BackgroundTofacitinib is a new small molecule, Janus kinase 1 and 3 inhibitor, interfering with the JAK-STAT signaling pathway. The JAK-STAT transmits the extracellular information in the cell nucleus, influencing DNA transcription. Its efficacy and safety in Rheumatoid Arthritis (RA) has been demonstrated in different phase II, III and long-term clinical studies. It has been approved in Argentina for the treatment of patients with moderate to severe rheumatoid arthritis RA with failure to conventional DMARDs.ObjectivesTo communicate real world safety data from patients with RA under treatment with Tofacitinib.MethodsA retrospective, descriptive study from patients with RA (ACR/EULAR2010) under treatment with Tofacitinib from September 2014 to December 2016 was conducted. Medical records from patients being treated with Tofacitinib were reviewed and demographic data were recorded. Comorbidities, concomitant treatments, and reported adverse effects were documented.Results62 patients were treated with Tofacitinib. 53 were female and 9 were male, with a mean age of 57.91±14.72 years and average disease duration of 140.09±130.83 months. 18 patients (29%) had at least one comorbidity, the most frequent being hypertension (77%).Of the 62 patients studied, 54 (87%) had established RA (duration of illness greater than 24 months) and 8 patients (13%) with early RA (less than 24 months).In 54 patients Tofacitinib was indicated in combination with another DMARD (87%), and only 6 patients received treatment as monotherapy.The most commonly used DMARD in combination therapy was methotrexate (MTX) in 92.5%Treatments were indicated by failure to MTX or other conventional DMARDs, 12/62 treatments were indicated by failure to treatment with 1 biological DMARD and 13/62 treatments were indicated by failure to two or more biological DMARDs.The maximum exposure time was 21 months.During the time of exposure to Tofacitinib the following adverse events were observed: Herpes Zoster infection 2 cases (monometameric, no visceral involvement in unvaccinated patients), upper airway infection 1 case, transient increase in liver enzymes 1 case, peripheral facial paralysis 1 case, tachycardia 1 case. There were no cases of serious infections, opportunistic infections, cytopenias, dyslipidemia, or increased CPK.Three patients discontinued Tofacitinib: one due to tachycardia, another case peripheral facial paralysis and another case due inefficacy.ConclusionsMost patients received combined treatment with DMARDs being the most commonly used Methotrexate. There were no cases of serious infections, opportunistic infections, cytopenias or dyslipidemia. The use of Tofacitinib in RA patients in our cohort showed a comparable safety profile with long-term extension studies in the treatment of patients with RA diagnosed with failure of conventional or biological DMARDs.Disclosure of InterestNone declared

BackgroundIdiopathic inflammatory myopathies (IIMs) include a group of muscular diseases characterized by the presence of muscle inflammation. The mortality of the IIMs has been estimated between 13 and 50%.ObjectivesTo evaluate mortality rate and associated factors in patients with IIMs.MethodsRetrospective, observational study, where patients with IIMs (Bohan & Peter 1975) were included. Data were obtained from medical records from patients with myopathy (Increase CK, muscle weakness, cutaneous involvement, interstitial lung involvement) evaluated in a reference rheumatology center of Argentina (1992–2016). Descriptive statistics were performed. Chi2 test, Student's test or Mann Whitney as appropriate multivariate logistic regression analysis.ResultsFrom 102 patients evaluated 89 enter the study, 73% were female. Mean age at diagnosis 48±14 years. Clinical Manifestations: Skin involvement 77% (erythema Heliotrope 51%, rash on the neck and V-sign 60%, back and shoulders 50%, photosensitivity 60%, Gottron's papules 50%, pruritus 33%, erythema peri nail 21%), pulmonary involvement 19% Raynaud 28%, muscle weakness 86%, muscle weakness of the neck 33%, respiratory muscles 13%, myalgias 60% and dysphagia 53%.Muscle biopsy: performed in 36/89 with pathological findings in 83%, electromyogram performed in 35%. Intensive care unit admission 14/89 (16%). Laboratory: raised CPK 68% with an mean value 3527 IU/ml, raised Transaminase 60%, ANA positive 65%, SSA/RO 25%, Jo1 4.4%, RNP 7%, increased CRP 28% and ERA 59%.Clinical Subtypes IIMs: Dermatomyositis (DM): 61%, Antisynthetic syndrome (AS): 6%, Myopathy associated with connective tissue disease: 19%, Associated with statins: 4, 4%, Polimyositis: 10%. Association with neoplasia was observed in 15%. Treatments: Corticoids pulses 21%, corticoids 97% (mean starting dose 45 mg meprednisone), methotrexate 77%, hydroxychloroquine 36%, azathioprine 30%, cyclophosphamide 16%, intravenous immunoglobulin 15%, biological 10% and cyclosporine 3%.Mortality was 22.5% (20/89 patients), CI95 (14.3–32.5). Mean time from diagnosis to the event was 18 months. The primary cause of death was sepsis 14/20 (70%).Univariate analysisVariablesMortality (Odds Ratio)95% IC Male sex31,03–8,4P<0,039Respiratory muscle weakness5,47IC: 1,4–20,59p<0,007ANA positive61,27–27P<0,01Neoplasms3,81,1–1,3pP<0,026Glucocorticoid pulses5,71,81–17,8P<0,001Intravenous immunoglobulin3,671,06–12,6P<0,03Serious infections174,6–61,5P<0, 0000012Multivariate analysis of logistic regressionVariableORIC (95,0%) p Malignant neoplasm8,7851,22962,797 0.03 Serious infections69,16810,079474,666 0.0001 Glucocorticoid pulses3,7450,63522,0920.145Male sex5,8991,14130,504 0.034 Intravenous immunoglobulin0,9060,1008,2170.93Respiratory muscle weakness0,5240,0505,5270.59ANA positive4,2470,63828,2590.135ConclusionsMortality of patients with inflammatory myopathies was 22%, and the primary cause was infectious. In the analysis of multiple variables, male sex, presence of neoplasms and serious infectious complications were significantly fac...

Methods: We included a cohort of patients with diagnosis of early RA of less than 2 years of disease duration who not respond to MTX monotherapy, according to medical judgment, and added step-up combination with LEF. Data were collected every 3 months, including sociodemographic characteristics, functional status, disease activity and treatment. The primary outcome was the time to remission with the combined therapy, defined according to disease activity index of 28 joints (DAS28). Combination treatment failure was defined as not achieving remission. Time of outcome was assessed from date of the start of MTX plus LEF combination to date of remission or last follow-up. The Kaplan-Meier product limit method was used to estimate the probability of each outcome. Results: A total of 106 patients were included. The median disease duration was 4 (IQR 2-8) months. Median followup was 34 ± 18 months (300 patients-year). Mean age was 50 ± 12 years and 83% were female. At the time of LEF addition, 95 (90%) of patients were not in remission. During follow-up, 47 (50%) achieved clinical remission at a median time of 8 months. The rest of the patients failed to achieve remission. The overall probability of remission per patients-months of follow-up was 0.49. Twenty seven out of 47 patients (58%) were still in remission at the last follow up visit (median follow-up after first remission=19 months).