Background: In the last years, there was a dramatic increase of advanced DMARDs for psoriatic arthritis (PsA). There are many b/tsDMARDs with different mechanisms of action (MoA) to consider after the failure of the first advanced line of therapy. As a consequence, the rheumatologists can implement a cycling (same MoA) or swap strategy. Objectives: The aim of this real world based study is to investigate if, after the failure of a TNF inhibitor (TNFi), another TNFi or an interleukin 17 inhibitor (IL17i) is the most effective choice (from a clinical practice point of view). Methods: For this retrospective observational multicenter study, PsA (according to CASPAR criteria) patients who failed a first line TNFi and subsequently received a TNFi or IL17i were enrolled. For each subject, the following characteristics were recorded: anamnestic (age, sex) and disease-related (duration, presence of axial PsA, DAPSA, advanced therapies carried out, csDMARDs and steroids association) data, treatment duration and cause of failure. Patients were divided in two groups according to the strategy used: cycling (i.e. from TNFi to TNFi) (CG) or swap (i.e from TNFi to IL17i) (SG). The Kaplan-Meier curves compared the effectiveness of the two strategies, while multivariable Cox analysis (stepwise) identified the risk factors affecting treatment retention rate. Results: 347 subjects were enrolled (M:F 160:187; age 56 years IQR 47-63). In CG and SG were 217 and 130 patients, respectively. The 5 years retention rate in SG was higher than in CG (57,8% vs 45,2%; p=0.1) (Figure 1). Taking into account the whole cohort, the factors predictive of treatment interruption were DAPSA (HR 1.03 CI95% 1.01-1.05; p=0.0009) and swap strategy (HR 0.49 CI95% 0.27-0.90; p=0.02). Conclusion: The swap strategy (i.e. from TNFi to IL17i) was the best choice in PsA patients who failed the first line of advanced treatment. This finding supports the hypothesis that changing the MoA can improve the chances to identify the most effective PsA treatment. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Alarico Ariani Amgen, Janssen, Federica Lumetti: None declared, Simone Parisi: None declared, Olga Addimanda: None declared, BERND RAFFEINER: None declared, Alberto Lo Gullo: None declared, Rosario Foti: None declared, Antonella Farina: None declared, Francesco Girelli: None declared, Maddalena Larosa Abbvie, Amgen, UCB, Romina Andracco: None declared, Marino Paroli: None declared, Patrizia Del Medico: None declared, Aldo Molica Colella: None declared, Marta Priora: None declared, Aurora Ianniello: None declared, Francesca Ometto: None declared, Elena Bravi: None declared, Alessandra Bezzi: None declared, Palma Scolieri: None declared, Rosetta Vitetta: None declared, Alessandro Volpe: None declared, Massimo Reta: None declared, Mirco Magnani: None declared, Elisa Visalli: None declared, Giorgio Amato: None declared, Francesco De Lucia: None declared, Roberta Foti: None declared, Simone Bernardi: None declared, Dario Camellino: None declared, Gerolamo Bianchi: None declared, Natalia Mansueto: None declared, Giulio Ferrero: None declared, Rosalba Caccavale: None declared, Veronica Franchina: None declared, FRANCESCO MOLICA COLELLA: None declared, Gilda Sandri: None declared, Carlo Salvarani: None declared, Dilia Giuggioli: None declared, Francesca Serale: None declared, Valeria Nucera: None declared, Cecilia Giampietro: None declared, Eleonora Di Donato: None declared, Giuditta Adorni: None declared, Gianluca Lucchini: None declared, Daniele Santilli: None declared, Ilaria Platè: None declared, Eugenio Arrigoni: None declared, Maria Cristina Focherini: None declared, Fabio Mascella: None declared, Vincenzo Bruzzese: None declared, Enrico Fusaro: None declared, Maria Chiara Ditto: None declared, Alessia Fiorenza: None declared, Guido Rovera: None declared, Antonio Marchetta: None declared, Andrea Becciolini: None declared.Figure 1

Background: Since 2022 clinicians have been consistently aware by the European Medical Agency (EMA) of prescribing Jak-inhibitors (JAKi) after assessing a risk/benefit ratio, especially in patients with rheumatoid arthritis (RA)1. Nevertheless, during the last years, uptake of selective JAKis has consistently increased, although limited data regarding differences between selective and unselective JAKis are available to date. Objectives: To assess differences between selective and unselective JAKIs in terms of discontinuation's rate. Methods: In this retrospective study, all patients with RA treated with JAKis were prospectively enrolled from 22 Italian centres since 2017. Selective JAKi included filgotinib and upadactinib, whereas unselective JAKIs included tofacitinib and baricitinib. Reasons of discontinuation rates were: primary and secondary inefficacy, remission, adverse events [deaths, infections, onset of major cardiovascular events-(MACEs)-, deep vein thrombosis-(DVT)-, pulmonary embolism-PE, cancers]. The following variables were collected at JAKi's first prescription: sex, age, disease duration (years), smoking, BMI, comorbidities (diabetes, hypertension, dyslipidaemia, cancer, major cardiovascular events-MACEs), positive RF/ACPA, associated cDMARDs, prednisone and prednisone dosage (mg/day), previous use of JAKi, time to discontinuation (days), reasons of discontinuation, discontinuation rates for each JAKi, line of treatment, DAS28-ESR, b/tsDMARDS naïve patients. Results: 693 patients were included in study. 395 (57%) patients received baricitinib, 150 (21.7%) tofacitinib, 94 (13.6%) upadacitinib and 54 (7.8%) filgotinib. The majority of patients were treated with unselective JAKi (78.6% vs 21.4% of selective JAKi). 157 (22.7%) patients discontinued JAKI after a median time of 334 days (IQR 152-869). Details of discontinuation rates for each drug are reported in Table 1. Reasons of discontinuation were primary inefficacy (n=55, 7.9%), secondary inefficacy (n=29, 4.2%), infections (n=9, 1.3%), PE/DVT (n=6, 0.9%), cancer (n=6, 0.9%), deaths (n=2, 0.3%), and other causes (n=7, 3.5%) including remission status in 1 patient. No MACEs were observed in this cohort during the follow up period, although 348 patients (50.2%) had at least one comorbidity at baseline. Notably, both VZV infection (n=3) and DVT/PE (N=6) occurred in patients on treatment with baricitinib. Among 157 patients who discontinued JAKi, a statistical difference between selective and unselective JAKIs was found (15.9% on selective JAKi vs. 84.1% on unselective JAKI, p value <0.001 at log-rank test, Figure 1). Finally selective JAKi were withdrawn before unselective JAKi (median 173 days, IQR 129-22 vs median 401.5 days, IQR 173.5-981). Conclusion: In this real-world cohort, only a minority of patients discontinued JAKi (22.7%). Primary and secondary inefficacy were the most common reasons of JAKi's withdrawal. All TVP/PE and VZV infections occurred in the baricitinib group, probably due to different overall time of drug's exposition. Finally, selective JAKis were discontinued earlier than unselective JAKi. REFERENCES: [1] Smolen JS, et al. Ann Rheum Dis 2023. Acknowledgements: NIL. Disclosure of Interests: Maddalena Larosa UCB, ABBVIE, AMGEN, Dario Camellino AStrazeneca, Boerhinger Ingelheim GSK, and Janssen, Andrea Becciolini: None declared, Eleonora Di Donato: None declared, Giuditta Adorni: None declared, Gianluca Lucchini: None declared, Daniele Santilli: None declared, Eugenio Arrigoni: None declared, Elena Bravi: None declared, Ilaria Platè: None declared, Alessandra Bezzi: None declared, Alessandra Bezzi: None declared, Maria Cristina Focherini: None declared, Fabio Mascella: None declared, Vincenzo Bruzzese: None declared, Palma Scolieri: None declared, Simone Parisi: None declared, Maria Chiara Ditto: None declared, Enrico Fusaro: None declared, Viviana Ravagnani: None declared, Guido Rovera: None declared, Alessia Fiorenza: None declared, Rosetta Vitetta: None declared, Antonio Marchetta: None declared, Alessandro Volpe: None declared, BERND RAFFEINER: None declared, Eleonora Celletti: None declared, Myriam Di Penta: None declared, Emanuela Sabatini: None declared, Francesco Cipollone: None declared, Francesca Ometto: None declared, Cecilia Giampietro: None declared, Valeria Nucera: None declared, Aurora Ianniello: None declared, Francesca Serale: None declared, Marta Priora: None declared, Dilia Giuggioli: None declared, Carlo Salvarani: None declared, Gilda Sandri: None declared, Federica Lumetti: None declared, FRANCESCO MOLICA COLELLA: None declared, Veronica Franchina: None declared, Aldo Molica Colella: None declared, Patrizia Del Medico: None declared, Rosalba Caccavale: None declared, Marino Paroli: None declared, Giulio Ferrero: None declared, Natalia Mansueto: None declared, Romina Andracco: None declared, Matteo Colina: None declared, Simone Bernardi: None declared, Francesco Girelli: None declared, Antonella Farina: None declared, Roberta Foti: None declared, Francesco De Lucia: None declared, Giorgio Amato: None declared, Rosario Foti: None declared, Alberto Lo Gullo: None declared, Mirco Magnani: None declared, Olga Addimanda: None declared, Massimo Reta: None declared, Alarico Ariani AMGEN, JANSSEN.

Objective The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity. Methods We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted kappa co-efficient. Results Our analysis demonstrates that local, real-world detection of anti-Jo] is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo] antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo] antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods. Conclusion Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo] detection methods. In contrast, challenges persist for anti-non-Jo] identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo] antibodies.

Background Recently, the new class of drugs, namely targeted synthetic (ts) DMARDs, has broadened the possibilities of treating rheumatoid arthritis (RA). In particular, Janus Kinase inhibitors (JAKi) are used in RA and are currently represented by four drugs: baricitinib, tofacitinib, upadacitinib and filgotinib. One of the first to be used in Italy was baricitinib, a JAKi acting on JAK1 and JAK2. Objectives The aim of this study was to evaluate the clinical efficacy of baricitinib in a real-life setting in a cohort of RA patients. Methods This multicenter retrospective observational study included patients from 25 rheumatology centers diagnosed with RA and treated with baricitinib. The following were recorded for each patient: gender; age; duration of disease; presence of rheumatoid factor and anti-citrulline antibodies; concomitant treatment with conventional synthetic (cs) DMARDs; previous treatments with biological (b) or ts DMARDs. In order to evaluate the clinical efficacy, the retention rate was evaluated, calculated by means of the Kaplan-Meier method. The variables under examination were reported as frequencies and median with relative interquartile range. Results We included 478 patients of which 380 (79.5%) were female. 286 (60.1%) patients tested positive for rheumatoid factor (RF) and 264 (55,2%) for anti-citrulline antibody (ACPA). The parameters analyzed are shown in Table 1. 105 (22.0%) patients were treated with baricitnib as first line (after csDMARD), the remaining patients had failed at least one bDMARD and 9 (1.9%) also failed a tsDMARD. In 34,7% of cases baricitinib was used as monotherapy, the most frequently used csDMARD was methotrexate (29.2%). The median period of therapy was 674 days (298-1087).The survival rate at 6 months was 94.6%, at 12 months it was 87,9%, at 24 months was 81.7% and at 48 months was 53.4% (Figure 1).The main causes that led to the discontinuation of baricitinib therapy were: primary ineffectiveness (7,3%), secondary ineffectiveness (4.2%) and adverse events (3,7% 5 TEP/DVT). The concomitant steroid therapy seems to be a negative prognostic factor (HR 1,65 95% CI 1.03-2.63; p=0.035) as well as the line of therapy (HR 1.35 95% CI 1.15-1.58; p=0.000). Conclusion The efficacy of baricitinib in the treatment of RA in a real-life context appears consistent with what was reported by the pivotal studies. Furthermore, from this preliminary experience, seropositivity and combo therapy seems to not correlate with a better retention rate, while concomitant steroid therapy and line of treatment are a negative prognostic factor. References [1] Guidelli GM et al. Clin Exp Rheumatol. 2021 Jul-Aug;39(4):868-873.[2] Spinelli FR et al. Clin Exp Rheumatol. 2021 May-Jun;39(3):525-531. Acknowledgements: NIL. Disclosure of Interests None Declared.Figure 14 year retention rate of baricitinibTable 1CharacteristicsValueM:F98:380Age, median [IQR] yrs60 [51-70]Smokers, n (%) (**)YesFormerNo84 (18,8)76 (17,0)288 (64,2)Body Mass Index, median [IQR] kg/m^2 (*)24,8 [23,0-27,0]Disease Duration, median [IQR], months78 [32-163]RF positivity, n (%)286 (60,1)ACPA positivity, n (%)264 (55,2)SJC, median [IQR]5 [3-8]TJC, median [IQR]8 [4-12]ESR, median [IQR], mm/h33 [20-46]CRP, median [IQR], mg/dl1,3 [0,5-2,9]VAS Patient (0-100), median [IQR]70 [50-80]DAS28, median [IQR]5,4 [4,8-6,1]Line of treatment, [IQR]2 [2-3]Concomitant csDMARDs use, n (%)MTXLFNSSZHCQ140 (29,2)11 (2,3)3 (0,6)12 (2,5)Concomitant steroids use, n (%)237 (49,6)Steroids dose (PDN-Eq), median, mg/die5 [4-5]Prior bDMARDs use, n (%)TNFiIL6iIL1iCD20iCD80i164 (34,3)84 (17,6)08 (1,7)54 (11,3)Prior tsDMARDs use, n (%)Tofacitinib9 (1,9)Concomitant relevant disease, n (%)DiabetesHypercholesterolemiaMACEArterial HypertensionCancer36 (7,5)119 (24,9)28 (5,9)179 (37,4)24 (5,0)

Background Janus kinase (JAK) inhibitors have been approved for the treatment of Rheumatoid Arthitis (RA) and other systemic or organ-specific autoimmune diseases. Sustained remission or low disease activity are target treatments recomended by European League Against Rheumatism (EULAR) in RA patients [1]. Upadacitinib (UPA), a reversible, oral JAK inhibitor, has been engineered to have a greater selectivity for JAK1 vs JAK2, JAK3, and tyrosine kinase. In the Phase 3 SELECT clinical trial program, UPA has been shown to be effective and well tollerate in patients with RA [2]. However, data on the use of UPA in real-world clinical practice are limited. Objectives To evaluate UPA effectiveness in RA patients and to report the main reasons of suspension and the most relevant factor related to treatment persistence. Methods In 25 Italian rheumatological referral centers, all RA consecutive patients who received UPA were enrolled. Anamnestic data, treatment history and RA disease activity at baseline were recorded.The 6 and 12 months UPA retention rate was assessed with the Kaplan-Meier curve methods. The Cox analysis investigated the effect of age, sex, smoke habit, ACPA/RF presence, disease duration, DAS28-CRP, line of treatment, concomitant csDMARD treatment on UPA retention rate. A p-value < 0.05 was considered statistically significant. Results The one-hundred-eleven enrolled patients median age 57 (IQR 50-65 yrs); M:F 28:83; disease duration 78 (IQR 40-170 months). The median observation period was 6.1 (IQR 3.2-10.2) months. The observation lasted 812 patients-months. The majority of patients (54.0%) were in mono-therapy and received steroids (respectively 54.0% and 58.6%) (Table 1).The UPA retention rate at 6, 12 months was, respectively 90.4% and 74.7% (Figure 1). The main discontinuation reason was lack of efficacy (42% of interruptions), cancer onset and infections (both 11%). No thromboembolic events were reported.According to the Cox analysis, no one of the above mentioned parameters were associated to high risk of treatment interruption. Conclusion UPA effectiveness appears to be confirmed. The safety profile of UPA 15 mg in real-world practice is consistent with data from Phase 3 SELECT trials, with no new safety signals. References [1]Smolen JS, et al. Ann Rheum Diseases 2023;82:3-18.[2]Burmester GR et al.Lancet 2018; 23;391(10139):2503-2512 Acknowledgements: NIL. Disclosure of Interests None Declared.Figure 1Table 1Baseline characteristics UPACharacteristicsValueM:F28:83Age, median [IQR] yrs58 [50-65]Smokers, n (%) (**)YesFormerNo16 (16,5)17 (17,5)64 (66,0)Body Mass Index, median [IQR] kg/m^2 (*)24,7 [22,4-27,7]Disease Duration, median [IQR], months78 [40-170]RF positivity, n (%)72 (64,9)ACPA positivity, n (%)68 (61,3)SJC, median [IQR]4 [3-8]TJC, median [IQR]8 [5-11]ESR, median [IQR], mm/h32 [20-53]CRP, median [IQR], mg/dl1,2 [0,5-3,3]VAS Patient (0-100), median [IQR]70 [50-80]DAS28, median [IQR]5,5 [4,9-5,9]Line of treatment, [IQR]3 [2-4]Concomitant csDMARDs use, n (%)MTXLFNSSZHCQ41 (36,9)3 (2,7)1 (0,9)5 (4,5)Concomitant steroids use, n (%)65 (58,6)Steroids dose (PDN-Eq), median, mg/die5 [5-6]Prior bDMARDs use, n (%)TNFiIL6iIL1iCD20iCD80i53 (47,7)13 (11,7)02 (1,8)11 (9,9)Prior tsDMARDs use, n (%)BaricitinibTofacitinib9 (8,1)2 (1,8)Concomitant relevant disease, n (%)DiabetesHypercholesterolemiaMACEArterial HypertensionCancer12 (10,8)23 (20,7)5 (4,5)34 (30,6)4 (3,6)

Introduction: Enthesitis and dactylitis are difficult-to-treat features of psoriatic arthritis (PsA), leading to disability and affecting quality of life. Objective: The aim of this study is to evaluate enthesitis (using the Leed enthesitis index (LEI)) and dactylitis at 6 and 12 months in patients treated with apremilast. Methods: Patients affected by PsA from fifteen Italian rheumatological referral centers were screened. The inclusion criteria were: (a) enthesitis or dactylitisphenotype; (b) treatment with apremilast 30 mg bid. Clinical and treatment history, including PsA disease activity, were recorded. Mann–Whitney and chi-squared tests were used to assess the differences between independent groups, and Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. A p-value of <0.05 was considered statistically significant. Results: The Eph cohort consisted of 118 patients (median LEI 3); the Dph cohort included 96 patients with a median dactylitis of 1 (IQR 1–2). According to an intention to treat analysis, 25% and 34% of patients with enthesitis achieved remission (i.e., LEI = 0) in T1 and T2. The remission of dactylitis was 47% in T1 and 44% in T2. The per protocol analysis (patients observed for at least 12 months) showed that both dactylitis and LEI significantly improved in T1 (median LEI 1 (IQR 1–3)) and T2 (median LEI 0 (IQR 1–2)). Conclusion: Eph and Dph PsA patients treated with apremilast experienced a significant improvement in enthesitis and dactylitis activity. After 1 year, enthesitis and dactylitis remission was achieved in more than one-third of patients.

Background Psoriatic arthritis (PsA) is an inflammatory rheumatic disease characterized by different phenotypes in terms of joint involvement. Apremilast, PDE4 competitive inhibitor, has been introduced in the treatment of adult psoriatic arthritis (PsA) with moderate disease activity. Musculoskeletal ultrasound (MUS) is useful in the assessment of disease, treatment response and follow up in PsA patients. Choosing an effective and safe treatment over time is an increasingly urgent goal given the greater availability of indicated drugs. Objectives The aim of this study is to evaluate if MUS assessment before apremilast treatment can improvement its retention rate. Methods We enrolled consecutive patients affected by PsA (according to the CASPAR Criteria) from 15 rheumatology centers. The following data were recorded for each patient: age, gender, duration of disease, DAPSA; smoke, comorbilities; concomitant treatment; duration of therapy with apremilast; reason of sospensione, PsA phenotype (poliarticular or oligoarticular) (Table 1). All patients were divided in two subset according to the presence of a MUS assessment before apremilast treatment. The differentes between two groups were calculated by means of the Mann-Whitney and Chi-quadro tests. The Kaplan Meier curve and Cox analysis assessed the retention rate and associated factors. P values < 0.05 were considered statistically significant. Results ON Three hundred and fifty patients (m/f: 198/152; median age 60 years, IQR 52-67 years), 40% received MUS examination. In the MUS group there was a moderate disease (medium 22,9 IQR 18,2-29 vs 26,9 IQR 20,3-33,9; p=0,0006) and a prevalence of the oligoarticular pattern (73% vs 44%, p<0,0001). The retention rate was statistically higher in MUS group (Figure 1) (HR 0,57 IC95% 0,35-0,95; p=0,03). Conclusion In PSA patients treated with apremilast, MUS assessment at baseline was associated with an higher retetion rate. MUS could be useful in the PsA treatment algorithm in order to better identify those patients whose characteristics are favourable to apremilast response. References [1]\Ramona Lucchetti et al. IMAJ 2021 JULY;23(7): 412-415. [2]\Fulvia Ceccarelli et al. Clin Rheumatol. 2019 Nov;38(11):3145-3151 Acknowledgements: NIL. Disclosure of Interests None Declared.

Background Current and previous EULAR recommendations (1,2) suggest using JAK-inhibitors (JAKis) for treating Rheumatoid Arthritis (RA). However, little is known about differences of patients who are JAK-inhibitors (JAKis) naïve and patients who have already experienced at least one JAKi. Objectives To analyse differences between JAK-naïve and JAKis not naive patients in a real life setting. Methods All patients with RA on JAKis were prospectively followed up for 12 months in this multicentric study conducted in 23 centres. For each patient, the following variables were recorded: sex, age, disease duration at JAKi prescription, smoking, BMI, comorbidities, positive RF/ACPA, DAS28-ESR at baseline, 6 and 12 months, cDMARDs and prednisone at baseline, JAKis discontinuation, JAK-naïve. Statistics were performed by R (2022.12.0). Results 864 patients were included (Table 1). Among them, 731 (84.60%) were JAKis naïve, whereas 122 (14.12%) were not naïve (missing data in 11-1.27%-patients). 473 (55.22%) patients were treated with baricitinib (JAK-naïve were 412, 87.3%), 213 (24.6%) with tofacitinib (JAKis-naïve 187, 87.79%), 111 (12.84%) with upadacitinib (JAKis-naïve 78.37%) and 62 (7.17%) with filgotinib (JAKis-naïve 72.58%). Significant differences between JAKis-naïve and not naïve were found for hypercholesterolemia (p=0.04), hypertension (p=0.02), previous cancer (p<0.001), disease duration (p<0.001), line of treatment (p<0.001). No difference was found for JAKis discontinuation (p=0.13) (Table 1). Conclusion Our data suggest that line of treatment and disease duration result higher in JAKis not naive compared to naïve ones. Notably, JAKis naïve and not naïve did not differ regarding drug discontinuation, suggesting a similar retention rate irrespective of previous JAKis. References [1] Smolen JS, et al. Ann Rheum Dis 2020.[2] Smolen JS, et al. Ann Rheum Dis 2023. Acknowledgements: NIL. Disclosure of Interests Maddalena Larosa: None declared, Andrea Becciolini: None declared, Elena Bravi: None declared, Dario Camellino Speakers bureau: Abiogen, GSK, Paid instructor for: Mylan, Ilaria Platé: None declared, eugenio arrigoni: None declared, Francesca Ometto: None declared, Eleonora Di Donato: None declared, Giuditta Adorni: None declared, Gianluca Lucchini: None declared, Daniele Santilli: None declared, Alessandra Bezzi: None declared, Maria Cristina Focherini: None declared, Fabio Mascella: None declared, Vincenzo Bruzzese: None declared, Palma Scolieri: None declared, Simone Parisi: None declared, Enrico Fusaro: None declared, Maria Chiara Ditto: None declared, Viviana Ravagnani: None declared, Gilda Sandri: None declared, Carlo Salvarani: None declared, Marta Priora: None declared, Marino Paroli: None declared, rosalba caccavale: None declared, Romina Andracco: None declared, Natalia Mansueto: None declared, Matteo Colina: None declared, Massimo Reta: None declared, Olga Addimanda: None declared, Alberto Lo Gullo: None declared, elisa visalli: None declared, Rosario Foti: None declared, Giorgio Amato: None declared, Francesco De Lucia: None declared, antonella farina: None declared, Francesco Girelli: None declared, Patrizia Del Medico: None declared, Aldo Molica Colella: None declared, Veronica Franchina: None declared, Francesco Molica Colella: None declared, Federica Lumetti: None declared, Aurora Ianniello: None declared, Valeria Nucera: None declared, Rosetta Vitetta: None declared, Alessia Fiorenza: None declared, Guido Rovera: None declared, Alessandro Volpe: None declared, Giulio Ferrero: None declared, Antonio Marchetta: None declared, Simone Bernardi: None declared, Gerolamo Bianchi: None declared, Alarico Ariani: None declared.Table 1Differences between JAKis naïve and not naïve patientsTotalTotal (N=864)JAKis naive (N=731)JAKis not naïve (N=122)P valueN (%)N (%)N(%)Mean age at baseline (SD) (N=852)58.83 (12.87)58.54 (12.92)60.61 (12.45)0.10Females (N=853)668 (78.31)564 (77.15)104 (85.25)0.05Mean BMI (Kg/cm2) (SD) (N=616)25.15 (3.77)25.18 (3.62)25.02 (4.46)0.68Smoking (N=788)0.13Yes150 (19.03)135 (19.97)15 (13.39)No496 (62.94)425 (62.87)71 (63.39)Former142 (18.02)116 (17.16)26 (23.31)Positive RF (N=800)527 (65.89)444 (64.91)83 (71.55)0.16Positive ACPA (N=787)491 (62.39)411 (61.43)80 (67.80)0.19Diabetes (N=760)68 (8.95)56 (8.78)12 (9.84)0.71Hypertension (N=761)297 (39.03)238 (37.25)59 (48.36)0.02Hypercholesterolemia (N=759)195 (25.36)155 (24.29)40 (33.06)0.04Previous MACE (N=758)47 (6.20)39 (6.13)8 (6.56)0.86Previous cancer (N=760)42 (5.52)39 (6.10)3 (2.48)<0.001Disease duration (months), (median, IQR) (N=844)76 (29-155)71 (24-142.50)142 (69-226)<0.001Mean DAS28-ESR at baseline (SD) (N=736)5.29 (1.06)5.27 (1.09)5.40 (0.89)0.22cDMARDs at baseline (N=771)280 (36.31)235 (36.21)45 (36.89)0.88PDN at baseline (N=438)438 (50.69)368 (57.38)70 (56.79)0.90Median dosage (IQR) of PDN (mg/day) (N= 438)5 (4.00-5.00)2.50 (0.00-5.00)4.00 (0.00-5-00)0.08Line of JAKis treatment (N=853)<0.0011^244 (28.60)244 (33.38)0 (0.00)2^211 (24.74)207 (28.32)4 (3.28)3^175 (20.63)172 (23.53)(3.28)4^109 (12.78)56 (7.66)53 (3.44)5^65 (7.62)32 (4.38)33 (27.05)6^28 (3.28)12 (1.64)6 (13.11)7^12 (1.41)6 (0.82)6 (4.92)8^3 (0.35)1 (0.14)2 (1.64)9^2 0.23)1 (0.14)1 (0.82)10^3 (0.35)0 (0.00)(2.46)Patients who discontinued JAKis (N=853)192 (22.51)158 (21.61)34 (27.87)0.13SD: standard deviation; BMI: Body Mass Index; RF: Rheumatoid Factor; ACPA: Autoantibodies against citrullinated proteins; MACE: Major cardiovascular events; PDN: prednisone; IQR: interquartile range; DAS28-ESR: Disease Activity Score-28 for Rheumatoid Arthritis with ESR; cDMARDs: conventional Disease-modifying antirheumatic agents; JAKis: JAK inhibitors.

ObjectivesThe persistence in therapy of rheumatoid arthritis drugs and particularly bDMARD is a limiting factor for their long-term use. The randomized controlled trials (RCTs) may not reflect real-world contexts due to strict inclusion and exclusion criteria. Baricitinib, which targets both JAK1 and JAK2, has been used in Italy for several years. The aim of this multi-center study is to assess the real world persistence on therapy of baricitinib in RA patients and to identify predictive factors of baricitinib's survival rate.MethodsThis is a retrospective, multicentric, Italian, longitudinal study. All patients were enrolled according to the following criteria: a) age ≥ 18 years old; b) diagnosed with RA according 2010 ACR/EULAR classification criteria; c) treated with baricitinib. In order to describe baricitinib clinical efficacy, the survival rate was evaluated by The Kaplan–Meier curve. Then, predictive factors of drug retention rate were assessed by performing the Cox analysis, identifying which risk factors influenced treatment persistence.ResultsOverall, we included 478 patients treated with baricitinib. Among them, 380 (79.5%) were females. Baricitinib's survival rate was 94.6% at 6 months, 87.9% at 12 months, 81.7% at 24 months and 53.4% at 48 months. The Cox analysis regression showed that a higher bDMARDs/tsDMARD line of therapy seems to be a negative prognostic factor for the drug retention rate (HR 1.26 CI 95% 1.07–1.49, p = 0.006.ConclusionReal-life study confirms baricitinib effectiveness up to 4 years, but previous treatment with bDMARDs was a negative prognostic factor for its survival rate.

BackgroundSystemic Sclerosis (SSc) is a complex autoimmune disease characterized by vascular damage, immune activation and fibrosis of skin and internal organs 1. Raynaud phenomenon (RP) is frequently the first symptom of the disease and growing evidences are supporting the hypothesis the SSc may be a vascular disease, with a pivotal role of endothelial cells, particularly in the very early phase2,3. Robust data support the use of vascular active drug to treat RP and to prevent vascular complication4–7.ObjectivesThe use of prostacyclin analog (PA) is evertything but standardized, with different regimen used all around the Country. We report data on the use of PA in a multicentric regional reality to understand which regimen are prevalent (and why) and if there is the opportunity to standardized them.MethodsWe collected data from an online survey exploring different items related to the use of PA.ResultsSurvey was fullfilled by 12 sites: 5 university hospital and 7 local hospitals, 7 driven by Rheumatologist and 5 from internal medicine specialists with/without concomitant rheumatologists. PA are ubiquitarly used for SSc-related digital ulcers (SSc-DU) and secondary RP but only a half of sites use it for primary RP. Seventy-five percent of sites (9/12) dispense PA at least once a month, but some other (1 each one respectively) on weekly basis, every other month or every 7 weeks. Drug administration may last from 2 to 5 consecutive days (mean 1.91+/- 1.5SD) with drug dose ranging from 0.5 to 2 ng/Kg/min with a minimum variability from site to site. Our regional hospitals may count on overall 68 spots, some available as beds (outpatient or inpatient), some as reclining chair or chair (outpatients only). University centers have usually more assigned personnel than local hospital (on average: 2 versus 1.5 physicians, 2 versus 1.2 nurse). Sites are able to offer meals (except one) and are able to accomodate from 1 to 12 patients at the same time (mean 3.45, +/- 3.2SD).ConclusionPA has known benefit in vascular involvement in SSc patients. Despite a multicenter palcebo-control study8 defining time and dose of this drugs and subsequent data based on the same regimen9, there is no homogeneity in treatment administration. The unequal treatment, based on our data, seems due to limited resources and personnel. High variability has been found in regimen duration and administration frequency.References[1]Ferri, C. et al. Systemic sclerosis evolution of disease pathomorphosis and survival. Our experience on Italian patients’ population and review of the literature. Autoimmunity Reviews vol. 13 1026–1034 (2014).[2]Mulligan-Kehoe, M. J. et al. Antiangiogenic plasma activity in patients with systemic sclerosis. Arthritis Rheum.56, 3448–58 (2007).[3]Wigley, F. M. Vascular disease in scleroderma. Clin. Rev. Allergy Immunol.36, 150–75 (2009).[4]Brueckner, C. S. et al. Effect of sildenafil on digital ulcers in systemic sclerosis: Analysis from a single centre pilot study. Ann. Rheum. Dis.69, 1475–1478 (2010).[5]Kowal-Bielecka, O. et al. EULAR recommendations for the treatment of systemic sclerosis: A report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann. Rheum. Dis.68, 620–628 (2009).[6]Matucci-Cerinic, M. et al. Bosentan treatment of digital ulcers related to systemic sclerosis: Results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann. Rheum. Dis.70, 32–38 (2011).[7]Herrick, A. L. & Wigley, F. M. Raynaud’s phenomenon. Best Practice and Research: Clinical Rheumatology (2020) doi:10.1016/j.berh.2019.101474.[8]Wigley, F. M. et al. Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis: A multicenter, placebo-controlled, double- blind study. Ann. Intern. Med.120, 199–206 (1994).[9]Cappelli, L. & Wigley, F. M. Management of Raynaud Phenomenon and Digital Ulcers in Scleroderma. Rheumatic Disease Clinics of North America vol. 41 419–438 (2015).Disclosure of InterestsNone declared

Background Apremilast, an inhibitor of the phosphodiesterase 4, is indicated for Psoriatic Arthritis (PsA) treatment. The 3 years retention rate, an outcome indirectly related to efficacy, observed in clinical trials [1] is 55,5%. A single subsequent real world setting study [2] suggested a lower efficacy as it reported that the six months retention rate was about 57%. Objectives The main aim of this retrospective observational study is the assessment of apremilast 3 years retention rate in a real world PsA patients’ cohort. Moreover, the secondary objective is reporting the reasons of apremilast suspension and the most relevant factor related to treatment persistence. Methods In thirteen Italian rheumatological referral centers, all PsA consecutive patients who received apremilast were enrolled. Anamnestic data, treatment history and PsA disease activity (DAPSA) at baseline and after 6 and 12 months were recorded. The Kaplan-Meier curve and the Cox analysis computed the apremilast retention rate and treatment persistence-related risk factors. A p-value < 0.05 was considered statistically significant. Results The three-hundred-twenty-four enrolled patients (median age 60 [InterQuartile Range IQR 52-67] yrs; female prevalence 57,0%) median observation period was 17 [IQR 7-36] months (6848 patients-months). The apremilast retention rate at 6, 12 and 36 months was, respectively, 95%, 86% and 66% (Figure 1). The main discontinuation reasons were: primary inefficacy (40% of interruptions), secondary inefficacy (18%) and gastro-intestinal intolerance (17%%). The oligo-articular onset was the only factor associated to apremilast persistence (Hazard ratio 0.57 IQR 0.34-0.96). Sex, age, and sever comorbidities (cancer, chronic infections etc) were not related to treatment discontinuation. The basal DAPSA (24.1, IQR 18.5-32.0) decreased after 6 and 12 months (respectively 14.5, IQR 10.1-22.6 and 10.5, IQR 8,0-15.2). Remission or minimal disease activity (DAPSA < 15) was achieved after 12 months in 38.0% of patients. Conclusion Almost two third of PsA patients receiving apremilast were still in treatment after 3 years. The study’s data, confirmed its efficacy and safety profile. Apremilast appear a good treatment choice in patients with oligo articular PsA or burdened by severe comorbidities. References [1]Mease et al. ACR Open Rheumatology (2020) [2]Favalli et al Clin Exp Rheum (2020) Disclosure of Interests Alarico Ariani Speakers bureau: Zentiva, Consultant of: Boeringher, Amgen, Bristol-Meyers-Squibb, Novartis, Sanofi, Novo Nordisk, Lilly, Janssen, Bruno Farmaceutici, Simone Parisi: None declared, Patrizia Del Medico: None declared, antonella farina: None declared, elisa visalli: None declared, Aldo Molica Colella: None declared, Federica Lumetti Consultant of: Amgen, rosalba caccavale: None declared, Palma Scolieri: None declared, Romina Andracco: None declared, Francesco Girelli: None declared, Elena Bravi: None declared, Matteo Colina: None declared, Veronica Franchina: None declared, Ilaria Platé: None declared, eleonora Di Donato Consultant of: Novartis, Giorgio Amato: None declared, Carlo Salvarani: None declared, Francesco De Lucia: None declared, Daniele Santilli Consultant of: Novartis, eugenio arrigoni: None declared, Flavio Mozzani Consultant of: Novartis, Abbvie, Rosario Foti: None declared, Gilda Sandri: None declared, Vincenzo Bruzzese: None declared, Marino Paroli: None declared, Enrico Fusaro: None declared, Andrea Becciolini: None declared

Background:ASSD is characterized by antisynthetase antibodies (ARS) and the triad arthritis/myositis/Interstitial Lung Disease (ILD). ASSD and systemic sclerosis (SSc) may share features, like Raynaud’s phenomenon (RP), capillaroscopic alterations, and also some SSc specific autoantibodies.Objectives:To evaluate the characteristics of ASSD + for anticentromere antibodies (ACA).Methods:Retrospective analysis of clinical and laboratory characteristics of ACA + ASSD. Patients were identified in an established international cohort, randomly matched 1:1 for sex, age, disease duration and ARS positivity with a group of ACA - ASSD.Results:18 ACA + ASSD (15 females, 83%, 15 anti-Jo1, 2 anti-PL7, 1 anti-PL12 ARS) patients were identified. In comparison to ACA - group, no differences were observed in disease clinical presentation and evolution. Though, 9 ACA + patients (50%) satisfied the ACR/EULAR 2013 classification criteria for SSc and only 1 in ACA - group (p=0.007) (Table 1).An incomplete ASSD (lack of at least one triad finding) was observed in 15 patients in both ACA + and – group (p=1). Among these patients, 13 ACA + and 11 ACA – developed de-novo triad finding during disease course (p=0.651). In ACA + group, a de-novo arthritis was observed in 4 patients (vs 1, p=0.565), a de-novo myositis in 8 (vs 5, p=1), and a de-novo ILD in 7 (vs 10, p=1). The prevalence of complete forms was similar between ACA + and – group at both disease onset (3 vs 3, 17%, p=1) and last follow-up, (10 vs 11, 56% vs 61%, p=1). Of note, only 1 patient (6%) for each group died (p=1).Conclusion:The clinical spectrum time course of ACA+ and - ASSD is similar, even when ACA + patients could be classified as SSc. By considering the high prevalence of arthritis and myositis we observed, we suggest that ACA+ patients with arthritis and myositis, should be tested for ARS antibodies even when an ASSD is not clearly suspected.References:[1]Mirrakhimov AE. Curr Med Chem 2015;22:1963–75[2]Cavagna L. J Clin Med 2019;8:E2013[3]Sebastiani M. J Rheum 2019:46:279-84[4]van den Hoogen F. Ann Rheum Dis 2013;72:1747-55Table 1.Patients characteristics. IQR, interquartile range; ILD, interstitial Lung Disease; SSc, systemic sclerosisACA+ (18)ACA - (18)pAge (years) at disease onset (median, IQR)47 (37-63)47 (39-63)0.834Disease duration (months) (median, IQR)81 (62-169)77 (58-165)0.486anti Ro52antibody (%)12(67)11 (61)1Arthritis onset10 (56)13 (72)0.489Arthritis last follow-up (%)14 (78)14 (78%)1Myositis onset (%)7 (39)11 (61)0.318Myositis last follow-up (%)15 (83)16 (89)1ILD onset (%)9 (50)6 (33)0.5ILD last follow-up (%)16 (89)16 (89)1Complete form onset (%)3 (17)3 (17)1Complete form last follow-up (%)10 (56)11 (61)1Raynaud phenomenon (%)13 (72)9 (50)0.305Mechanic’s hands (%)6 (33)7 (38)1Teleangectasias (%)2 (11)0 (0)0.486Cutaneous sclerosis (%)510.177Acral ulcers (%)1 (6)0 (0)1Scleroderma pattern at NVC8 (44)7 (39)1Pulmonary arterial hypertension (%)3 (17)2 (11)12013 ACR/EULAR SSc classification criteria9 (50)1 (6)0.007Disclosure of Interests:Giovanni Zanframundo: None declared, Gianluca Sambataro: None declared, Veronica Codullo: None declared, Alessandro Biglia: None declared, Emanuele Bozzalla Cassione: None declared, Elena Bravi: None declared, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Marco Fornaro: None declared, Konstantinos Triantafyllias: None declared, Alberto Pesci: None declared, Paola Tomietto: None declared, Øyvind Molberg: None declared, Salvatore Scarpato: None declared, Reinhard Voll: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Carlomaurizio Montecucco: None declared, Lorenzo Cavagna: None declared

Background: Interstitial lung disease (ILD) is the main cause of death in Systemic Sclerosis (SSc). Chest CT is the gold standard in detecting ILD although it is not easy to understand its prognostic value. ILD qualitative assessment is almost worthless. Goh et al. semi quantitative score of ILD extent is related to mortality risk but it is burdened by relevant inter/intra-readers variability. An operator independent algorithm based on voxel-wise analysis proved to identify SSc patients with an increased risk of mortality according to prediction models. Objectives: To verify if quantitative analysis of chest CT (QCT) predict 10 years-mortality in SSc patients. Methods: SSc patients with availability of a chest CT were enrolled in 13 different centers. The CT voxel-wise analysis with a free software ( www.horosproject.com ) provided QCT indexes: kurtosis, skewness, mean lung attenuation and standard deviation. Patients characteristics, autoimmune profile and pulmonary function test were collected. The follow-up interval lasted from the date of chest CT to the one of the last visit or death. Each QCT index cutoff, established in a previous study (1), clustered patients in two groups. Kaplan-Meier analysis estimated and compared survival in the above mentioned groups. p < 0.05 was considered statistically significant. Results: Five hundred sixty three SSc patients were enrolled (35938 patient-months); 52.4% had ILD detectable at CT scan. For each QCT index cutoff the cohort was split in two subgroups without differences in terms of sex, age, disease duration, autoimmune profile. All QCT indexes’ cutoff selected subgroups with statistically different survival rate (e.g in Figure 1). Figure 1 Conclusion: QCT can arise as the new gold standard in identifying SSc patients with poor prognosis. The real possibility to stratify SSc subjects according mortality risk will have a pivotal role in ILD treatment decisional process with the incoming anti-fibrotic drugs. References: [1]Ariani A et al. Rheumatology 2017 Disclosure of Interests: Alarico Ariani: None declared, Elena Bravi: None declared, Maria De Santis: None declared, Vanessa Hax: None declared, Simone Parisi: None declared, Federica Lumetti: None declared, Francesco Girelli: None declared, Marta Saracco: None declared, Fabio De Gennaro: None declared, Alessandro Giollo: None declared, Masen Abdel Jaber: None declared, Francesco Bozzao: None declared, Mario Silva: None declared, Maria Chiara Ditto: None declared, Claudia Lomater: None declared, Flavio Mozzani: None declared, Daniele Santilli: None declared, eleonora Di Donato: None declared, Andrea Becciolini Speakers bureau: Sanofi-Genzyme, UCB and AbbVie, Francesco Pucciarini: None declared, Lorenzo Canziani: None declared, Flavio Cesare Bodini: None declared, eugenio arrigoni: None declared, M Bredemeier: None declared, Rafael Mendonça da Silva Chakr: None declared, Amelia Spinella: None declared, Luca Idolazzi: None declared, Roberto Bortolotti: None declared, Paola Tomietto: None declared, Elisa Baratella: None declared, Saverio Tollot: None declared, Dilia Giuggioli: None declared, Fabio Fischetti: None declared, Enrico Fusaro: None declared, Nicola Sverzellati: None declared, Carlo Alberto Scirè: None declared

OBJECTIVE: Grana Padano, an Italian protected designation of origin (PDO) semi-fat cheese, undergoes a long ripening period during which the proteolysis carried out by natural starter lactic acid bacteria releases peptides having sustained angiotensin-converting enzyme (ACE)-inhibitory activity. The length (generally 3-8 amino acid residues) and the sequence of these peptides are responsible for their ability to elicit ACE-inhibitory activity. The aim of this study has been the evaluation of the effect of a daily dietary supplement consisting in a small amount (30 g/day) of Grana Padano cheese, in terms of the lowering of the blood pressure (BP) of mild - moderate hypertensive subjects. PATIENTS AND METHODS: Thirty mild - moderate hypertensive patients, with BP values not on target (> 140 and/or > 90 mmHg) after at least 3 months of stable treatment were considered in this randomized, double-blind placebo-controlled cross-over study. All patients randomly received a dietary integration (30 g/day) of Grana Padano cheese or a placebo (made from flavored grated bread mixed with fats and salts in concentrations equal to those of the cheese). BP was evaluated at baseline and at the end of the active and placebo treatments (2 months each) by: -Office BP (OBP): -Automated Office BP (AOBP) using the BpT-RU (R), an automated oscillometric device that provides the average of multiple (n=6) blood pressure measurements: -Ambulatory Blood Pressure (ABP) 24 hour monitoring. RESULTS: Dietary integration with Grana Padano cheese resulted in a significant decrease in Office, Automated Office and Ambulatory BP. The mean decrease (vs. placebo) for 24-hour ABP was -3.5 mmHg for systolic and -2.4 mmHg for diastolic BP (p = 0.0063 and p = 0.0065. respectively). CONCLUSIONS: Daily dietary integration with 30 g of Grana Padano DOP cheese effectively reduces BP and may help mild-to-moderate hypertensive patients to reach a target BP.

Objective: The electronic cigarettes (EC) is a device that heats a liquid containing nicotine and flavors into an aerosol for inhalation. There is some evidence from controlled trials that electronic cigarette (EC) may help to stop smoking long-term. However, a large proportion of smokers who successfully quit cigarette smoking continue to use EC for unlimited time, switching from an addiction to another. There is a clear similarity between the detrimental vascular effects of EC and conventional cigarette. Little is known about the acute influence on blood pressure (BP) of nicotine inhalation by EC and it's duration of action in hypertensive subjects. Aim of this study was to evaluate the magnitude and time-course of BP changes during EC smoking. Design and method: This is a randomized, cross-over and placebo controlled study. We evaluated 30 mild-to-moderate hypertensive patients on pharmacological treatment and adequate BP control (< 140/90 mmHg). Patients (22 males, mean age 54 ± 21 years) were former smokers, who quitted tobacco cigarette in favor of EC at least 6 months before. BP and heart rate (HR) were measured by continuous non-invasive ambulatory BP and ECG monitoring (SOMNOtouch NIBP). BP and HR were monitored during a 30 minute rest in the sitting position; during other 30 minutes after smoking EC (inhalation equivalent to 0.8 mg of nicotine of a regular cigarette) or placebo EC (same device, same flavor but no nicotine in the solution). Results: EC vaping was accompanied by significant increase blood pressure, which lasted about 30 minutes (average 28 ± 11 minutes). Compared to placebo the EC smoking increased systolic BP by 9,6 ± 4,1 mmHg, diastolic BP by 7.1 ± 3.9 mmHg and heart rate by 16,4 ± 13 beat per minute. All the differences resulted statistically significant (Student's t test P < 0.05). Conclusions: Under these experimental conditions, EC smoking caused a statistically significant increase in BP and HR in hypertensive patients. This effect seems also clinically relevant since the duration of BP increase was relatively long (28 minutes) and the daily number of inhalations, in EC smokers, is usually high (> 20).

Abstract. – OBJECTIVE: Grana Padano, an Italian protected designation of origin (PDO) semi-fat cheese, undergoes a long ripening period during which the proteolysis carried out by natural starter lactic acid bacteria releases peptides having sustained angiotensin-converting enzyme (ACE)-inhibitory activity. The length (generally 3-8 amino acid residues) and the sequence of these peptides are responsible for their ability to elicit ACE-inhibitory activity. The aim of this study has been the evaluation of the effect of a daily dietary supplement consisting in a small amount (30 g/day) of Grana Padano cheese, in terms of the lowering of the blood pressure (BP) of mild moderate hypertensive subjects. PATIENTS AND METHODS: Thirty mild moderate hypertensive patients, with BP values not on target (> 140 and/or > 90 mmHg) after at least 3 months of stable treatment were considered in this randomized, double-blind placebo-controlled cross-over study. All patients randomly received a dietary integration (30 g/day) of Grana Padano cheese or a placebo (made from flavored grated bread mixed with fats and salts in concentrations equal to those of the cheese). BP was evaluated at baseline and at the end of the active and placebo treatments (2 months each) by: – Office BP (OBP); – Automated Office BP (AOBP) using the BpTRU®, an automated oscillometric device that provides the average of multiple (n=6) blood pressure measurements; – Ambulatory Blood Pressure (ABP) 24 hour monitoring. RESULTS: Dietary integration with Grana Padano cheese resulted in a significant decrease in Office, Automated Office and Ambulatory BP. The mean decrease (vs. placebo) for 24-hour ABP was –3.5 mmHg for systolic and –2.4 mmHg for diastolic BP (p = 0.0063 and p = 0.0065, respectively). CONCLUSIONS: Daily dietary integration with 30 g of Grana Padano DOP cheese effectively reduces BP and may help mild-to-moderate hypertensive patients to reach a target BP.

Material and Methods: We studied 4 patients with diffuse systemic sclerosis (3 with recent alveolitis and 1 with chronic alveolar fibrosis) who received mycophenolate mofetil(MMF) and low dose (<=10 mg/d) corticosteroids. At the beginning of their treatment and at predetermined points during the study, patients except from clinical evaluation, were submitted to pulmonary function tests (Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) and Forced Vital Capacity (FVC) and HighResolution Computed Tomography (HRCT)

Background: Interstitial Lung Disease (ILD) is the main cause of death in Systemic Sclerosis (SSc). Serious lung involvement increase the hospitalization rate and sometimes oxygen therapy is required. An prompt treatment in ILD-SSc patients is essential, but nowadays there is not a feasible method to identify patients with poor prognosis. Although chest Computed Tomography (CT) is the gold standard to detect ILD, there is no standardized assessment of its severity. Quantitative CT (QCT) is an innovative and operator independent method to assess ILD-SSc extent and severity. An increasing number of evidences confirm that QCT is extremely useful for detecting SSc-ILD with the worst prognosis. However is not well established if QCT can predict death or comorbidity associated to ILD. Objectives: The main aim of this study is to verify if QCT predict 8-years mortality or clinical worsening (i.e. hospitalization for respiratory complications or chronic oxygen therapy) in SSc. Methods: Consecutive SSc patients (according to ACR/EULAR classification criteria) from ten different centers underwent a chest CT. Their clinical history was carefully recorded in the following 96 months. A rheumatologist post-analyzed every CT with an open source DICOM viewer in order to obtain QCT indexes. Patients were clustered in two subgroups: according to QCT indexes’ cutoff previously found (see Ariani et al., 2017). The survival time of each patient was considered the time interval between the CT date and death, hospitalization related to lung worsening, beginning of chronic oxygen therapy or last medical examination Results: We enrolled 342 patients; during the 8-years follow-up 15.5% (53/342) died and 4,4% (15/342) had a clinical worsening. The Kaplan-Meier survival analysis demonstrates a worse survival in patients with QCT indexes above or below the previously observed cutoffs. (p<0.01). In particular the QCT index cutoff which the best performance was total lung kurtosis (tKurt) equal to 4.89 (p<0.0001). References: The QCT indexes’ cutoffs previously found (see Ariani, et al., 2017) identify the SSc-ILD subjects with an high risk of 8-years mortality and comorbidity. These findings suggest that QCT could became a pivotal assessment in SSc management because its role in identifying patients with poor prognosis and who deserve an early aggressive treatment. Disclosure of Interest: None declared