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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

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

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

BackgroundPatients with immune-mediated rheumatic diseases (IMRD) are commonly treated with immunosuppressors and prone to infections. Recently introduced mRNA SARS-Cov2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-Cov2 mRNA vaccines.ObjectivesTo fully characterize B and T cell immune responses elicited by mRNA SARS-Cov2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccine´s immunogenicity.MethodsHumoral, CD4 and CD8 immune-responses were investigated in 100 SARS-Cov2-naïve patients with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-Cov2 mRNA vaccine. Responses were compared with age, gender, and disease-matched IMRD patients not receiving immunosuppressors and with healthy controls.ResultsIMRD patients showed decreased seroconversion rates (80% vs 100%, p= 0.03) and cellular immune responses (75% vs 100%, p= 0.02). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept decreased humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed impaired humoral responses, but cellular responses were often preserved. Antibody titers were reduced with mycophenolate and azathioprine but preserved with leflunomide and anticytokines.ConclusionIMRD patients exhibit impaired SARS-CoV-2 vaccine-immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine’s immunogenicity.Graph 1: Multivariate analysisAbataceptHCQCumulative glucocorticoid doseCumulative methotrexate doseAge > 65 yearsDisease duration >10 yearsSeronversionβ - 0.1p= 0.04β 0.22 p= 0.01β - 0.26p= 0.44β - 0.19p= 0.03β - 0.27p= 0.002β - 0.10 p= 0.22IgG anti-spike levelsβ - 0.13p= 0.001β 0.27p= 0.01β - 0.25p= 0.004β - 0.29p= 0.001β - 0.19p= 0.02β - 0.14p= 0.04CD4 T-cell responseβ - 0.1p= 0.03β 0.10p= 0.24β - 0.04p= 0.61β - 0.03p= 0.64β - 0.05 p= 0.56β - 0.14 p= 0.11CD8 T -cell responseβ - 0.08p= 0.02β 0.20 p= 0.12β - 0.1p= 0.43β - 0.02p= 0.24β - 0.1 p= 0.56β - 0.1 p= 0.15References[1]Arad U, Tzadok S, Amir S, et al. The cellular immune response to influenza vaccination is preserved in rheumatoid arthritis patients treated with rituximab. Vaccine 2011; 29:1643-1648[2]Amanna IJ, Slifka MK. Contributions of humoral and cellular immunity to vaccine-induced protection in humans. Virology. 2011;411(2):206-215.[3]Spiera R, Jinich S, Jannat-Khah D. Rituximab, but not other antirheumatic therapies, is associated with impaired serological response to SARS- CoV-2 vaccination in patients with rheumatic diseases. Ann Rheum Dis. 2021 May 11:annrheumdis-2021-220604. doi: 10.1136/annrheumdis-2021-220604. Epub ahead of print. PMID: 33975857.Disclosure 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

BackgroundInterstitial lung disease (SSc-ILD) and pulmonary hypertension are the leading causes of death in patients with systemic sclerosis (SSc). Identifying SSc-ILD development and initiating treatment is essential to optimize therapeutic benefit.ObjectivesWe aimed to identify predictors of SSc-ILD and compared early (5 years from diagnosis) onset.MethodsWe conducted a retrospective cohort study by including patients diagnosed with SSc from 1980 to 2020 followed in our unit and compared the clinical profile of patients with SSc-ILD to control SSc-non-ILD patients. Demographic features, clinical and immunological characteristics, baseline pulmonary function and capillaroscopy data were retrieved. Logistic regression modelling was run to identify factors associated with SSc-ILD development. Factors associated with ILD were then determined as factors associated with early or late onset using multivariate analysis. Bonferroni correction was used to limit Type I errors.ResultsWe have included 103 patients from our patient registry from 1980 to 2021 (42% with SSc-ILD). Logistic regression identified risk factors associated with increased or decreased odds ratio for developing ILD is summarized in Table 1. Smoking history, male sex, the presence of myositis, anti-Scl70 and anti-Ro52 positivity, baseline pulmonary function including FVC and DLCO, mMRC (Modified Medical Research Council) dyspnea scale>2, mMSS (Modified Rodnan Skin Score), and late pattern in capillaroscopy were identified as SSc-ILD predictors. Older age at SSc diagnosis, the presence of telangiectasias and smoking status were correlated with of SSc-ILD onset before 5 years, while male gender, the presence of myositis and antiphospholid antibodies were correlated with late-onset SSc-ILD.Table 1.Significant logistic regressions for predictors for SSc-ILDPredictorOR (95% CI)P valueMale2.8 (1.16-6.8)0.02Smoking history2.15 (1.33-3.46)0.001Diffuse cutaneous involvement10.4 (2.2-48.3)0.003Raynaud duration0.89 (0.79-1.0)0.04Myositis3.45 (1.09-10.9)0.03Anti-Scl705.45 (2.02-14.7)0.001Anti-Ro523.37 (1.49-9.45)0.002FVC0.97 (0.91-0.98)0.03DLCO0.96 (0.93-0.98)0.003mMSS3.73 (1.64-8.5)0.01mMRC>22.01 (1.52-4.2)0.04Late capilaroscopy pattern2.3 (1.02-5.27)0.04Early onset SSc-ILDβ valueP valueOlder age at onset0.470.0017Telangiectasias0.290.04Smoking stauts0.370.02Late onset SSc-ILDβ valueP valueMale gender0.570.001Myositis0.340.02Antiphospholipid antibodies0.310.04ConclusionWe identified 10 factors significantly associated with risk of developing SSc-ILD: smoking, male sex, diffuse cutaneous involvement, the presence of myositis, shorter Raynaud duration to SSc diagnosis, anti-Scl70 and anti-Ro52 positivity and baseline pulmonary function (lower baseline DLCO and FVC increasing risk) and late capillaroscopy pattern and identified predictors for early and late-onset SSc-ILD.References[1]Onat A, Zengin O, Balci M, et al AB0670 The Survival and Prognostic Factors of Patients with Systemic Sclerosis: Experience of Two Centers. Annals of the Rheumatic Diseases 2015;74:1122.[2]Kapralik J, Morton R, Farooqi M, Beattie K, Hambly N, Larche M. Predictors of ILD Development and Timing of Onset in Systemic Sclerosis: A Canadian Cohort [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10).Disclosure of InterestsNone declared

BackgroundIdiopathic Inflammatory myopathies are a heterogenous group of diseases which main common characteristic is muscle injury. Specific autoantibodies related with different phenotypes have become an important diagnostic and prognostic tool. These antibodies may be associated with different histopathological features in muscle biopsies.ObjectivesTo describe the demographic, clinical and serological characteristics of Idiopathic Inflammatory Myopathies (IIM); the most frequent corticoid sparing agents used and the frequency of associated neoplasms in a sample of patients with a compatible biopsy result. To compare these characteristics in patients with positive and negative ANA and the association of different biopsy patterns with specific myositis antibodies.MethodsMuscle biopsies results that were compatible with inflammatory myopathy were collected from the Pathology Unit database of Leon´s hospital between January 2010 and March 2021.Demographic, clinical and serological characteristics, associated malignancies and treatments used were collected from clinical records.ResultsWe included 30 patients in the study. Patient`s characteristics are shown in Table 1. Median age of diagnosis was 59 years. Arthritis and lung disease were found in 20% of patients. The patterns of lung involvement found in HRCT were NSIP in 2, UIP in 1, and bronchiectasis in 3 patients. Associated collagenopathies were found in 26,7%, being vasculitis the most frequent (2 patients). Associated Malignancies were found in 13,3%: lung carcinoma in 1, Urothelial carcinoma in 1, cervix carcinoma in 1 and prostate carcinoma 1 patient. Specific myositis antibodies were negative in 56,7%; positive ANA was found in 60%.Table 1.Demographic, clinical, serological characteristics and treatment in the sample studiedCharacteristicsPatients (n=30)Median; IQR or n(%)Age at diagnosis (years)59; 18,5Sex F/M17(56,7)/13(43,3)Artralgias11(36,7)Arthritis6(20)Raynaud3(10)Lung disease6 (20)Skin disease7 (23,3)Autoimmunity biomarkers (+/-/ not done)ACPA2(6,7) /3 (10) /25(83,3)Positive Rheumatoid Factor4(13,3) /13 (43,3) /13(43,3)ANA18 (60%) /12(40%)Specific Myositis AntibodiesAnti SRP1(3,3)Anti-HMG CoA reductase5 (16,7)Anti Jo12(6,7)Negative17 (56,7)Not done5 (16,4)Biopsy patternnecrotizing8 (26,7)inflammatory15(50)Inclusion Bodies4 (13,3)dermatomyositis3 (10)DiagnosisDermatomyositis3 (10)Statin Myopathy5(16,7)Inclusion body myopathy3(10)Polymyositis8(26,7)Immune-mediated necrotizing myopathy2 (6,7)Antisynthetase syndrome1(3,3)Other collagenopathies8(26,7)TreatmentMethotrexate11(36,7)Azathioprine3(10)immunoglobulins5(16,7)Rituximab5(16,7)Mycophenolate4(13,3)Cyclophosphamide2 (6,7)None11 (36,7)2 or more treatments8(26,7)Associated malignancies4 (13,3)The median of levels at diagnosis of CK was: 1181; IQR:6252,5; aldolase 14,4; IQR: 34,65; AST 62; IQR:181,25; ALT 55,5; IQR:119,25; CRP 7,6; IQR 13,55.When compared, CK and ALT levels in patients with negative and positive ANA, this were higher in negative patients (6365; IQR:9592vs888;3045; P=0.044) and (182; IQR:287vs43; 85; P=0,035) respectively. Anti HMGCoA reductase antibodies were more frequently found in patients with necrotizing pattern in biopsies 5/8 patients; (62,5%); p=0.002.Methotrexate was the corticoid sparing agent most frequently used (36,7% of patients), 36,7% of patients were treated only with corticoids and 26,7% needed more than one treatment.ConclusionSpecific myositis antibodies are helpful tools in the diagnosis when present, meanwhile biopsy can be an important tool when antibodies are negative. ANA positivity seems to be associated with milder disease at the muscular domain.References[1]Zanframundo G,Tripoli A, Cometi L, et al. One year in review 2020: idiopathic inflammatory myopathies. Clin Exp Rheumatol 2021; 39: 1-12.Disclosure of InterestsNone declared

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

BackgroundUveitis is the most frequent extra-articular manifestation of spondylarthritis (SpA), characterized by a sudden onset, often unilateral, anterior and recurrent and may be the first clinical manifestation of the disease. The lack of standardized and validated outcome measures in uveitis makes it difficult to evaluate the efficacy and refractoriness to treatment and determine factors associated with adverse outcomes.ObjectivesTo develop a prognostic outcome score for patients with uveitis associated with spondylarthritis (SpA-U) and determine factors associated with adverse outcomes in uveitis associated to SpA-U in patients under systemic treatment.MethodsClinical records of patients with SpA-U from 1990 to 2020 were retrospectively reviewed, including sociodemographic features, factors related to articular involvement, therapeutic choices and data related to uveitis outbreaks. The prognostic outcome score was defined by visual acuity, inflammation in anterior chamber (anterior chamber cells, hypopyon, presence of fibrin, active posterior keratic precipitates), presence of synechia, pupilar membrane, epiretinal membrane or any complications (macular oedema, vitritis, panuveitis, peripheral ulcerative keratitis), and refractoriness to 2 or more d/csDMARDs (conventional synthetical disease-modifying anti-rheumatic drug) or 1 or more bDMARD (biological disease-modifying anti-rheumatic drug) treatment. The prognostic outcome score ranked from 0 (good) to 5 (bad). Factors associated with adverse outcomes in uveitis were studied using linear regression. For categorical factors, marginal averages and their standard errors are displayed together with linear regression coefficients with 95% confidence intervals (CI). For continuous factors, averages and standard deviations are reported in addition to linear regression coefficients with 95% CI. For each variable, two regression coefficients are reported: unadjusted and adjusted for age at diagnosis and sex.Results42 patients were included, 59.5% were male, with a mean age at diagnosis of 36.6±11.9 years and with a total of 190 uveitis outbreaks. Time since diagnosis was 12.5±7.9 years. 64.4% of patients had uveitis as disease onset. 52.4% were overweight (BMI≥30 kg/m2), 16.7% were former/active smokers. 28.6% of patients had a family history of SpA. 14.3% had 1-2 uveitis outbreaks, 47.6% had 3-5 uveitis outbreaks and 38.1% had 6-11 uveitis outbreaks. 102 (53.7%) uveitis outbreaks fulfilled 1 criterion, 38 (20%) uveitis outbreaks fulfilled 2 criteria, 19 (10%) uveitis outbreaks fulfilled 3 criteria and 5 (2.6%) uveitis outbreaks fulfilled 4 or more. The results of the linear regression model revealed that the uveitis was more severe in patients with smoking history (β=0.34), axial and peripheral involvement (β=0.43), a BASDAI (Bath Ankylosing Spondylitis Disease Activity Index)>4 (β=0.32), positive HLA-B27 (β=0.29), female sex (β=0.19), patients with CRP (C-reactive protein) elevation (β=0.002) and a history of bilateral ocular involvement (β=0.32) while shorter disease evolution (β=-0.02) and normal vitamin D levels (β= -0.03) were associated with a better outcome.ConclusionWe identified factors associated with adverse outcomes in SpA-U by developing a prognostic outcome score that integrates ocular inflammatory activity, ocular complications and refractoriness to treatment.References[1]Pato Cour E, Martin MA, MuÑoz Fernandez S, Castello A, Sanchez-Alonso F, Diaz-Valle D, MendezR. Development of an Activity Disease Score in Patients with Uveitis [abstract]. ArthritisRheumatol. 2015; 67 (suppl 10).https://acrabstracts.org/abstract/development-of-an-activity-disease-score-in-patients-with-uveitis/. Accessed October 30, 2021.Disclosure of InterestsNone declared

BackgroundSystemic sclerosis (SSc) is associated with increased risk of malignancy. Risk factors predisposing a SSc patient for development of malignancy are not well defined, and the pathogenic basis of the association is yet to be explained. Some autoantibodies have been associated with a close temporal relationship with cancer. The absence of malignancy screening guidelines tailored for SSc patients raise the importance of the need for more studies on the association of SSc and cancer.ObjectivesTo study the prevalence of cancer in SSc and the association between SSc-specific and SSc-associated autoantibodies and cancer in a third-level center.MethodsWe conducted a retrospective cohort study by including patients diagnosed with SSc followed from 1980 to 2020 fulfilling the 2013 ACR/EULAR SSc criteria. Demographic features, clinical and immunological characteristics were retrieved. The primary outcome was cancer-associated SSc, defined as cancer occurring within 2, 3 and 5 years of first non-Raynaud SSc manifestation. The exposure was defined by the presence of SSc-specific/associated autoantibodies, including anti-centromere (ACA), topoisomerase I (Scl70), RNA polymerase III, fibrillarin, Th/To, PM-Scl, Ku, TIF1g, Ro52. Descriptive analysis was used to compare clinical characteristics of subjects with cancer to those without cancer. Univariate logistic regression was used to compare the odds of cancer-associated SSc between the autoantibody subgroups.ResultsOut of 103 SSc subjects, 27 (26%) had a history of cancer following SSc diagnosis. Mean age was 61.9 (57-69) years, 70% were female and 88% had a smoking history. Median time between cancer and disease onset was 6.33 (3-9) years. Among patients with cancer, 12 (44%), 8 (29%) and 7 (26%) were diagnosed within 2, 5 and 10 years of SSc onset. The most frequent types were breast cancer (n=9), gastrointestinal cancer (n=5), prostatic cancer (n=4), hematological (n=3) cancers, cervical/uterine cancers (n=2), non-melanoma skin (n=2), lung cancer (n=2). Patients with cancer were more likely to be Sc70+(OR 2.55, 95% CI1.03-6.3, p 0.04), anti-TIF1g (OR 19.5, 95% CI 5.6 – 68.3, p 0.001) and RNA pol III (OR 10.9 CI 95% 1.08-109.3, p 0.04), have a history of smoking (OR 7.24, 95% CI 2.6-197, p 0.001), myositis (OR 5.2 IC 95% 2.06-13.2, p 0.005) and older age at SSc onset (61.9 vs 57, p 0.04). Breast cancer was more frequent in anti-TIF1g (OR 3.75 IC 95% 1.8-17.5) and RNA pol-III (OR 7.14 IC 95% 1.56-90.8) subgroups. The risk of cancer-associated SSc was significantly increased among anti-TIF1g-positive subjects at 5 years after SSc onset (OR 2.1 CI 95% (1.45-9.94), p 0.04) and among RNA-pol III-positive subjects at 2 years after SSc onset (OR 3.5 95% CI (1.2-51.4), p 0.02) (Table 1).Table 1.Logistic regression analysis for the risk of cancer within 2,5 and 10 years of SSc onset according to antibody positivityOR 95% CI for cancer diagnosis within 2 years of SSc onsetOR 95% CI for cancer diagnosis within 5 years of SSc onsetOR 95% CI for cancer diagnosis within 10 years of SSc onsetAnti-Scl701.56 (0.51-44.5)1.41 (0.27-12.7)2.1 (0.55-13.4)Anti-centromere1.72 (0.62-52.1)1.52 (0.32-32.1)1.69 (0.14-21.3)Anti-TIF1g3.9 (0.35-43.4)2.1 (1.45-9.94)0.42 (0.04-5.32)ARN Pol III3.5 (1.2-51.4)1.9 (0.72-62.1)-Anti-PM Scl75/100--0.87 (0.04-1.98)Anti-Ro522.5 (0.66-66.8)2.0 (0.45-50.2)0.63 (0.05-7.74)ConclusionAnti-Scl70, anti-TIF1g and RNA pol III were predictive of cancer-associated SSc for cancers. Breast cancer was the most frequent. Subjects with cancer were more likely to have a history of smoking, myositis and an older age at SSc onset. Autoantibodies should be taken into account in cancer screening. Larger studies are needed to define the risk of cancer-associated SSc in different autoantibody subgroups.References[1]Mecoli CA, Adler BL, Yang Q, Hummers LK, Rosen A. Cancer in Systemic Sclerosis: Analysis of Antibodies Against Components of the Th/To Complex. Arthritis Rheumatol. 2021 Feb;73(2):315-323. doi: 10.1002/art.41493. Epub 2020 Dec 26. PMID: 33241644; PMCID: PMC7884482Disclosure of InterestsNone declared

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.

BackgroundPregnancies in systemic lupus erythematosus (SLE) are considered high risk and associated with maternal and obstetric complications.ObjectivesOur goal with this study was to determine the most important predictors for each of the main adverse pregnancy outcomes in SLE patients.MethodsWe conducted a retrospective case-controls study by including multiparous women diagnosed with SLE from 1980 to 2020 followed in our unit and compared the clinical profile of patients with adverse pregnancy outcomes to control SLE patients. We excluded elective terminations of pregnancy and cases lost to follow-up. Qualitative data were analyzed by Chi-square test and Fisher’s exact test and continuous variables were analyzed by using Student’s t test. Multiple logistic regression models were performed to determine the predictive factors for adverse pregnancy outcomes with adjustment of confounding factors. In all tests, P values less than 0.05 were considered to be statistically significant.Results135 multiparous women were included (43% with adverse pregnancy outcomes). The mean age of patients at inclusion was 55.8 (46-64) years. Abortion occurred in 33 patients (57%), pre-eclampsia in 10 patients (17%), ectopic pregnancy in 5 patients (8%), preterm labor in 5 patients (8%), placental abnormalities in 4 patients (6%), stillbirth in 4 patients (6%), premature rupture of membranes (PROM) and neonatal lupus in 3 patients (5%), respectively. 121 patients (89%) have pre-existing lupus and 14 (11%) referred with SLE onset in pregnancy. Renal involvement (p=0.03), anti-DNAds positivity (p=0.002), antiphospholipid antibody (APA) positivity (p=0.001), anti-Ro/SSA (p=0.003) and a younger age at disease onset (p=0.01) were significantly associated with unfavorable pregnancy outcomes. Abortion was correlated with anti-DNAds (β=0.71. p=0.04), renal involvement (β=0,28, p 0.03) and APA (β=0.2, p 0.03). Stillbirth was also correlated with renal involvement (β= 0.26, p =0.04) and APA (β=0.22, p=0.03). Preeclampsia was correlated with direct Coombs positivity (β=0.42, p=0.01) and serositis (β=0.31, p=0.02). Neonatal Lupus was correlated with anti-RNP (β=0.16, p=0.03) and anti-Ro/SSA (β=0.16, p 0.02). Renal involvement and APA had a 2.6-fold increased risk of unfavorable pregnancy outcomes (OR 2.6 95% (1.1-6.1), p 0.03) and APA had a 4.3-fold increased risk of unfavorable pregnancy outcomes (OR 4.3 95% IC 2.1-8.8), p 0.002).ConclusionThe most unfavorable pregnancy outcomes in women with SLE was spontaneous abortion. Renal involvement, anti-DNAds and anti-Ro/SSA, antiphospholipid antibody positivity, and a younger age at disease onset increased the risk of pregnancy complications.Table 1.Multiple logistic regression analysisAbortionStillbirthPre-eclampsiaPROMEctopic pregnancyNeonatal LupusAnti-DNAdsβ =0,71, p=0.04β =0.26, p=0.04β =0.12, p=0.38β =0.15, p =0.24β = 0.10, p =0.64β = 0.16, p=0.24APAβ = 0.2, p = 0.03β = 0.22, p=0.03β = 0.11, p = 0.85β = 0.26, p = 0.04β = 0.16, p = 0.21β = 0.83, p = 0.08Renal involvementβ=0,28, p 0.03β = 0.26, p = 0.38β = 0.33, p = 0.83β = 0.07, p = 0.53β = 0.17, p = 0.20β = 0.58, p = 0.07Serositisβ = 0.85, p = 0.95β = 0.11, p = 0.41β=0.31, p=0.02β = 0.06, p = 0.46β = 0.13, p = 0.35β = 0.08, p = 0.46Direct Coombs positivityβ =0.11, p = 0.41β = 0.03, p = 0.81β = 0.42, p=0.01β=0.03, p =0.83β= 0.14, p = 0.81β=0.03, p=0.83Anti-Ro/SSAβ=0.19, p = 0.13β=0.03, p = 0.83β=0.07, p =0.62β=0.11, p=0.39β=0.09, p=0.52β= 0.16, p 0.02Anti-RNPβ =0.5, p=0.69β = 0.09, p=0.49β = 0.16, p= 0.23β = 0.09, p= 0.81β=0.03, p=0.81β=0.16, p=0.03References[1]Palma dos Reis, C.R., Cardoso, G., Carvalho, C. et al. Prediction of Adverse Pregnancy Outcomes in Women with Systemic Lupus Erythematosus. Clinic Rev Allerg Immunol 59, 287–294 (2020). https://doi.org/10.1007/s12016-019-08762-9[2]Zamani, B., Shayestehpour, M., Esfahanian, F. et al. The study of factors associated with pregnancy outcomes in patients with systemic lupus erythematosus. BMC Res Notes 13, 185 (2020). https://doi.org/10.1186/s13104-020-05039-9Disclosure of InterestsNone declared

Background:Rituximab (RTX) is a drug composed of chimeric monoclonal antibodies against the CD20 protein that leads to B cell lymphocyte depletion and is currently licensed for rheumatoid arthritis. There is growing evidence of off-label use of rituximab for severe and refractory systemic autoimmune diseases (SAD).Objectives:Analysing the clinical effectiveness of RTX for SADs such as vasculitis (VS), systemic lupus erythematosus (SLE), systemic sclerosis (SS), primary sjögren syndrome (pSS), necrotizing myopathy (NM) and dermatomyositis (DM) in a rheumatology outpatient clinic in a third level hospital during a 5 year-period (2015 –2020).Methods:We conducted a retrospective analysis of patients with SAD treated with RTX in the last 5 years. We evaluated demographic and clinical data, indication for RXT, previous treatments, cumulative dose of rituximab and corticosteroids, clinical response, and the presence of adverse events. We considered follow-up period between the first and the last clinical evaluation. Clinical response was considered complete with symptom and analytical remission; incomplete with partial symptom or analytical response and no response if there was no symptom or analytical response.Results:35 patients were included (54% women, mean age 60.16 ±17 years). The diagnosis were: pSS (31.4%), SS (17%), SLE (17%), VS (20%), NM (8.8%) and DM (5.8%). Indications for treatment were pulmonary disease in 37% of cases, renal disease in 17%, articular manifestations in 11.4%, haematological manifestations in 14.3%, skin involvement in 8.8%, neurologic manifestations in 5.7% and myopathy in 5.8%. RTX was used after therapeutic failure with previous treatments in 80% (20% of which had receiving treatment with biological disease-modifying antirheumatic drugs) and as first line treatment in only 20% of the cases. After rituximab, 60% of patients had complete response, 17% partial response, and 20% nonresponding. Mean corticosteroid dose post-rituximab was significantly reduced by 60% in pSS (p 0.02), 65% in VS (p 0.03), 50% in SS (p 0.04) and NM (p 0.046). Five patients (14%) had infectious complications, 2 of which needed hospitalization. 7 patients (17%) discontinued therapy, 5 due to ineffectiveness (2 SLE, 1 NM, 1 DM and 1 SS) and 2 patients (14%) due to infectious complications (1 pSS and 1 VS). Patients underwent a median of 2 treatment cycle. The median follow-up after starting RTX was 48.5 (IQR 25.9-74.4) months.Table 1.Clinical characteristicspSSVSSLESSNMDM%31.4%20%17%17%8.8%5.8%Age (years)63.8 (19-73)63.5 (43-82)59.2 (43-78)65.8 (56-78)58.5 (54-63)48.5(26-52)Female100%71%50%66%50%50 %Duration of disease (months)80.5 (24-108)39 (12-60)38.4 (36-90)56.4 (14-96)69 (48-90)60 (25-82)Cumulative RTM dose (g/m2)2.5 (0.75-6)3.2 (0.5-8)1.4 (0.75-5)2.8 (0.5 – 7)1.2 (0.5 – 5)0.56 (0.38-0.75)Complete clinical response63%86%33%71%33%0%Incomplete response18%14%33%14%0%50%No response18%0%33%14%66%50%Glucocorticoid dose (mg/day)Before RTMX12.5 (5-20)21.3 (5-30)9 (0-15)9 (5-15)15 (7.5 – 25)15 (7.5 – 25)Glucocorticoid dose (mg/day)After RTX5 (2.5-15)7.5 (5-15)5 (2.5-15)4.5 (2.5-10)10 (7.5-25)12.5 (8 – 20)ImmunosuppressantsBefore RTX81%71%90%50%33%50%ImmunosuppressantsAfter RTX54%28%57%66%67%50%Severe infusion-related side effects including need for admission0%14%16%0%0%0%Other infusion-related side effects9%29%17%17%0%0%Conclusion:Treatment with RTX was very effective in SADs, particularly in VS, SS and pSS. Further studies are needed to clarify RTX efficacy and safety in SADs, as well as indications and optimal RTX regimens.References:[1]Berghen N, Vulsteke JB, Westhovens R, Lenaerts J, De Langhe E. Rituximab in systemic autoimmune rheumatic diseases: indications and practical use. Acta Clin Belg. 2019 Aug;74(4):272-279.[2]Hofmann K, Clauder AK, Manz RA. Targeting B Cells and Plasma Cells in Autoimmune Diseases. Front Immunol. 2018 Apr 23;9:835.Disclosure of Interests:None declared

Background Patients with Systemic Autoimmune Diseases (SADs), in particular, systemic sclerosis, are prone to suffer from severe Raynaud9s phenomenon (RP), accompanied with digital ulcers secondary to ischemia and associated with a high rate of morbidity and mortality. Bosentan, a dual endothelin receptor antagonist, is a therapeutic option for refractory cases with an inadequate response to conventional management. Objectives The objectives of our study were: i) to assess safety and efficacy of bosentan in patients suffering from different kinds of SADs and active digital ulcers secondary to RP, ii) to determine predictive factors of response, and iii) to identify predictive factors for survival. Methods This is a retrospective observational study of patients suffering from SADs and digital ulcers secondary to RP, treated with bosentan in our department between January 1st, 2005 and December 31st, 2014. Patients with ischemic ulcers caused by other factors were excluded. The following baseline independent variables were considered: type of SAD, exposition to cold or to toxic substances, clinical and epidemiological characteristics, concomitant treatments, the coexistence of pulmonary hypertension, and number and location of digital ulcers. Therapeutic response, adverse effects, the need for amputation and death were considered as dependent outcome variables. Chi-square, Student t test, and Mann-Whitney U test were used to establish statistical significance in the univariate analysis between independent baseline variables and outcomes. A p Results We included 31 patients (26 women, mean age 57 years). Twenty patients had systemic sclerosis (10 cases the limited form, and 10 cases the diffuse form). Eight patients had concomitant pulmonary hypertension. Mean follow-up after starting bosentan was 1470 days. Six patients had, at least, an adverse effect, being the most frequent alterations of liver function tests. In 87% of the cases, ulcers improved significantly, with a clinical response within the first 12 weeks of treatment in 77% of the cases. Ninety percent of the patients received concomitant treatment with calcium channel blockers and 45% had received previous treatment with prostaglandins. Despite bosentan therapy, amputation was done in 4 patients. Type of SAD, gender, or exposition to cold did not show any significant correlation with morbidity and mortality. Nine patients died. Smoking habit showed a correlation with death (p=0.05). There was a significant correlation between the duration of the disease and death (p=0.0235), as well as with the age of the patient (p=0.0013). Pulmonary hypertension was predictive of a poor therapeutic response (p=0.043) and mortality (p=0.015). Conclusions This open study suggests that bosentan is an effective agent for ischemic digital ulcers in patients with SADs, with a favorable safety profile. Age and associated pulmonary hypertension are predictors of mortality and poor outcome. Disclosure of Interest None declared