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BackgroundApremilast, 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%.ObjectivesThe 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.MethodsIn 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.ResultsThe 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.ConclusionAlmost 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 InterestsAlarico 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

BackgroundPatients with autoimmune systemic diseases (ASDs) can be counted among frail populations as regards the predisposition to COVID-19 due to the frequent visceral organ involvement and comorbidities, as well as the ongoing immunomodulating treatments.ObjectivesOur long-term multicenter telephone survey prospectively investigated the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients during the first 3 pandemic waves.MethodsA large series of 3,918 ASD patients (815 M, 3103 F; mean age 59±12SD years) was consecutively recruited at the 36 referral centers of COVID-19 & ASD Italian Study Group. In particular, ASD series encompassed the following conditions: rheumatoid arthritis (n: 981), psoriatic arthritis (n: 471), ankylosing spondylitis (n: 159), systemic sclerosis (n: 1,738), systemic lupus (172), systemic vasculitis (n: 219), and a miscellany of other ASDs (n: 178). The development of COVID-19 was recorded by means of telephone survey using standardized symptom-assessment questionnaire (1).ResultsA significantly increased prevalence of COVID-19 (8.37% vs 6.49%; pInterestingly, a significantly higher COVID-19-related death rate was observed in systemic sclerosis patients compared to the Italian general population (6.29% vs 2.95%; p=0.018). Other adverse prognostic factors to develop COVID-19 were the patients’ older age, male gender, pre-existing ASD-related interstitial lung involvement, and chronic steroid treatment. Conversely, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a significantly lower prevalence of COVID-19 compared to those without (3.58% vs 46.99%; p=0.000), as well as the chronic administration of low dose aspirin in a subgroup of SSc patients (with 5.57% vs without 27.84%; p=0.000).ConclusionThe cumulative impact of COVID-19 on ASD patients after the first 3 pandemic waves revealed less severe than that observed during the first phase of pandemic (1), especially with regards to the death rate that was comparable to the Italian general population in spite of the increased prevalence of complicating COVID-19 in the same ASD series.Ongoing long-term treatments, mainly csDMARDs, might usefully contribute to generally positive outcomes of in this frail patients’ population.Of note, a significantly increased COVID-19-related mortality was recorded in only SSc patients’ subgroup, possibly favored by pre-existing lung fibrosis. Among different ASD, SSc deserves special attention, since it shares the main pathological alterations with COVID-19, namely the interstitial lung involvement and the endothelial injury responsible for diffuse microangiopathy.Besides SSc, the patients’ subgroups characterized by older age, chronic steroid treatment, pre-existing interstitial lung disease, and/or impaired COVID-19 vaccine response (1-3), may deserve well-designed prevention and management strategies.References[1]Ferri C, et al. Ann Rheum Dis. 2020 Oct 14 doi: 10.1136/annrheumdis-2020-219113.[2]Ferri C et al. J Autoimmun. 2021 Dec;125:102744. doi: 10.1016/j.jaut.2021.102744.[3]Visentini M et al. Ann Rheum Dis. 2021 Nov 24. doi: 10.1136/annrheumdis-2021-221248Disclosure of InterestsNone declared

BackgroundSystemic Sclerosis (SSc) is a life-threatening connective tissue disease characterized by endothelial dysfunction, autoimmune abnormalities and aberrant fibrosis. Several reports showed an increased risk of cancer in SSc compared to general population, including breast cancer (BC). The relationship between BC and SSc has long been discussed with contradictory results. In our recent Sclero-Breast study we analyzed clinical-pathological features of BC in SSc; we finally observed the development of BC with early stages and good prognosis among these patients.ObjectivesThe aim of this project was to explore the immunohistochemical (IHC) expression of potential biomarkers involved in the molecular pathways at the basis of SSc and BC etiophatogenesis as update analysis from the Sclero-Breast study.MethodsOur observational multicenter retrospective study, performed at Modena University Hospital and Reggio Emilia Hospital in northern Italy, enrolled 33 SSc women with a personal history of BC between January 2017 and December 2019. Clinical and pathological characteristics of BC and SSc were collected. For 22 patients, BC tissues were available and IHC analysis was performed using specific antibodies to evaluate biomarkers and pathways potentially involved. The antibodies used included: PI3K/mTOR/TGFβ/PDGFRα/PDGFRβ/VEGF/EGFR/IL-6/CTLA-4/PDL1. We also reported TILs percentage (stromal tumor-infiltrating lymphocytes) of each sample. The following scores were assigned for general IHC analysis: (-) negative, (1+) positive tumor cells 50%. For PDL1 we considered a positivity in case of PD-L1 expression ≥1% in infiltrating inflammatory cells. For TILs quantification we applied the score: 0 (negative), ≤ 50% (low-median expression), >50% (high expression).ResultsThe first IHC analysis was performed on the samples of invasive BC patients (20 pts) and showed a prevalence of high PI3K expression (score of 3+ in 55% of cases) with mTOR overexpression in 45%. A PDL1 positivity was detected in 30%, with high TILs expression in 30%. Biopsies from the 2 pts with ductal carcinoma in situ were characterized by a negativity of almost all parameters, except for a medium-high TILs expression reported (40%/90% respectively). See Figure 1. IHC analysis was also performed according to BC subtypes. The group of HR+/HER2 negative showed high PI3K expression (score 3+) in most of cases (59%) with mTOR overexpression in 50%. CTLA-4 and PDL1 were positive in 25%, with high TILs expression in 25%. HER2 positive patients showed a high PI3K positivity in 50% of cases with mTOR positivity (score 3+) in 25% and high TGFβ expression (score 3+) in 25%. PDL1 was positive in 50% with high TILs expression in 25%. In Triple Negative group, PI3K overexpression was found in 75% of pts with half of cases represented by mTOR score 3+. PDL1 was positive in 50% with high TILs representation (80% of total cell count) in 50% of pts.Figure 1.IHC analysis and TILs% expression in histological samples of SSc patients with invasive BC.ConclusionAccording to our results, SSc patients with BC showed high positivity for PDL1 and high TILs representations in all subtypes. Furthermore, the high expression of PI3K, did not always correlate with mTOR overexpression. Further investigations on larger numbers are needed; however, these aspects seem to confirm that SSc subjects might develop BC at good prognosis, suggesting again a de-escalation strategy of cancer therapies. Finally, the possibility to personalize oncological targeted treatments in this subset of fragile patients could be promising.Disclosure of InterestsNone declared

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