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Background:Biosimilar drugs has supposed a huge savings in our health systems and there are data that conclude that they work as original molecules when we making these switchings. There are limited studies that analize these patients across the time (1-3).Objectives:Long term follow up of patients after switching from original etanercept to biosimilar drug.Methods:We reviewed 187 patients who started Etanercept original in Rheumatology department at Navarra Hospital Complex and their switch to Etanercept biosimilar with a follow-up of 18 months.Results:The switch was performed in 176 patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA).At 18 months of follow-up 26,1% discontinued treatment; 13% at 6 months, 9,1% at 12 months and 4% patients at 18 months. The median time in etanercept original drug before switching was 52 months.There were 46 withdrawal patients with etanercept biosimilar: 34 inefficacy, 3 skin reaction, 2 malignancies (lymphoma and GIST), 1 injection site reaction, 1 headache, 1 diarrhea, 1 recurrent urinary infection, 1 heart failure and 2 deaths. 25 patients returned to Etanercept original but 3 did not achieve good response; all of them in RA group.Conclusion:In our series 50 % of withdrawal happened at 6 months of follow-up. 73,9% had a good response with etanercept biosimilar at 18 months. The main reason to stop biosimilar drug was inefficacy.Longer-term follow-up and greater number of patients are necessary to ratify these data.References:[1]Selmi C, et al. BENEFIT: real-world effectiveness of SB4 after transition from reference etanercept in rheumatoid arthritis and axial spondyloarthritis. Clin Exp Rheumatol. 2020 Jun 30. Epub ahead of print.[2]Glintborg B, et al. To switch or not to switch: results of a nationwide guideline of mandatory switching from originator to biosimilar etanercept. One-year treatment outcomes in 2061 patients with inflammatory arthritis from the DANBIO registry. Ann Rheum Dis. 2019 Feb;78(2):192-200.[3]Tweehuysen L, et al. Open-Label, Non-Mandatory Transitioning From Originator Etanercept to Biosimilar SB4: Six-Month Results From a Controlled Cohort Study. Arthritis Rheumatol. 2018 Sep;70(9):1408-1418.Table 1.WITHDRAWAL (months)BACK TO ENBREL (n)CONTINUEENBREL (n)TIME TO SWITCH (months)REASON FOR WITHDRAWALInefficacyA.event*CancerDeathRA2211853 14521PsA166653,515001SpA888455300TOTAL4625225234822*Infections (1), Heart failure (1), skin reaction (3), injection point reaction (1)RA: rheumatoid arthritis; PsA: psoriatic artrhritis; SpA: spondyloarthritisDisclosure of Interests:None declared

Background:The Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome (RS3PE) is a rare rheumatological disease, considered a benign process.Objectives:This study aims to describe its clinical features and serological markers, and also to analyze its possible association with neoplasms.Methods:An observational retrospective study was performed to assess demographic and clinical characteristics of patients diagnosed from RS3PE at a reference hospital amongst the Rheumatology and Internal Medicine departments, from 2010 to 2021.Results:Twenty-seven patients were included, with a mean age of 82.74 y.o. (IC95% 80.45-85.04; range 66 to 93), and a 51.85% proportion of males. Only 22.22% were from rural areas.All patients presented bilateral hand edema although some associated feet edema (40.74%) or morning stiffness (70.37%). Blood tests demonstrated anemia in 44.44% of patients. Inflammatory markers were elevated, such as C-Reactive Protein (29.23 mg/L, IC95% 18.17-40.29), erythrocyte-sedimentation rate (33.74 mm/hour, IC95% 24.22-43.26) and fibrinogen (531.6 mg/dL, IC95% 482.91-580.30). Only a few patients presented any autoimmune serological marker such as antinuclear antibodies (18.18%) or rheumatoid factor (8.70%).X-ray screening was realized to 22 patients. 14 showed of osteoarthritis radiologic presentation, 4 had radiological findings of chondrocalcinosis and one of them presented both. Only one patient had bone erosion.Malignancy screening was performed at diagnosis in only 29.63% of patients (all negative). During follow-up only two tumors were detected (mean accumulated follow-up: 40.37 months, IC95% 26.70-54.04; range 1 to 122) and there were adenocarcinoma primary neoplasms.All but one patient received low-dose corticosteroids, with a good and rapid response in all cases. Three patients received treatment with methotrexate (2) or leflunomide (1).Conclusion:RS3PE must be contemplated in elderly patients presenting with bilateral hand pitting edema and articular symptoms. No specific biomarkers have been described, but inflammatory reaction is often found in the absence of rheumatoid arthritis biomarkers. Rapid response to corticosteroids is prevalent. Only two neoplasms were detected during follow-up.References:[1]Paira S, Graf C, Roverano S, Rossini J. Remitting seronegative symmetrical synovitis with pitting oedema: a study of 12 cases. Clin Rheumatol. 2002 May;21(2):146-9. doi: 10.1007/pl00011218. PMID: 12086166.[2]Cobeta García JC, Martínez Burgui J. RS3PE syndrome or benign edematous polysynovitis in the elderly. Study of 8 cases. Rev Clin Esp. 1999 Dec;199(12):785-9. Spanish. PMID: 10687410.[3]Moreno Obregón F, Del Castillo Madrigal M, Díaz Narváez F, Pérez Delgado FJ. RS3PE syndrome with positive rheumatoid factor. Reumatol Clin. 2019 Nov-Dec;15(6):e168-e169. English, Spanish. doi: 10.1016/j.reuma.2017.11.009. Epub 2017 Dec 15. PMID: 29254743Disclosure of Interests:None declared

Background:With the arrival of biosimilar drugs and savings policies to make the health system sustainable, hospital managers have chosen to make changes from original molecules to biosimilar drugs.Objectives:This work aims to reflect what happens when making these switchings.Methods:We reviewed 235 patients who started Etanercept original in Rheumatology at Navarra Hospital Complex and Henares University Hospital and their switch to Etanercept biosimilar with a follow-up of 6 months.Results:The switch was performed in 174 patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), ankylosing spondylitis (AS), juvenile idiopathic arthritis, SAPHO and spondyloarthritis.9.8% discontinued treatment: 6 RA (8.1%), 5 PsA (9.8 %) and 6 AS (20.7%); all of them in the injection presentation. 12 patient stopped treatment due to ineffecacy, 2 due to reaction at the injection site, 2 due to diarrhea and 1 due to headache. Among 88.2% of patients who returned to Etanercept original, 28.6% did not achieve good response and had to change of treatment. The median time from Etanercept original beginning until the moment of switching was 54 (40-87) months.Conclusion:In our series, approximately 10% of switching patients failed after a 6-month of follow-up; when trying to return to Etanercept original 28.6% did not achieve response.The median persistence time in the original molecule and the percentage of failures observed in AS could be two conditions to consider before switching.A longer-term follow-up and a greater number of patients are necessary to ratify these data.Table 1DISEASESTOPPED CAUSEBACK TO Etanercept originalCONTINUE Etanercept originalTIME UNTIL SWITCH (meses)ASReaction at the injection siteYesYes28ASHeadacheYesYes54ASIneffecacyYesYes126RAIneffecacyYesNo25ASDiarrheaYesYes87RAIneffecacyYesYes37PsAIneffecacyNoNo43RAIneffecacyYesYes54PsAIneffecacyYesNo93PsAIneffecacyNoNo132PsAIneffecacyYesYes62RAIneffecacyYesYes142RAReaction at the injection siteYesYes51RAIneffecacyYesNo56PsAIneffecacyYesNo40ASIneffecacyYesYes26ASDiarrheaYesYes48Disclosure of Interests:Vicente Aldasoro Speakers bureau: Roche, Abbvie, MSD, UCB, Pfizer, Menarini, Grunenthal, Gebro, Novartis, Janssen, Javier Mendizabal: None declared, Sara Perez Garcia: None declared, Guillen Sada Urmeneta: None declared, Juliana Restrepo Vélez: None declared, Natividad del Val del Amo: None declared, Inmaculada Paniagua Zudaire: None declared, Ricardo Gutiérrez Polo: None declared, Loreto Horcada: None declared, Laura Garrido Courel: None declared, C. Fito-Manteca: None declared

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

Objectives To describe patients with Systemic Lupus Erythematosus (SLE) treated with Belimumab (BLM). Material and methods Review of patients with SLE treated with BLM from 2012 to 2017. Results We enrolled 18 patients, 16 women and 2 men. The median age at of SLE diagnose was 34.3 (IQR 27–45.7) years and the median age at BLM start was 2.2 (IQR 38.9–47) years. The received sDMARDs median number was 2.5 (IQR 2–4). Before starting BLM 7 patients had received rituximab, 4 cyclophosphamide, 1 abatacept and 1 one efalizumab. At BLM begin 17 patients were taking prednisone, 13 hydroxycloroquine, 7 methotrexate, 1 azatioprine, 1 mycophenolate and 1 leflunomide (table 1). The median BLM bolus received was 8.5 (IQR 2–32.7) and it was stopped in 4 patients due to lack of efficacy; this 4 patients had persistence of arthritis and non of them had received bDMARD before. 13 patients had at least one antiphospholipid autoantibody positive and 4 developed antiphospholipid syndrome. The median titer of antinuclear antibodies (ANA) was 1/360 (IQR 1/160–1/1280). All patients but one had ANA positive; among them 9 patients were antiRo positive, 4 antiLa, 4 antiSm and 4 antiRNP positive antibodies. 9 patients were antiDNA positive and 5 were positive for rheumatoid factor (RF) able 1 shows SLEDAI, C3 and C4, antiDNA levels. At BLMin 5 patients had renal involvement; 3 of them improved after 3 months of treatment. Among 14 patients with joint involvement, 3 improved by month 3, 2 by month 6 and 1 by month 7 after treatment beginning. 3 patients had heart and lung disease; no one of them improved with BLM. Among 9 patients with skin disease only one showed improvement after 12 months of treatment. 9 patients had haematological disorders: 1 improved by month one, 1 by month 3, one by month 5 and 2 my month 6 of treatment. Conclusion In this series BLM improved SLEDAI and complement levels allowing sparing of maintenance corticosteroid in SLE patients.

Case report A patient diagnosed with necrotizing scleritis, c-ANCA+, an orbital pseudotumour, and possible multiple sclerosis in 2003 was treated with oral cyclophosphamide and steroids with partial response. Between 2005 and 2010 she suffered self-limited episodes. In 2010 a first scleral transplant was performed with poor outcome. She was treated with rituximab, and a second graft was performed with good results. At 12 months there was no change in magnetic resonance and the second graft healed. Discussion Wegener's disease with limited involvement of the orbit and/or the eye is a rare condition. The histopathology, blood analysis, symptoms and good response to treatment are the key to its diagnosis.

Background Non-infectious aortitis associated with polymyalgia rheumatica (PMR) is a rare entity (1). Sometimes the conventional immunosuppressive therapy is not enough, forcing us to find new therapeutic options (2,3). We present our experience in a local hospital. Objectives To evaluate symptoms, clinic, diagnosis and therapeutic options. Methods During the years 2010–2015 we search for patients diagnosed with PMR which at the same time were diagnosed with non infectious aortitis. Their medical records were reviewed and the following data were collected: initial clinical diagnosis, diagnosis method used, time elapsed since the onset of symptoms to diagnosis, ESR and CRP at diagnosis and after the use of treatment. Results 5 patients were found: 4 women and 1 man. The average age onset of initial symptoms was 67.2 (74–58) years and the average delay in the diagnosis of the disease was 26 (1–50) months. The most common onset clinic was classic PMR symptom. Patients 2, 3, 4 and 5 also showed parietooccipital or parietal headache. Other symptoms were lower limb claudication, temporomandibular joint pain, dyspnea, fatigue and pseudofibromyalgia. All patients underwent temporal artery biopsy. In patient 5 bilateral temporal artery biopsy was performed. The definitive diagnosis test was PET (4). In patient 2 PET was compatible with aortitis being angioMRI negative. The average ESR at the beginning and after the treatment was 87.4 (114–65) and 10.2 (15.6) respectively. The initial and final average CRP (mg /dL) was 8.03 (14.54–1.86) and 1.2 (3 to 0.5) respectively. All patients underwent autoimmune analytical battery, being this study negative. 1,2,3 and 4 patients performed concomitant weekly methotrexate (MTX) with maximum dose of 25 mg weekly sc. Patients 1 and 5 made concomitant treatment with steroids and azathioprine at doses of 100 and 150 mg daily, respectively. Patients 1,2,3 and 5 were treated with tozilizumab which was well tolerated and without adverse effects to date. The average time from diagnosis of the disease until the start of treatment was 9.75 months (2,3). Patient 4 at the time of publication of these data remained asymptomatic with weekly MTX 15 mg sc and 5 mg of prednisone. Conclusions Non-infectious aortitis associated with PMR may go unnoticed due to high variability of presentation. This can make, sometimes, a delayed diagnosis (1). PET seems to be a good tool for the diagnosis (4) and tozilizumab seems to be a suitable treatment for those patients refractory to steroids and DMARDs (2,3). More patients are needed to generalize these data. References Non-infectious aortitis: a report of 32 cases from a single tertiary centre in a 4-year period and literature review. Loricera J, Blanco R, et al. Clin Exp Rheumatol. 2015 Mar-Apr;33(2 Suppl 89):S-19–31. Tocilizumab in refractory aortitis: study on 16 patients and literature review. Loricera J, Blanco R, et al. Clin Exp Rheumatol. 2014 May-Jun;32(3 Suppl 82):S79–89. Biologic therapy in ANCA-negative vasculitis. Loricera J, Blanco R, et al. Int Immunopharmacol. 2015 Aug;27(2):213–9. (18)F-FDG PET/CT for the detection of large vessel vasculitis in patients with polymyalgia rheumatica. Lavado-Perez C, Martinez-Rodriguez I, et al. Rev Esp Med Nucl Imagen Mol. 2015 Sep-Oct;34(5):275–81. Disclosure of Interest None declared

Background Secondary macrophage activation syndrome (MAS) is a group of diseases, especially due to autoimmune (AI) and hemato-oncology (HO). It would be interesting to find any clinical and analytics data to differentiate both etiologies. Objectives To describe and compare demographics, clinical and laboratories features and mortality of patients diagnosed with secondary MAS due to HO and AI diseases at the Donostia University Hospital. Methods A cohort of patients diagnosed with MAS was studied by reviewing medical reports in the period Dec/2008-Jan/2015. We analyzed and compared only patients with AI and HO diseases. The variable studied were diagnosis, age, sex, fever, organomegaly, hospital and overall mortality, analytical findings, hospital stay, days from admission to diagnosis and days from diagnosis to the end of the study or death after discharge. Quantitative variables are shown with the median and interquartile range. For the bivariate analysis Wilcoxon and Chi square test were used. Median survival in months and Hazar Ratio (HR) was calculated with the Kaplan Meier plot. Results Nineteen patients were found diagnosed with MAS, 6 and 9 were due to AI and HO diseases respectively. The AI diseases found were: 3 Systemic Lupus Erythematosus, 2 Adult Still9s Disease and 1 disease associated with IgG4. HO diseases found were: 3 acute myeloid leukemias, 2 B cells Not Hogkin Lymphoma (NHL), 1 T anb B cells NHL, 1 Natural Killers cells extranodal lymphoma, 1 myelodysplastic syndrome and 1 gastric plasmacytoma. The table shows the descriptive analysis of 19 patients and the bivariate analysis between AI and HO. The median survival of HO diseases was 1.2 months and AI diseases can not be calculated. The mortality of HO and AI diseases was 77.8% and 16.7% respectively with a p=0.04 in the log rank test. The HR of mortality among HO against AI diseases was 6.84. Conclusions In the present study the following differences were found: 1) Patients with MAS due to AI diseases have a higher elevated liver enzymes compared to HO disease. 2) Patients with MAS due to HO diseases have a greater pancytopenia compared to AI diseases, especially in leukocytes and neutrophils. 3) Patients with MAS due to HO have a higher mortality compared to AI diseases. Disclosure of Interest None declared

Background Hemophagocytic Lymphohistiocytosis (HLH) is a severe and acute inflammatory syndrome, underdiagnosed, difficult to treat and can occur at any stage of life. The macrophage activation syndrome is a variant of secondary HLH occurs in autoimmune diseases.1 Objectives Describe the clinical, laboratory, treatment and outcome of patients diagnosed with secondary HLH, identifying probable etiological and triggers causes. Methods A retrospective study was performed between 2008 and 2012 at the Donostia University Hospital, Spain. Inclusion criteria were to met diagnostic criteria for HLH and had a bone marrow biopsy with hemophagocytics cells. Mains endpoints were: demographics, diagnostic criteria, probable etiology, triggers causes and treatments. Secondary endpoints were: time delay in diagnosis, days of hospitalization, need for admission to the Intensive Care Unit (I.C.U.) and the cause, and overall mortality. Results We recruited 11 patients (7 men and 4 women) with a mean age of 48.9 years (16 - 78 years). The below table describes the probable etiologies and triggers of secondary HLH. As no data in the literature described, we found as etiologies and triggers causes of secondary HLH: Campylobacter jejuni in a previously healthy patient without comorbidities; Pneumocystis jirovecii in a patient with Human immunodeficiency virus (H.I.V.); and patient with grade IV glioblastoma multiforme after starting chemotherapy with temozolomide. Hemophagocytics cells were found in ascitic fluid in one patient with Adult Still´s Disease. The mean delay in diagnosis was 14.5 days (3 – 31 days) and average time of hospitalization was 46.7 days (10 – 130 days). The 45% of patient required admission in I.C.U, the leading cause was the multiple organ failure (MOF). The overall mortality rate was 36.4% (4 MOF and 1 massive hemoptysis). Treatment given was steroids, synthetic immunosuppressants and biological drugs. Conclusions The secondary HLH should be suspected in any patient with prolonged fever unresponsive to broad-spectrum antibiotics, hepatosplenomegaly, cytopenias, coagulation and liver disorders. Hemophagocytics cells might be found in pathological body fluids before a bone marrow biopsy had been done or when there are doubts in the result of it. Meet all the diagnostic criteria is not necessary to start treatment when you have a high clinical suspicion and a bone marrow biopsy with hemophagocytics cells. Mortality can be influenced by etiology, trigger cause, and diagnosis and treatment delay. References Henter JI, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007; 48:124. Disclosure of Interest None Declared