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In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 841.1-842

Abstract: Apremilast (APR) has demonstrated efficacy in orogenital ulcers of Behçet´s disease (BD). Response of other clinical manifestations remains unknown. Objectives: To assess the efficacy and safety of APR in monotherapy or combined with disease-modifying anti-rheumatic drugs (DMARDs) in non-aphthous ulcers of BD. Methods: National multicenter open-label study on 34 BD patients treated with APR at maintained standard dose of 30 mg twice daily. Results: From a cohort of 51 patients with APR by refractory orogenital ulcers of BD, we selected 34 (24 women/10 men, mean age 43.8±14.3 years), cases with another clinical manifestation/s. Excluding CTs, colchicine or NSAIDs, APR was given in monotherapy (n=21) or combined with conventional and/or biologic DMARDs in 13 cases (5 methotrexate, 3 azathioprine, 3 hydroxychloroquine, 1 sulfasalazine, 1 dapsone, 2 tocilizumab, 1 IFX). Other active manifestations present at APR onset were: arthralgia/arthritis (16, true arthritis in 5), folliculitis/pseudofolliculitis (14), erythema nodosum (3), furunculosis (2), paradoxical psoriasis by TNFi (2), intestinal ileitis (2), deep venous thrombosis (2), leg ulcers (1), erythematosus and scaly skin lesions (1), fever (1), unilateral anterior uveitis (1) and neurobehçet (1). After a median follow-up of 6 [3-12] months, folliculitis and ileitis improved, neurobehçet remained stable and musculoske letal manifestations evolved in a variable way. (TABLE) TABLE. Conclusion: In addition of orogenital ulcers, APR in monotherapy or combined, seems to be useful in skin manifestations of BD Disclosure of Interests: Alba Herrero Morant: None declared, Belen Atienza Mateo: None declared, J. Loricera: None declared, Vanesa Calvo del Rio Grant/research support from: MSD and Roche, Speakers bureau: Abbott, Lilly, Celgene, Grünenthal, UCB Pharma, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Janssen and Celgene, Speakers bureau: Pfizer and Lilly, Gerard Espinosa: None declared, Jenaro Graña: None declared, Clara Moriano: None declared, Trinidad Pérez Sandoval: None declared, Manuel Martín Martínez: None declared, Elvira Diez: None declared, María Dolores García-Armario: None declared, Esperanza Martínez: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Patricia Moya Alvarado: None declared, Francisca Sivera: None declared, Jaime Calvo Grant/research support from: Lilly, UCB, Consultant of: Abbvie, Jansen, Celgene, Isabel de la Morena: None declared, Francisco Ortiz Sanjuán: None declared, José Andrés Román Ivorra: None declared, Ana Pérez Gómez: None declared, Alejandro Olive: None declared, Carolina Díez: None declared, Juan José Alegre: None declared, D Ybáñez-García Speakers bureau: Lilly, Roche, Sanofi, Ángels Martínez-Ferrer: None declared, Javier Narvaez: None declared, Ignasi Figueras: None declared, Ana Isabel Turrión: None declared, Susana Romero-Yuste: None declared, Pilar Trénor: None declared, Soledad Ojeda Speakers bureau: AMGEN, LILLY, GEBRO, Miguel Á. González-Gay Grant/research support from: AbbVie, MSD and Roche, Speakers bureau: AbbVie, MSD and Roche, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2020-eular.4720

Language: English

Publisher: BMJ

Publication Date: 2020

detail.hit.zdb_id: 1481557-6

In: Annals of the Rheumatic Diseases, BMJ, Vol. 81, No. Suppl 1 ( 2022-06), p. 704.3-705

Abstract: Ocular 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. Objectives To assess efficacy and safety of BT in refractory subtypes of NBD. Methods Open-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. Results We 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-NBD Total p-NBD np-NBD P p-NBD vs np-NBD Age at biological therapy initiation, years (mean±SD ) 44±13.9 41.4±9.6 39.4±10.6 0.412 Gender, n (m/f) (% ) 21/20 (48.8/52.2) 18/15 (54.5/45.5) 5/12 (29.4/70.6) 0.091 HLAB51 +/ patients tested, n (% ) 15/31 (57.7) 14/25 (58.3) 4/10 (40) 0.391 Oral aphthae, n (% ) 40 (97.6) 32 (97) 15 (88.2) 0.323 Cutaneous involvement, n (% ) 28 (63.4) 23 (69.7) 10 (58.8) 0.603 Ocular involvement, n (% ) 21 (48.8) 15 (45.5) 9 (52.9) 0.616 Vascular involvement, n (% ) 9 (22) 10 (30.3) 7 (41.2) 0.442 Articular involvement, n (% ) 9 (22) 7 (21.2) 3 (17.6) 0.765 Previous conventional Immunosuppressive drugs to BT Azathioprine 24 (58.5) 20 (60.6) 10 (58.8) - Methotrexate 16 (39.0) 12 (36.4) 3 (17.6) - Cyclophosphamide 13 (31.7) 13 (39.4) 5 (29.4) - Cyclosporine A 9 (22.0) 8 (24.2) 3 (17.6) - Mycophenolate Mofetil 2 (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). Conclusion In 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 Interests Alba 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

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2022-eular.2681

Language: English

Publisher: BMJ

Publication Date: 2022

detail.hit.zdb_id: 1481557-6

In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 382.2-382

Abstract: Apremilast (APR) has demonstrated efficacy in the treatment of oral and/or genital aphthous ulcers in Behçet´s disease (BD). Combination of APR to other disease-modifying anti-rheumatic drugs (DMARDs) has not been assessed. Objectives: To compare the efficacy and safety of APR in monotherapy or combined with DMARDs in refractory BD. Methods: National multicenter open-label study on 51 BD patients with oral and/or genital ulcers refractory to conventional treatment. Results: We included 51 patients (35 women/16 men), mean age 44.7±13.2 years. Before APR, all patients had received several systemic conventional drugs. The main clinical symptoms for starting APR were oral (n=19) and genital (2) aphthous ulcers or both (30). Excluding corticosteroids, colchicine or NSAIDs, APR was given at standard dose of 30 mg twice daily in monotherapy (n=31), or combined with conventional DMARDs in 16 cases (6 azathioprine, 5 methotrexate, 4 hydroxychloroquine, 4 sulfasalazine, 1 dapsone) or with biologic DMARDs in 4 (2 tocilizumab, 1 adalimumab, 1 infliximab). There were not found statistically significant differences in demographic features, previous therapy, clinical manifestations or reported adverse effects. After a median follow-up of 6 [3-12] months, most of the patients experienced improvement of the orogenital ulcers in both groups (89.8% in the first 2 weeks), without statistically significant differences. (TABLE ) Conclusion: APR leads to a rapid and maintained improvement in most patients with refractory BD orogenital ulcers. APR seems as effective and safe in monotherapy as combined. TABLE: Week 1-2 Week 4 Month 6 Month 12 Month 24 Outcome of oral and/or genital ulcers n, (% ) C n=19 M n=30 C n=19 M n=26 C n=12 M n=17 C n=7 M n=6 C n=1 M n=1  Complete resolution 8 (42.1) 11 (36.7) 12 (63.2) 20 (77) 7 (58.4) 14 (82.4) 3 (42.8) 3 (50) 1 (100) 1 (100)  Partial resolution 9 (47.4) 16 (53.4) 7 (36.8) 3 (11.5) 5 (41.6) 2 (11.7) 4 (57.2) 3 (50) 0 0  No response 2 (10.5) 3 (9.9) 0 3 (11.5) 0 1 (5.9) 0 0 0 0 p value 0.9 0.1 0.1 0.8 0.7 Abbreviations : C= combined; M= monotherapy; n= available data. Disclosure of Interests: Alba Herrero Morant: None declared, Belen Atienza Mateo: None declared, J. Loricera: None declared, Vanesa Calvo del Rio Grant/research support from: MSD and Roche, Speakers bureau: Abbott, Lilly, Celgene, Grünenthal, UCB Pharma, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Janssen and Celgene, Speakers bureau: Pfizer and Lilly, Jenaro Graña: None declared, Gerard Espinosa: None declared, Clara Moriano: None declared, Trinidad Pérez Sandoval: None declared, Manuel Martín Martínez: None declared, Elvira Diez: None declared, María Dolores García-Armario: None declared, Esperanza Martínez: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Patricia Moya Alvarado: None declared, Francisca Sivera: None declared, Jaime Calvo Grant/research support from: Lilly, UCB, Consultant of: Abbvie, Jansen, Celgene, Isabel de la Morena: None declared, Francisco Ortiz Sanjuán: None declared, José Andrés Román Ivorra: None declared, Ana Pérez Gómez: None declared, Sergi Heredia: None declared, Alejandro Olive: None declared, Águeda Prior: None declared, Carolina Díez: None declared, Juanjo J Alegre-Sancho Consultant of: UCB, Roche, Sanofi, Boehringer, Celltrion, Paid instructor for: GSK, Speakers bureau: MSD, GSK, Lilly, Sanofi, Roche, UCB, Actelion, Pfizer, Abbvie, Novartis, D Ybáñez-García Speakers bureau: Lilly, Roche, Sanofi, Ángels Martínez-Ferrer: None declared, J. Narváez: None declared, Ignasi Figueras: None declared, Ana Isabel Turrión: None declared, Susana Romero-Yuste: None declared, Pilar Trénor: None declared, Soledad Ojeda Speakers bureau: AMGEN, LILLY, GEBRO, Miguel Á. González-Gay Grant/research support from: AbbVie, MSD and Roche, Speakers bureau: AbbVie, MSD and Roche, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2020-eular.6246

Language: English

Publisher: BMJ

Publication Date: 2020

detail.hit.zdb_id: 1481557-6

In: Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. Suppl 1 ( 2021-06), p. 755.1-755

Abstract: Patients with axial spondyloarthritis (axSpA) may present with concomitant psoriasis (Ps) in approximately 10% of cases. As with axSpA, Ps is also associated with an accelerated atherosclerosis process 1 . However, it is unknown whether the presence of Ps confers an increased cardiovascular (CV) risk in patients with axSpA. Objectives: To compare factors related to the disease, CV risk factors, atherosclerotic burden, and CV events in patients with axSpA with and without Ps. Methods: Cross-sectional analysis of the AtheSpAin cohort, a Spanish multicenter cohort designed for the study of atherosclerosis in axSpA. We compared axSpA patients with and without concomitant psoriasis, focusing mainly on CV risk characteristics. Background information on CV risk factors, CV events, and disease-related factors was reviewed, and data on maximum body index, blood pressure, lipid profile, and disease status at the time of the study were also obtained. Carotid ultrasound (US) was performed in all patients at the time of the study, including measurement of carotid intima-media wall thickness (cIMT) and plaque detection according to the Mannhein consensus criteria. Results: A set of 882 axSpA patients were included. 786 (89.1%) of them had no concomitant Ps, which was present in 96 (10.9%) patients. Although the mean age was similar, male sex was more prevalent in axSpA patients with Ps (79.1% Vs 66.5%, p=0.01) (Table 1). Furthermore, it was found that axSpA with Ps had a more frequent history of synovitis (50% vs 33%, p = 0.001), dactylitis (13% vs 6%, p = 0.011) and concomitant inflammatory bowel disease (13% vs 6%, p = 0.01). AxSpA patients with Ps had a non-significant trend towards a higher prevalence of asymmetric sacroiliitis (23 vs 16%, p = 0.064) and had a lower frequency of positive HLA-B27 status (56% vs 72%, p = 0.003). Regarding the management of the disease, prednisone (23% vs 12%, p = 0.02), methotrexate (30% vs 15%, p = 0.000) and anti-TNFα therapy (50% vs 34%, p = 0.002) were more commonly used in the group with Ps. Regarding CV risk characteristics, no differences were observed either in the prevalence of traditional CV risk factors (Table 1), nor in the total serum level, HDL and LDL, blood pressure and body mass index at that time of the study. However, axSpA patients with Ps showed a higher prevalence of CV events (9% vs 4%, p = 0.05), including ischemic heart disease (6% vs 3%, p = 0.042) and ischemic stroke (4% vs 1%, p = 0.016) (Table 1). The subclinical atherogenic burden was also more severe in the group with Ps, with a higher prevalence of carotid plaques (39% vs 31%, p = 0.098), and higher values of cIMT (0.664 ± 0.170 mm vs 0.642 ± 0.142 mm, p = 0.16), although the differences did not reach statistical significance. Table 1. Main sociodemographic and cardiovascular differences among axSpA patients with and without psoriasis. axSpA without psoriasis (n=786 ) axSpA with psoriasis (n=96 ) p Men/Women, n 523/268 76/20 0.010 Mean age (years) ±SD at the time of study 49 ± 13 49 ± 13 0.81 AS/nr-AxSpa 625/166 77/19 0.79 History of CV risk factors Current smokers 267 (34) 30 (31) 0.60 Obesitty 174 (22) 26 (27) 0.29 Dyslipidemia 262 (33) 35 (36) 0.48 Hypertension 211 (27) 28 (29) 0.57 Diabetes Mellitus 56 (7) 8 (8) 0.65 Chronic Kidney Disease 19 (2) 3 (3) 0.72 History of cardiovascular events, n (% ) 33 (4) 9 (9) 0.023 Ischemic heart disease 20 (3) 6 (6) 0.042 Congestive heart failure 2 (0) 1 (1) 0.29 Ischemic stroke 6 (1) 4 (4) 0.016 Peripheral artery disease 6 (1) 0 (0) 0.99 CV data at the time of study Carotid plaques 244 (31) 38 (39) 0.098 IMT mm 0.642 ± 0.142 0.664 ± 0.170 0.16 IMT 〉 = 900 mm 40 (5) 6 (6) 0.66 Abbreviations: AS = ankylosing spondylitis. AxSpA= axial spondylitis. CV = cardiovascular. IMT = intima-media wall thickness. Nr-axSpA = no-radiographic axial spondylitis. Conclusion: The presence of Ps may confer additional CV risk to axSpA patients and is associated with particular disease related factors. References: [1]Fang N, Jiang M, Fan Y. Association Between Psoriasis and Subclinical Atherosclerosis: A Meta-Analysis. Medicine (Baltimore ). 2016;95(20):e3576. Disclosure of Interests: None declared.

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2021-eular.2025

Language: English

Publisher: BMJ

Publication Date: 2021

detail.hit.zdb_id: 1481557-6

In: Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. Suppl 1 ( 2021-06), p. 967-968

Abstract: Neuro-Behçet’s disease (NBD) is a severe complication of Behcet’s disease (BD). Despite well-established therapies with glucocorticoids and conventional immunosuppressants (cIS), a significant proportion of patients are refractory. Objectives: To assess efficacy and safety of biologic therapy (BT) in NBD refractory to glucocorticoids and at least one cIS. Methods: Open-label multicenter study of refractory NBD from 23 different referral Spanish Hospitals. Main outcome was neurological response. Secondarily, analytical efficacy was measured by Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP) and Hemoglobin (Hb) at baseline, 6 months, 1 year and 2 years. Results: We studied 42 patients (21 women/ 21 men; mean age 40.4±10.8 years). HLA B51 was positive in 15 out of 37 (40.5%) patients tested. Non-neurological manifestations were oral ulcers (n=41, 97.6%), genital ulcers (n=31, 73.8%), skin lesions (n=28, 66.7%), arthralgia (n=27, 64.3%), uveitis (n=21, 50.0%), arthritis (n=9, 21.4%), venous thrombosis (n=9, 21.4%) and arterial thrombosis (n=4, 9.5%). The underlying neurologic manifestation were parenchymal (n=34, 81.0 %) and non-parenchymal (n=17, 40.5%) involvement (Table 1). The first BT used was infliximab (n=20), adalimumab (n=13), golimumab (n=3), tocilizumab (n=3) and etanercept (n=2). After 58.2±51.4 months since initiation of BT, neurological response was complete (n=27; 64.3%), or partial (n=11, 26.1%) (Figure 1). Only 4 (9.5%) patients did not respond. After 6 months of BT, ESR improved from.31.5±25.6 to 15.3±11.9 mm/h (p=0.005), CRP from 1.4 [0.2-12.8] to 0.3[0.1-3] mg/dL (p= 0.002) and Hb from 13.1±1.6 to 13.8±1.3 g/dL (p=0.005). Figure 1. Neurological clinical response to biological therapy. Primary failure was observed in 16 (38.1%) patients due to inefficacy (n=11, 68.8%) or adverse effects (n=5, 31.3%). Similarly, causes of secondary failure (n=6, 14.3%) were inefficacy (n=5, 83.3%) and adverse effects (n=1, 16.7%). No serious adverse effects were observed. Conclusion: BT, especially monoclonal anti-TNF drugs, seems to be effective and safe in refractory NBD. Table 1. Neurologic manifestation of 42 patients with refractory neurobehçet's disease treated with biologic therapy. Parenchymal subtype, n (% ) 34 (81.0 ) -Hemiparesis 8 (19.1) -Polineuropathy 8 (19.1) -Encephalopathy 6 (14.3) -Cognitive impairments 4 (9.5) -Optic neuropathy 4 (9.5) -Ophtalmoparesis 4 (9.5) -Other cranial nerve involvement 3 (7.1) -Hemihypoesthesia 3 (7.1) -Cerebellar dysphasia 1 (2.4) -Cerebellar involvement 1 (2.4) -Non-steroidal psicosis 1 (2.4) Non-parenchymal subtype, n (% ) 17 (40.5 ) -Aseptic meningitis 12(28.6) -Thrombosis 4 (9.5) -Intracranial hypertension 1 (2.4) Disclosure of Interests: Alba Herrero-Morant: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Lilly, Janssen, and Celgene, Santos Castañeda: None declared, Iñigo González-Mazón: None declared, Olga Maiz: None declared, Ana Blanco Speakers bureau: AbbVie, Julio Sánchez: None declared, Norberto Ortego: None declared, Enrique Raya Speakers bureau: MSD, Grant/research support from: AbbVie, Alejandro Olive: None declared, Anahy Brandy-Garcia: None declared, Águeda Prior-Español: None declared, Clara Moriano: None declared, Elvira Diez Alvarez: None declared, Rafael Melero: None declared, Jenaro Graña: None declared, Álvaro Seijas-López: None declared, ANA URRUTICOECHEA-ARANA: None declared, Angel Ramos Calvo: None declared, Concepción Delgado Beltrán: 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, Gerard Espinosa: None declared, Miguel Á. 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, Janssen, Sanofi, Lilly and MSD, Grant/research support from: AbbVie, MSD, and Roche

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2021-eular.3407

Language: English

Publisher: BMJ

Publication Date: 2021

detail.hit.zdb_id: 1481557-6

In: Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. Suppl 1 ( 2021-06), p. 32-32

Abstract: Posterior segment involvement is the most serious affection of uveitis in Behçet’s disease (BD), with cystoid macular edema (CME) being the leading cause of blindness. Anti-TNF, especially adalimumab (ADA) and infliximab (IFX), have demonstrated efficacy as first-line biologic agents in BD-related uveitis [1,2] . Moreover, the anti-IL6R tocilizumab (TCZ) has shown excellent results in highly refractory BD-uveitis and noninfectious uveitic CME [3-6] . Objectives: To compare the efficacy of ADA vs IFX vs TCZ in patients with refractory CME due to BD. Methods: Observational multicenter study of patients with BD-associated CME refractory to conventional and/or biological immunosuppressive drugs. From a cohort of 177 patients treated with anti-TNF and 14 patients treated with TCZ, we selected those with CME at baseline. CME was defined as macular thickness 〉 300μm (measured by optic coherence tomography). We analyzed in the 3 groups of treatment (ADA, IFX, TCZ) from baseline up to 4 years the evolution of macular thickness (main outcome) and best-corrected visual acuity (BCVA). Differences between basal and final follow-up were evaluated. Multivariable linear regression was used to assess the differences between the 3 groups. Results: A total of 49 patients were included. ADA was used in 25 patients (40 eyes with CME), IFX in 15 (21 eyes with CME) and TCZ in 9 (11 eyes with CME). No statistically significant baseline differences were observed between the 3 groups (Table) except for previous anti-TNF therapy, which was used only in patients treated with TCZ (5 patients received ADA, 1 received IFX and 2 received both ADA and IFX, in different times). Most patients from all groups had received several conventional immunosuppressive drugs. Biological therapy was used in monotherapy or combined with azathioprine (n=10, 5 and 1 in ADA, IFX and TCZ group, respectively), cyclosporine A (n=10, 5 and 1) or methotrexate (n=4, 2 and 3). Macular thickness progressively decreased in the 3 groups, with no signs of CME after 1 year of treatment. Similarly, BCVA improvement and inflammatory ocular remission was reached in all groups (Figure). Table 1. Demographic and clinical characteristics of 49 patients with cystoid macular edema due to Behçet’s disease receiving ADA, IFX or TCZ. ADA (n=25 ) IFX (n=15 ) TCZ (n=9 ) Eyes with cystoid macular edema, n 40 21 11 Age, years 41 ± 11 38 ± 9 43 ± 16 Sex, men/women 12/13 7/8 5/4 HLA–B51 +, n 19 10 6 Duration of uveitis before anti-TNF/ anti-IL6R, months 30 [12-82] 15 [8-60] 32 [24-144] Ocular features at start of anti-TNF/anti-IL6R  Macular thickness, μm 432 ± 118 483 ± 126 417 ± 113  Visual acuity, BCVA 0.4 ± 0.2 0.3 ± 0.2 0.2 ± 0.2  Tyndall, inflammation grade 2 [1-3] 1 [0-1.5] 1 [0-1.5]  Vitritis, inflammation grade 2.5 [1.5-3] 1 [0-2] 2 [1-2] Previous treatment, n  Oral glucocorticoids // i.v. pulse methylprednisolone 18 // 13 4 // 9 7 // 8  MTX //CsA //AZA 13 // 22 // 14 8 // 13 // 8 8 // 6 // 2  ADA // IFX 0 // 0 0 // 0 7 // 3 Prednisone dosage at start of anti-TNF/anti-IL6R, mg/day 45 [30-60] 30 [20-60] 30 [30-30] Combined treatment, n  CsA // AZA // MTX 10 // 10 // 4 5 // 5 // 2 1 // 1 // 3 Data are presented as mean ± SD or median [IQR] when data were not normally distributed. ADA, adalimumab; AZA, azathioprine; CsA, cyclosporine A; MTX, methotrexate; IFX, infliximab; TCZ, tocilizumab. Figure 1. Evolution of ocular parameters in 49 patients with cystoid macular edema due to Behçet’s disease receiving ADA, IFX or TCZ. Conclusion: Refractory CME associated to BD’s uveitis can be effectively treated with ADA, IFX or TCZ. Moreover, TCZ is effective in patients resistant to anti-TNF therapy. References: [1] Arthritis Rheumatol. 2019;71(12):2081-2089. doi: 10.1002/art.41026 [2] Ophthalmology. 2018;125(9):1444-1451. doi: 10.1016/j.ophtha.2018.02.020 [3] Rheumatology (Oxford). 2018;57(5):856-864. doi: 10.1093/rheumatology/kex480 [4] Am J Ophthalmol. 2019;200:85-94. doi: 10.1016/j.ajo.2018.12.019 [5] Clin Exp Rheumatol. 2014;32(4 Suppl 84): S54-7. PMID: 25005576 [6] Clin Exp Rheumatol. 2016;34(6 Suppl 102): S34-S40. PMID:27054359 Disclosure of Interests: None declared

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2021-eular.307

Language: English

Publisher: BMJ

Publication Date: 2021

detail.hit.zdb_id: 1481557-6

In: Annals of the Rheumatic Diseases, BMJ, Vol. 75, No. Suppl 2 ( 2016-06), p. 1243.1-1243

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2016-eular.2014

Language: English

Publisher: BMJ

Publication Date: 2016

detail.hit.zdb_id: 1481557-6

In: Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. Suppl 1 ( 2021-06), p. 977.3-978

Abstract: Anterior uveitis (AU) is one of the most frequent extra articular manifestations of axial spondyloarthritis (axSpA), present in around 25% of patients. As with axSpA, AU has also been associated with the development of accelerated atherosclerosis 1 . If the presence of AU confers an increased cardiovascular (CV) risk or specific disease-related features to patients with axSpA remains unclear. Objectives: To compare the atherosclerotic burden, CV events, CV risk factors and disease related factors including structural damage in axSpA patients with and without AU. Methods: Cross-sectional analysis of the AtheSpAin cohort, a Spanish multicenter cohort designed for the study of atherosclerosis in axSpA, comparing axSpA patients with and without concomitant uveitis. Background information on CV and disease-related factors was reviewed. Data on CV risk and disease status at the time of the study were also obtained, including the structural damage assessed by the presence of syndesmophytes, the severity of the sacroiliitis (defined as grade 3 or 4 according to New York criteria), and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Carotid ultrasound (US) was performed in all patients at the time of the study, including measurement of carotid intima-media wall thickness (cIMT) and plaque detection according to the Mannhein consensus criteria. Results: A set of 886 axSpA patients were included. 709 (80.0%) of them had no history of concomitant AU, which was present in the remaining 177 (20.0%). The group with AU was older (50 ± 11 vs 48 ± 13 years, p=0.05), had a higher proportion of patients with AS (90.1% vs 76.3%, p=0.00) (Table 1) and a longer disease duration 13(7-23) vs 7(2-16) years, p=0.00]. The prevalence of HLA-B27 was higher in AU patients (82% vs 67%). Remarkably, structural damage showed interesting differences between both groups (Table 1). AU patients had a higher prevalence of severe sacroiliits (69% vs 49%, p=0.00), which remained significant after adjustment for age, disease duration and AS/nr-axSpA ratio. Furthermore, a non-significant trend towards a higher prevalence of syndesmophytes (44% vs 36%, p=0.06) and hip involvement (20% vs 15%, p=0.09) was observed in the group of AU. Regarding CV risk features, no differences were observed in the prevalence of CV risk factors and events (Table 1). Patients with AU showed a higher cIMT in the crude analysis (665 ± 156 mm vs 640 ± 142 mm, p = 0.047), but no significant differences were observed after adjustment by age and sex (p=0.6). Prevalence of carotid plaques was comparable in both groups (32% Vs 32%, p=0.84). Table 1. axSpA without uveitis (n=709 ) axSpA with uveitis (n=177 ) p P (adjusted model ) Men/Women, n 477/232 122/55 0.68 Mean age (years) ±SD at the time of study 48 ± 13 50 ± 11 0.049 AS/nr-AxSpa 541/168 160/17 0.000 History of CV risk factors, n (% )  Current smoker 247 (35) 50 (28) 0.096  Obesitty  Dyslipemia 233 (33) 63 (36) 0.48  Hypertension 188 (27) 50 (28) 0.63  Diabetes Mellitus 50 (7) 14 (8) 0.69  Chronic Kidney Disease 18 (3) 4 (2) 0.99 History of cardiovascular events, n (% ) 29 (4) 12 (7) 0.13 Structural damage at the time of study Presence of syndesmophytes, n (%) 253 (36) 77 (44) 0.063 mSASSS 5 (1-15) 6 (0-16) 0.31 Severe sacroiliitis (grade 3,4), n (%) 348 (49) 122 (69) 0.000 0.000* Carotid US data at the time of study Carotid plaques, n (%) 225 (32) 57 (32) 0.84 IMT (mm) 640 ± 142 665 ± 156 0.047 0.6** IMT 〉 = 0.900 mm 36 (5) 10 (6) 0.72 *: adjusted by age, disease duration and AS/nr-axSpA ratio **: adjusted by age and sex Abbreviations: AS = ankylosing spondylitis. AxSpA= axial spondylitis. CV = cardiovascular. IMT = intima-media wall thickness. Nr-axSpA = no-radiographic axial spondylitis. Conclusion: The presence of AU does not confer additional CV risk to axSpA patients, although it is associated with a more severe structural damage in our series. References: [1]Conkar S, Güven Yilmaz S, Koska İÖ, Berdeli A, Mir S. Evaluation of development of subclinical atherosclerosis in children with uveitis. Clin Rheumatol. 2018 May;37(5):1305-1308. Disclosure of Interests: None declared

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2021-eular.909

Language: English

Publisher: BMJ

Publication Date: 2021

detail.hit.zdb_id: 1481557-6

In: Annals of the Rheumatic Diseases, BMJ, Vol. 81, No. Suppl 1 ( 2022-06), p. 458.2-458

Abstract: Intercellular adhesion molecule-1 (ICAM-1) and E-Selectin are adhesion molecules considered as markers of underlying endothelial activity and damage. These molecules are known to play an important role in autoimmune disease (AD) [1]. Accordingly, they may contribute to the development of interstitial lung disease (ILD), one of the main causes of death in patients with AD [2] . In fact, they have been proposed as prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) [3]. However, studies on the role of ICAM-1 and E-Selectin in AD-ILD + are scarce. Objectives To study the role of ICAM-1 and E-Selectin in the pathogenesis of AD-ILD + . Methods Peripheral venous blood was collected from 57 patients with AD-ILD + and three comparative groups: 45 AD-ILD - patients, 21 IPF patients and 21 healthy controls (HC). All the subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. ICAM-1 and E-Selectin levels were measured in serum samples by enzyme-linked immunosorbent assay. Results Higher levels of ICAM-1 and E-Selectin were found in patients with AD-ILD + compared to AD-ILD - patients (p 〈 0.001 and p=0.001, respectively) and HC (p 〈 0.001 in both cases). Likewise, IPF patients showed increased levels of ICAM-1 and E-Selectin in relation to AD-ILD - patients (p 〈 0.001 and p=0.002, respectively) and HC (p 〈 0.001 in both cases). However, no statistically significant difference in ICAM-1 and E-Selectin concentrations was observed between AD-ILD + and IPF patients. Conclusion Our study suggests that increased levels of ICAM-1 and E-Selectin are associated with the presence of ILD in AD patients. References [1]Int J Mol Sci 2014;15(7):11324-49; [2]Expert Rev Clin Immunol 2018;14(1):69-82; [3]Eur Respir J 2019;54(3):1900295 Acknowledgements VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL18/01); SR-M is supported by funds of the RETICS Program (RD16/0012/0009) from `Instituto de Salud Carlos III´ (ISCIII), co-funded by the European Regional Development Fund; RL-M is a recipient of a Miguel Servet type I programme fellowship from ISCIII, co-funded by the European Social Fund, `Investing in your future’ (grant CP16/00033). Disclosure of Interests Verónica Pulito-Cueto: None declared, Sara Remuzgo-Martínez: None declared, Fernanda Genre: None declared, Belén Atienza-Mateo: None declared, Virginia Portilla: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe Fernández: None declared, Leticia Lera-Gómez: None declared, Diana Prieto-Peña: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Alfonso Corrales: None declared, Oreste Gualillo: None declared, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD, GSK, Grant/research support from: Abbvie, MSD, Janssen, Roche.

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2022-eular.2271

Language: English

Publisher: BMJ

Publication Date: 2022

detail.hit.zdb_id: 1481557-6

In: Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. Suppl 1 ( 2021-06), p. 1076.1-1076

Abstract: Endothelial progenitor cells (EPC), involved in vasculogenesis and endothelial tissue repair, have been described as relevant players in vascular and connective tissue diseases [1-2]. In this regard, a previous study of our group disclosed that the degree of EPC frequency may help to identify the presence of interstitial lung disease (ILD) in rheumatoid arthritis patients [3] . Given that ILD is the main cause of mortality in patients with systemic sclerosis (SSc) [1, 4-6], the understanding of the role of EPC in the mechanism of SSc-ILD + vasculopathy is crucial. Objectives: To assess the potential role of EPC on vascular dysfunction associated with the presence of ILD in patients with SSc. Methods: Peripheral venous blood was collected from a total of 39 patients with SSc, 20 with ILD (SSc-ILD + ) and 19 without ILD (SSc-ILD - ). All subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. Quantification of EPC was analyzed by flow cytometry. EPC were considered as CD34 + , CD45 Low , CD309 + and CD133 + . Results: Statistically significant differences in EPC frequency between patients with SSc-ILD + and patients with SSc-ILD - were disclosed. Specifically, an increase of EPC frequency was observed in SSc-ILD + patients when compared to patients with SSc-ILD - (mean ± standard deviation: 0.033 ± 0.012 versus 0.021 ± 0.017, respectively, p=0.012). Conclusion: Our results suggest a potential role of EPC on vascular damage associated with the manifestation of ILD in patients with SSc. References: [1]Eur J Rheumatol 2020;7(Suppl 3):S139-S146. [2]Arthritis Rheum 2009;60(11):3168-79. [3]J Clin Med 2020;9(12):4098. [4]Ann Rheum Dis 2007;66(7):940-4. [5]Rheumatology (Oxford) 2010;49(12):2375-80. [6]Eur Respir Rev 2015;24(135):102-14. Acknowledgements: Personal funds, VP-C: PREVAL18/01 (IDIVAL); SR-M: RD16/0012/0009 (ISCIII-ERDF); LL-G: INNVAL20/06 (IDIVAL); RP-F: START PROJECT (FOREUM); RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF). Disclosure of Interests: Verónica Pulito-Cueto: None declared, Sara Remuzgo Martinez: None declared, Fernanda Genre: None declared, Belén Atienza-Mateo: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe-Fernández: None declared, Leticia Lera-Gómez: None declared, Raquel Pérez-Fernández: None declared, Diana Prieto-Peña: None declared, Virginia Portilla: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Alfonso Corrales: None declared, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Speakers bureau: Pfizer, Abbvie, MSD, Grant/research support from: Pfizer, Abbvie, MSD

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2021-eular.2350

Language: English

Publisher: BMJ

Publication Date: 2021

detail.hit.zdb_id: 1481557-6