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Background:Chronic pain is one of the most critical symptoms reported by patients with Rheumatoid Arthritis, and even when joint inflammation improves, disabling residual pain may persist in a significant number of patients. During chronic inflammation, microglial cells, characterized by TMEM119 expression, acquire an activated phenotype characterized by the production of different pro-inflammatory cytokines and pain-related molecules, leading to a neuroinflammation process. Among these mediators, the brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is pivotal in generating abnormal pain perception, leading to nociplastic pain (1). IL-6, a Janus Kinase 1 (JAK1)-dependent pro-inflammatory cytokine, seems critical for the production of BDNF (2). Treatment with Upadacitinib, a JAK1 inhibitor, has been proven effective in improving disease activity and relieving pain quickly (3); nonetheless, the biological mechanisms underlying its efficacy in pain perception still need further investigation.Objectives:This study aims to investigate whether and how Upadacitinib may affect pain-related and neuroinflammation-related molecules expression in monocyte-derived microglia, specifically regarding BDNF.Methods:Microglia were differentiated from monocytes by treatment with NGF, MCP-1, IL-34, GM-CSF, and M-CSF for 14 days and further activated toward a pro-inflammatory phenotype using LPS and IFN-gamma, as summarized in Figure 1A. For all the experiments, microglia were exposed to six conditions in a culture medium for 48 hours: A1 untreated, A2 IL-6, A3 IL-6+Upadacitinib 0.1 uM, B1 IL-6+Upadacitinib 1 uM, B2 Upadacitinib 0.1 uM, and B3 Upadacitinib 1 uM. TMEM119 and BDNF expression in microglia was evaluated by immunofluorescence. Intracellular BDNF levels were analyzed by flow cytometry and Western Blot. In all the culture conditions, microglia underwent RNA-sequencing analysis. RNA from microglia was extracted using all prep DNA/RNA/miRNA universal kits (Qiagen, Germany), and bulk RNA sequencing was carried out using the Illumina system. Heatmaps were generated in RStudio statistical software (R version 3.3.0+; Boston, MA, USA) with the NMF package. All the other statistical analyses have been performed using GraphPad Prism v.10 (Boston, MA, USA).Results:TMEM199, a microglia marker, was expressed at baseline condition (Figure 1B) and BDNF (Figure 1C). Flow cytometry analysis showed that the treatment of Upadacitinib, both at the concentration of 0.1 uM and 1 uM, alone and in combination with IL-6, reduced BDNF levels in microglial cells compared to the untreated (A1) and IL-6 (A2) conditions (Figure 1D, * p<0.05). Western blot analysis confirmed that microglia treated with the combination of IL-6 and Upadacitinib (both 0.1 uM and 1 uM) showed a decreased production of BDNF compared to the microglia treated with IL-6 alone (p<0.0001). Transcriptomic analysis showed that Upadacitinib is able to reduce gene expression of JAK/STAT signaling (Figure 1E). Moreover, the neuroinflammation-related pathways are affected by Upadacitinib treatment toward a less pro-inflammatory phenotype (Figure 1F). Furthermore, Upadacitinib treatment, alone or in combination with IL-6, induces a modulation of acute and chronic pain-related genes.Conclusion:Our results show that Upadacitinib is crucial in modulating gene expression in microglia, characterized by decreased JAK/STAT, neuroinflammatory, acute, and chronic pain-related pathways. Moreover, in this cell type, Upadacitinib reduces the production of BDNF, a molecule involved in pain perception and nociplastic mechanisms.REFERENCES:[1] Atta AA et al, Inflammopharmacology 2023;31:1053-67[2] Schulte-Herbrüggen O et al, J Neuroimmunol 2005;160:204-9[3] Bergman M et al, Arthritis Res Ther 2022;24:155Acknowledgements:NIL.Disclosure of Interests:Luca Navarini Sanofi, GSK, AbbVie, Novartis, AbbVie, MSD, Italfarmaco, UCB, Novartis, Janssen-Cilag, GSK, Eli-Lilly, Sanofi, Marta Vomero: None declared, Erika Corberi: None declared, Onorina Berardicurti: None declared, Giulia Imperatori: None declared, Damiano Currado: None declared, Lyubomyra Kun: None declared, Francesca Trunfio: None declared, Francesca Saracino: None declared, Ludovica Lamberti: None declared, Annalisa Marino: None declared, Livia La Barbera: None declared, Paraskevi Krashia: None declared, Marcello D’Amelio: None declared, Roberto Giacomelli: None declared

BackgroundA consistent connection between rheumatoid arthritis (RA) and type 2 diabetes (T2D) has been recently reported highlighting interleukin-1β (IL-1β) as shared pathogenic pathway and therapeutic target [1]. In a clinical trial enrolling patient with RA and T2D, we demonstrated that IL-1 inhibition led to a marked reduction of glycated haemoglobin together with a decrease of RA disease activity [2].ObjectivesTo evaluate the synovial expression of IL-1 related genes and the relationship to the ubiquitin-proteasome system in the synovial tissues of RA patients with and without T2D. To assess the effects of high concentration of insulin in vitro, mimicking the hyperinsulinism of the early phases of T2D, on ubiquitinated proteins in fibroblast-like synoviocytes (FLSs).MethodsEarly (<1 year) treatment-naïve RA patients with T2D (RA/T2D n=16) were compared with age- and gender-matched RA patients without T2D (n=16) enrolled in the Pathobiology of Early Arthritis Cohort (PEAC) [3]. Synovial tissue biopsies obtained under ultrasound guidance underwent RNA-sequencing as previously described [3], and we compared IL-1 pathway genes in patients without and with T2D. The synovial expression of ubiquitin in macrophages and synovial lining fibroblasts was assessed by immunohistochemistry/immunofluorescence and correlated with synovial pathotypes [4]. Finally, FLSs from RA patients (n=5) were isolated and treated with human insulin (200 and 500 nM) and ubiquitinated proteins were assessed by western blot.ResultsSynovial RNA-sequencing showed that one third of IL-1 pathway genes (41/138) were significantly different in RA/T2D patients compared to RA patients without T2D. In parallel, synovial tissues of RA/T2D patients were characterised by a consistent reduced expression of ubiquitin-proteasome genes. More specifically, ubiquitin genes (UBB, UBC, and UBA52) were significantly lower in T2D/RA patients. Furthermore, 22 genes codifying proteasome subunits were significantly lower in RA/T2D patients (PSMA2, PSMA6, PSMA7, PSMB1, PSMB3, PSMB4, PSMB6, PSMB7, PSMB8, PSMB9, PSMB10, PSMC1, PSMC3, PSMC5, PSMC13, PSMD4, PSMD7, PSMD8, PSMD9, PSME1, PSME2, and PSMF1). Additionally, several genes regulating ubiquitin and proteasome system were significantly different in the synovial tissue of RA/T2D patients. Specifically, APP, BAG4, and BTRC were upregulated in RA/T2D patients. Conversely, RACK1, RBX1, RPS27A, SEM1, SHARPIN, and SIGIRR were significantly downregulated in RA/T2D patients.Immunohistochemistry showed a significant reduction of the percentage of ubiquitin-positive cells in synovial tissues of RA/T2D patients. The percentage of ubiquitin-positive cells was also increased in patients with a lympho-myeloid pathotype compared to diffuse myeloid or pauci-immune-fibroid. Despite its widespread expression in synovia, immunofluorescence showed that ubiquitin mainly colocalized with synovial macrophages and lining fibroblasts.Finally, in vitro experiments showed a reduction of ubiquitinated proteins in RA-FLSs treated with a high concentration of insulin (500 nM).ConclusionIncreased IL-1 gene expression was observed in the synovial tissues of RA/T2D patients linked with decreased ubiquitin-proteasome system. These findings may provide a mechanistic explanation of the observed clinical benefits of IL-1 inhibition in patients with RA and concomitant comorbid T2D, as the reduction of the ubiquitin-proteasome system may enhance the levels of precursor IL-1β and the production of bioactive IL-1β.References[1] Giacomelli R, et al. Expert Rev Clin Immunol. 2016;12:849-55[2] Ruscitti P, et al. PLoS Med. 2019;16:e1002901[3] Lewis MJ, et al. Cell Rep. 2019;28:2455-70[4] Humby F, et al. Ann Rheum Dis. 2019;78:761-72Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Background:Hope is a goal-orientated cognitive construct comprising two components: pathways (achieving goals strategy) and agency (inspiring thoughts motivating to pursue goals). In rheumatic diseases, Hope is related to compliance and correlates with depression and symptoms worsening. Patients who experience chronic pain often tend to develop anxiety, depression, and a lack of hope regarding the improvement of their clinical condition. All of these can further increase the severity of the disease and resistance to various treatments.Objectives:The present study aims to assess Hope levels in patients with Fibromyalgia (FM) compared to healthy subjects (HS) and investigate whether a Mindfulness-based stress reduction (MBSR) intervention could increase Hope levels in FM patients and improve their physical and psychological status.Methods:64 FM female patients were consecutively enrolled in Campus Bio-Medico of Rome outpatient clinics and randomly assigned to either an MBSR intervention (n=31, consisting of 6 online sessions once a week) or not (n = 32). Moreover, 47 age- and sex-matched HS were recruited. All the groups completed the Adult Hope Scale (AHS) questionnaire at baseline. Only FM patients completed psychometric questionnaires at baseline and after three months: AHS, HADS to detect anxiety and depression symptoms, VAS-pain to assess pain, SCS to assess self-compassion, RS-14 to assess resilience, PCS to assess pain catastrophizing, SF-36 to assess health-related quality of life, PSS to assess stress, TAS-20 to assess alexithymia. FM disease severity has been evaluated by WPI, SSS, FSS, and FIQ-R. Continuous variables have been analyzed using the Mann-Whitney test for independent observations and the Wilcoxon test for paired data, while contingency tables have been analyzed using the Chi2 test. The statistical analysis has been performed using Stata v.14.Results:Comparative analysis at baseline showed that patients with FM have lower levels of hope as compared with HS [AHS 26 (24-27) and 22 (19-24), respectively, p<0.0001]. Both AHS Agency [13 (12-14) in FM group and 10 (9-12) in HS, p<0.0001] and AHS Pathways [13 (12-14) in FM group and 12 (10-13) in HS, p <0.0001] are reduced in FM patients compared to HS (Table 1). FM patients assigned to the MBSR group showed a significant improvement comparing baseline and after MBSR in WPI (p= 0.0300), SSS (p= 0.0141), FSS (p= 0.0104), FIQ-R (p <0.0001), HADS (p= 0.0005), PCS (p=0.0004), VAS-pain (p=0.0006) and PSS (p=0.0431). However, comparing baseline and after MBSR FM patients did not show improvement in SCS (p= 0.0888) [although statistically significant results were achieved in the SCS self-judgement (p= 0.0345) and SCS Isolation (p= 0.0078) subdomains], TAS-20 (p= 0.4535), RS-14 (p=0.0885) and SF-36 (p= 0.0545) [although significant variations were observed in the SF-36 Physical Functioning (p=0.0493), SF-36 Role-physical (p= 0.0028), SF-36 Social Functioning (p= 0.0003), and SF-36 Bodily Pain (p= 0.0001)] (Table 2). FM patients not undergoing MBSR intervention did not improve comparing baseline and after MBSR in any questionnaire.Conclusion:Hope levels in FM patients are significantly reduced compared to the healthy population. In FM, MBSR intervention induces improvement in the levels of Hope and, more specifically, its Agency component. This increase is associated with simultaneous improvement in physical function and various psychometric variables. Indeed, there is a reduction in anxiety, depression, perceived stress, and VAS-pain, as well as an improvement in FIQ-R and FSS, scores commonly used in clinical practice to assess the severity and impact of the disease on daily life. Therefore, MBSR is a promising treatment method for Fibromyalgia Syndrome. This chronic and debilitating condition still requires studies to investigate various aspects of the disease, including the identification of specific and effective therapies to improve patients’ quality of life.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:In rheumatic diseases, increasing emphasis is put on the role of psychosocial factors in the experience of pain. Among these factors, pain catastrophizing (PC), an inclination to exaggerate in describing pain, to ruminate, or to feel helplessness about it, has emerged. While associated with subjective perception, PC doesn’t align with inflammation biomarkers. The mechanisms underlying these effects remain not fully elucidated, positioning PC as a key variable that might shed light on why certain patients struggle to achieve treatment targets. Many studies demonstrate impact of Rheumatoid Arthritis (RA) on physical, psychological, and social aspects, impairing quality of life. In RA patients, PC is more prevalent than in the general population, impacting drug retention.Objectives:We aimed to evaluate PC and its related domains (Rumination, Magnification, and Helplessness) in RA patients and assess its impact on disease activity in models adjusted for different psychometric domains, such as anxious and depressive symptoms.Methods:We conducted a multi-center, cross-sectional, observational study on consecutive RA patients fulfilling ACR/EULAR criteria. Comorbidities and antibody status were collected at enrolment. Disease activity has been assessed with composite indices, such as Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI). For assessment of physical, psychological, and social status validated questionnaires have been administered: Health Assessment Questionnaire, Hospital Anxiety and Depression Scale, Trait Hope Scale and its domain Agency and Pathway, Acceptance and Action Questionnaire and Compassionate Engagement and Action Scales. Furthermore, PC has been assessed using the Pain Catastrophising Scale (PCS), characterized by 3 domains: rumination, magnification and helplessness. Univariate and multivariable regressions were performed to evaluate possible predictors of disease activity, including PC and its domains. All the statistical analysis has been performed using Stata v. 14 (College Station, Texas, USA)Results:We enrolled 158 RA patients (age 61 (51-69) years, males/females 29.11/70.9%). In this subset, we observed that the median CDAI value was 8.05 (2-14.5) and SDAI 8.14 (2.26-14.7). Concomitant fibromyalgia was present in 17.97% and lung involvement (LI) in 6.8% of participants. The analysis of the PCS showed a median value of 17 (8-26) and its specific domains showed helplessness 6 (2-11), Rumination 7 (3-11), Magnification 2 (1-4). The main demographic, anthropometric, and clinical characteristics of the study population are reported in Table 1. Using the cut-off point marking the difference of clinically significant from non-significant PC (PCS=30), patients with PCS >30 showed a positive association with the values of tender joints (p=0.0007), swollen joints (p=0.0336), VAS pain (p=0.0086), patients’ global assessment (p=0.0002), physician global assessment (p=0.0129), CDAI (p<0.0001), SDAI (p=0.0001) and LI (p=0.013). Univariable and multivariable regression considering SDAI as a dependent variable are summarized in Table 2. In multivariable analysis, PCS is independently associated with SDAI (coeff 0.22467, 95%CI 0.923 to 0.357, p=0.001), whilst anxious and depressive symptoms are not. The same results were reported for the PCS domains helplessness (coeff 0.5947942, 95%CI 0.3032154 to 0.8863731, p<0.0001) and rumination (coeff 0.4921229, 95%CI 0.2190804 to 0.7651653, p=0.001) but not for magnification (p=0.4).Conclusion:In our study, we found that PC, a maladaptive cognitive perception of pain, negatively impacts disease activity, thus limiting the achievement of therapeutic targets. We established a significant association between PCS (total PCS and domains: rumination, magnification, helplessness) and SDAI levels, confirming PC’s interference with achieving low disease activity and remission. Notably, PC is associated with SDAI independently from anxious and depressive symptoms, the latter previously associated with disease activity. Thus, PC might mediate the relationship between depressive symptoms and RA disease activity.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Systemic sclerosis (SSc) is a multiorgan autoimmune fibrotic disease, determining a significant burden on patients’ psycho-social life. In the field of major depressive disorders, hopelessness is a defining subjective emotion characterized by a bleak pessimistic view of the future and the idea that “nothing good is going to happen to me”. To this regard, a previous study showed the inefficacy of mindfulness-based strategy in decreasing hopelessness levels in SSc. Hopelessness is associated with therapeutic compliance, suicidal risk and chronic pain, as observed in different chronic diseases (including rheumatoid arthritis and systemic lupus erythematosus).Objectives:To measure the hopelessness levels, according to the validated Beck Hopelessness Scale(BHS), in SSc patients and identify the possible correlation between hopelessness and clinical parameters.Methods:76 (97% female) patients responding to ACR/EULAR 2013 SSc classification criteria and 32 healthy controls, matched per age and sex, were recruited. SSc patients were evaluated at each timepoint (0, 2, 4 and 6 months) for: presence/severity of digital ulcers (DUCAS and DUVAS), Patient Global Assessment (PtGA), Raynaud Condition Score (RCS), HAMIS scale, BHS, Hospital Anxiety and Depression Scale (HADS), Facit Fatigue Scale e Body Image Scale (BIS), Short Form Health Survey 36 (SF-36). At baseline and 6 months evaluation for disease severity (mRSS, Medgser Severity Scale-MSS and presence of ILD, history of DU), was performed. Mann-Whitney test has been applied for statistical differences for continuous variables, while Chi-square test has been used for contingency tables. We performed a linear mixed model to assess the association between BHS and demographic, clinical, and psychometric variables. Statistical significance was p<0.05. Statistics have been performed on Stata v.10 (College Station, Texas, USA).Results:BHS was significantly higher in SSc patients vs control (p<0.0001). In SSc patients, all SF-36 domains were significantly decreased and FACIT fatigue and HADS were significantly increased, compared to healthy controls (Table 1). Dividing the population according to the cut-off of BHS = 8, marking the difference between minimal/mild and severe hopelessness at baseline (Table 2), higher BHS levels were associated with higher RCS (p=0.0018), HAMIS scale (p=0.0271), HADS (p<0.0001), BIS (p<0.0001), FACIT fatigue (p<0.0001) and lower SF-36 PCS (p=0.0117) and MCS (p<0.0001). Performing a mixed linear model, corrected for age and sex, on the total SSc population the dependent variable BHS was related to RCS (CI 95% [0.0028 - 0.2516]; p= 0.045) and PtGA (CI 95% [0.0071 - 0.2463], p= 0.038). Furthermore, in patients with digital ulcers during follow-up, a mixed linear model corrected for age and sex showed that BHS was related to DUCAS (CI95% [0.1474 - 1.2680], p=0.013) and RCS (CI95% [0.0392 - 0.6594], p =0.027).Conclusion:Hopelessness was significantly higher in SSc patients compared to healthy controls. BHS score showed significant association with increased Raynaud’s severity (RCS) and decreased hand functionality, assessed by HAMIS scale. Furthermore, RCS is independently associated with hopelessness levels in SSc patients, suggesting the crucial impact of Raynaud’s phenomenon on this domain. In patients with digital ulcers, DUCAS score is independently related to the BHS score, thus suggesting that digital ulcers are a major cause of hopelessness in SSc patients. In conclusion, better control of Raynaud’s phenomenon and efficacious treatment of digital ulcers might affect hopelessness levels in SSc patients, thus increasing therapeutic compliance and psychosocial well-being.REFERENCES: NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Psoriatic Arthritis (PSA) is one of the most common inflammatory arthritis. PSA induces joint pain and inflammation, as well as a reduction in quality of life and workability. According to EULAR recommendations, regular physical activity is strongly recommended in patients with inflammatory arthritis, to maintain adequate joint movement and reduce cardiovascular risk, which is increased in PsA. However, the presence of pain and joint deformities could limit the ability of PsA patients to exercise. Furthermore, psychosocial factors are important determinants of pain experience in patients with inflammatory arthritis. The Fear Avoidance Model is used widely to explain how psychological factors affect the experience of pain and the development of chronic pain and disability, suggesting that patients with fear avoidance beliefs are less likely to confront pain-related problems and are less active in the coping process.Many questionnaires have been developed to identify fear avoidance beliefs. Among them, the Fear-Avoidance Beliefs Questionnaire (FABQ) is a 16-item questionnaire that assesses a person’s fear-avoidance beliefs about physical activity and work.Objectives:Our study aimed to evaluate the prevalence of physical activity avoidance in patients with PsA. Moreover, we assessed the demographic, PsA-related, and psychometric variables independently associated with physical activity avoidance.Methods:A single-center, cross-sectional, observational study has been carried out on consecutive PsA patients, fulfilling CASPAR criteria. Physical activity avoidance and associated potential psychological domains have been assessed with validated questionnaires. In particular, FABQ (Fear Avoidance Beliefs Questionnaire) has been used to assess how a patient’s fear of pain may contribute to avoiding physical activity. Additionally, uni- and multivariate linear regressions have been performed to evaluate demographic, pathology-related, or psychometric factors potentially related to physical activity avoidance. All the statistical analysis has been performed using Stata v.14 (College Station, Texas, USA).Results:The main demographic, anthropometric, and clinical characteristics of the study population are reported in Table 1. Particularly, patients showed age 56 (33-74) years, males/females ratio 30.8%/69.2%, Disease Activity in PsA (DAPSA) 14.3 (1.5-29.7), BASDAI 5.45 (1.1-8.72). PsA patients with FABQ PA≥ 15 (cut-off point marking high levels of fear-avoidance beliefs related to physical activity) represent 27.69 % of the population. Concomitant fibromyalgia was present in 37.1% of the participants. We observed that the proportion of patients with fibromyalgia among those with FABQ PA≥ 15 was 52.9 %.PCS (Pain Catastrophising Scale) median value was 20.97 (1-40), SF36 PCS (Physical Component Score) median value was 35.3 (21.5-56.6) and FABQ PA median value was 11.4 (1-23).Moreover, patients with FABQ ≥15 showed a higher BASDAI, PCS, and SF36 PCS than patients with FABQ PA <15 (p-values 0.0002, 0.030, and 0.002, respectively).As reported in Table 2, in multivariable linear regression, independent predictors of physical activity avoidance were the SF36-PCS and anxiety symptoms assessed by HADS. No disease activity index was independently associated with FABQ.Conclusion:This study suggests that avoiding physical activity in PsA patients may depend on physical functioning and anxiety symptoms rather than disease activity.TJ: Tender Joints; SJ: Swollen Joints; PP: Patient Pain, PtGA: Patient Global Assessment; CRP: c-reactive protein; PASI: Psoriasis Area Severity Index; DAPSA: Disease Activity in PSoriatic Arthritis; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; mFABQ: modified Fear-Avoidance Belief Questionnaire; FABQ PA: FABQ Physical Activity; HAQ: Health Assessment Questionnaire; HADS: Hospital Anxiety and Depression Scale; PCS: Pain Catastrophising Scale; IPAQ: International Physical Activity Questionnaire; SF36 PCS: Short Form Health Survey 36, Physical Component Summary; SF36 MCS: SF36, Mental Component SummaryREFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Primary Sjögren’s disease (SD) is a systemic autoimmune disorder characterized by a lymphocytic infiltrate affecting exocrine glands, resulting in gland dysfunction and sicca symptoms. While oral damage is commonly acknowledged, end-organ damage is considered relatively rare in SD patients. Presently, no specific treatment is available for SD, and the diagnostic delay is typically at least 3 years after the onset of symptoms. These characteristics, coupled with the broad spectrum of clinical manifestations, contribute to the complexity of disease management. Despite the generally low rate of disease progression, patients may still encounter end-organ damage and a decline in the quality of life during the course of the disease. In this study, we present data from an Italian cohort designed to evaluate damage accrual over a 5-year period.Objectives:This study aims to assess:Systemic, ocular, and oral damage development in a large multicentre cohort of SD patientsRisk factors associated with damage presence and development over a 5-year periodMethods:The GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) Sjögren’s disease cohort is an inception cohort that recruited 448 consecutive SD patients. These patients were enrolled in tertiary rheumatology centers across Italy, each with expertise in SD diagnosis and management. All patients were ≥ 18 years old, and fulfilled the 2016 American–European Consensus Criteria for SS. The Sjogren’s syndrome damage index (SDI) was employed to evaluate damage both at baseline and during the follow-up period. Due to missing data, our statistical analysis encompassed 429 patients. Survival analysis was conducted to describe the survival rate and identify risk factors associated with damage development.Results:At the enrolment, the median SDI was 0.69 (SD ± 0.93). Over half of the patients exhibited damage at baseline (225 patients, 52.4%). The most common domain of reported damage at baseline was the ocular domain (25.8%), followed by the systemic and oral domains (21.9% and 13.4%, respectively).Higher systemic SDI at baseline was associated with ESSDAI (r = 0.60, p < 0.0001), ESSPRI (r = 0.15, p = 0.0079), and CRP (r = 0.14, p = 0.0011), anti-Ro autoantibodies (r = 0.10, p 0.036), recurrent oral infections (r = 0.17, p = 0.0006). Ocular damage at baseline associated with impaired Schirmer test I (r = 0.20, p < 0.0001), CRP (r = 0.16, p = 0.0017), ESSDAI (r = 0.14, p = 0.003) and anti-La antibodies (r = 0.10, p = 0.044). Oral damage at baseline was associated with ESSDAI (r = 0.26, p < 0.0001), RF (r = 0.20, p < 0.0001), FS (r = 0.18, p = 0.012), CRP (r = 0.18, p 0.0008), recurrent oral infections (r = 0.16, p = 0.0011), ESSPRI (r = 0.15, p = 0.001), anti-Ro antibodies (r = 0.14, p 0.0039), xerostomia and xeropthalmia (r = 0.11, p = 0.028 and 0.022 respectively). After one year, the estimated survival rates for systemic, ocular, and oral damage development were 73%, 69%, and 86%, respectively. A significant increase in the mean of SDI after 1 year (0.86 ± 1.14, p < 0.0001) was observed. ESSDAI values and CCS usage during the first year of follow-up were risk factors for developing systemic damage over 60 months of observation (HR 1.080; 95% CI 1.02, 1.14; p = 0.0041; HR 3.44; 95% CI 1.22, 9.68; p = 0.019, respectively). CCS usage during the first year was a risk factor for ocular damage development (HR 2.16; 95% CI 0.31, 2.48; p = 0.013). Reported data and Kaplan-Meier curves are shown in Figure 1(A–D) and Table 1.Conclusion:Our findings suggest that at baseline, more than half of SD patients present systemic, ocular, or oral damage, and damage accumulation persists even after the diagnosis and the initiation of therapy. Different baseline factors, linked to the patients and/or the disease, could contribute to the damage development. The assessment of damage throughout the follow-up of SD patients could prove beneficial in preventing treatment failure and the progression of the disease.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Primary Sjogren’s syndrome (pSS) is a systemic autoimmune disorder primarily impacting salivary and lacrimal glands, with systemic manifestations occurring in nearly half of the patients. While the prognosis for this disease is generally favorable, approximately 5% of patients develop hematologic malignancies, particularly non-Hodgkin’s lymphoma (NHL) during its course. In contrast to well-established data on lymphoma development, information on solid malignancies is both scarce and contentious. A systematic review and meta-analysis, encompassing 25 articles and involving over 47,607 pSS patients, revealed an increased risk of overall cancer, encompassing solid malignancies, among individuals with pSS.Objectives:-To assess the prevalence of different types of cancers, subdividing them into lymphomas, MGUS, and solid malignancies, in a cohort of 495 patients with pSS.-To analyze the characteristics of patients at baseline in patients without malignancies, with MGUS, with lymphoma, and with solid malignancies.Methods:The GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) Sjogren’s disease (SD) cohort is an inception cohort enrolling 495 consecutive patients with pSS followed in different rheumatology centers in Italy with experience in SS diagnosis and treatment. All patients were ≥18 years old and fulfilled the 2016 American–European Consensus Criteria for pSS. We provided descriptive statistic analysis, and normally distributed continuous variables were expressed as mean ± SD. Data distribution was tested by using the Shapiro-Wilk test. To compare the clinical characteristics, parametric or nonparametric t-tests were used for all the continuous variables, and the chi-square test for the categorical variables, as appropriate.Results:We examined data from 495 patients with primary Sjogren’s syndrome (pSS), with a median age of 52.15 (SD±12.61), of whom 94.7% were female, and with an average ESSDAI of 4.16 (SD±5.71). At the baseline assessment, individuals with monoclonal gammopathy of undetermined significance (MGUS) exhibited a younger age at diagnosis compared to other groups, with no differences based on diagnostic delay. A higher baseline ESSDAI value was associated with the presence of MGUS, lymphoma, and solid tumors. Notably, a correlation between a higher ESSPRI value and malignancies was evident solely in patients with MGUS. Elevated focus score values were linked to the presence of MGUS. Gamma globulin values were significantly elevated in patients with MGUS and solid neoplasia. Rheumatoid factor positivity was more frequent in patients developing MGUS, whereas anti-La positivity was observed in individuals with solid neoplasia. An intriguing association emerged between an increase in CRP value and the presence of solid neoplasms, likely attributed to the systemic inflammation induced by this type of malignancy. Comprehensive data are presented in Table 1.Conclusion:This study revealed certain connections between the baseline characteristics of SS patients and the occurrence of malignancies, not only for lymphomas. Notably, a high ESSDAI value and increased levels of gamma globulins were identified as associated with lymphomas and also with solid malignancies diagnosis. RF presence was significantly associated with MGUS presence but not with lymphoma diagnosis. CRP elevation could also be an interesting finding, after the exclusion of other underlying causes, to better screen these patients for a possible malignant cause of this condition. Intriguingly, the percentage of patients with anti-La antibodies was significantly higher in patients with solid malignancies. These data could contribute to the SS patients profiling, with the scope of an early identification of patients with malignancies for early recognition and better management.REFERENCES:NILAcknowledgements:NIL.Disclosure of Interests:None declared.

Background:Chronic pain and inflammation are common features of rheumatic conditions such as Psoriatic Arthritis (PsA) and Axial Spondyloarthritis (axSpA), often necessitating prolonged medication use for effective management. Maintaining drug retention is essential for achieving disease control and improving patients’ quality of life. In recent years, several studies have turned their attention to real-world scenarios, examining the extended-term usage of biologic disease-modifying antirheumatic drugs (bDMARDs) in spondyloarthritis; furthermore, the factors linked to the retention rate of bDMARDs in remain a pivotal question to be addressed.Objectives:This study investigates the influence of pain catastrophizing, a psychological response to pain, on the drug retention rates of PsA and axSpA patients.Methods:A two-year prospective multicenter observational study involved 135 PsA and 71 axSpA patients. To assess the drug discontinuation rate, any occurrence of withdrawal therapy and adverse events recognized or suspected as linked to therapies were recorded. Pain Catastrophizing, including its domains of Helplessness, Rumination, and Magnification, was assessed using the Pain Catastrophizing Scale (PCS). Univariable and multivariable regression analyses were utilized to identify factors associated with drug retention.Results:In the PsA group, patients who discontinued therapy early had higher baseline disease activity and a higher incidence of comorbid fibromyalgia. Notably, pain catastrophizing, specifically the domains of Helplessness, Magnification, and Rumination, were significantly elevated in PsA patients who interrupted their treatment. The univariable linear regression (Table 1) confirmed fibromyalgia comorbidity, corticosteroids assumption, Disease Activity for Psoriatic Arthritis (DAPSA) at baseline and PC levels as predictors for drug suspension within two years follow-up. Of note, the multivariable logistic regression (model adjusted for age, sex, DAPSA and corticosteroids use) showed significant relationship between PsA participants drug discontinuation and PCS (OR 1.04, 95% CI 1.004- 1.074, p=0.02), helplessness (OR 1.09, 95% CI 1.01-1.18, p=0.03), rumination (OR 1.10, 95% CI 1.01- 1.20), but not for magnification domain (OR1.15, 95% CI 0.97-1.36, p=0.09). In axSpA, drug discontinuation was more frequent among females, those with shorter disease duration, higher baseline disease activity, and elevated levels of pain catastrophizing. Of note, the univariable logistic regression (Table 2) established female gender, baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), PCS and all its components helplessness, magnification, and rumination as disease predictor of treatment suspension before two years follow-up. However, limited events in axSpA patients precluded a multivariate analysis.Conclusion:Pain catastrophizing has emerged as a significant factor affecting drug retention in PsA and axSpA patients. The findings from the study discussed here shed light on the importance of assessing and addressing pain catastrophizing in clinical practice. By recognizing and intervening in the psychological aspects of pain, healthcare providers can contribute to better outcomes for patients with PsA and axSpA, ultimately improving their quality of life and overall well-being.Table 1.Two-year discontinuation (PsA participants)UnivariableIndependent variablesOR95%CIpFibromyalgia3.221.42-7.280.005CCS2.351.02-5.400.04TJ1.101.02-1.180.01PP1.091.00- 1.180.04PtGa1.31.12 1.49<0.0001DAPSA1.061.02 1.100.001PCS1.051.02 1.08<0.0001Helplessness1.121.05 1.190.001Rumination1.131.05 1.21<0.001Magnification1.221.05 1.420.009Table 2.Two-year discontinuation (AxSpA participants)UnivariableIndependent variablesOR95%CIpSex3.681.01 13.400.04BASDAI1.811.281398 2.5723260.001Asdas pcr2.491.304764 4.7234660.006PCS1.131.05533 1.202472<0.0001Helplessness1.241.092015 1.4093920.001Rumination1.251.07672 1.4577350.004Magnification1.351.024664 1.7890550.03REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

BackgroundResistin is a soluble factor produced by adipose tissue, implicated in the regulation of inflammatory processes and in microvascular damage.1 When incubated with resistin, endothelial cells respond by a greater production of endothelin-1, a potent endothelium-derived vasoactive factor that engenders endothelial dysfunction (ED) in many cardiovascular and autoimmune diseases, such as Systemic Sclerosis (SSc).2 SSc is a complex connective tissue disease, whose pathogenesis results from the variable interaction of three main processes: microvascular damage, autoimmunity-mediated inflammation and fibroblast activation.3 ED is at the base of the development of painful ischaemic events due to chronic hypoxia, namely digital ulcers (DUs),4 considered a prognostic marker of disease severity.5 ObjectivesTo evaluate the association between baseline serum resistin levels and the development of new DUs in a cohort of patients with SSc.MethodsWe conducted a one-year prospective cohort study. Patients with SSc and healthy controls (HC) were consecutively enrolled. Baseline serum resistin was assessed by commercial ELISA kit. The development of new DUs was prospectively evaluated during the follow-up after the cross-sectional point in which the resistin levels were measured.ResultsWe enrolled 70 SSc patients and 26 HC matched by gender and vital parameters. Mean basal resistin levels were increased in SSc patients compared to HC (6.58±5.48 vs 2.56±0.95, p=0.0004). In SSc group, resistin was higher among patients with active DUs (p=0.0007), infected DUs (p=0.0009) and active pattern at nailfold videocapillaroscopy (p=0.01). During one-year follow-up, 27 (38%) SSc patients presented new skin ulcers. Baseline resistin was increased in patients who developed new DUs (8.4±6.4 vs 5.4±4.5, p=0.026). In multiple logistic regression, the development of new DUs was associated to basal serum resistin concentration (OR 2.1, 95% CI 1.1–3.9), to the presence of active DUs at baseline (OR 3.4, 95% CI 1.0–11.9), and to basal Disease Activity Score (DAI) according to European Scleroderma Study Group6 (OR 1.3, 95% CI 1.0–1.6). In proportional Cox regression, the time to new DUs was associated to basal resistin concentration (HR 1.7, 95% CI 1.1–2.8) and DAI (HR 1.2, 95% CI 1.0–1.4).ConclusionsSerum resistin seems to be associated to the presence and to the development of DUs, suggesting a possible involvement in micro-vascular dysfunction in patients affected by SSc.References[1] Pang SS, Le YY. Role of resistin in inflammation and inflammation-related diseases. Cell Mol Immunol2006;3:29–34.[2] Verma S, Li SH, et al. Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation2003;108:736–40.[3] Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med2009;360:1989–2003.[4] Hughes M, Herrick AL. Digital ulcers in systemic sclerosis. Rheumatology (Oxford)2017;56:14–25.[5] Mihai C, Landewe R, et al. Digital ulcers predict a worse disease course in patients with systemic sclerosis. Ann Rheum Dis2016;75:681–6.[6] Valentini G, Della Rossa A, et al. European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis2001;60:592–8.Disclosure of InterestNone declared