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Background:Metotrexate (MTX) is usually the first line therapy for Rheumatoid Arthritis (RA) because of its favorable efficacy-toxicity ratio. However the exact mechanism and treatment response time in both a clinical and ultrasonographic setting are still uncertain.Objectives:To describe the clinical and ultrasound response to MTX during the first 6 months of treatment in early RA patients who started subcutaneous methotrexate as the first disease-modifying drug (DMARD).Methods:Ongoing prospective cohort of patients with early RA (ACR-EULAR 2010 criteria), over 18 years and starting MTX-SC. Patients had a clinical and ultrasonographic evaluation at baseline, 1, 3 and 6 months. We collected demographic data, C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], rheumatoid factor [FR], anti-citrullinated protein antibody [ACPA]), inflammatory activity indexes (DAS28esr and DAS28crp) and EULAR’s response to treatment (delta value of -1.2 in DAS28 scores). Joints explored with ultrasound were elbows and wrists (radio-carpal and inter-carpal joint) counted as a single joint, 1st-5th metacarpophalangeal (MCF), proximal interphalangeal (IFP), knees, tibio-talar and subtalar joints and 2nd-5th metatarsophalangeal (MTF) joints. Bone erosions were evaluated in 2nd and 5th MCF, styloid, distal ulna and 5th MTF. Synovitis was graduated semi-quantitatively from 0 to 3 (OMERACT) and calculated on B mode and Doppler.Results:35 patients were included (mean age 61.2 years, 65.7% women) with a median of 0.8 (+/-8) months delay to diagnosis. 34 patients (97.1%) started 15mg MTX-SC/weekly. A higher DAS28esr was found in baseline data for the group that had a response by month 1 (DAS28esr baseline 5.5 vs 4.2 p=0.01), no other significant differences were found. During the first month, a significant response was achieved in 13 (41%) patients and remission in 11 (35%) (Table 1). 17 patients have 6thmonth data. 11 (64.7%) have achieved EULAR response compared to baseline(P=0.0005) out of which 7 (54.5%) had already reached it by month 1. A difference in MTX dose (month1 14.8 vs month6 17.1 p=0.003) was found between month 1 and 6, with no differences in disease activity. In the ultrasonographic baseline data; 8 patients (22.9%) had erosions, with a mean of 2,75 erosions/patient (22 of the 280 locations). During the follow up the global rating lowered, with no differences in B mode but significant differences in Doppler at the 6 month mark (Table 2). As of this report, 10 patients (28.5%) had stopped MTX treatment due to lack on response or adverse effects and 8 (22.9%) are waiting 6thmonth evaluation.Table 2.Ultrasound synovitis global rating.BaselineMonth 1P ValueEULAR response013 (41)0.00005MTX Dose mg (SD)14.8 (+/-0.8)14.8 (+/-1.6)1Prednisone Dose mg(SD)5.9 (+/-6.5)2.9 (+/-3)0.02DAS28crp (SD)4.3 (+/-1.5)3,4 (+/-1.4)0.02DAS28esr (SD)(4.8 (+/-1.5)3.7 (+/-1.4)0.006Remission (DAS283(9.6)11(35.5)0.04Table 1.Baseline characteristics of the patients with RA (n=102).BaselineN=351 monthN=313 monthsN=256 monthsN=17B Mode:Median (interquartile range)8 (3.5-12)8 (3-12.5)6 (4-11)5 (2-11)p 0,16Doppler Mode: Median (interquartile range)2 (0.5-6)2 (0-6)2 (0-6)0 (0-2)p 0,005Conclusion:In this cohort half of the patients that responded to treatment had achieved this by month 1. A higher baseline inflammatory profile was related to the response. Little difference is found between month 1 and 6 on clinical data, however ultrasonographic results suggest that at least 6 months are needed for Doppler improvement. Perhaps MTX has a faster effect over joint pain and lowers DAS28 scores requiring longer to completely suppress inflammatory activity.References:[1]Braun, J. et al. Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis. Arthritis Rheum 2008Disclosure of Interests:Liz R. Caballero Motta: None declared, Ana Melissa Anzola Alfaro: None declared, Luis A Torrens Cid: None declared, Christian Y Soleto: None declared, Belén Serrano Benavente: None declared, Iustina Janta: None declared, Juan Molina Collada: None declared, Carlos Gonzalez Consultant of: Gilead, Janssen, Novartis,, Speakers bureau: Abbvie, Celgene, Gilead, Janssen, Novartis, Pfizer, Roche, Indalecio Monteagudo: None declared, Jose Maria Alvaro Gracia: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi

Background:Monosodium urate crystals deposition arthritis (Gout) is the most prevalent inflammatory arthropathy in our society. The use of muskuloskeletal ultrasound (MSUS) is emerging as a diagnostic method of patients with gout, mainly in the past few years.Objectives:Our objective is to establish the prevalence of articular and periarticular ultrasound lesions in patients with known or recent gout diagnosis without urate-lowering therapy (ULT) as well as to analyze the influence of disease duration on these findings.Methods:Observational, cross-sectional and descriptive study, including patients with diagnosis of Gout (fulfilling the ACR / EULAR Classification Criteria 2015) between September and November 2019 in our Rheumatology service of a tertiary center. Demographic and clinical records were collected (table 1) and MSUS was performed on each patient systematically by two rheumatologists, exploring a total of 20 structures (8 tendons and 12 joints). Suggestive images of MSU crystals deposition were defined following the OMERACT 2015 ultrasound elementary lesions definitions. Deposits included lesions as tophus, hyperechoic aggregates (HA) and double contour (DC).Table 1.Demographic and laboratory dataFeaturesPatients (n=38)%SexMen 34 Women 489,5 10,5Age (years)Mean ±SD 60±14,43ComorbiditiesArterial hypertension18 Mellitus diabetes 4 Dyslipidemia 13 Smoking 7 Alcohol 1447,4 10,5 34,2 18,4 36,8BMI (Kg/m2)Mean±SD 27,3±4,23Blood urate levels (mg/dL)Mean±SD 8,2±1,74Blood creatinine levels (mg/dL)Mean±SD 1,09±0,75Results:A total of 38 patients were included, 34 men (89.5%) and 4 women (10.5). Twenty seven (71.1%) presented MSU crystals in synovial fluid samples, while rest of them (28.9%) met 2015 ACR / EULAR Clasiffication Criteria for Gout. Disease duration (since onset of symptoms) was less than 6 months in 20 patients (52.6%) and longer than 6 months in 18 (47.36%). Thirty seven patients (97.36%) presented some type of MSU deposits on the explored areas. One hundred and thirty (17,10%), out of 760 explored locations, had MSU deposits. Patients with disease duration less than 6 months had 56 locations with deposits (43.07%), while those with a symptomathology longer than 6 months had 74 locations with deposits (56.92%). Left knee was the most frequent location of UMS deposits (78.95%). Out of the 145 MSUS images with elementary lesions due to MSU crystal deposits, 28 were tophi (19.31%), 33 HA (22.75) and 84 DC (57.93%). Out of the total images with deposits (DC, HA and tophi), DC in the left knee was the most frequent (21.38%), followed by DC in right knee (17.24%) and DC in 1st MTP (10.24%).Conclusion:Almost 100% of patients with recently diagnosed gout without ULT, presented on at least one of the scanned locations MSUS images suggestive by MSU crystals deposition. Most of MSU crystals deposits were on knees and 1st MTP. Patients with non-treated longer than 6 months of disease duration gout had a greater number of MSU crystals deposit locations detected by MSUS. The presence of tophi and HA was statistically higher in patients with disease duration longer than 6 months (table 2).Table 2.MSU crystals median locations and MSUS images in both groups)>6months (n,%)p valueDeposits locations56 (43,07)74 (56,92)0,0751MSUS images with deposits -Tophi Median, IR () - HA Median, IR () - DC Median, IR ()8 (28,57) 0 (0-0) 7 (21,21) 0 (0-0) 39 (46,43) 0,5 (0-1)20 (71,43) 0 (0-1) 26 (78,79) 0 (0-1) 45 (53,57) 0 (0-2)0,01810,02310,85311Mann-Whitney U test comparing medians between both groups IR: interquartile rangeReferences:[1]Norkuviene E, Petraitis M, Apanaviciene I, Virviciute D and Baranauskaite A. An optimal ultrasonographic diagnostic test for early gout: A prospective controlled study. J Int Med Res. 2017 Aug.[2]Neogi T, Jansen TLA A, Dalbeth N, Fransen J, Schumacher HR, Berendsen D et al. 2015 Gout Classification Criteria. An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Arthritis & Rheumatology. Vol. 67, No. 10, October 2015.Disclosure of Interests: :Luis A Torrens Cid: None declared, Juan Molina Collada: None declared, Christian Y Soleto: None declared, Liz R. Caballero Motta: None declared, Ana Melissa Anzola Alfaro: None declared, Alfonso Ariza: None declared, Isabel Castrejón Fernández: None declared, Javier Rivera: None declared, Jose-Maria Alvaro-Gracia Grant/research support from: Abbvie, Elli-Lilly, MSD, Novartis, Pfizer, Consultant of: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB, Paid instructor for: Elli-Lilly, Pfizer, Roche, Speakers bureau: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, Gedeon Richter, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi

Background:Tofacitinib is an oral JAK 1 and 3 inhibitor for the treatment of moderate to severe active rheumatoid arthritis (RA) or psoriatic arthritis (PsA) in adults with inadequate response or intolerant to one or more conventional disease-modifying antirheumatic drugs (cDMARDs). Since its approval by the European Medicines Agency (EMA), there is limited data about its use in daily practice in Europe.Objectives:To describe rates and reasons for discontinuation of Tofacitinib in patients with RA and other inflammatory conditionsMethods:We identified patients with a prescription for tofacitinib at our academic center from January 2017 to January 2020. Patients were treated according to their rheumatologist evaluation following standards of care. The following variables were retrospectively collected from the electronic medical chart: age, gender, diagnosis, date of treatment initiation, date and reasons for treatment discontinuation, the use of concomitant or previous cDMARDs and of biologics. A comparison between patients continuing and stopping tofacitinib was performed through chi2or t-test for qualitative and quantitative variables, respectively. Survival analysis was done by Kaplan-Meier methodResults:Ninety patients receiving tofacitinib were identified, 81 with RA, 6 with PsA, 1 with Dermatomyositis, 1 with Sjögren´s and 1 with juvenile idiopathic arthritis. Table 1 shows the baseline characteristics. 84% percent patients were women and the mean (SD) age was 58.5 (14.2) years. 51% patients started tofacitinib in monotherapy. When used, methotrexate was the most frequent cDMARD (61.3%); 10% patients used tofacitinib as first line after cDMARD and the majority used it after 1 or 2 previous biologics (46.7%).Table 2.Clinical coutcome of patients who developed HZ at initiation of baricitinibAll patients(n=90, 100%)Continue Tofacitinib(n=58; 64%)Not continue Tofacitinib(n=32; 35.5%)p-valueFemale (%)76 (84.4)48 (82.7)28 (87.5)0.55Age (year) – mean (SD)58.5 (14.2)58 (12.9)59.5 (16.5)0.63Diagnosis0.66Rheumatoid arthritis81 (90)52 (89.6)29 (90.6)Psoriatic arthritis6 (6.7)4 (6.8)2 (6.2)Other3 (3.3)2 (3.4)1 (3.1)Treatment duration (months) – mean (SD)10.6 (6.9)11.9 (7.3)8.2 (5.5)0.02Prednisone (mg) – mean (SD)1.75 (3.2)1.20 (2.5)2.73 (4.1)0.03Monotherapy (%)46 (51.1)28 (48.2)18 (56.2)0.244Concomitant csDMARDs (%)44 (48.8)30 (51.7)14 (43.7)0.62Methotrexate (%)27 (30)17 (29.3)10 (31.2)Leflunomide (%)10 (11.1)8 (13.7)2 (6.2)Other (%)7 (7.7)5 (8.6)2 (6.2)Prior biologic treatment0.13None (%)9 (10)6 (10.3)3 (9.3)1-2 (%)42 (46.6)28 (48.2)14 (43.7)≥3 (%)39 (43.3)24 (41.3)15 (46.8)Survival rates when used as first or second line were 85% at 6 months and 70% at 12 months; when used as third line or further, 76% and 70%, respectively (graphic 1).Factors associated to tofacitinib discontinuation were treatment duration and baseline prednisone dose. In contrast concomitant csDMARD and number of previous biologics were not. Reasons for tofacitinib discontinuation were: lack/loss of efficacy 46.9%, adverse events 50% (including intolerance -22%- herpes zoster -16%-, other infections 12%) and others.Conclusion:Tofacitinib in our experience is mostly used in RA patients after biologic failure. Overall survival rate at 12 months was good regardless line of therapy. Adverse event rates were similar to other biologic treatments. Herpes zoster was the most common infectious AE.Graphic 1:References:[1]Wollenhaupt J, Lee EB, Curtis JR, et al. Safety and efficacy of tofacitinib for up to 9.5 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study. Arthritis Res Ther. 2019;21(1):89.Disclosure of Interests:Christian Y Soleto: None declared, Belén Serrano Benavente: None declared, Luis A Torrens Cid: None declared, Julia Martínez-Barrio Consultant of: UCB Pharma, Juan Molina Collada: None declared, Javier Rivera: None declared, Teresa González: None declared, Indalecio Monteagudo: None declared, Carlos Gonzalez Consultant of: Gilead, Janssen, Novartis,, Speakers bureau: Abbvie, Celgene, Gilead, Janssen, Novartis, Pfizer, Roche, Isabel Castrejon: None declared, Jose-Maria Alvaro-Gracia Grant/research support from: Abbvie, Elli-Lilly, MSD, Novartis, Pfizer, Consultant of: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB, Paid instructor for: Elli-Lilly, Pfizer, Roche, Speakers bureau: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, Gedeon Richter, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB

Background It is accepted that donor-derived immunity is transferred with allogeneic bone marrow transplantation (BMT)1. Objectives To show evidence of the transfer of systemic sclerosis by allogeneic BMT. Methods In this report we describe a pacient with T acute lymphoblastic leukaemia who underwent BMT and developed systemic sclerosis. Results 34-year-old man in complete remission from a T acute lymphoblastic leukaemia treated with allogeneic BMT from his mother in february of 2012. First seen in november 2017 for digital ulcers that appeared one year before. He presented two necrotic ulcers: one on the second finger of the left hand and other on the third finger of the right hand (IMAGE 1). He was admited to receive intravenous prostaglandins and complete the study. After the BMT he developed Raynaud’s phenomenon and in the examination he only presented facial and corporal telangiectasia, attributed before to chronic graft versus host disease (cGVHD). The analysis showed ANA 1/640 centromere pattern, anticentromere antibodies, reumatoid factor (RF) (652 UI/mL) and C3 of 86.4 mg/dL. Previously to the BMT he had negative ANA, but we do not know the rest of the previous autoimmunity. On the videocapillaroscopy we observe an active scleroderma pattern (IMAGE 2–3). He was diagnosed with systemic sclerosis based on Raynaud’s phenomenon, digital ulcers, anticentromere antibodies and abnormal nailfold capillaries. He had not familiar background of connective tissue diseases, but his mother presented Raynaud’s phenomenon since she was thirty. So we studied her. She presented facial telangiectasia, puffy fingers and fingertip pitting scars and the same autoantibodies: ANA 1/320 centromere pattern, anticentromere antibodies, RF (159 UI/mL) and consumption of C3 (74.3 mg/dL) and C4 (7.6). We do not have previous autoimmune studies of her. On the videocapillaroscopy we observed a late scleroderma pattern (IMAGE 4–5). She was also diagnosed with systemic sclerosis, based on Raynaud’s phemomenon, puffy fingers, fingertip pitting scars and facial telangiectasia, anticentromere antibodies and abnormal naifold capillaries. Conclusions Experimental animal studies and human clinical reports have described the transfer of immune-mediated diseases from affected donors to unaffected recipients, because of that the importance of screening this diseases in the donor before a BMT2. To our knowledge, this will be the first described case of transmission of systemic sclerosis by this mechanism. However, other explanations should also be taken into consideration. This include recipient’s own persistent intrathymic lymphocyte population that may produce autoantibodies and autoimmunity in the context of cGVHD. However, this last hypothesis is not supported since there is a familiar background and presence of anticentromere antibodies. References [1] Sherer, Y. and Shoenfeld, Y. (1998). Autoimmune diseases and autoimmunity post-bone marrow transplantation. Bone Marrow Transplantation. [2] Hough, R.(2005). Haemopoietic stem cell transplantation in autoimmune diseases: a European perspective. British Journal of Haematology. Disclosure of Interest None declared