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Giant cell arteritis is a systemic vasculitis with significant intra and extracranial involvement that, with early diagnosis and treatment in primary care, can improve its prognosis as it is a medical emergency. Our working group on vascular diseases of the Spanish Society of Primary Care Physicians (SEMERGEN) proposes a series of recommendations based on current scientific evidence for a multidisciplinary approach and follow-up in primary care.

BackgroundAutoinflammatory syndromes are characterized by dysregulation of innate immunity and recurrent episodes of fever, cutaneous and other. Janus Kinase inhibitors (JAKINIB) may inhibit innate and acquired immunity. They have been approved in several immune mediated diseases, but not in autoinflammatory syndromes.ObjectivesTo assess the efficacy and safety of JAKINIB in refractory autoinflammatory syndromes.MethodsStudy of patients from a single University Hospital and Literature review of refractory autoinflammatory syndromes treated with JAKINIB.ResultsWe have identified 2 cases in our hospital. One of them was a 25-year-old girl diagnosed with Blau syndrome refractory to different conventional and biological therapies. Tofacitinib (TOFA) had a good clinical response but was switched to Bariticitinib (BARI) due to severe lymphopenia. The 2nd patient was a 65-year-old man, diagnosed with an autoinflammatory syndrome (WDR1 mutation) and policytemia vera (positive JAK-2; V617F mutation). Based on the JAK2 mutation, BARI was started with complete improvement. In literature review, we found 59 patients (41 women/ 18 men), mean age 38.1±13 years. TOFA (n=23) was the most used JAKINIB, followed by BARI (n=20) and Ruxolitinib (RUXO) (n=16). After starting JAKINIB treatment, most patients presented clinical complete (n=45, 76.3%) or partial (n=11; 18.6%) improvement, only 3 (5.1%) did not respond. (Table 1)Table 1.Case reports and literature review of patients with refractory autoinflammatory syndromes treated with Janus Kinase Inhibitors.Study, yearCases, nAge/SexUnderlying DiseaseJAKINIBPrevious immunosuppressive treatmentClinical Evolution(Ref)García-Robledo et al, 2022 (1)116, FFMFTOFAMTX, TCZ, CANAC.I.Gök K et al, 2017 (2)127, FFMFTOFAMTXC.I.Forbes et al, 2018 (3)1712.4±7.5*, F=9STAT1 and TAT3 GOFRUXO (n=16)TOFA (n=1)AZA(n=1), iv immunoglobulins (n=3), CsA (n=2), RTX (n=2) ECU (n=1), ANA (n=1), MTX (n=2), CYC (n=2), MMF (n=1)C.I. (n=14)N.R. (n=3)Landhari et al, 2020 (4)143, FAOSDBARIMTX, SSZ, ANA, IFX, TCZ, ABAC.I.Sánchez et al, 2018 (5)1812.5 (1.2-24.1) ** (F=12)CANDLE n=10BARIImmunomodulators (n=17)C.I. (n=16)CANDLE-related n=4SAVI n=4Biologics (n=13)P.I. (n=2)Karadeniz et al, 2020 (6)41. 28, MFMFTOFA1. AZA, MTX, ANA, CANA, IFX, TCZ1. C.I.2. 58, F2. SSZ, MTX, LEF, ANA, ADA, TCZ2. C.I.3. 64, F3. SSZ, MTX, LEF, HCQ, CsA, ADA, ABA, ANA3. P.I.4. 43, F4. SSZ, ADA, ETA, ANA4. C.I.Hu et al, 2020 (7)1434,8±14*AOSDTOFAMTX (n= 8), HCQ (n=5), CsA (n=5), TCZ (n=2), ANA (n=1)C.I. (n=7)F=12P.I. (n=7)Honda et al, 2020 (8)168, FAOSDTOFATCZ, Tacrolimus, CYCP.I.Present study, 202221.25, F1. Blau Syndrome1.TOFA/BARI1. MTX, ETN, ANA, ABA1. C.I.2. 64, M2. Autoinflammatory syndrome (WDR1 mutation)2.BARI2. ANA2. C.I.*Mean±Standard deviation, **Median (range)Abbreviations: ABA: abatacept, ADA: adalimumab, ANA: anakinra, AOSD: adult onset Still disease, AZA: azathioprine, BARI: baricitinib, CANA: canakinumab, CANDLE: Cronichle atypical neutrophilic dermatosis with lypodistrophy and elevated temperature, C.I.: Complete improvement, CsA: cyclosporine A, ECU: eculizumamb, ETN: etanercept, FMF: familial mediterranean fever, HCQ: hydroxychloroquine, IFX: infliximab, LEF: leflunomide, MMF: mycophenolate mofetil, MTX: methotrexate, N.R: no response, P.I.: partial improvement, RUXO: ruxolitinib, SAVI: STING-associated vasculopathy with onset in infancy, SSZ: sulfasalazine, STAT1 and STAT3 GOF: STAT1 and STAT 3 gain of function, TCZ: tocilizumab, TOFA: tofacitinib.ConclusionJAKINIB may be an effective therapy in autoinflammatory syndromes refractory to conventional and/or biologic therapy.References[1]García-Robledo. Rheumatology. 2019; 58:553-554.[2]Gök. Acta Reumatol Port. 2017; 42:88-90.[3]Forbes. J Allergy Clin Immunol. 2018; 142:1665-1669.[4]Landhari. Rheumatology. 2019; 58:736–737.[5]Sánchez. J Clin Invest. 2018; 128:3041-3052.[6]Karadeniz. Rheumatology. 2020; 40: 169-173.[7]Hu. Ann Rheum Dis. 2020; 79: 842-844.[8]Honda. Scand J Rheumatol. 2020; 49:336-338Disclosure of InterestsCarmen Álvarez-Reguera: None declared, Diana Prieto-Peña: None declared, Lara Sanchez-Bilbao: None declared, Alba Herrero-Morant: None declared, David Martínez-López: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi and MSD., Grant/research support from: Abbvie, MSD, Janssen and Roche., Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen Lilly and MSD., Grant/research support from: Abbvie, MSD and Roche.

BackgroundJanus Kinases (JAK) can promote cytokine production in immune and hematopoietic cells. The JAK-2 (V617F) mutation is the most frequently detected mutation in myeloproliferative neoplasms (MPN) which include essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF) and undifferenciated MPN. JAK-2 (V617F) mutation displays a pro-inflammatory phenotype that may be associated to a higher risk of immune mediated diseases (IMID).ObjectivesIn a wide series of JAK2 (V617F) mutation, we assess the presence of a) IMID (rheumatic and non-rheumatic), b) treatment of rheumatic IMID.MethodsWe studied all the patients diagnosed with a positive JAK-2 (V16F) mutation in a single University Hospital from January 2004 to December 2019. JAK-2 (V16F) mutation was detected by using both peripheral blood and bone marrow samples. Associated IMID and treatment of rheumatic IMID were evaluated.ResultsWe included 130 patients (73 men/57 women; mean age, 70.1±14.5 years). All of them were diagnosed of MPN; ET (n=64, 49.2%), PV 46 (35.4%), undifferentiated MPN (n=12, 9.2%) and PMF (n=8, 6.1%). In 10 of these 130 patients (7.7%) a rheumatic IMID was diagnosed: rheumatoid arthritis (RA) (n=4; 40%), polymyalgia rheumatica (PMR) (n=3; 30%), Sjögren syndrome (SS) (n=1; 10%), antiphospholipid syndrome (APS) (n=1; 10%) and autoinflammatory syndrome (WDR1 mutation) (n=1; 10%). Patients with RA, SS, PmR, and APS were clinically mild. RA patients were seronegative, non-erosive and without extraarticular involvement. Treatment and response are summarized in Table 1. All patients diagnosed with PMR were treated with glucocorticoids (prednisone 5 mg/12 hours), SS with hydroxychloroquine (HCQ) (200 mg/day), APS was anticoagulated with acenocumarol and one autoinflammatory syndrome was finally treated with baritinib (4 mg/day) after failure to anakinra (100 mg/day).ConclusionExcept in autoinflammatory syndrome, most rheumatic IMID associated to JAK-2 (V16F) mutation are clinically mild, and treatment and response of patients seems similar or even better than those without this mutation.Table 1.Treatment of 10 patients with rheumatic IMIDs and JAK-2 (V16F) mutation.Abbreviation:ANA: anakinra, BARI: baricitinib, NSAIDs: Non-Steroidal Anti-inflammatory Drugs, PDN: prdnisone, RA: Rheumatoid arthritis, SS: Sjögren syndrome, PMR: polymyalgia rheumatica.Disclosure of InterestsCarmen Álvarez-Reguera: None declared, Lara Sanchez-Bilbao: None declared, Sara Fernández López: None declared, Ana Batlle-López: None declared, Alba Herrero-Morant: None declared, David Martínez-López: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD, Grant/research support from: Abbvie, Pfizer, Roche, Sanofi and MSD., Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Grant/research support from: Abbvie, MSD and Roche.

BackgroundNeurosarcoidosis (NS) is a severe complication of sarcoidosis [1,2]. NS may be classified according to several subtypes [1]. Data on therapy, including biological therapy (BT) is scarce.ObjectivesTo assess efficacy and safety of BT in refractory NS subtypes.MethodsStudy of NS from a large cohort (n=234) of all consecutive patients diagnosed with sarcoidosis in a single university hospital from January 1, 1999 to December 31, 2019. Diagnosis of sarcoidosis was established according to ATS/ERS/WASOG criteria [3].Efficacy was considered as complete or partial response and no-response according to the resolution of the neurological syndrome (signs and/or symptoms) after the BT onset.ResultsNS was observed in 30 (19 women/11 men) of 234 (12.8%) patients; mean age, 55.0±15.8 years. NS subtypes were chronic headache (n=13, 43.4%), peripheral neuropathy (n=6, 20%), cranial neuropathy (n=5, 16.7%), spinal cord abnormalities (n=3, 10%) and aseptic meningitis (n=3, 10%). A total of 26 (86.7%) patients received oral corticosteroids (CT) (mean maximum dose: 50±19.2 mg/dL) and 7 (23.3%) IV CT. In addition, conventional immunosuppressants were administered to 18 (60%) patients and BT to 12 (40%) patients. No treatment was administered to 4 (13.3%) patients. Table 1 shows treatment according to NS subtypes.Table 1.Treatment of 30 patients with neurosarcoidosisNeurosarcoidosis subtypen (%)Other clinical manifestationsn (%)Conventional immunosuppressant,N=23n (%)monoclonal anti-TNFα, N=22 n (%)Etarnecept, N=1n (%)Tocilizumab, N=1n (%)Secukinumab, N=1 n (%)Rituximab, N=1 n (%)Chronic headache*13 (43.4)P (n=9, 69.2%)A (n=9, 69.2%)C (n=6, 46.2%) O (n=4, 30.8%)D (n=4, 30.8%)MTX (n=6, 26.1%) AZA (n=1, 4.3%)IFX (n=1, 4.5%)ADA (n=1, 4.5%)GLM (n=1, 4.5%)0 (0)01 (4.5)1 (4.5)Peripheral neuropathy6 (20.0)P (n=5, 83.3%)A (n=3, 50%)O (n=3, 50%) C (n=2, 33.3%)MTX (n=4, 17.4%) AZA (n=2, 8.7%)IFX (n=3, 13.6%)ADA (n=2, 9.1%)GLM (n=1, 4.5%)1 (4.5)000Cranial neuropathy5 (16.7)P (n=4, 80%) O (n=3, 60%)C (n=1, 20%)A (n=1, 20%)D (n=1, 20%)AZA (n=4, 17.4%)MTX (n=3, 13.1%)IFX (n=3, 13.6%)ADA (n=1, 4.5%)0000Spinal cord abnormalities3 (10.0)P (n=3, 100%)O (n=1, 33.3%)C (n=1, 33.3%)A (n=1, 33.3%)MTX (n=1, 4.3%)IFX (n=1, 4.5%)GLM (n=1, 4.8%)0000Aseptic meningitis3 (10.0)P (n=2, 66.7%)O (n=1, 33.3%)C (n=1, 33.3%)A (n=1, 33.3%)MTX (n=2, 8.7%)IFX (n=2, 9.1%)ADA (n=1, 4.5%)01 (4.5)00TOTAL(n= 30)30 (100)P (n=23, 76.7%)A (n=15, 50%)O (n=12, 40%)C (n=11,36.7%)D (n=5, 16.7%)MTX (n=16, 69.6%) AZA (n=7, 30.4%)IFX (n=10, 45.5%)ADA (n=5, 22.7%)GLM (n=3, 13.6%)1 (4.5)1 (4.5)1 (4.5)1 (4.5)Abbreviations: A: Articular, ADA: Adalimumab, AZA: Azathioprine, C: Cutaneous, D: Digestive, GLM: Golimumab, IFX: Infliximab, MTX: Methotrexate, O: Ocular, P: Pulmonar*With MRI, CSF, and/or EMG/NCS findings typical of granulomatous inflammation of the nervous system after rigorous exclusion of other causes and not meeting criteria for other neurosarcoidosis subtypes.A total of 12 patients received treatment with 22 BT. Most used BT were monoclonal anti-TNFα (n=18, 81.8%), infliximab (IFX) (n= 10, 45.5%) and adalimumab (ADA) (n=5, 22.7%). After 12 months since the initiation of BT, complete, partial or no response was observed in 14 of 17 (82.4%), 2 (11.8%) and 1 patient (5.9%), respectively (Figure 1). Severe allergic reaction was observed in one patient on both IFX and ADA. No more severe adverse events were observed.Figure 1.Neurological clinical response to biological therapyConclusionBT, especially monoclonal anti-TNFα, seems to be effective and safe in NS, regardless of subtype.References[1]J. Bradshaw M, et al. Neurol Neuroimmunol Neuroinflamm 2021;8:e1084. doi:10.1212/NXI.0000000000001084[2]Riancho-Zarrabeitia L, et al. Clin Exp Rheumatol. 2014 Mar-Apr;32(2):275-84. PMID: 24321604.[3]Statement on Sarcoidosis. Am J Respir Crit Care Med [Internet] 1999;160(2): 736–55. https://doi.org/10.1164/ajrccm.160.2.ats4-99Disclosure of InterestsAlba Herrero-Morant: None declared, David Martínez-López: None declared, Lara Sanchez-Bilbao: None declared, Iñigo Gonzalez-Mazon: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Lilly, Janssen, UCB, and Celgene, Raúl Fernández Ramón: None declared, Carmen Álvarez-Reguera: 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

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

BackgroundHydroxychloroquine (HCQ) is a widely used drug in Systemic Lupus Erythematosus (SLE). It may cause cardiac alterations which includes short term arrhythmic events (via QT interval prolongation) and medium-late term dose dependent cardiomyopathy1. The few research articles published on the medium-late term effects of HCQ in cardiac conduction disorder do not show relevant alterations2-3.ObjectivesTo assess the effect of HCQ in cardiac conduction in a consecutive SLE population.MethodsObservational, single University hospital study of all consecutive SLE patients with an electrocardiogram (EKG) at HCQ onset and at least one EKG in follow-up, with a period of at least 3 months on HCQ treatment was performed. We assessed conduction alteration (CA) by EKG, defined as atrio-ventricular block, bundle branch block or QT interval prolongation. The EKGs were gathered from the clinical history and interpreted at the beginning of the treatment and during the 15.2 years (CI95% 13.24-17.16) follow-up period. We defined cumulated HCQ (cHCQ) as the multiple of the mean annual dose of the sample. A Multiple logistic regression model, adjusted by different variables according to statistical significance and clinical relevance, was performed.ResultsWe studied 109 (96 women/13 men) SLE patients with a mean (±SD) age of 61 ±. 2.78 years. A statistically significant association was observed between the cHCQ, and the development of CA [OR 1.1 CI95% 1.02-1.9; p = 0.011] (Table 1 & Figure 1). A total of 8 covariates were included. Among them, those that had the greatest influence on the development of the primary event were previous CA [OR 4.15 CI95% 6.39-624.54; p Table 1.Results of univariable and multivariable logistic regressions evaluating the association between cumulated hydroxychloroquine and the development of cardiac conduction alterations.VariableUnadjusted OR95%CIP-valueAdjusted OR95%CIP-valueCumulated hydroxychloroquine1.071.021.120.011.101.021.190.01CovariatesPrevious cardiac conduction alterations28.235.67140.540.0063.216.40624.540.00Cardiac valve disease4.711.6613.370.007.151.3138.910.02Age1.061.021.100.001.071.001.140.04Diabetes mellitus3.791.2611.410.023.440.5920.110.17Cerebrovascular disease2.951.028.500.050.100.011.030.05Chronic renal disease6.651.7724.980.054.880.6536.910.13Pulmonary Hypertension6.400.5673.580.143.840.13114.960.44Alcohol consumption6.400.5673.580.1410.590.58194.870.11Gender0.330.100.110.07Hypertension2.320.915.900.08Dyslipemia1.460.613.500.40Obesity1.850.418.320.42Smoking1.670.694.020.26Cardiac ischaemic disease2.080.3313.160.44Heart Failure5.911.3126.680.02Pericarditis2.080.3313.160.44OR: Odds Ratio; CI: ConfidenceFigure 1.Cardiac conduction alterations development according to cumulated Hydroxychloroquine dose.ConclusionAccording to our study, it seems to be an association between the cHCQ and development of CA regardless of other variables evaluated. Wider longitudinal studies are required with a protocolized EKG performance in successive visits to further analyze this association.References[1]Chatre C, Roubille F, Vernhet H, et al. Cardiac complications attributed to chloroquine and hydroxychloroquine: a systematic review of the literature. Drug Saf. 2018;41(10):919–931.[2]Costedoat-Chalumeau N, Hulot JS, Amoura Z, Leroux G, Lechat P, Funck-Brentano C, Piette JC. Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases. Rheumatology (Oxford). 2007 May;46(5):808-10.[3]Godeau P, Guillevin L, Fechner J et al (1981) Disorders of conduction in lupus erythematosus. Frequency and incidence in a group of 112 patients (author’s transl). AnnMed Interne (Paris) 132:234–240.Disclosure of InterestsAlba Herrero-Morant: None declared, Jon Zubiaur-Zamacola: None declared, Adrián Margarida-de Castro: None declared, Raquel Pérez-Barquín: 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.

BackgroundBehçet’s disease (BD) may present with different clinical phenotypes. Ocular and Neurobehçet’s Disease (NBD) are severe complications [1-4]. Data on NBD epidemiology, clinical phenotype and therapy are scarce and controversial.ObjectivesIn a wide unselected single-center series of BD our aims were to assess a) NBD prevalence, b) associations with other clinical clusters and c) treatment.MethodsCross-sectional study of all 120 patients diagnosed with BD in Northern Spain, between January 1, 1999 to December 31, 2019. Finally, 96 patients were included in this study according to 2014 International Criteria for Behçet Disease (ICBD) [5]. NBD was diagnosed according to the International Consensus Recommendation (ICR) criteria [4].ResultsNBD was diagnosed in 23 of 96 (24%) patients (15 women/8 men) (mean age: 44±13.9 years). NBD was classified as parenchymatous (n=10, 43.5%), non-parenchymatous (n=10, 43.5%) and mixed (n=3, 13%). HLAB51 was positive in 5 out of 13 (38.4%) patients tested. The main cluster of clinical associations were oral aphthae (n=20, 87%); ocular (n=14, 60.9%), cutaneous (n=10, 43.5%), articular (n=9, 39.1%), vascular (n=4, 17.4%) and intestinal (n=1, 8.7%) involvement (Figure 1).Figure 1.Clusters of clinical associations of NBDTreatments were oral corticosteroids (n=16; 69.6%; mean maximum dose 42±12.5 mg/ day, conventional immunosuppressants (n=13, 56.5%) and Biological Therapy (BT) (n= 7; 30.4%). BT was used in patients who were refractory to conventional immunosuppressants. Monoclonal anti-TNFα were used as the first option in all patients who received BT. In 3 out of 7 (42.7%) patients BT was switched due to inefficacy. Table 1 shows the main NBD clinical subtypes and treatment.Table 1.Main clinical features and treatment of 23 patients with NBDn (%)Mean maximum oral prednisone dose, (SD) mg/dayConventional immunosuppressants, n (%)monoclonal anti-TNFα, n (%)Tocilizumab, n (%)Anakinra, n (%)Parenchymal phenotype10 (43.5)51.7±19.36 (46.2)4 (57.1)00-Hemiparesis5 (50)52.5±7.52 (50)3 (75)-Optic neuropathy-Encephalopathy3 (30)1 (10)52.3±26.3452 (66.7)1 (16.7)00-Ophtalmoparesis1 (10)01 (16.7)1(25)Non-parenchymal phenotype10 (43.5)42±12.55 (38.5)2 (28.6)00-Aseptic meningitis10 (43.5)42±12.55 (38.5)2 (28.6)Mixed3 (13)45±152 (15.4)1(14.3)1 (14.3)1 (14.3)-Aseptic meningitis and ophtalmoparesis1 (33.4)600000-Aseptic meningitis and other cranial nerve involvement1 (33.4)01 (50)000-Encephalopathy and intracranial hypertension1 (33.4)301(50)1(100)1(100)1(100)Complete remission was achieved in 18 of 23 cases (78.2%), partial response in 2 out of 23 cases (8.7%). No severe adverse effects were observed.ConclusionNBD was observed in 24% of patients with BD. The most frequent clinical clusters of NBD were oral aphthae and ocular involvement. All patients treated with either conventional immunosuppressant or BT achieved clinical remission.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.[5]International Team for the Revision of the International Criteria for Behçet’s Disease (ITR-ICBD). J Eur Acad Dermatol Venereol. 2014 Mar;28(3):338-47.Disclosure of InterestsAlba Herrero-Morant: None declared, Carmen Álvarez-Reguera: None declared, Lara Sanchez-Bilbao: None declared, David Martínez-López: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Lilly, Janssen, UCB, and Celgene, Guillermo Suárez-Amorín: None declared, Raúl Fernández Ramón: None declared, M. Cristina Mata Arnaiz: 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

The aim of this study was to determine the potential role of three IRF3 gene polymorphisms (rs2304204, rs7251 and rs2304207) with systemic lupus erythematosus (SLE). Our study population consisted of 610 patients with SLE and 730 healthy controls. All individual were of Spanish Caucasian origin. The IRF3 polymorphisms were genotyped using a PCR system with pre-developed TaqMan allelic discrimination assay. No statistically significant differences were found when allele and genotype distribution of rs2304204, rs7251 and rs2304207 polymorphisms were compared between patients with SLE and controls [overall P values: rs7251, P = 0.06; rs2304204, P = 0.26 and rs2304207, P = 0.36, by chi-squared test on a 3 × 2 contingency table. Overall allelic P values: rs7251, P = 0.8, OR (95%CI) = 1.03 (0.87–1.22); rs2304204, P = 0.2, OR (95%CI) = 1.12 (0.93–1.34) and rs2304207, P = 0.8, OR (95%CI) = 1.02 (0.82–1.26)]. In addition, no evidence of association with haplotypes and clinical features of SLE was found. Our data suggest that the IRF3 polymorphisms do not appear to play a major role in the susceptibility or severity of SLE in a Spanish population.

Background: Functional polymorphisms of the solute carrier family 22, member 4 ( SLC22A4 ), runt related transcription factor 1 ( RUNX1 ) and small ubiquitin-like modifier 4 ( SUMO4 ) genes have been shown to be associated with several autoimmune diseases. Objective: To test the possible role of these variants in susceptibility to or severity of systemic lupus erythematosus (SLE), on the basis that common genetic bases are shared by autoimmune disorders. Methods: 597 SLE patients and 987 healthy controls of white Spanish origin were studied. Two additional cohorts of 228 SLE patients from Sweden and 122 SLE patients from Colombia were included. A case–control association study was carried out with six single nucleotide polymorphisms (SNP) spanning the SLC22A4 gene, one SNP in RUNX1 gene, and one additional SNP in SUM04 gene. Results: No significant differences were observed between SLE patients and healthy controls when comparing the distribution of the genotypes or alleles of any of the SLC22A4 , RUNX1 , or SUMO4 polymorphisms tested. Significant differences were found in the distribution of the SUMO4 genotypes and alleles among SLE patients with and without nephritis, but after multiple testing correction, the significance of the association was lost. The association of SUMO4 with nephritis could not be verified in two independent SLE cohorts from Sweden and Colombia. Conclusions: These results suggest that the SLC22A4 , RUNX1 , and SUMO4 polymorphisms analysed do not play a role in the susceptibility to or severity of SLE.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with a complex pathogenesis which involves genetic and environmental factors.1 CD24 is a glycosylphosphatidylinositol-anchored cell surface protein with expression in a wide variety of cell types which participate in the pathogenesis of RA. This molecule has been proposed as a genetic checkpoint in T-cell homoeostasis and pathogenesis of autoimmune diseases.2 A non-synonymous variation (A57V) and a dinucleotide deletion in the 3′ untranslated region (TG/del) have been associated with different autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus.3–6 Furthermore, both polymorphisms appear to play a functional role in CD24 expression and CD24 mRNA stability. This gene is located …