. PMID: 30655091[2]Prieto-Peña D, et al. Ther Adv Musculoskelet Dis. 2021; 13: 1759720X211020917. PMID: 34211589[3]Villiger PM, et al. Lancet. 2016; 387:1921-1927. PMID: 26952547[4]Stone JH, et al. N Engl J Med. 2017; 377:317-328. PMID: 28745999Hellmich B, et al. Ann Rheum Dis. 2020; 79: 19-30. PMID: 31270110Disclosure of InterestsNone declared

BackgroundVisual involvement is the most feared complication of Giant Cell Arteritis (GCA) (1-5). Permanent visual loss (PVL) may be preceded by transient visual loss. Once blindness is established, the prognosis is poor. Most of the series of predictive factors of visual involvement in GCA are old and with a small number of patients.ObjectivesTo assess the predictive factors of visual involvement and PVL in GCA.MethodsMulticenter observational study of 471 patients with GCA. The diagnosis of GCA was performed between 2016 and 2021 according to: a) ACR criteria, and/or b) temporal artery biopsy, and/or c) imaging techniques.From the 471 patients, we selected patients who developed a) visual involvement at any time during GCA and b) PVL. PVL was defined as partial or complete visual loss of >24 hours. Predictive factors were identified by multivariate analysis.ResultsVisual involvement was observed in 122 cases and PVL in 60 (Table 1). The ischemic and systemic manifestations set of variables associated with visual involvement were headache, and jaw claudication, whereas large-vessel involvement was a protective variable (Figure 1). The area under the curve (AUC) for the model was 0.72 (95%CI 0.67-0.77; pFigure 1.Forest plot of multivariate analysis.Table 1.Main features of the patientsOverall (n= 471)GCA without visual involvement (n=349)GCA with visual involvement (n= 122)GCA with PVL (n=60)P visual vs non visual involvementP PVL vs non visual involvementAge at diagnosis of GCA (mean±SD)72±971±975±875±90.0010.001Female/Male (% of female)342/129 (73)265/84 (76)77/45 (63)41/19 (68)0.0060.21Positive TAB, n (%)201 (43)146 (42)55 (45)33 (55)0.530.34Cardiovascular risk factorsHigh blood pressure, n (%)272 (58)189 (54)83 (68)40 (67)0.0130.058Dyslipidemia, n (%)241 (51)175 (50)66 (54)32 (53)0.610.63Diabetes, n (%)81 (17)50 (14)31 (25)16 (27)0.0070.016Previous or current smoking history, n (%)47 (10)31 (9)16 (13)8 (13)0.210.27CHADS2 score, median [IQR]1 [1-2]1 [0-2]2 [1-2]2 [1-2]0.0010.004Ischemic manifestationsHeadache, n (%)259 (55)167 (48)92 (75)42 (70)0.0000.002Jaw claudication, n (%)112 (24)63 (18)49 (40)26 (43)0.0000.000Systemic manifestationsFever, n (%)57 (12)47 (13)10 (8)4 (7)0.120.20Constitutional syndrome, n (%)175 (37)132 (38)43 (35)20 (33)0.550.47PmR, n (%)284 (60)218 (62)66 (54)29 (48)0.0940.022Large-vessel involvement, n (%)254 (54)211 (60)43 (35)20 (33)0.0000.000ESR, mm/1st hour, median [IQR]32 [12-57]30 [11-54]34 [15-67]42 [12-67]0.220.28CRP (mg/dL), median [IQR]1.5 [0.5-3.4]1.4 [0.5-3.0]1.5 [0.4-4.7]1.5 [0.4-3.6]0.0420.30In the same line, the set of variables associated with PVL were headache, and jaw claudication. By contrast, polymyalgia rheumatica (PmR), and large-vessel involvement were protective factors (Figure 1). The AUC for this model was 0.77 (95%CI 0.71-0.83; pConclusionHeadache, and jaw claudication seem to be associated with visual involvement in GCA, while large vessel involvement seems to be a protective factor. PmR also appears to be a protective factor for the development of PVL.References[1]Calderón-Goercke M, et al. Semin Arthritis Rheum. 2019; 49: 126-135. PMID: 30655091[2]Baalbaki H, et al. Clin Rheumatol. 2021; 40: 3207-3217. PMID: 33580374[3]González-Gay MA, et al. Arthritis Rheum. 1998; 41: 1497-1504. PMID: 9704651[4]Prieto-Peña D, et al. Semin Arthritis Rheum. 2019; 48: 720-727. PMID: 29903537[5]Martínez-Rodríguez I, et al. Semin Arthritis Rheum. 2018; 47: 530-537. PMID: 28967430AcknowledgementsTocilizumab in Giant Cell Arteritis Spanish Collaborative Group.Disclosure of InterestsLara Sanchez-Bilbao: None declared, Javier Loricera Speakers bureau: Roche, Novartis, UCB Pharma, Celgene, and Grünenthal, Clara Moriano: None declared, Santos Castañeda Speakers bureau: UAM-Roche, EPID- Future chair, Department of Medicine, Universidad Autónoma de Madrid, Madrid, Spain., Iván Ferraz-Amaro: 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, 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

BackgroundOcular and Neurobehçet’s Disease (NBD) are the most severe manifestations of Behcet’s disease (1-4). NBD can be classified as a) primary neural parenchymal lesions, also known as parenchymal NBD (p-NBD) or b) secondary to vascular involvement or non-parenchymal NBD (np-NBD) (4). Response to biologic therapy (BT) in these two refractory subtypes of NBD is unknown.ObjectivesTo assess efficacy and safety of BT in refractory subtypes of NBD.MethodsOpen-label multicenter study of refractory NBD from 21 different referral National Hospitals. NBD diagnosis was based on the International Consensus Recommendation criteria (4). Efficacy was determined by complete or partial response and no-response. Complete, partial or no response was defined according to the resolution of the neurological syndrome (signs and/or symptoms) after the BT onset.ResultsWe studied 41 patients (21 women/20 men; mean age: 40.6±10.8 years). NBD was classified as p-NBD (n= 33, 80.5%) and np-NBD (n=17, 41.5%). There were no significant differences in baseline general features and in neurological clinical response in both subgroups (Table 1 and Figure 1). The first BT used in p-NBD were Infliximab (IFX) (n=15), Adalimumab (ADA) (n=11), Golimumab (GLM) (n=3), Tocilizumab (TCZ) (n=2) and Etanercept (ETN) (n=2) and in np-NBD were IFX (n=9), ADA (n=6), TCZ (n=1) and ETN (n=1).Table 1.Main features of p-NBD and np-NBDTotalp-NBDnp-NBDP p-NBD vs np-NBDAge at biological therapy initiation, years (mean±SD)44±13.941.4±9.639.4±10.60.412Gender, n (m/f) (%)21/20 (48.8/52.2)18/15 (54.5/45.5)5/12 (29.4/70.6)0.091HLAB51 +/ patients tested, n (%)15/31 (57.7)14/25 (58.3)4/10 (40)0.391Oral aphthae, n (%)40 (97.6)32 (97)15 (88.2)0.323Cutaneous involvement, n (%)28 (63.4)23 (69.7)10 (58.8)0.603Ocular involvement, n (%)21 (48.8)15 (45.5)9 (52.9)0.616Vascular involvement, n (%)9 (22)10 (30.3)7 (41.2)0.442Articular involvement, n (%)9 (22)7 (21.2)3 (17.6)0.765Previous conventional Immunosuppressive drugs to BTAzathioprine24 (58.5)20 (60.6)10 (58.8)-Methotrexate16 (39.0)12 (36.4)3 (17.6)-Cyclophosphamide13 (31.7)13 (39.4)5 (29.4)-Cyclosporine A9 (22.0)8 (24.2)3 (17.6)-Mycophenolate Mofetil2 (4.9)2 (6.1)0-Figure 1.Response to biological therapy according to NBD subtypes.After an overall mean follow-up of 57.5±50.9 months BT was switched in 22 patients due to inefficacy (n=16) or Adverse Effects (AE) (n=6) and in 4 cases was definitively discontinued because of complete prolonged remission (n=3) or AE (n=1). AE were observed in 7 (17.1%) patients. Severe AE were observed in 2 cases, one due to demyelinating disease and the other due to pulmonary tuberculosis, both in patients undergoing IFX therapy. The other 6 AE were infusion reaction to IFX (n=1), IFX-induced psoriasis (n=1), IFX-induced acneiform eruption (n=1), infusion reaction to TCZ (n=1), intolerance to IFX and recurrent mild infections (n=1) and erosive lichen planus and bullous impetigo (n=1).ConclusionIn our series, BT seems equally effective and safe in both refractory p-NBD and np-NBD.References[1]Martín-Varillas JL, et al. Ophthalmology 2018 Sep;125(9):1444-1451. doi: 10.1016/j.ophtha.2018.02.020.[2]Atienza-Mateo B, et al. Arthritis Rheumatol 2019 Dec;71(12):2081-2089. doi: 10.1002/art.41026.[3]Santos-Gómez M, et al. Clin Exp Rheumatol 2016 Sep-Oct;34(6 Suppl 102): S34-S40.[4]Kalra S, et al. Diagnosis and management of Neuro-Behçet’s disease: international consensus recommendations. J Neurol. 2014 Sep;261(9):1662–76.Disclosure of InterestsAlba Herrero-Morant: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Lilly, Janssen, UCB, and Celgene, Santos Castañeda Paid instructor for: Assistant professor of the Cátedra UAM-ROCHE, EPID-Future, UAM, Madrid, Spain, Olga Maiz-Alonso: None declared, Julio Sanchez-Martin: None declared, Norberto Ortego: None declared, Enrique Raya: None declared, Águeda Prior-Español: None declared, Clara Moriano: None declared, Rafael Melero: None declared, Jenaro Graña: None declared, ANA URRUTICOECHEA-ARANA: None declared, Angel Ramos Calvo: None declared, Marta Loredo Martínez: None declared, Eva Salgado-Pérez: None declared, Francisca Sivera: None declared, Ignacio Torre-Salaberri: None declared, J. Narváez Speakers bureau: Bristol-Myers Squibb, José Luis Andréu Sánchez: None declared, Olga Martínez González: None declared, Ricardo Gómez de la Torre: None declared, Sabela Fernández: None declared, Susana Romero-Yuste: None declared, Iñigo Gonzalez-Mazon: None declared, Carmen Álvarez-Reguera: None declared, David Martínez-López: None declared, J. Luis Hernández: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Roche, Sanofi, Lilly, Celgene, Sobi, and MSD, Grant/research support from: Abbvie, MSD, Janssen, and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, BMS, Janssen, and MSD, Grant/research support from: Abbvie, MSD, and Roche

BackgroundTocilizumab (TCZ) has shown to be useful in the treatment of large-vessel vasculitis, including giant cell arteritis (GCA) (1-4). There is general agreement on the initial and the standard maintenance dose of TCZ. However, information on duration and optimization of TCZ in GCA is really scarce.ObjectivesOur aim was to assess the effectiveness and safety of TCZ therapy optimization in an unselected wide series of GCA in real-world clinical practice.MethodsMulticenter study on 471 patients with GCA who received TCZ therapy. Once complete remission was reached (n=231) TCZ was optimized in 125 patients. We compared patients in whom TCZ was optimized (TCZOPT group) or not (TCZNON-OPT group). Complete remission was defined as normalization of clinical and analytical (CRP and ESR) data. Optimization was done by decreasing the dose and/or prolonging the TCZ dosing interval progressively. We performed a comparison in effectiveness and safety parameters between optimized and non-optimized patients.ResultsWe evaluated 231 GCA patients treated with TCZ with complete remission. No demographic or laboratory data differences was observed at TCZ onset between both groups (Table 1). The mean prednisone dose was higher in the TCZNON-OPT group at TCZ onset. The first TCZ optimization was performed after a median [25-75th] follow-up of 12 [6-17] months.Table 1.Main general features at TCZ onset of 231 GCA patients with prolonged remission.OPTIMIZED-TCZ GROUP (n=125)NON-OPTIMIZED TCZ GROUP (n=106)pGENERAL FEATURES Age, years, mean± SD72.7±8.674±8.70.197 Sex, female/male n (% female)91/34 (72.8)74/32 (69.8)0.616 Time from GCA diagnosis to TCZ onset (months), median [IQR]8 [2-21.5]5 [2-21]0.384SYSTEMIC MANIFESTATIONS Fever, n (%)14 (11.2)15 (14.2)0.500 Constitutional syndrome, n (%)54 (43.2)39 (36.8)0.322 PMR, n (%)75 (60)69 (65.1)0.426ISCHEMIC MANIFESTATIONS Visual involvement, n (%)14 (11.2)16 (15.1)0.380 Headache, n (%)66 (52.8)62 (58.5)0.386 Jaw claudication, n (%)24 (19.2)25 (23.6)0.417AORTITIS (large-vessel involvement), n (%)65 (52)42 (39.6)0.060ANALYTICAL FINDINGS ESR, mm/1st hour, mean (SD)39.1±29.337.5±33.50.334 CRP, mg/dL mean (SD)2.6± 3.42.7± 40.305 Hemoglobin, g/dL, mean (SD)13.5±9.612.9±1.50.153GLUCOCORTICOIDS Prednisone dose, mg/d mean (SD)20.3±16.427±17.80.001Abbreviations: CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; GCA: giant cell arteritis; IQR: interquartile range; IV: intravenous; PMR: polymyalgia rheumatica; SC: subcutaneous; SD: standard deviation; TCZ: tocilizumab.The median prednisone dose at first TCZ optimization was 2.5 [0-5] mg/day. At the end of follow-up prolonged remission was observed in 78.2% of TCZOPT group compared with 66.7% in the TCZNON-OPT group (p= 0.001) (Figure 1). Seven (5.6%) of the 125 optimized cases relapsed. Serious adverse events were similar in both groups, while serious infections were more frequent in the TCZNON-OPT group (p=0.009).ConclusionOnce complete remission is reached in GCA patients under TCZ treatment, optimization of biologic may be performed. Based on our experience it could be performed by reducing the dose or by prolonging dosing interval of TCZ. It seems to be an effective and safe practice.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]Prieto-Peña D, et al. Ther Adv Musculoskelet Dis. 2021; 13: 1759720X211020917. PMID: 34211589[4]Loricera J, et al. Int Immunopharmacol. 2015; 27: 213-9. PMID: 25828585Disclosure of InterestsCarmen Álvarez-Reguera: None declared, Monica Calderón-Goercke: None declared, J. 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, Julio Sanchez-Martin: None declared, Lara Sanchez-Bilbao: None declared, Jose Luis Hernández Hernández: None declared, Miguel Á. González-Gay Consultant of: Abbvie, Pfizer, Roche, Sanofi and MSD., Grant/research support from: Abbvie, MSD, Jansen and Roche., Ricardo Blanco Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD, Grant/research support from: Abbvie, MSD and Roche.

Advances in cryo-electron microscopy (cryo-EM) have made it possible to obtain structures of large biological macromolecules at near-atomic resolution. This "resolution revolution" has encouraged the use and development of modeling tools able to produce high-quality atomic models from cryo-EM density maps. Unfortunately, many practical problems appear when combining different packages in the same processing workflow, which make difficult the use of these tools by non-experts and, therefore, reduce their utility. We present here a major extension of the image processing framework

Background: Eosinophilic esophagitis (EoE) is a chronic and isolated inflammation of the esophagus characterized by a marked infiltration of eosinophilic leukocytes. Diagnosis and course of the disease are based exclusively on histopathology. Therefore, patients must undergo several esophageal biopsies, implying a risk associated with the procedure and considerable use of resources. Objective: The presence of active circulating eosinophils, which are quantifiable through the expression of specific cellular activation proteins in their membrane, could be consistent with histopathological findings, which are currently the only valid parameters in studies on EoE. Methods: The activity of peripheral blood eosinophils from patients with EoE was analyzed by identifying 5 surface molecules (CD69, IL- 5Rα, CD44, ICAM-1, CD63), which are seen to be expressed by the active eosinophils in flow cytometry. The results were compared with the infiltrate of eosinophils present in patients’ esophageal biopsies. Results: ICAM-1 levels decreased significantly in patients with active EoE compared with nonactive EoE patients, allergic patients, and healthy controls. In patients with EoE, an inverse correlation was observed between the number of eosinophils in the esophageal biopsy and the percentage of ICAM-1 expression in peripheral blood eosinophils. No differences were observed for the remaining molecules studied. Conclusion: Expression of ICAM-1 in blood eosinophils could be a useful noninvasive marker for the diagnosis and assessment of patients with EoE.

Background:Interstitial Lung Disease (ILD) is an extra-articular complication of rheumatoid arthritis (RA) that is associated with increased morbidity and mortality. Conventional disease-modifying drugs (DMARDs) such as methotrexate (MTX) have been implicated in the development and exacerbation of a pre-existing ILD.Objectives:The aim of our study was to check the influence of combined MTX treatment in patients with RA-ILD treated with abatacept (ABA).Methods:National multicentre retrospective registry of 263 patients with RA-ILD treated with ABA. RA was diagnosed according to the ACR classification criteria of 1987 or by the EULAR/ACR criteria of 2010. ILD was diagnosed by high resolution computed tomography (HRCT). In this study we have done a subanalysis of the 46 patients treated with ABA in combination with MTX (ABA+MTX) vs. 217 patients treated with ABA in monotherapy or in combination with other synthetic DMARDs. Efficacy was evaluated according to the following parameters: a) Dyspnoea (MMRC) considering variations ≥ 1; b) Lung function test (LFT) considering variations ≥ 10% in FVC and a variation of DLCO ≥ 10%; c) Imaging test (HRCT) d) DAS28 score e) prednisone dose. Variables were collected at the beginning of the study and at months 3, 6, 12 and then every 12 months until a maximum of 60 months.Results:263 patients with ILD associated with RA were included in the study with mean age 64.64±10 years. RF or CCPA were positive in 235 (89.4%) and 233 (88.6%) cases, respectively, with a mean follow-up of 22.7±19.7 months. Baseline characteristics of both groups are shown in table 1, while data obtained during evolution of this complication are presented in Figure 1.Conclusion:Despite the baseline differences of both groups, the good evolution in the ABA+MTX subgroup suggests that this therapeutic strategy can be a safe combination for patients with RA-ILD.ABA with MTX (n=46)ABA w/t MTX (n=217)PSex (F/M)28/18122/950.625Age (years)65.11±10.216.2±9.80.202RF/CCPA + (%)91.3/91.389.8/90.10.810Smoking or past smoking (%)47.855.10.417Follow-up (months)22.73±18.0022.3±20.850.916DAS28 at baseline4.08±1.514.61±1.470.056DAS28 at last visit3.00±1.463.13±1.310.642Prednisone at baseline, median (IQR) (mg)5 (5-7.5)7.75 (5-15)0.008*Prednisone at the end of study, median (IQR) (mg)5 (1-5)5 (5-7.5)0.032*DLCO at baseline (%)66.85±19.0465.43±18.210.823DLCO at the end of study (%)66.05±20.9565.17±19.720.831FVC at baseline (%)90.06±17.7785.40±21.560.164FVC at the end of study (%)90.58±15,4584.21±21.490.038*Disclosure of Interests:Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Santos Castañeda: None declared, Rafael Melero: None declared, J. Loricera: None declared, Francisco Ortiz-Sanjuán: None declared, A. Juan-Mas: None declared, Carmen Carrasco-Cubero Speakers bureau: Janssen, MSD, AbbVie, Novartis, Bristol Myers Squibb, and Celgene, S, Rodriguéz-Muguruza: None declared, S. Rodrigez -Garcia: None declared, R. Castellanos-Moreira: None declared, RAQUEL ALMODOVAR Speakers bureau: Abbvie, Celgene, Janssen, Lilly, Novartis, Pfizer., CLARA AGUILERA CROS: None declared, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Sergi Ordoñez: None declared, Susana Romero-Yuste: None declared, C. Ojeda-Garcia: None declared, Manuel Moreno: None declared, Gemma Bonilla: None declared, I. Hernández-Rodriguez: None declared, Mireia Lopez Corbeto: None declared, José Luis Andréu Sánchez: None declared, Trinidad Pérez Sandoval: None declared, Alejandra López Robles: None declared, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Natalia Mena-Vázquez: None declared, C. Peralta-Ginés: None declared, ANA URRUTICOECHEA-ARANA: None declared, Luis Marcelino Arboleya Rodríguez: None declared, J. Narváez: None declared, DESEADA PALMA SANCHEZ: None declared, Olga Maiz-Alonso: None declared, J. Fernández-Leroy: None declared, I. Cabezas-Rodriguez: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, A. Ruibal-Escribano: None declared, JR De Dios-Jiménez Aberásturi: None declared, Paloma Vela-Casasempere: None declared, C. González-Montagut Gómez: None declared, J M Blanco: None declared, Noelia Alvarez-Rivas: None declared, N. Del-Val: None declared, M. Rodíguez-Gómez: None declared, Eva Salgado-Pérez: None declared, Carlos Fernández-López: None declared, E.C. Cervantes Pérez: None declared, A. Devicente-DelMas: None declared, Blanca Garcia-Magallon Consultant of: MSD, Speakers bureau: Pfizer, Amgen, Celgene, MSD, Cristina Hidalgo: None declared, Sabela Fernández: None declared, Edilia García-Fernández: None declared, R. López-Sánchez: None declared, S. Castro: None declared, P. Morales-Garrido: None declared, Andrea García-Valle: None declared, Rosa Expósito: None declared, L. Exposito-Perez: None declared, Lorena Pérez Albaladejo: None declared, Ángel García-Aparicio: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD

Background:Interstitial Lung Disease (ILD) is a severe complication of Rheumatoid Arthritis (RA). Several conventional disease-modifying anti-rheumatic drugs (cDMARDs) and biologic (b) DMARDs may induce or impaired ILD-RA. Abatacept (ABA) may be useful in ILD-RA (1).Objectives:To assess the efficacy and safety of ABA in a large series of ILD-RA for a long-term follow-up.Methods:Multicenter open-level study of ILD-RA treated with at least 1 dose of ABA. ILD was diagnosed by high-resolution computed tomography (HRTC). We study these outcomes: a) 1-point change Modied Medical Research Council (MMRC); b) forced vital capacity (FVC) and/or DLCO improvement or decline ≥10%; c) change in HRCT, d) change in DAS28. e) Prednisone dose. Values were collected at 0, 3, 6, 12 and then every 12 months.Results:We studied 263 patients (150 women/113 men) (mean age;64.6±10 years), with ILD-RA. At ABA-onset they were smokers or exsmoker (53.8%), positive APCC (88.6%), median [IQR] duration of ILD of 12 [3-41.25] months, mean DLCO (65.7±18.3) and FVC (85.9±21.8).The ILD-pattern were usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%).ABA was prescribed at standard subcutaneous (125 mg/w) in 196 (74.5%) or intravenously (10 mg/kg/4 w) in 67 (25.5%); in monotherapy (n=111) or combined with cDMARDs (n=152); especially leflunomide (n=55), MTX (n=46), or antimarials (n=21).After a mean follow-up of 22.7±19.7 months most outcomes remain stable (Figure). Moreover, DAS28 improved from 4.5±1.5 to 3.1±1.3; prednisone dose reduced from a median 7.5 [5-10] to 5 mg [5-7.5] and retention rate was 76.4%. The main adverse effects were serious infections (n=28), neoplasia (n=3), serious infusion reaction (n=1) and myocardial infarction (n=1).Conclusion:ABA seems effective and relatively safe in ILD-RA.References:[1]Fernández-Díaz C et al. Semin Arthritis Rheum. 2018; 48:22-27Disclosure of Interests:Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Santos Castañeda: None declared, Rafael Melero: None declared, J. Loricera: None declared, Francisco Ortiz-Sanjuán: None declared, A. Juan-Mas: None declared, Carmen Carrasco-Cubero Speakers bureau: Janssen, MSD, AbbVie, Novartis, Bristol Myers Squibb, and Celgene, S, Rodriguéz-Muguruza: None declared, S. Rodrigez -Garcia: None declared, R. Castellanos-Moreira: None declared, RAQUEL ALMODOVAR Speakers bureau: Abbvie, Celgene, Janssen, Lilly, Novartis, Pfizer.CLARA AGUILERA CROS: None declared, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Sergi Ordoñez: None declared, Susana Romero-Yuste: None declared, C. Ojeda-Garcia: None declared, Manuel Moreno: None declared, Gemma Bonilla: None declared, I. Hernández-Rodriguez: None declared, Mireia Lopez Corbeto: None declared, José Luis Andréu Sánchez: None declared, Trinidad Pérez Sandoval: None declared, Alejandra López Robles: None declared, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Natalia Mena-Vázquez: None declared, C. Peralta-Ginés: None declared, ANA URRUTICOECHEA-ARANA: None declared, Luis Marcelino Arboleya Rodríguez: None declared, J. Narváez: None declared, DESEADA PALMA SANCHEZ: None declared, Olga Maiz-Alonso: None declared, J. Fernández-Leroy: None declared, I. Cabezas-Rodriguez: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, A. Ruibal-Escribano: None declared, JR De Dios-Jiménez Aberásturi: None declared, Paloma Vela-Casasempere: None declared, C. González-Montagut Gómez: None declared, J M Blanco: None declared, Noelia Alvarez-Rivas: None declared, N. Del-Val: None declared, M. Rodíguez-Gómez: None declared, Eva Salgado-Pérez: None declared, Carlos Fernández-López: None declared, E.C. Cervantes Pérez: None declared, A. Devicente-DelMas: None declared, Blanca Garcia-Magallon Consultant of: MSD, Speakers bureau: Pfizer, Amgen, Celgene, MSD, Cristina Hidalgo: None declared, Sabela Fernández: None declared, Edilia García-Fernández: None declared, R. López-Sánchez: None declared, S. Castro: None declared, P. Morales-Garrido: None declared, Andrea García-Valle: None declared, Rosa Expósito: None declared, L. Exposito-Perez: None declared, Lorena Pérez Albaladejo: None declared, Ángel García-Aparicio: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background:Interstitial Lung Disease (ILD) is a severe extraarticular manifestation of rheumatoid arthritis (RA). In this line, several radiological patterns of RA-ILD have been described: i) usual interstitial pneumonia (UIP), ii) nonspecific interstitial pneumonia (NSIP), iii) obliterating bronchiolitis, iv) organized pneumonia and mixed patterns. Abatacept (ABA) could be an effective and safe option for patients with RA-ILD, although the response in the different radiological patterns is not well defined.Objectives:Our aim was to assess the response to ABA in different radiological patterns of ILD.Methods:Observational retrospective multicenter study of RA-ILD treated with ABA. ILD was diagnosed by HRCT and classified by radiological patterns in 3 different subgroups of RA-ILD: a) UIP, b) NSIP and c) “other”. ABA was used sc. or iv. at standard dose. We assessed: a) Dyspnoea (MMRC scale; significant variation ≥1); b) Respiratory function tests (significant changes ≥10% in FVC and DLCO); c) HRCT imaging; d) DAS28 e)prednisone dose.Variables were collected at months 0, 3, 6, 12 months and subsequently every 12 months until a maximum of 60 months.Results:We included 263 patients: 106 UIP, 84 NSIP and 73 others (150 women / 113 men), mean age 64.64±10 years. Total patients positive for RF or CCPA were 235 (89.4%) and 233 (88.6%), respectively. In 26 out of 263 patients, the development of ILD was closely related to the administration of sDMARDs (MTX n = 11 and LFN n = 1) or bDMARDs (ETN n = 5, ADA n = 4, CZP n = 2 and IFX n = 3). Patient characteristics are shown in table 1. Figure 1 shows the evolution of the cases with available data after a mean follow-up of 22.7±19.7 months. Mean DLCO and FVC remained stable in the 3 groups without statistically significant changes, and all the groups showed a statistically significant reduction in DAS28 and prednisone dose.Conclusion:ABA could be a good choice of treatment in patients with RA-ILD independently of the radiological pattern of ILD.Disclosure of Interests:Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Santos Castañeda: None declared, Rafael Melero: None declared, J. Loricera: None declared, Francisco Ortiz-Sanjuán: None declared, A. Juan-Mas: None declared, Carmen Carrasco-Cubero Speakers bureau: Janssen, MSD, AbbVie, Novartis, Bristol Myers Squibb, and Celgene, S, Rodriguéz-Muguruza: None declared, S. Rodrigez -Garcia: None declared, R. Castellanos-Moreira: None declared, RAQUEL ALMODOVAR Speakers bureau: Abbvie, Celgene, Janssen, Lilly, Novartis, Pfizer., CLARA AGUILERA CROS: None declared, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Sergi Ordoñez: None declared, Susana Romero-Yuste: None declared, C. Ojeda-Garcia: None declared, Manuel Moreno: None declared, Gemma Bonilla: None declared, I. Hernández-Rodriguez: None declared, Mireia Lopez Corbeto: None declared, José Luis Andréu Sánchez: None declared, Trinidad Pérez Sandoval: None declared, Alejandra López Robles: None declared, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Natalia Mena-Vázquez: None declared, C. Peralta-Ginés: None declared, ANA URRUTICOECHEA-ARANA: None declared, Luis Marcelino Arboleya Rodríguez: None declared, J. Narváez: None declared, DESEADA PALMA SANCHEZ: None declared, Olga Maiz-Alonso: None declared, J. Fernández-Leroy: None declared, I. Cabezas-Rodriguez: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, A. Ruibal-Escribano: None declared, JR De Dios-Jiménez Aberásturi: None declared, Paloma Vela-Casasempere: None declared, C. González-Montagut Gómez: None declared, J M Blanco: None declared, Noelia Alvarez-Rivas: None declared, N. Del-Val: None declared, M. Rodíguez-Gómez: None declared, Eva Salgado-Pérez: None declared, Carlos Fernández-López: None declared, E.C. Cervantes Pérez: None declared, A. Devicente-DelMas: None declared, Blanca Garcia-Magallon Consultant of: MSD, Speakers bureau: Pfizer, Amgen, Celgene, MSD, Cristina Hidalgo: None declared, Sabela Fernández: None declared, R. López-Sánchez: None declared, Edilia García-Fernández: None declared, S. Castro: None declared, P. Morales-Garrido: None declared, Andrea García-Valle: None declared, Rosa Expósito: None declared, L. Exposito-Perez: None declared, Lorena Pérez Albaladejo: None declared, Ángel García-Aparicio: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background Giant cell arteritis (GCA) can be refractory to corticosteroids1–3. Tocilizumab (TCZ) demonstrated to be effective in two short-term clinical trials. Objectives To assess efficacy of TCZ in refractory GCA or with side effects to corticosteroids in clinical practice. Methods Multicenter study on 134 patients with GCA in treatment with TCZ due to lack of efficacy and/or unacceptable adverse events of previous therapy. Results 134 patients (101 w/33 m); mean age of 73.0±8.8 years. Main clinical features at TCZ onset were: PMR (n=73), constitutional syndrome (n=31), headache (n=70), visual (n=28) and jaw (n=14) affection. Besides steroids, 98 patients also received immunosuppressive agents. table 1 shows evolution during follow-up period. After a median follow-up of 12 [3.7–24] months, it was observed a decrease in:a)CRP from 1.7 [0.4–3.2] to 0.1 [0.0–0.3] mg/dL b)ESR from 33 [14.5–61] to 42–9 mm/1st hour and c) Prednisone dose from 1510–30 to 5 [0–7.5] mg/day. Outcome of patients was:a)discontinuation of TCZ (n=15) due to sustained remission, b)dose reduction due to improvement (n=17) or side effects (n=11), c)withdrawal of TCZ because of side effects (n=12) and d)same dose that at onset (n=73). TCZ had to be discontinued due to: infections, haematological and cardiovascular alterations, neoplasms and heptic toxicity among the most frequent. Table 1 Conclusions TCZ leads to a rapid and maintained improvement in patients with refractory GCA and/or with unacceptable side effects related to corticosteroids. However, the risk of neutropenia and infection should be kept in mind. References [1] Loricera J, et al. Semin Arthritis Rheum2015;44:717–723. [2] Loricera J, et al. Clin Exp Rheumatol2014;32(3Suppl82):S79–89. [3] Loricera J, et al. Clin Exp Rheumatol2016; 34 (3 Suppl 97):S44–53. Disclosure of Interest None declared

The invasive species Aedes (Stegomyia) albopictus (Skuse 1894) (Diptera: Culicidae) has reached several European countries, including Albania, Belgium, Bosnia and Herzegovina, Croatia, France, Greece, Israel, Italy, Montenegro, Serbia, Slovenia, Switzerland, The Netherlands, and recently Spain (Med. Vet. Entomol. 20: 150-152, 2006). Here, we present the initial characterization of the distribution of Ae. albopictus in the municipality of Sant Cugat del Valles, Barcelona, Spain, where it was found for the first time in the Iberian Peninsula. An ovitrap sampling campaign was developed from September to December 2004 to assess the spatial distribution and abundance of Ae. albopictus to evaluate the potential of an eradication attempt. The population of Ae. albopictus in the whole area was shown to be widespread within the municipality, and it included at least another one neighboring town, so authorities were advised to develop large-scale control measures. Some indirect evidence was collected on the introduction means and date.

The used tire trade has facilitated the introduction, spread, and establishment of the Asian tiger mosquito, Aedes albopictus, and other mosquito species in several countries of America, Africa, Oceania, and Europe. A strategy for detecting these imported mosquito vectors was developed in Spain during 2003-2004 by EVITAR (multidisciplinary network for the study of viruses transmitted by arthropods and rodents). A survey in 45 locations found no invasive species. Eight autochthonous species of mosquitoes were detected in used tires, including Culex pipiens, Cx. hortensis, Cx. modestus, Anopheles atroparvus, An. claviger, Culiseta longiareolata, Cs. annulata, and Aedes caspius. Dominant species were Cx. pipiens and Cs. longiareolata. Aedes caspius was found in only once, near its natural breeding habitat. Considering the recent discovery of an established population of Ae. albopictus in Catalonia, the increasing commerce of used tires in Spain for recycling, storage, and recapping might greatly contribute to the rapid spread of this species across the Iberian Peninsula.

Objectives The objectives of this paper are to study the impact of disease activity in a large cohort of patients with systemic lupus erythematosus (SLE) and estimate the rate of response to therapies. Methods We conducted a nationwide, retrospective, multicenter, cross-sectional cohort study of 3658 SLE patients. Data on demographics, disease characteristics: activity (SELENA-SLEDAI), damage, severity, hospitalizations and therapies were collected. Factors associated with refractory disease were identified by logistic regression. Results A total of 3658 patients (90% female; median SLE duration (interquartile range): 10.4 years (5.3–17.1)) were included. At the time of their last evaluation, 14.7% of the patients had moderate-severe SLE (SELENA-SLEDAI score ≥6). There were 1954 (53.4%) patients who were hospitalized for activity at least once over the course of the disease. At some stage, 84.6% and 78.8% of the patients received glucocorticoids and antimalarials, respectively, and 51.3% of the patients received at least one immunosuppressant. Owing to either toxicity or ineffectiveness, cyclophosphamide was withdrawn in 21.5% of the cases, mycophenolate mofetil in 24.9%, azathioprine in 40.2% and methotrexate in 46.8%. At some stage, 7.3% of the patients received at least one biologic. A total of 898 (24.5%) patients had refractory SLE at some stage. Renal, neuropsychiatric, vasculitic, hematological and musculoskeletal involvement, a younger age at diagnosis and male gender were associated with refractory disease. Conclusions A significant percentage of patients have moderately-to-severely active SLE at some stage. Disease activity has a big impact in terms of need for treatment and cause of hospitalization. The effectiveness of the standard therapies for reducing disease activity is clearly insufficient. Some clinical features are associated with refractory SLE.

Dirofilaria immitis is the causal agent of heartworm diseases and of human pulmonary dirofilariosis. The infection is transmitted by several species of culicid mosquitoes that are frequently able to bite both animal reservoirs and humans. Canary Islands (Spain) constitute a well documented endemic area of canine dirofilariosis in which the mosquito species involved in the transmission of D. immitis are not known. The objectives of the present work were the identification of vectors of this parasite in Canary Islands and their molecular characterization. A total of 1219 female mosquitoes were captured. The most abundant species was Culex theileri (52.26%) followed by Cx. pipiens (35.44%), Anopheles cinereus hispaniola (6.23%), Culiseta longiareolata (5.74%), and Culex laticintus (0.33%). PCR was applied for the detection of larval D. immitis DNA in mosquitoes. D. immitis DNA was observed in the abdomen of one Cx. theileri female: 0.082% of the entire mosquito population and 0.17% in Cx. theileri. A molecular identification of Cx. theileri, the potential mosquito vector of dirofilariosis in this zoonotic focus in Canary Islands of Spain, has been made for first time based on sequences of the 18S rRNA gene, the second internal transcribed spacer (ITS2) of ribosomal DNA and the barcode region of the cytochrome c oxidase I (cox1) gene of mitochondrial DNA, allowing a broad mosquito molecular basis for future populations genetic analyses of this vector species. Parasitological and entomological molecular results suggest that Cx. theileri is a potential natural vector of D. immitis in Canary Islands.

The invasive species Aedes (Stegomyia) albopictus (Skuse 1894) (Diptera: Culicidae) has reached several European countries, including Albania, Belgium, Bosnia and Herzegovina, Croatia, France, Greece, Israel, Italy, Montenegro, Serbia, Slovenia, Switzerland, The Netherlands, and recently Spain (Med. Vet. Entomol. 20: 150-152, 2006). Here, we present the initial characterization of the distribution of Ae. albopictus in the municipality of Sant Cugat del Vallès, Barcelona, Spain, where it was found for the first time in the Iberian Peninsula. An ovitrap sampling campaign was developed from September to December 2004 to assess the spatial distribution and abundance of Ae. albopictus to evaluate the potential of an eradication attempt. The population of Ae. albopictus in the whole area was shown to be widespread within the municipality, and it included at least another one neighboring town, so authorities were advised to develop large-scale control measures. Some indirect evidence was collected on the introduction means and date.

The pupa of Ochlerotatus gilcolladoi is described and illustrated for the first time. Specimens were caught near Madrid. A table lists the range and mode of the branches of each pupal seta.

Background Daily clinical practice not always corresponds with the standard use of biologic therapies (BT) in rheumatic patients.st Objectives To determine the real vs. theoretical annual cost of BT per patient with chronic arthritis at a University tertiary Hospital. Methods Descriptive, observational, retrospective and cross-sectional study. Information over a 5-year period (2009-2014) is collected. Inclusion criteria: a) adult patients with RA (ACR), AE (New York modified/ASAS) or PsA (CASPAR) attended at the Rheumatology Service of the University Hospital of Vigo and b) >6 months of treatment with BT. Variables: a)demographics, b)clinical, c)pharmacotherapeutic history and d)per each BT: number of dispensations, adverse events, therapeutic failures, transitory or definitive discontinuation, survival of each BT line, real and theoretical (price to retailer) annual cost/patient of each BT line. Variables are described per disease and BT. Results 484 patients were studied (total: 755 BT lines). Mean age (years): 53.8±14.8; females: 263 (54.3%). The diseases treated were RA 226 (46.8%), AE 107 (22.2%), PsA 117 (24.2%) and other spondyloartrhopaties 33 (6.8%). Mean disease duration (years): 13.1±8.2. Mean global BT duration (months) from the beginning of the evaluation (January 2009) was: 40.9±58.9. The table shows the different BT lines used and their mean duration (months) from that date. There were 359 (47.4%) definitive withdrawals of BT, being secondary failure 156 (43.4%) and adverse events 82 (22.8%) the most frequent reasons. There were 94 (12.4%) temporal discontinuations of doses of BT. The most frequent reasons of temporal discontinuations were surgery 13 (13.8%) and non-infectious adverse events 12 (12.8%). There was modification of BT doses by optimization in 236 (31.2%) BT lines. The number (%) of patients optimized per disease was: RA 77 (34.1%), AE 35 (32.7%) and PsA 44 (37.6%). The mean duration (months) of optimization was: RA 42.0±12.7; AE 22.9±20.0 and PsA 21.9±18.2. There was modification of BT doses by intensification regimes in 24 (3.2%) of the BT lines. The number (%) of optimizations and intensifications of each BT and the mean duration (months) of optimization of the 3 more used BT are shown in the table. The mean theoretical global BT cost per year of treatment was 12,569€ ±1,707. The mean real global cost per year was 11,167€ ±3,266. The mean real and theoretical annual cost and its ratio, for the 3 more used BT are shown in the table. The mean theoretical annual cost per the 3 main diseases was: RA 12,538€ ±1,509; EA 12,703€ ±1,536 y APs 12,647€ ±1,165. The mean real annual cost per disease was: RA 11,400€ ±2,988; AE 10,993€ ±3,024 and PsA 10,870€ ±2,797. The annual real/theoretical cost ratios per disease were: 91.4, 87.6 and 86.5%, respectively. Conclusions In daily practice there are different reasons that make that BT use differs from the standard recommendations. This makes that the real cost usually is less than the theoretical one. The detailed analysis of our data will give us relevant information about the factors that determine these variations and their involvement on the pharmaceutical cost. Disclosure of Interest J. M. Pego-Reigosa Grant/research support from: Pfizer, M. Ucha: None declared, F. Maceiras: None declared, R. Melero: None declared, M. Άlvarez: None declared, C. Mourino: None declared, A. Martin: None declared, M. Rodriguez: None declared, M. Rodriguez: None declared, V. Balboa: None declared, J. Una: None declared, I. Hernandez: None declared, C. Barbazan: None declared, G. Pineiro Grant/research support from: Pfizer, N. Martinez: None declared

This is the first description of 3rd and 4th instars of Anopheles (Cellia) carnevalei. Adults were caught in the mainland region (Rio Muni) of Equatorial Guinea. Larvae present characteristic palmate setae different from Anopheles nili.

Vasculitis is diagnosed with increasing frequency in the elderly. We hereby present the case of an 84-year-old male, who had weight loss, low-degree fever, anemia and epigastric pain. After 14 days of study with the tentative diagnosis of digestive neoplasia, a progressive renal insufficiency was detected. This clinical picture was secondary to ANCA-positive vasculitis. The case poses the differential diagnosis of non-oliguric acute renal failure (FRA) in elder people and the systematics of the study of renal insufficiency in individuals with previously unknown renal function. Also, this patient's history emphasizes the importance of acute deterioration of renal function as a guiding symptom for orienting the interpretation of clinical data. In the present case, a diagnostic hypothesis based only in the pursue of an occult digestive tumor misguided the attention from the main cause of the disease.

Sevelamer is a non-absorbable phosphorus chelator that is not a source of aluminium, calcium or base. The clinical experience with sevelamer in peritoneal dialysis and in daily clinical practice is scarce. The aim of this study is to evaluate the results of therapy of hyperphosphoremia with sevelamer on serum phosphorus and phosphorus chelators requirements, in a peritoneal dialysis clinical practice.Sevalamer 400 mg was prescribed to peritoneal dialysis patients with hyperphosphoremia who were treated with aluminium hydroxide or with calcium salts in the absence of hypocalcemia. Fourteen patients completed 12 months of therapy.The initial sevelamer dose was 2,280 +/- 760 mg/day, and was increased to 2,760 +/- 1,160 mg/day at 12 months. At 12 months no patient was on aluminium salts and calcium salts had been significantly reduced. Phosphoremia (5.9 +/- 0.6 to 5.0 +/- 1.4 mg/dL, p = 0.049), calcium-phosphorus product (59.8 +/- 5.8 to 48.6 +/- 12.5 mg2/dL2, p = 0.01) and serum cholesterol (191 +/- 29 to 167 +/- 33 mg/dL, p = 0.02) decreased at 12 months. No significant changes were observed in serum triglycerides, total CO2 or PTH. Serum alkaline phosphatase increased at 6 months, but values returned to normal at 12 months. No changes were observed in serum gamma-glutamyl-transpeptidase. Five patients were started on 1.25 (OH)2 vitamin D therapy.In peritoneal dialysis patients, sevelamer allows a satisfactory control of serum phosphorus levels and calcium-phosphorus product, while decreasing the amount of aluminium and calcium salts prescribed.

The plasma metallothionein concentration was studied in renal transplant patients. These patients are submitted to an attack of free radicals catalyzed by metals such as copper, zinc, cadmium, and others. The function of metallothionein is to bind toxic metals inhibiting the attack of free radicals and oxidative stress that patients receiving renal transplants are submitted to. This is the reason for studying this protein in this work. The metalloprotein was separated from the plasma by thermoprecipitation and molecular exclusion chromatography with Sephadex G-75 followed by anionic-ionic exchange chromatographic purification with a CINa gradient. Identification was done by SDS electrophoresis in acrylamide gel with markers and commercial protein. Finally, determinations were made by atomic absorption, silver saturation method. In this work, determinations were made in the plasma of 11 patients before and 48 h and 1 and 2 weeks after renal transplantation. The same study was carried out in parallel in a control group of 11 blood donors. The results obtained show the existence in the plasma of metallothionein, with lower concentrations in patients than in controls (19 +/- 1.2 mg vs. 12 +/- 1.2 mg). The levels were lowest in the patient group analyzed 48 h after having received the transplant (6.34 mg) and had recovered slightly one and two weeks later.

Chironomid larvae (red midge larvae) are often used by aquarists as fish food. Their hemoglobins can cause IgE-mediated allergic diseases in exposed and unexposed people. The aim of this study was to find out the prevalence of positive skin tests to chironomids in patients suffering from rhinitis and/or bronchial asthma in Ciudad Real (Spain). A total of 465 patients were submitted to skin prick tests with chironomids in addition to common inhalant allergens. The patients with positive skin prick test (whealor = 3 mm) to these larvae answered a questionnaire. Skin prick tests with Acarus siro, shrimp, cockroach and mosquito (Culex pipiens) were carried out. Serum levels of total IgE and anti-Chironommus thummi, anti-Dermatophagoides pteronyssinus, anti-shrimp, and anti-mosquito (Aedes communis) IgE were determined. Conjunctival or nasal provocation tests were carried out with chironomids. Of the 465 patients skin tested, 19 showed a positive skin prick test with chironomids, corresponding to 4.1% of all patients and 6% of the atopic patients. None were monosensitized. Significant correlations were found between skin prick test results with chironomids and mites (p0.005). Of the 19 patients, 15 had positive skin prick test with the common mosquito C. pipiens. Seven patients showed elevated anti-D. pteronyssinus IgE, six elevated anti-shrimp IgE, and 10 showed elevated anti-A. communis IgE. Provocation tests with chironomids were positive in 14 patients (four nasal and 10 conjunctival tests). Conjunctival provocation tests were carried out in 16 controls and were positive in three; all three showed positive skin prick test with chironomids. One patient had occupational allergy from the larvae (aquarist). After mosquito bites, five patients showed immediate wheal reactions and one patient suffered an anaphylactic reaction after several mosquito bites. Only two patients remembered having been in contact with chironomids as fish food. We found hypersensitivity to these larvae in patients without apparent contact to them. These patients could have become sensitized in various ways, including: 1) inhaling particles of chironomids or others that are cross-reactive with them; 2) exposure to products used as fish food containing chironomids; and, 3) through cross-reactivity with other allergens such as mites, shrimp or mosquitoes.

The use of a precolumn or microreactor with KOH and NaOH packings is described for the degradation of twenty halogenated pesticides and PCBs. In both cases the recoveries and their time degradation development are studied. It is found that after 48 h of conditioning of the precolumn or the microreactor, the recovery of aldrin and several other organochlorines is quantitative. For those pesticides which give a partial recovery, the microreactor is more convenient to use. For trifluralin, heptachlor, heptachlor epoxide and mirex the recoveries are lower than those obtained with ethanolic KOH.

Cryo-electron microscopy (cryoEM) has become a well established technique to elucidate the 3D structures of biological macromolecules. Projection images from thousands of macromolecules that are assumed to be structurally identical are combined into a single 3D map representing the Coulomb potential of the macromolecule under study. This article discusses possible caveats along the image-processing path and how to avoid them to obtain a reliable 3D structure. Some of these problems are very well known in the community. These may be referred to as sample-related (such as specimen denaturation at interfaces or non-uniform projection geometry leading to underrepresented projection directions). The rest are related to the algorithms used. While some have been discussed in depth in the literature, such as the use of an incorrect initial volume, others have received much less attention. However, they are fundamental in any data-analysis approach. Chiefly among them, instabilities in estimating many of the key parameters that are required for a correct 3D reconstruction that occur all along the processing workflow are referred to, which may significantly affect the reliability of the whole process. In the field, the term overfitting has been coined to refer to some particular kinds of artifacts. It is argued that overfitting is a statistical bias in key parameter-estimation steps in the 3D reconstruction process, including intrinsic algorithmic bias. It is also shown that common tools (Fourier shell correlation) and strategies (gold standard) that are normally used to detect or prevent overfitting do not fully protect against it. Alternatively, it is proposed that detecting the bias that leads to overfitting is much easier when addressed at the level of parameter estimation, rather than detecting it once the particle images have been combined into a 3D map. Comparing the results from multiple algorithms (or at least, independent executions of the same algorithm) can detect parameter bias. These multiple executions could then be averaged to give a lower variance estimate of the underlying parameters.