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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

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

BackgroundGlucocorticoids (GC) are the mainstay therapy in Giant Cell Arteritis (GCA), initially at high doses (40-60 mg/day) followed by gradual glucocorticoid tapering. This treatment, especially in older patients, is associated with numerous adverse effects (AE). In addition, there are frequent relapses. Therefore, conventional synthetic immunosuppressants such as methotrexate (MTX), leflunomide, azathioprine, cyclophosphamide or mycophenolate, have been used with controversial results. Studies with biological immunosuppressants, such as TNFi have been ineffective; in contrast, tocilizumab (TCZ) has obtained positive results and was approved for the treatment of GCA.ObjectivesIn the ARTESER study we describe a) treatment with GC, synthetic or biological immunosuppressants; b) AE of CG; and c) evolution.MethodsARTESER is a retrospective observational study sponsored by the Spanish Society of Rheumatology. 26 Spanish centers participated and all new patients diagnosed with GCA from June 1, 2013 to March 29, 2019 were included. Data on GC and immunosuppressants were collected at the beginning and during the follow-up of GCA patients. For the calculation of the cumulative dose of GC, an application was developed that, by including the periods of time, dose and type of GC received during follow-up, performs the automatic calculation in mg of prednisone.ResultsOf the 1675 patients included, GC treatment was adequately recorded in 1650 patients (Table 1). All received oral treatment, being prednisone the most frequently drug used (N=1602, 97.09%). In addition, 426 (25.82%) patients received at least one iv pulse of methylprednisolone, being the 1000 mg regimen the most frequent (n=217; 50.9%). The total mean duration of GC treatment was 22.65 months. The mean cumulative dose per patient at the end of follow-up was 8514.98 mg of prednisone.Table 1.Corticosteroid treatment and immunosuppressive treatmentPatients taking oral corticosteroid1650 Prednisone, n (%)1602 (97.09) Methylprednisolone, n (%)164 (9.94) Deflazacort, n (%)64 (3.88)Patients receiving intravenous corticosteroid, n (%)426 (25.82)Mean duration of steroid treatment, mean (SD)22.65 (17.36)Mean cumulative dose at the end of follow-up per patient, mg of prednisone, mean (SD)8514.98 (6570.21)Methotrexate at diagnosis*, n (%)165 (9.9)Leflunomide at diagnosis*, n (%)2 (0.1)Azathioprine at diagnosis*, n (%)3 (0.2)Cyclophosphamide at diagnosis*, n (%)7 (0.4)Mycophenolate at diagnosis*, n (%)1 (0.1)Tocilizumab at diagnosis*, n (%)22 (1.3)Methotrexate during follow-up, n (%)532 (31.8)Leflunomide during follow-up, n (%)19 (1.2)Azathioprine during follow-up, n (%)26 (1.5)Cyclophosphamide during follow-up, n (%)10 (0.6)Mycophenolate during follow-up, n (%)10 (0.6)Tocilizumab during follow-up, n (%)153 (9.1)The most widely used immunosuppressant was MTX both at diagnosis (n=165; 9.9%) and during follow-up (n=532; 31.8%), followed by TCZ, at diagnosis (22; 1.3%) and at follow-up (153; 9.1%).AE with GC were described in 393 patients (23.8%), highlighting serious infections (n=67; 10.03%) followed by diabetes mellitus (n=63; 9.43%), steroid myopathy (n=53; 7.9%), vertebral fractures (n=47; 7.04%), non-vertebral fractures (n=36; 5.39%), heart failure (n=36; 5.39%), arterial hypertension (n=34; 5.09%) and neuropsychiatric alterations (n=27; 4.04%).During the follow-up, 334 (19.9%) patients had relapses, 532 (31.8%) were hospitalized on some occasion, and 142 patients (8.48%) died. The main cause of death were infections (n=44; 30.99%), neoplasms (n=23; 16.2%), cardiovascular (n=15; 10.56%), and cerebrovascular (n=10; 7.04%).ConclusionThe main treatment for GCA was oral GC, which were required for almost two years on average, in a quarter of patients associated with IV pulses. The cumulative steroid dose was high as well as the side effects. MTX was the most widely used immunosuppressant and TCZ was prescribed in 10%. Relapses and admissions at the hospital were relatively frequent.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

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.

BackgroundAnti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotizing myopathy (IMNM) is an entity of growing interest. However, data on epidemiology and clinical spectrum are still scarce and there is a need for the identification of its potential risk factors.ObjectivesTo characterize the demographic, genetic, clinical, and serological features of patients with anti-HMGCR IMNM in a region of northern Spain.MethodsStudy of all patients diagnosed with anti-HMGCR IMNM during a 5-year period at a reference hospital in Northern Spain. Besides clinical and laboratory data, we analyzed the genetic influence of HLA genes and the rs4149056 (c.521T>C) single nucleotide polymorphism (SNP) in the SLCO1B1 gene.Results8 patients (5 women, 3 men) with a mean ± SD age of 64.9±7.3 years, fulfilled the criteria for anti-HMGCR IMNM. The incidence rate was 0.6 per 100.000 person-years and the prevalence 3 per 100.000 population. All patients had dyslipidemia and had been exposed to statins. Seven of the 8 of cases complained of myalgia. All of them had predominant lower limb proximal and symmetric muscle weakness that was severe in 2 of them. None of the patients had extra-muscular involvement. No evidence of malignancy was found. All patients had elevated serum CK levels with a median [IQR] of 4488 [2538-9194] IU/L. Serum 25-hydroxy vitamin D levels were decreased in all patients in whom it was determined. The 3 patients with a previous diagnosis of hypothyroidism had abnormal levels of TSH at the time of diagnosis. All patients experienced improvement with different schemes of immunosuppressive therapy. Noteworthy, 7 of 8 patients carried the HLA-DRB1*11 allele. The frequency of the rs4149056 C allele in the SLCO1B1 gene (12.5%) was similar to that of the general population.ConclusionIn northern Spain, the IMNM anti-HMGCR preferentially affects people over 50 years of age who are carriers of the HLA-DRB1*11 allele and take statins. Both low vitamin D levels and hypothyroidism may play a potential predisposing role in the development of this diseaseTable 1.PatientAge/SexHLA DRB1*11rs4149056 genotypeMRC at the weakest muscle group*DysphagiaCK (IU/L) at diagnosisAnti-HMGCR titer (CU)Induction therapy*Maintenance therapyClinical improvement**CK (IU/L) at last follow-up visit156/MYesTT2No8963277.8GC. IVIG.MTXGC. IVIG. MTX. RTXMarked134269/FYesTT0Yes9271235.9GC iv bolus. IVIG.GC. MTX. RTX.Marked890364/FYesTT3No4000242.6IVIG.IVIG.RTXMarked1284479/MYesTT4No4977145.6GC. IVIG.GC. IVIG.Complete92562/FNoTT3No2116210.0GCGC.MTX.Marked236657/FYesTC4No2294259.3IGIVIGIVComplete235768/FYesTT3No3273236.0GC. IGIV. AZA.GC. AZAComplete249864/MYesTC4Yes11000179.0GC iv bolus. AZA.GC. AZAComplete161AZA: azathioprine; CK: creatinine kinase; CU: chemiluminescence units; F: female; GC: glucocorticoids; IVIG: intravenous immunoglobulins; M: male; MRC: medical research council scale; MTX: methotrexate; RTX: rituximab; ** Induction therapy initiated within 3 months of diagnosis. **Clinical improvement: no improvement (no improvement in MRC grade), mild improvement (improvement of MRC grade but still requiring assistance for activities of daily living), marked improvement (persistence of mild weakness without functional limitation), and complete improvement (return to baseline with no symptoms or signs of weakness).Disclosure of InterestsNone declared

Saint Lucia at one time had levels of schistosomiasis prevalence and morbidity as high as many countries in Africa. However, as a result of control efforts and economic development, including more widespread access to sanitation and safe water, schistosomiasis on the island has practically disappeared. To evaluate the current status of schistosomiasis in Saint Lucia, we conducted a nationally representative school-based survey of 8–11-year-old children for prevalence of Schistosoma mansoni infections using circulating antigen and specific antibody detection methods. We also conducted a questionnaire about available water sources, sanitation, and contact with fresh water. The total population of 8–11-year-old children on Saint Lucia was 8,985; of these, 1,487 (16.5%) provided urine for antigen testing, 1,455 (16.2%) provided fingerstick blood for antibody testing, and 1,536 (17.1%) answered the questionnaire. Although a few children were initially low positives by antigen or antibody detection methods, none could be confirmed positive by follow-up testing. Most children reported access to clean water and sanitary facilities in or near their homes and 48% of the children reported contact with fresh water. Together, these data suggest that schistosomiasis transmission has been interrupted on Saint Lucia. Additional surveys of adults, snails, and a repeat survey among school-age children will be necessary to verify these findings. However, in the same way that research on Saint Lucia generated the data leading to use of mass drug administration for schistosomiasis control, the island may also provide the information needed for guidelines to verify interruption of schistosomiasis transmission.

Palms are ubiquitous across Neotropical landscapes, from pristine forests or savannahs to large cities. Although palms provide useful ecosystem services, they also offer suitable habitat for triatomines and for Trypanosoma cruzi mammalian hosts. Wild triatomines often invade houses by flying from nearby palms, potentially leading to new cases of human Chagas disease. Understanding and predicting triatomine-palm associations and palm infestation probabilities is important for enhancing Chagas disease prevention in areas where palm-associated vectors transmit T. cruzi. We present a comprehensive overview of palm infestation by triatomines in the Americas, combining a thorough reanalysis of our published and unpublished records with an in-depth review of the literature. We use site-occupancy modeling (SOM) to examine infestation in 3590 palms sampled with non-destructive methods, and standard statistics to describe and compare infestation in 2940 palms sampled by felling-and-dissection. Thirty-eight palm species (18 genera) have been reported to be infested by ∼39 triatomine species (10 genera) from the USA to Argentina. Overall infestation varied from 49.1-55.3% (SOM) to 62.6-66.1% (dissection), with important heterogeneities among sub-regions and particularly among palm species. Large palms with complex crowns (e.g., Attalea butyracea, Acrocomia aculeata) and some medium-crowned palms (e.g., Copernicia, Butia) are often infested; in slender, small-crowned palms (e.g., Euterpe) triatomines associate with vertebrate nests. Palm infestation tends to be higher in rural settings, but urban palms can also be infested. Most Rhodnius species are probably true palm specialists, whereas Psammolestes, Eratyrus, Cavernicola, Panstrongylus, Triatoma, Alberprosenia, and some Bolboderini seem to use palms opportunistically. Palms provide extensive habitat for enzootic T. cruzi cycles and a critical link between wild cycles and transmission to humans. Unless effective means to reduce contact between people and palm-living triatomines are devised, palms will contribute to maintaining long-term and widespread, albeit possibly low-intensity, transmission of human Chagas disease.

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10−54, per-allele OR = 1.79; and rs9275592, p = 1.14 × 10−40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 × 10−10, OR = 1.28; and rs128738, p = 4.60 × 10−9, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis.

This study attempted to quantify the transmission of Trypanosoma cruzi in children less than 15 years of age in Barinas State, Venezuela and investigate risk factors for infection. Among 3,296 children, 4 (0.12%) were seropositive. The mother of one child also was also seropositive, which suggested that congenital transmission is a possible risk factor for Chagas disease in this area. Seroprevalence among the dwellers of 10 localities was 3.3%. Rhodnius prolixus was detected in 7 localities and in 8% of 125 dwellings. A multivariate logistic regression model showed that infection was associated with age, a dirt floor, and distance from houses to palm trees. The risk of infection is increased by the presence of adventitious sylvatic R. prolixus and transient or residual colonies. Insecticide spraying does not seem justified in this scenario, a finding that was also observed in other Latin American countries. New methods are therefore needed for Chagas disease control programs.

Recent studies have focused attention on the involvement of NLRP1 to confer susceptibility for extended autoimmune/inflammatory disorders, being considered a common risk factor in autoimmunity.1–3 NLRP1 provides a scaffold for the assembly of the inflammasome that activates caspases 1 and 5, required for processing and activation of the proinflammatory cytokines interleukin 1β (IL-1β), IL-18 and IL-33 and promoting inflammation.4 In this study, we examined for the first time whether NLRP1 is associated with giant cell arteritis (GCA), a chronic systemic vasculitis affecting large and medium-sized arteries derived from the aorta, in particular the cranial branches of the carotid artery. GCA is the most common vasculitis in the elderly in Western countries with a female predominance.5 To investigate the possible genetic association of NLRP1 with this disease, we genotyped a single-nucleotide polymorphism (rs8182352), which has been reported to confer risk to the development of autoimmune processes in previous studies,1 ,2 in a total of 3583 individuals, comprising a discovery set from Spain (574 patients diagnosed with biopsy-proven GCA and 2366 healthy controls) and a replication set of subjects from Italy (111 biopsy-proven GCA patients and 532 controls) using a predesigned TaqMan allele discrimination assay. All individuals were of …

Objective: To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA). Methods: Our study population was composed of 911 patients diagnosed with biopsy-proven GCA and 8136 unaffected controls from a Spanish discovery cohort and three additional independent replication cohorts from Germany, Norway and the UK. Two functional PTPN22 polymorphisms (rs2476601/R620W and rs33996649/R263Q) and two variants of the CSK gene (rs1378942 and rs34933034) were genotyped using predesigned TaqMan assays. Results: The analysis of the discovery cohort provided evidence of association of PTPN22 rs2476601/R620W with GCA (PFDR=1.06E-04, OR=1.62, CI 95% 1.29 to 2.04). The association did not appear to follow a specific GCA subphenotype. No statistically significant differences between allele frequencies for the other PTPN22 and CSK genetic variants were evident either in the case/control or in stratified case analysis. To confirm the detected PTPN22 association, three replication cohorts were genotyped, and a consistent association between the PTPN22 rs2476601/R620W variant and GCA was evident in the overall meta-analysis (PMH=2.00E-06, OR=1.51, CI 95% 1.28 to 1.79). Conclusions: Our results suggest that the PTPN22 polymorphism rs2476601/R620W plays an important role in the genetic risk to GCA.

The Andean Pact Initiative (1997) committed Andean countries to eliminate vectorial transmission of Chagas disease by 2010 via widespread residual insecticide spraying. In Venezuela, this aim could be compromised by reinvasion of houses by palm tree populations of the major vector Rhodnius prolixus. To test this hypothesis, a multivariate logistic regression was undertaken of risk factors for triatomine infestation and colonization in 552 houses and 1068 peri-domestic outbuildings in Barinas State. After adjusting for other risk factors, including palm roofs, R. prolixus infestation and colonization of outbuildings (and, to some extent, houses) was significantly associated with proximity to high densities of Attalea butyracea palm trees. House infestation and/or colonization was also positively associated with bug density in peri-domestic outbuildings, the presence of pigsties and nests. Hence, R. prolixus populations in ineffectively sprayed outbuildings could also provide an important source of house re-infestations. The secondary vector Triatoma maculata was mainly found associated with the presence of hens nesting both indoors and outdoors.

The main vector of Chagas disease in Venezuela is Rhodnius prolixus. Specimens of Rhodnius sp., identified elsewhere as R. prolixus by molecular tools, were collected in Barinas State (Venezuela) before insecticide application, and compared by morphometric techniques with post-spraying, re-infesting insects after control. Geometric morphometry was applied, allowing separate analyses of shape and size. The idea of a single species sharing silvatic and domestic/peri-domestic ecotopes was supported, suggesting new evolutionary scenarios for the controversial R. prolixus origins. The same data allowed to understand the possible mechanisms of villages re-infestation after a control campaign, either recolonization by local recovery of survivors or re-infestation by external migrants. Both mechanisms were apparent. Although shape properties could distinguish very close subpopulations such as insects from houses and insects from peri-domestic shelters, they were unable to identify the insects from palm trees as a distinct subpopulation. This strongly suggested that human environment could receive immigrants from palm trees. The pattern of size variation supported the hypothesis of a one-way exchange from silvatic to human environments, but did not support the reverse movement. Thus, morphometric data indicated that a silvatic population of the local vector is probably responsible for re-infesting villages after insecticide application, and they also pointed to the existence of re-infestation by local recovery of survivors. According to this interpretation, new epidemiological scenarios must be considered to improve Chagas disease control in Venezuela.

In this paper an electro-mechanical model to describe the behavior of a PVDF multi-layer smart structure is presented and proposed for I-Swarm mm 3 microrobot actuators. The study is based on the modal analysis of the partial differential equations governing the motion of an Euler-Bernouilly cantilever beam. A pair of linearly coupled piezoelectric equations between the mechanical and the electrical domains is presented. An important element in the modelization of such materials is the energy losses term. A viscous damping contribution is considered which allows us to extract more realistic constituent equations for the material to work as sensor or actuator. The development of this equation as an infinite linear combination of each mode allows us to extract a compact lumped equivalent electrical circuit to work at any frequency region instead of the classical reduced models.

Background The PTPN22 / CSK signalling represents one of the most relevant pathways in the innate immunity, and it has been implicated in the susceptibility to develop a wide number of autoimmune diseases. Objectives To analyse the possible role of different single-nucleotide polymorphisms of the PTPN22 and CSK genes in the predisposition and clinical phenotypes of giant cell arteritis (GCA) in a large Caucasian population. Methods Our study population consisted of 623 patients diagnosed with biopsy-proven GCA and 1,729 healthy controls of Spanish Caucasian origin. Two functional PTPN22 polymorphisms (rs24746601, R620W and rs33996649, R263Q) and two variants of the CSK gene (rs1378942 and rs34933034), previously associated with autoimmunity, were genotyped using specifically designed TaqMan® assays. Results A significant association of the PTPN22 non-synonymous change rs2476601 with GCA susceptibility was yielded after the analysis of the allele frequencies ( P =1.06E-04, OR= 1.62, CI 95% 1.29-2.04). No statistically significant differences between cases and controls of the rest of SNPs analysed were observed. Similarly, when patients were stratified according to specific clinical features of GCA, such as polymyalgia rheumatica (PMR), visual ischemic manifestations (VIM) or irreversible occlusive disease (IOD), only significant differences were found between the case subgroups and the control set for PTPN22 rs2476601 ( P =2.26E-04, OR=1.77 CI 95% 1.30-2.40; P =1.03E-03, OR=1.82 CI 95% 1.27-2.62; P =5.47E-04, OR=2.14 CI 95% 1.38-3.33, respectively). Conclusions Our results clearly suggest that the PTPN22 polymorphism rs2476601 is associated with susceptibility to GCA. Disclosure of Interest None Declared

Background Rhodnius prolixus is the main vector of Chagas disease in Venezuela. Here, domestic infestations of poor quality rural housing have persisted despite four decades of vector control. This is in contrast to the Southern Cone region of South America, where the main vector, Triatoma infestans, has been eliminated over large areas. The repeated colonisation of houses by silvatic populations of R. prolixus potentially explains the control difficulties. However, controversy surrounds the existence of silvatic R. prolixus: it has been suggested that all silvatic populations are in fact Rhodnius robustus, a related species of minor epidemiological importance. Here we investigate, by direct sequencing (mtcytb, D2) and by microsatellite analysis, 1) the identity of silvatic Rhodnius and 2) whether silvatic populations of Rhodnius are isolated from domestic populations. Methods and Findings Direct sequencing confirmed the presence of R. prolixus in palms and that silvatic bugs can colonise houses, with house and palm specimens sharing seven cytb haplotypes. Additionally, mitochondrial introgression was detected between R. robustus and R. prolixus, indicating a previous hybridisation event. The use of ten polymorphic microsatellite loci revealed a lack of genetic structure between silvatic and domestic ecotopes (non-significant FST values), which is indicative of unrestricted gene flow. Conclusions Our analyses demonstrate that silvatic R. prolixus presents an unquestionable threat to the control of Chagas disease in Venezuela. The design of improved control strategies is essential for successful long term control and could include modified spraying and surveillance practices, together with housing improvements., Author Summary Chagas disease is spread by blood-feeding insects (triatomine bugs) that colonise poor-quality houses. Disease control relies primarily on killing domestic bugs by spraying dwellings with residual insecticide. In Venezuela, sustained control has proved difficult despite four decades of campaigns. Considered the main vector in Venezuela, the bug Rhodnius prolixus may also infest palm trees and might repeatedly recolonise houses from palms. A complication is that a morphologically similar species, R. robustus, also infests palms but is of minor medical importance. Therefore, confusion exists as to the true identity of palm bugs and their importance in disease transmission. We applied two molecular methods (sequencing DNA of the cytochrome b gene, and analysing microsatellites) to triatomines collected in Venezuela so that we could identify unequivocally the species of palm-dwelling Rhodnius and establish their role in maintaining house infestations. We demonstrated that R. prolixus is indeed present in palms, and that such silvatic populations can colonise houses and are a threat to the successful control of Chagas disease in Venezuela. This finding resolves a longstanding controversy of fundamental epidemiological importance. It is also an example of the application of molecular epidemiology to correct vector identification and successful disease control.

A summary is made of the results obtained from the study of the adsorption and interaction mechanisms of a series of organophosphorus pesticides (phosphates, phosphorothiolates, phosphorothionates and phosphorothiolothionates) with montmorillonite, with the aim of establishing relationships between the chemical structure of these compounds and the adsorption and interaction mechanisms with this clay. Many of the organophosphorus pesticides studied are adsorbed into the interlayer space of montmorillonite. The intercalation causes different degrees of expansion (different types of complexes) principally as a function of the chemical structure of the organic compound. The presence in the organic molecules of the P0 and PS groups and the size and composition (functional groups present) of the radicals are the two most important factors. Both the nature of interlayer cations and the previous hydration status of montmorillonite influence adsorption. In some cases the polarizing power of the interlayer cation is a conditioning factor of the degree of interlayer expansion, whereas in others the cation charge is responsible for this. Results of infrared spectroscopy show that interaction is of the dipole ion type and that it depends on the presence of the P0 or PS group in the molecule and also on the functional groups present in the side chains. These factors, together with the situation of these latter groups in the side chains, condition the arrangement adopted by the molecules of a pesticide in the interlayer space.

ResumenSe ha estudiado la interacción de fosdrín (pesticida organofosforado) con montmorillonita mediante difracción de rayos X y espectroscopia infrarroja. Este insecticida forma con montmorillonita dos tipos de complejos, con espaciados basales 16·05 y 20·06 Å. La formación de uno u otro tipo depende del estado de hidratación y del catión interlaminar de las muestras, de la naturaleza del disolvente y de la concentración de fosdrín. En los espectros de infrarrojo de los complejos, las vibraciones de valencia P =O y C =O del fosdrín se desplazan hacia frecuencias más bajas. La magnitud del desplazamiento de estas vibraciones es función del poder polarizante del catión interlaminar. El desplazamiento de la vibración de valencia C =O depende además del tipo de complejo y de su grado de hidratación. La vibración de valencia C=C se desplaza hacia frecuencias altas en los complejos de espaciado basal 16·05 Å. Los resultados obtenidos indican que el complejo de 16·05 Å es monocapa y que las moléculas de fosdrín (forma trans) deben interaccionar con los cationes interlaminares a través de ambos grupos P =O y C =O. El complejo de 20·06 Å es de dos capas y las moléculas (forma cis) interaccionan solamente a través del grupo P =O.