Objective To compare the long-term disease state, in terms of activity and damage, of children with juvenile idiopathic arthritis (JIA) who had their disease onset in methotrexate (MTX) or biologic eras. Methods Patients were included in MTX or biologic era cohort depending on whether their disease presentation occurred before or after January 2000. All patients had disease duration ≥ 5 years and underwent a prospective cross-sectional assessment, which included measurement of disease activity and damage. Inactive disease (ID) and low disease activity (LDA) states were defined according to Wallace, JADAS10, and cJADAS10 criteria. Articular and extraarticular damage was assessed with the Juvenile Arthritis Damage Index (JADI). Results MTX and biologic era cohorts included 239 and 269 patients, respectively. Patients were divided in the “functional phenotypes” of oligoarthritis and polyarthritis. At cross-sectional visit, patients in the biologic era cohort with either oligoarthritis or polyarthritis had consistently higher frequencies of ID and LDA by all criteria. The measurement of disease damage at cross-sectional visit revealed that the frequency of impairment of > 1 JADI-Articular items was higher in MTX than in biologic era cohort (17.6% versus 11% in oligoarthritis and 52.6% versus 21.8% in polyarthritis). Likewise, frequency of involvement of > 1 JADI-Extraarticular items was higher in the MTX than in the biologic era cohort (26.5% versus 16.2% in oligoarthritis and 31.4% versus 13.5% in polyarthritis). Conclusion Our study provides evidence of the remarkable outcome improvement obtained with the recent therapeutic advance in JIA.

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

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BackgroundIt is accepted that donor-derived immunity is transferred with allogeneic bone marrow transplantation (BMT)1.ObjectivesTo show evidence of the transfer of systemic sclerosis by allogeneic BMT.MethodsIn this report we describe a pacient with T acute lymphoblastic leukaemia who underwent BMT and developed systemic sclerosis.Results34-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.ConclusionsExperimental 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 disea...