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Background Serum anti-mitochondrial antibodies (AMA) are the hallmark of primary biliary cholangitis (PBC) and are identified also in systemic sclerosis (SSc) patients with limited variant and serum anti-centromere antibodies (ACA). Indirect immunofluorescence (IIF) shows the cytoplasmic pattern that characterizes AMA positivity, but it is usually performed when a suspect of PBC is already present. Protein-immunoprecipitation (IP) and IP-Western Blot (WB) have the advantage of 1) identify AMA in an early screening phase, before the onset of PBC and liver function abnormalities; 2) detect the proteins that constitute the pyruvate dehydrogenase complex (PDC) complex (the subunits E1α, E1β, E2/E3, and E3BP) which seem to be associated to different risk of PBC onset. Objectives To determine the prevalence and clinical significance of the PDC complex subunits in AMA positive SSc patients with and without PBC. Methods Sera from 279 consecutive patients with rheumatic disease (146 with SSc, 77 with undifferentiated connective tissue disease –UCTD-, and 56 with polymyositis/dermatomyositis -PM/DM) were tested by protein-IP for the screening of serum autoantibodies. In 58/279 (21%) sera we report a complete or partial protein-IP pattern of 75-50-40-34kD bands corresponding to the 4 proteins of the PDC complex recognized by AMA. In these sera we performed IIF and IP-WB to confirm the identity of these bands, by using established protocols. Clinical charts were used to analyze clinical and laboratory data for possible statistical correlation. Results In 15/58 (26%) patients with protein-IP AMA pattern we confirm a diagnosis of PBC, and all of them had a diagnosis of SSc without additional rheumatic disease. Their expression of the PDC subunits is variable by IP-WB (Figure panel A), but this variability is not associated with specific clinical and laboratory features. In the 42/58 (72%) cases with AMA protein-IP pattern but without clinical and histological evidence of PBC, the E2 component of the PDC was detected in all except one patient, while the expression of the other proteins of the PDC was significantly less represented, i.e. E3BP in 14/42 (33%), E1β in 13/42 (31%), E3 in 6/42 (14%), and E1α in 4/42 (10%) patients. The IIF analysis on Hep2 cells of AMA positive samples also shows different patterns of expression, which spans from cytoplasmic positive staining with a reticular pattern in AMA positive sera for all the PDC proteins recognized by AMA, to cytoplasmic speckled pattern in cases with incomplete expression of PDC antigens (Figure panel B). So far, no specific clinical correlation was identified in these patients, as they did not have a diagnosis of PBC or other autoimmune liver disease or manifested elevated liver function tests. Conclusion The expression of the PDC antigenic components is variable both in SSc patients with AMA positive PBC and in SSc patients AMA positive without PBC or altered liver function tests, but we could not identify a clinical significance of this variability. It may be necessary to maintain a strict follow-up of these patients and to perform longitudinal studies to determine the prognostic value of this variable expression of PDC components in the onset of PBC. References [1] Fujimoto M, et al. Arthritis Rheum. 1995Jul; 38(7): 985-9 [2] Ceribelli A, et al. J Immunol Methods. 2018Jan; 452: 1-5 Disclosure of Interests Angela Ceribelli: None declared, Natasa Isailovic: None declared, Carolina Gorlino: None declared, Elena Generali: None declared, Maria De Santis: None declared, Giacomo Maria Guidelli: None declared, Marta Caprioli: None declared, Piercarlo Sarzi-Puttini: None declared, Minoru Satoh: None declared, Carlo Selmi Grant/research support from: AbbVie, Janssen, MSD, Novartis, Pfizer, Consultant for: AbbVie, Alfa-Sigma, Biogen, Bristol-Myrs Squibb, Celgene, Eli-Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB, Speakers bureau: AbbVie, Alfa-Sigma, Biogen, Bristol-Myrs Squibb, Celgene, Eli-Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB

Background: Baricitinib is an oral selective JAK1/2 inhibitor recently approved in the EU for the treatment of rheumatoid arthritis (RA). No real-life data are available about its efficacy and safety. Objectives: To investigate the efficacy and safety profiles of baricitinib in a real-life setting. Methods: We performed a multicenter prospective observational study on adult RA patients starting JAK inhibitors between 12/2017 and 12/2018. Demographic and clinical data as well as laboratory values and adverse events were collected at baseline and after 12 and 24 weeks. Disease activity was measured by DAS28-CRP at baseline, after 12 and 24 weeks. Results: We obtained data from 150 patients with RA (women 116 – 77.3%; median age 60 years, inter-quartile range IQR 54-68; median disease duration 10 years, IQR 4-18) treated with baricitinib 2 or 4 mg QD, however only 2/150 (1.3%) at the reduced dosage. At the time of database lock 95/150 (63%) patients have completed the 12 weeks follow-up, 38/150 (25%) patients have completed the 24 weeks follow-up. Baricitinib was started after at least one conventional synthetic DMARD in all 148/150 cases (99%), being in all of cases methotrexate, while was started prior to a biologic DMARD in 57 (38%) patients. It was prescribed as a second line in 17/93 (18%) patients, third in 27 (29%), fourth or higher in 49 (53%). Baricitinib was prescribed as monotherapy in 57/150 (38%) patients, while combined with methotrexate in 65/150 (43%), at a median dosage of 15 mg/week. Oral corticosteroids were used by 105/150 (70%) patients, at a median dosage of 5 mg/day. Mean DAS28-CRP at baseline was 4.92 (standard deviation 1.22), with 65 (43.3%) patients having a DAS28-CRP>5.1. At both 12 and 24 weeks, a significant reduction of disease activity scores was observed (DAS28-CRP mean 3.07, SD 1.36, and 2.85, SD 1.35, respectively; p values Conclusion: In our real-world dataset, baricitinib is effective in reducing RA disease activity, after 12 weeks, being generally well-tolerated with few severe adverse events. Disclosure of Interests: Giacomo Maria Guidelli: None declared, Elena Generali: None declared, Chiara Bazzani: None declared, Roberto Gorla: None declared, Garifallia Sakellariou: None declared, Massimiliano Limonta: None declared, Maria Sole Chimenti: None declared, Roberto Perricone: None declared, Edoardo Conticini: None declared, Bruno Frediani: None declared, nicola boffini: None declared, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI., Marta Riva: None declared, Maria Rosa Pozzi: None declared, Rosa Daniela Grembiale Grant/research support from: BMS, Consultant for: JANSSEN, CELGENE, Speakers bureau: PFIZER, JANSSEN, BMS, NOVARTIS, Teodora Serban: None declared, Gerolamo Bianchi Consultant for: Alfa-Sigma, Amgen, BMS, Celgene, Medac, UCB, Speakers bureau: Abbvie, Abiogen, Alfa-Sigma, Amgen, BMS, Celgene, Carlo Selmi Grant/research support from: Abbvie, Janssen, MSD, Novartis, Pfizer, Consultant for: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB, Speakers bureau: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB

Background Systemic sclerosis (SSc) is an autoimmune fibrotic disease characterised by variable clinical manifestations based on the predominant organ involvement. With the exceptions of acute fulminant myocarditis with pericardial effusion and heart failure, myocardial involvement in SSc is clinically silent until arrhythmias appear, while representing the major cause of sudden death or atrio-ventricular (AV) blocks in SSc. There are no reliable screening algorithm to discriminate myocardial involvement nor established treatments. Objectives To identify early/clinically silent myocardial involvement in SSc and define a possible treatment. Methods We used Holter electrocardiography (ECG) to investigate our cohort of patients with SSc (n=221, all fulfilling the ACR classification criteria) for ventricular ectopic beats (VEB)/AV blocks/unexplained tachycardia as sensitive signs of myocardial involvement. In 24 patients (women 23%–95.8%, anti-centromere-ACA 16%–66.6%, anti-topoisomerase-aScl70 3%–12.5%, anti-RNA polimerase III 3%–12.5%, anti-Ku 2%–8.3%, limited skin disease-lSSc 12%–50%, diffuse skin disease 5%–20.8%, sine scleroderma 7%–29.2%, median age 66.5 years, IQR 57.8–72.5), never treated with anti-fibrotic agents, we performed heart magnetic resonance (hMR) searching for myocardial oedema (on T2 STIR sequences, using the signal ratio between myocardium and skeletal muscle with a cut-off value of ≥1.9 for oedema) or fibrosis (presence of any late gadolinium enhancement (LGE) with intramyocardial or subepicardial pattern). Patients with myocardial oedema at hMR were treated with mycophenolate mofetil (MFM) 2 g/day or with azathioprine (AZA) 100 mg/day and underwent a control hMR after six months. Results In 10/24 (42%) of the SSc cases with Holter ECG alterations (8 VEB, 1 tachycardia, 1 type II AV block) we observed SSc myocardial involvement at hMR. In more detail, 6 patients had myocardial oedema at T2 STIR sequences (including cases as follows: 1 aScl70-positive with lSSc and lung fibrosis, 2 ACA-positive with lSSc, 3 ACA-positive sine scleroderma), and 4 only fibrosis (1 Scl70-positive with lSSc and lung fibrosis, 1 ACA-positive with lSSc, 1 ACA-positive sine scleroderma, 1 anti-Ku-positive sine scleroderma). At 6 months of medical treatment, myocardial oedema disappeared in 3 patients treated with Aza and in 1 treated with MFM, the additional 2 patients are still receiving MFM treatment at the time of analysis. Conclusions We observed that 42% of patients with SSc and minor arrhythmias on 24 hour Holter ECG have clinically silent myocardial involvement at hMR; those with potential reversible disease (oedema rather than fibrosis) favourably respond to immunosuppressants. Detectable serum ACA and the absence of skin involvement are over-represented in this subgroup of patients. Disclosure of Interest None declared

Background Psoriatic arthritis (PsA) often affects women of reproductive age. Secukinumab (SEC), a monoclonal antibody against interleukin-17A is effective in contrasting the progression of articular and cutaneous manifestations of PsA but has not been extensively studied in pregnancy, despite 84 cases of accidental exposure reported with reassuring safety outcomes. Objectives To evaluate the maternal and fetal outcomes in women with PsA exposed to SEC during pregnancy. Methods During a 10 months observational period, we enrolled 6 patients, treated by SEC 150 mg subcutaneously every month after weekly induction. All of them stopped the treatment by the time pregnancy test turned positive. All women had previously been counselled about contraceptive methods adoption and the potential risk of becoming pregnant during SEC administration, signing an informed consent. We collected demographic and clinical data of both patients and babies, with a peculiar focus on maternal-fetal safety issues. APGAR scores at 1 min (APGAR1) and 5 min (APGAR5) from delivery were recorded. Results We observed 6 pregnancies from 6 mothers (4 of European, 1 Asian and 1 Latin-American ethnicity). Patient mean age at conception was 336±131 months; disease duration, 62±27 months; pre-conceptional exposure, 46±9 weeks; the (estimated) post-conceptional exposure 7±2 weeks. No major gestational complications were reported. One mother consulted the Emergency Department for a syncopal episode, but after a routine evaluation and an observation of 6 hours, was discharged; her pregnancy was otherwise unremarkable. Four girls (mean weight: 3170±200 g) and 2 boys (mean weight: 3460±60) were born. Mean gestational age was 38±2 weeks; 3 vaginal deliveries (1 oxytocine-induced for scarce dilation) and 3 caesarean sections were observed. The APGAR scores were above 8, excepting for an APGAR1 of 6 (born with caesarean section), then turned on 10 at APGAR5. Results are summarised on table 1. DAPSA, for the whole population, was under 4 (remission) at conception, and remained stable after delivery. Conclusions The present study, despite the limited number of observations, represents the first report on pre-conceptional exposure to SEC. The available data, due to the lack of controlled studies, place the drug’s use on FDA “B” category. Of note, SEC failed to cause teratogenicity, when administered throughout the whole pregnancy in a study conducted on primates (Cynomolgus monkeys). The limited knowledge on human beings suggests, nevertheless, not to administer SEC during pregnancy, unless a clear benefit overwhelm the potential risk. SEC, in conclusion, seems to have an acceptable safety profile, even when accidentally taken in the very first pregnancy phase. Reporting the cases of pregnancy exposures, as recommended by the ongoing Producer’s policy, is the only way that would allow to confirm, or reject, this statement. A long-term follow-up of the mother and the offspring health, similarly, is needed. References [1] Mouyis MA, et al. J Rheumatol2017;44:1. [2] Skorpen CG, et al. Ann Rheum Dis2016;75(5):795–810. [3] Warren R, et al. P2134 25th EADVC2016, Vienna (AUT). [4] Cosentyx® Core Data Sheet. Version 1.1. Disclosure of Interest None declared

Background Skin psoriasis affects 3% of the general population and as much as 20%–40% of patients will develop psoriatic arthritis (PsA), with the two conditions representing a clinical and immunological continuum within a prototype for chronic inflammation. Different from most rheumatic diseases, no serum autoantibody is associated with PsA, and there are currently no biomarkers for an early diagnosis and prediction of PsA onset in psoriasis, frequently causing a delayed diagnosis. Monozygotic twins discordant for psoriasis/PsA represent a unique setting to investigate the influence of environmental and stochastic factors on disease phenotype. Through a high-throughput proteomic analysis (SomaLogic) we have previously identified a set of 13 proteins differentially expressed in the serum of monozygotic twins discordant for psoriatic disease. Objectives To validate serum proteomic biomarkers of psoriatic disease using commercially available ELISA in monozygotic twins and in unrelated patients with psoriasis or PsA. Methods Our study included sera from our cohort of monozygotic twins previously described and from 70 unrelated patients with psoriatic disease (psoriasis without PsA 34%–49%, PsA with/without psoriasis 36%–51%; women 46%, median age 52 years, interquartile range 41–59) followed at Humanitas Research Hospital, and 25 healthy subjects (52% women, median age 52 years, IQR 44–62). Candidate serum proteomic biomarkers obtained by SomaLogic analysis were validated using commercially available ELISA kits and proteins are herein anonymized due to a pending patent request. Results We found a significant correlation between SomaLogic results in monozygotic twins and ELISA results in unrelated psoriatic cases in the serum levels of 2 proteins (figure 1), which are involved in inflammatory and immune response, and one has been previously reported in psoriatic plaques. Four proteins showed a significantly different expression between psoriasis and PsA versus controls, in particular two proteins have a potential role in disease pathogenesis, as protein #1 acts as cell-surface receptor and regulates differentiation, proliferation and survival of dendritic cells, while protein #2 is involved in regulation of UV radiation-induced apoptosis and protein folding. Conclusions Two serum proteomic biomarkers, previously identified in a cohort of monozygotic twins discordant for psoriatic disease, can discriminate psoriatic disease, thus representing potential biomarkers of disease and possibly playing a pathogenetic role in disease. Disclosure of Interest None declared

Background Systemic sclerosis (SSc) is characterized in virtually all patients by anti-nuclear antibodies (ANA) with anti-centromere (ACA), anti-topoisomerase I (ant-Scl70), and anti-RNA polymerase III antibodies identifying patient subgroups. However, there are no reliable biomarkers predicting SSc susceptibility and internal organ involvement. Objectives We aimed to identify serum protein biomarkers associated with SSc and interstitial lung disease (ILD), using a highly multiplexed proteomic technology. Methods We analyzed serum samples of 3 patients with SSc and ILD (2 limited SSc: one ANA positive and one anti-Scl70 positive, and one diffuse SSc anti-Scl70 positive), 3 patients with SSc and no ILD (ACA positive limited SSc), and 4 healthy controls. All subjects were women and age matched. Serum proteomics profiling was performed using the SOMAscan platform (SomaLogic, Inc., Boulder, CO, USA). Statistical analysis included Student9s t-test and were performed using the SomaSuite software (SomaLogic, Boulder, CO, USA). Results Proteomic analysis identified 33 proteins which differentiate SSc from HC and 9 proteins which differentiate SSc patients with and without ILD. Compared to healthy controls, SSc cases showed an altered expression of proteins involved in extracellular matrix formation and cell-cell adhesion, angiogenesis, and lymphocyte recruitment, activation, and signaling, while an overall inhibition of neutrophil function was noted. An interferon and IL-1 signatures were also found. Patients with SSc and ILD manifested increased protein levels related to intracellular signaling and cell cycle, along with an increase of monocyte chemoattractants and ligands for the leukocyte adhesion compared to SSc without ILD. We further observed a decrease in B cell stimulating factor and IL-22 signaling in SSc with ILD. Conclusions Serum proteomic profiles can differentiate SSc from healthy controls and SSc patients with and without ILD; moreover, our results identify biomarkers with a putative pathogenetic significance. Disclosure of Interest None declared