BACKGROUND:The integration of artificial intelligence (AI) into healthcare has shown significant promise in addressing complex diagnostic and therapeutic challenges in rheumatology. This review examines the current state of AI applications across rheumatological practice. OBJECTIVE:To systematically evaluate AI applications in rheumatology, assess their clinical performance and identify future research directions. METHODS:We conducted a comprehensive literature review of AI applications in rheumatology, focusing on diagnostic imaging, clinical decision support and disease monitoring across major rheumatic conditions. RESULTS:AI demonstrates promising performance across multiple domains, with diagnostic accuracies frequently exceeding 80%-90% for imaging interpretation and disease classification. Applications span from automated radiographic scoring to real-time disease monitoring. CONCLUSIONS:While AI shows significant potential in rheumatology, successful clinical implementation requires addressing challenges related to data quality, algorithm transparency and clinical integration.

This review examines the molecular mechanisms driving structural damage in Spondyloarthritis (SpA), a chronic inflammatory condition characterized by new bone formation that can lead to partial or complete spinal ankylosis. We explore the complex interplay between inflammation, mechanical stress, and bone metabolism in SpA, focusing on key signaling pathways and cytokines that contribute to disease progression. The review analyzes both structural and inflammatory aspects, particularly the role of enthesis biology and the impact of mechanical factors. Additionally, we assess how current therapeutic approaches, including biologic treatments targeting specific inflammatory pathways such as tumor necrosis factor inhibitors, affect disease progression. While these treatments can reduce inflammation and manage clinical symptoms, their limited ability to completely prevent new bone formation highlights the complexity of the underlying pathological processes. We also evaluate emerging therapeutic strategies targeting specific molecular pathways involved in bone formation. Understanding these intricate molecular mechanisms and their interactions is crucial for developing more effective targeted therapies that could potentially not only manage symptoms but also prevent or reverse structural damage in SpA patients.

Background Psoriatic arthritis is a chronic immune-mediated disease that may appear with arthritis and/or enthesitis and systemic manifestations, affecting 0.1-1% of the general population and up to 30% of patients with psoriasis. A greater understanding of the pathogenesis has led to an increase of therapeutic options, namely biotechnological drugs which may prevent the progression of the disease and improve the quality of life by acting on specific pathways. Among these drugs, anti-TNFα agents play an important role. Adalimumab (ADA) and Etanecept (ETA) were the first developed ones, indeed they are defined as “originator” drugs. Subsequently, “biosimilars” have been developed. They are defined by the EMA as highly similar to other biological agents already on the market in terms of qualitative characteristics, biological activity, safety, and efficacy. Spending review and pharmaco-economic policies have almost “imposed” the use of non-medical switching (NMS). Objectives The aim of this study is to evaluate the retention rate of ETA and ADA originators, compared to their biosimilar counterparts, in the first line and after NMS, detecting discontinuation for adverse events (AEs) or ineffectiveness, in patients with psoriatic arthritis. Methods Fifty-four patients diagnosed with psoriatic arthritis were enrolled (F: 61%; mean age 53.4±13 years, BMI 24.9±3.6), Baseline disease activity was 4, 1 ± 1.1. Inclusion criteria were age >18 years, fulfillment of CASPAR 2006 criteria for PsA, therapy with originators or biosimilar etanercept or adalimumab in the first line, with the possibility of no NMS, stable combined therapy with methotrexate during the observation time. Statistical significance was set at p⩽0.05. Results The retention rate of ETA and ADA originators was 541 ± 70 weeks and 486 ± 24 weeks, respectively. The retention rates of biosimilar ETA and biosimilar ADA in the first line were 265 ± 20 weeks and 79 ± 21 weeks, respectively (p=0.231). After NMS, the retention rate of biosimilar ETA and biosimilar ADA was 49.1 ± 13 weeks and 108 ± 12 weeks, respectively. Discontinuation due to AEs were recorded in 8.3% of patients receiving originator ETA, 5% of patients receiving originator ADA, and 31% of patients receiving biosimilar ADA. Discontinuation due to ineffectiveness occurred in 54% of patients treated with originator ETA, in 40% of patients treated with originator ADA, and in 44% of patients treated with biosimilar ADA. In patients treated with biosimilar ETA, no suspensions were recorded either for AEs or for ineffectiveness. Conclusion Our data show that the retention rate of originator drugs was higher than that of biosimilars, both when administered in the first line and after a NMS. A greater number of suspensions were recorded for AEs and, to a lesser extent, for ineffectiveness with biosimilar ADA compared to originator ADA, while in patients treated with biosimilar ETA no suspensions were recorded either for AEs or for ineffectiveness. References [1]Gossec L, Baraliakos X, Kerschbaumer A, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis. 2020;79(6):700-712. doi:10.1136/annrheumdis-2020-217159; [2]Veale DJ, Fearon U. The pathogenesis of psoriatic arthritis. Lancet. 2018;391(10136):2273-2284. doi:10.1016/S0140-6736(18)30830-4; [3]Taylor W, Gladman D, Helliwell P, et al. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006;54(8):2665-2673. doi:10.1002/art.21972 [4]Ogdie A, Coates LC, Gladman DD. Treatment guidelines in psoriatic arthritis. Rheumatology (Oxford). 2020;59(Suppl 1):i37-i46. doi:10.1093/rheumatology/kez383; [5]Gherghescu I, Delgado-Charro MB. The Biosimilar Landscape: An Overview of Regulatory Approvals by the EMA and FDA. Pharmaceutics. 2020;13(1):48. Published 2020 Dec 31. doi:10.3390/pharmaceutics13010048 Acknowledgements: NIL. Disclosure of Interests None Declared.

Background Janus kinase inhibitors (JAK-i) are increasingly used in the treatment of Rheumatoid Arthritis (AR). Hypertransaminasemia is one of the described side effects of this class of drugs. Objectives The aim of the study is to evaluate the possible hepatotoxicity, the risk of NAFLD onset, and the reactivation of HBV and HCV in patients with AR and JAK-i therapy. Methods 78 patients with AR (81%F) were enrolled with an average disease duration of 15±7 years, BMI 26±4. The inclusion criteria were age > 18 years, fulfillment of ACR/EULAR 2010 criteria for AR, and stable intake for at least 3 months of JAK-i in monotherapy or combined therapy with methotrexate (MTX) and/or steroid. Results The average therapy duration of JAK-i treatment (Baricitinib, Filgotinib, Tofacitinib or Upadacitinib) was of 67±50 weeks. 32% of patients were on combined therapy with MTX and 22% took steroids (mean dose in prednisone equivalents of 5.5±2.5 mg/day). No patients had positivity for HCV antibodies at the beginning of JAK-i therapy, and no one reported alcohol abuse. At the beginning of JAK-i therapy, 9% of patients had hepatic steatosis on abdominal ultrasound and 26% had occult HBV infection. 8% of patients had hypertransaminasemia before starting therapy with JAK-i. During treatment with JAK-i, hypertransaminasemia occurred in 6% of patients; of these 20% had already known hepatic steatosis, 40% were occult HBV carriers and 40% were with combined therapy with MTX. Particularly, hypertransaminasemia was detected in 8% of patients treated with Baricitinib and in 8% of patients with Tofacitinib. No patients treated with Filgotinib and Upadacitinib developed hypertransaminasemia during follow-up. JAK-i treatment was not stopped in any patient with hypertransaminasemia. 14% had NAFLD during treatment with JAK-i, and no patients had hepatic steatosis with hypertransaminasemia above 3 times normal values. Among patients who developed NAFLD after JAK-i treatment, 18% were overweight, 36% were obese, 27% were in therapy with steroids, and 18% were with combined therapy with MTX. NAFLD has been detected in 16% of patients treated with Baricitinib, 8% of patients treated with Tofacitinib, and 15% of patients treated with Upadacitinib, no patients treated with Filgotinib showed onset of NAFLD. Among patients with previous episodes of hypertransaminesia for other reasons, JAK-i treatment didn’t cause alterations of bio-humoral indexes of hepatic function. No HBV reactivation occurred in patients with occult HBV infection during treatment with JAK-i. Conclusion JAK-i treatment in patients with occult HBV infection or previous NAFLD has a good safety profile. In terms of hypertransaminasemia with or without NAFLD, the risk of liver dysfunction appears to be very low during JAK-i treatment, both in monotherapy or in MTX combination treatment. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.

Background Considering the highest adverse events risk (predominantly infectious disease and osteoporosis) of glucocorticoids (GCs), EULAR recommended a short-term use of GCs with rapid tapering as soon as clinically feasible in rheumatoid arthritis (RA) patients. Although a prednisone dose less than or equal to 7,5 mg/die is considered more safety, the complete discontinuation of the GCs would be desirable. Few data are available on real tapering or withdrawal of GCs in RA patients treated with DMARDs both in clinical trial and registry study. Objectives To evaluate the steroid tapering rate and the discontinuation of GCs in RA patients treated with biological-DMARDs (b-DMARDs) or target synthetic DMARDs (ts-DMARDs) in different treatment lines. Methods We revised retrospectively 1616 clinical records of RA patients who started b/ts-DMARDs between December 2017 and June 2021. We recruited 420 RA patients who were stably treated for at least 6 months with b/ts-DMARDs with or without cs-DMARDs and were taken GCs at baseline visit. The evaluations of GCs discontinuation time were realized by Kaplan-Meier estimate, followed by log-rank (Mentel-Cox) test for the comparison among different b/ts-DMARDs groups. Statistical significance was set at p ⩽ 0.05. Results RA patients treated with different b/ts-DMARDs were comparable for disease duration (anti TNF-alpha: 76 weeks ± 64; JAK-I: 121 weeks ± 122; anti-IL6: 78 weeks ± 70; abatacept: 111 weeks ± 121), disease activity (DAS 28 ESR: anti TNF alpha: 3,9 ± 1,3; JAK-I: 4,1 ± 1; anti IL-6: 4 ± 1,3; abatacept: 4 ± 1,2; p=0,958), and GCs dose (anti TNF alpha: 5,7 mg ± 7,5; JAK-I 5,5 mg ± 2,5; anti IL-6 5,7 mg ± 4,1; abatacept 5,6 mg ± 2,5; p=0,879) at baseline visit. 158 RA patients started for the first-time b/ts-DMARDs, 83 patients started 2 nd line of b/ts-DMARDs, 66 patients started 3 rd line b/ts-DMARDs and 113 patients were failure to more than 3 b/ts-DMARDs. Considering RA patients who started b/ts-DMARDs for the first time, the groups treated with anti-IL6 or JAK-I showed a shorter discontinuation time than those treated with anti TNF-alpha or Abatacept (respectively 22 weeks ± 0,7, 22,6 weeks ± 0,7, 23,8 weeks ± 0,1, 23,1 weeks ± 0,4; p=0,046). As regards the steroid sparing in 6 th month of follow-up, the rates of GCs dose spared than the staring GCs dose were higher in JAK-I (44%) and anti-IL 6 (42%) compared to abatacept (30%) and anti-TNF alpha (33%). Considering the group of RA patients treated in 2 nd or other lines of b/ts-DMARDs, no differences were found among various treatments in GCs discontinuation time. Conclusion In clinical practice GCs are useful therapeutic tools to reach as rapidly as possible low disease activity in RA patients; but the possible adverse effects of long-term GCs treatment limit their use. The introduction of biotechnological drugs has significantly improved clinical management of RA patients, achieving the aim of rapid GCs discontinuation or their dose reduction. In particular, the mechanisms of action of anti-IL6 and JAK-I seems perform more quickly on steroid discontinuation than anti TNF alpha or abatacept, above all in 1 st line of b/ts-DMARDs in RA patients. Disclosure of Interests None declared

Objectives: IL-17 modulates the synthesis of several molecules involved in the pathogenesis of Systemic Sclerosis (SSc). Vitamin D (1,25(OH)2D3) shows anti-fibrotic properties and it is able to affect the IL-17 production in several experimental conditions. The aim of this study is to assess the production of IL-17A and pro-fibrotic cytokines in peripheral blood mononuclear cells (PBMCs) from subjects with SSc in basal conditions and after treatment with 1,25(OH)2D3 and IL-17A neutralizing antibodies. Methods: The production of IL-17A and pro-fibrotic cytokines (TGFβ, CTGF and FGF2) in PBMCs obtained from 51 SSc patients and 31 healthy subjects was assessed both in basal conditions and in presence of anti-IL17A antibodies and several concentrations of 1,25(OH)2D3. The association of cytokines production with clinical disease characteristics and the in vitro effect of 1,25(OH)2D3 and IL-17A inhibition were assessed. Results: PBMCs from SSc subjects produced higher amount IL-17A, TGFβ, CTGF and FGF2 compared to healthy controls. IL17, TGFβ, CTGF and FGF2 levels were higher in SSc patients with interstitial lung disease and digital ulcers, whereas IL-17A production was lower in patients with PAH. IL- 17A inhibition reduced the production of FGF2, whereas enhanced the synthesis of TGFβ and CTGF. 1,25(OH)2D3 decreased the production of IL17A and pro-fibrotic cytokines in a dose- dependent manner. Conclusions: IL-17A is involved in the regulation of fibrogenesis in SSc, and could represent an intriguing potential therapeutic target, even if its role remains controversial. 1,25(OH)2D3 inhibits both IL-17A and pro-fibrotic cytokines, confirming its potential anti-fibrotic effect.

INTRODUCTION:The objective of this study was to assess the 10-year prevalence of latent tuberculosis infection (LTBI) among Apulian patients with rheumatic diseases (RDs). Secondary endpoint was to record new cases of active TB disease and LTBI among patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs).METHODS:We analysed the results from the patients included in the BIOPURE registry from 2009 to 2018, who underwent QuantiFERON-TB Gold In-tube (QFT-GIT) test as screening before bDMARDs treatment. Demographic and clinical data were recorded at the time of the first QFT-GIT test. Administration of preventive therapy and bDMARD treatments were recorded for patients with positive QFT-GIT test. All new tuberculosis infections were recorded during the follow-up.RESULTS:The final study population included 3028 patients (855 rheumatoid arthritis, 1001 psoriatic arthritis, 833 spondyloarthritis, 130 connective tissue diseases, 33 systemic vasculitis and 176 other inflammatory rheumatic conditions), more frequently female (67.2%), with a mean age of 52 ± 18 years. Patients with QFT-GIT-positive test were elderly people, predominantly male with higher prevalence of diabetes as comorbidity. The 10-year prevalence of LTBI was 10.8%. Of note, no cases of TB reactivation were recorded in patients who completed preventive therapy treatment. Three thousand and sixteen patients were followed over time (42.6 ± 30 months), and five (.2%) developed active TB, which corresponds to .47 cases per 1000 person-years.CONCLUSIONS:In the 10-year observation, the use of bDMARDs seems to be safe in rheumatologic patients with positive QFT-GIT test treated according to current recommendations. Nevertheless, cases of primary TB disease did occur during treatment with biologicals.

: HCV is a global health problem affecting mainly the liver and is often characterized by extrahepatic manifestations mediated by autoimmune reactions. Among these, arthritis and arthralgia are most frequent, as well as the presence of cryoglobulinemia that may induce vasculitis and sicca syndrome. Thus, HCV appears to be a trigger for an autoimmune response, as demonstrated by the finding of autoantibody in a high percentage of serum of these patients. Therefore, it is important that clinicians recognize these autoimmune manifestations as symptoms due to an autoimmune activity triggered by HCV in order to give the correct diagnosis and start an effective therapeutic strategy. Therefore, clinical examination, searching of markers of infection, as well as autoantibody patterns should be performed to make a correct differential diagnosis. The treatment should be based on antiviral drugs associated with immunosuppressive drugs according to autoimmune manifestations.

Calcium Pyrophosphate Crystal Deposition (CPPD) disease is characterized by the deposition of calcium pyrophosphate crystals in the cartilage. In most cases, it can manifest as a subclinical condition named chondrocalcinosis, often revealed by joint x-ray examination. In other cases, deposition can cause flares of arthritis, known as acute CPP crystal arthritis. In the last few years, many pathogenic pathways have been discovered. Interleukin-1 (IL-1) plays a key role in the pathogenesis of CPPD disease, both as a mediator of inflammatory response to crystals and as a promoter of damage to articular cartilage. In this review, we investigated the role of IL-1R inhibitor, such as Anakinra, as an alternative to the various therapeutic strategies for CPPD disease, especially among patients resistant to traditional treatment with NSAIDs, corticosteroids and colchicine.

In the pathogenesis of several rheumatic diseases, such as rheumatoid arthritis, spondyloarthritis, osteoarthritis, osteoporosis, alterations in osteoblast growth, differentiation and activity play a role. In particular, in rheumatoid arthritis bone homeostasis is perturbed: in addition to stimulating the pathologic bone resorption process performed by osteoclasts in course of rheumatoid arthritis, proinflammatory cytokines (such as Tumor Necrosis factor-α, Interleukin-1) can also inhibit osteoblast differentiation and function, resulting in net bone loss. Mouse models of rheumatoid arthritis showed that complete resolution of inflammation (with maximal reduction in the expression of pro-inflammatory factors) is crucial for bone healing, performed by osteoblasts activity. In fact, abnormal activity of factors and systems involved in osteoblast function in these patients has been described. A better understanding of the pathogenic mechanisms involved in osteoblast dysregulation could contribute to explain the generalized and focal articular bone loss found in rheumatoid arthritis. Nevertheless, these aspects have not been frequently and directly evaluated in studies. This review article is focused on analysis of the current knowledge about the role of osteoblast dysregulation occurring in rheumatoid arthritis: a better knowledge of these mechanisms could contribute to the realization of new therapeutic strategies.

We performed a systematic literature review to summarize the underlying pathogenic mechanisms by which adipokines influence rheumatological diseases and the resulting clinical manifestations. Increasing evidence display that numerous adipokines may significantly influence the development or clinical course of various rheumatological diseases. Despite the normal anti- or pro-inflammatory role of the cytokines, the serum level varies enormously in various rheumatological diseases. The expression of high levels of pro-inflammatory cytokines such as leptin or visfatin, respectively in systemic lupus erythematosus and in rheumatoid arthritis, represents a negative prognostic factor; other adipokines such as adiponectin, broadly known for their anti-inflammatory effects, showed a correlation with disease activity in rheumatoid arthritis. In the near future pro-inflammatory cytokines may represent a potential therapeutic target to restrain the severity of rheumatological diseases. Further studies on adipokines may provide important information on the pathogenesis of these diseases, which are not yet fully understood. The mechanisms by which adipokines induce, worsen, or suppress inflammatory and degenerative musculoskeletal pathologies and their clinical significance will be discussed in this review.

A review of the available literature was performed in order to summarize the pathogenic and clinical connections between HIV infection and rheumatological syndromes. The increasing life expectancy during human immunodeficiency virus (HIV) infection has led to the observation of many rheumatological manifestations over the years in these types of patients. Although the pathological mechanisms are still not fully understood, several rheumatological diseases have been more commonly observed in the general population, especially after the advent of highly active antiretroviral therapy (HAART), and sometimes clinical and serological findings are influenced by the underlying condition which defines a characteristic onset or development of the disease. Autoimmune diseases occur during specific stages of the HIV infection, depending on the underlying pathogenic mechanism being mainly influenced by the CD4+ cells count. Several rheumatological diseases show peculiar clinical manifestations influenced by the underlying HIV infection leading to specific features less commonly observed in the healthy population. Conversely to pathological findings, broadly, HIV-1-neutralizing antibodies (BnAb) observed in several autoimmune diseases, such as SLE, could play a protective role in HIV infection. It is important to evaluate the onset of autoimmune diseases in HIV patients in order to start the appropriate treatment to avoid harmful events. More studies are needed to enlighten the trend of autoimmune diseases during HIV infection. Pathogenic mechanisms and clinical manifestations of rheumatological diseases during HIV infection are discussed in this review.

Objective In rheumatoid arthritis (RA), "traditional" cardiovascular (CV) risk factors continue to be underdiagnosed and undertreated, thus increasing the risk of developing atherosclerosis. In this work, we evaluated the occurrence and predictive factors of "traditional" cardiovascular risk factors, with a focus on high blood pressure (IMP), type 2 diabetes (T2D), and metabolic syndrome (MetS), in participants with RA, in a 3-year, multicentre, prospective, observational study. Methods To assess the occurrence and predictive factors of HBP, T2D, and MetS, consecutive participants with RA, admitted to Italian Rheumatology Units, were evaluated in the GIRRCS (Gruppo Italian di Ricerca in Reumatologia Clinica e Sperimentale) cohort, a 3-year, multicentre, prospective, observational study. Results In the present evaluation, 841 participants, who were fully followed up with 3-year of prospective follow-up were assessed. At the end of follow-up, a significant increased incidence of HBP, T2D, and MetS was recorded. Assessing predictive factors, the mean values of C-reactive protein during the follow-up were independent predictors of occurrence of those comorbidities, whereas participants maintaining remission showed a significant lower risk. Furthermore, therapy with hydroxychloroquine (HCQ) reduced the risk of occurrence of T2D and MetS. Conclusion An increased incidence of HBP, T2D, and MetS was observed in assessed participants, prospectively followed-up. Furthermore, the analysis of predictive factors suggested that the rheumatoid pro-inflammatory process could increase the occurrence of these comorbidities. Conversely, metabolic and cardiovascular benefits of maintaining remission as well as of therapy with HCQ were reported.

Background:Latent tuberculous infection (LTBI) is very common in the world and screening for it is essential before starting treatment with biotechnological drugsObjectives:The aims of our study were to assess the prevalence in Apulia of LTBI among patients affected with rheumatic disease and to record the cases of tuberculosis (TB) infection among patients treated with biologic agents.Methods:We analysed data of patients included in BIOPURE registry from 2008 to 2018, who underwent Quantiferon (QTF) test as routinely screening for biologic treatment. Demographic and clinical data were recorded at the time of the first QTF assessment and this time point was considered the “baseline” of the study. Data regarding further QTF tests performed during follow-up was also acquired by electronic charts. Prophylaxis administration and bDMARD treatments were recorded for patients with positive QTF test. All tuberculosis infections were recorded during the entire time of follow-up.Results:Three thousand thirty-five patients (female 67.2%, mean age 52 ± 18.3 years) were included in these study, 2692 patients (88.7%) had inflammatory arthritis (28.2% rheumatoid arthritis, 33% psoriatic arthritis and 27.4% spondyloarthritis), 129 (4.2%) patients had connective tissue disease, whereas 214 (7.1%) patients were affected by others rheumatic diseases. The prevalence of LTBI was 10.7% (326 patients) at baseline. Comparisons between positive and negative patients for QTF are reported in Table 1. We acquired data of LTBI prophylaxis of 284 patients; 235 out 265 patients treated with isoniazid completed the treatment, whereas 19 out 19 patients treated with rifampicin completed the prophylaxis regimen. The main cause of isoniazid withdrawal was hypertransaminasemia, but 8 patients then completed prophylaxis with rifampicin. During the entire follow-up (42.6±30.5 months), we recorded 5 (0.02%) cases of primary TB infection in patients on anti-TNFα agents treatment, which had baseline screening negative for LTBI. Data and outcome of these patients are reported in Table 2. The mean time of follow-up of patients on bDMARDs treatment with positive QTF at baseline was 52.7±35.2 months. bDMARD treatment regimens are reported in Table 3. No case of TB reactivation was found among patients with positive baseline QTF. Moreover, of 1563 (51.5%) patients who repeated QTF during follow-up, 62 (4%) of them showed a change in the test result. We observed a change to a positive state in 36 patients with previous negative QTF test, whereas 26 patients with previous positive QTF showed a shift to a negative test during follow-up.Conclusion:Our study shows a prevalence of LTBI of 10.7% in Apulian patients affected with rheumatic disease. bDMARDs therapy appears to be safe in patients with positive QTF test treated according to current recommendations1. However, cases of primary TB infections, especially in patients receiving anti-TNFα drugs, have been observed.References:[1]Cantini F, et al, Guidance for the management of patients with latent tuberculosis infection requiring biologic therapy in rheumatology and dermatology clinical practice, Autoimmun Rev (2015).Disclosure of Interests:None declared

Background:Previous study evidenced a cross-reactivity between Sars-Cov-2 antibodies and autoimmune tissue antigen involved in connective tissue diseases, as nuclear antigen (NA), extractable nuclear antigen (ENA), histone and collagen (1). No study has been published about the titer of Sars-Cov-2 antibodies in non-infected patients with autoimmune disease.Objectives:To evaluate the titer of SARS-CoV-2 antibodies in non-COVID-19 patients and compare it between systemic sclerosis (SSc) patients and healthy controls (HC).Methods:A total of 58 patients with SSc (who fulfilled ACR/EULAR 2013 SSc classification criteria) and 18 HC were enrolled. Sera of all participants were collected, and SARS-CoV-2 antibodies (IgG and IgM) were evaluated by means ELISA. In all participants swabs for SARS-CoV-2 by real-time reverse-transcriptase-polymerase-chain-reaction assay were reported negative. Demographic, clinical, and autoimmune serological characteristics of SSc patients were recorded. The normal distribution was assessed using the Shapiro–Wilk’s test. Exclusion criteria was previous or actual Sars-Cov-2 infection. Comparisons between study groups of patients were evaluated by the Student’s t-test or Mann – Whitney U-test as appropriate. The differences between categorial variables were assessed by Pearson chi-square or Fisher’s exact test, as opportune. Statistical significance was set at p ≤ 0.05.Results:We observed significant differences between SSc patients and HC in serum levels of Sars-Cov-2 antibodies (IgG: 1,4±2,1 AU/ml vs 0,36±0,19 AU/ml respectively (p=0,001); and IgM: 2,5±3,1 AU/ml vs 0,8±0,7 AU/ml (p=0,022)). In 5 SSc patients was found titer of Sars-Cov-2 antibodies (IgG) exceeding the cut-off, but the control of swabs for SARS-CoV-2 by real-time reverse-transcriptase-polymerase-chain-reaction assay were negative. No significative differences in Sars-Cov-2 autoantibodies titer were found in subgroup of SSc patients with or without ILD or PAH, limited or diffuse skin subset, and different autoantibodies profile. Furthermore, antibodies titer was not associated with different drugs (steroid, methotrexate, mofetil-mycophenolate and bosentan) in use.Conclusion:A cross mimicking between Sars-Cov-2 antibodies and antinuclear antibodies or anti ENA could be hypothesized. Further studies are necessary to unravel the reliability of Sars-Cov-2 antibodies detection in autoimmune disease.References:[1]Vojdani, A., Vojdani, E., & Kharrazian, D. (2021). Reaction of human monoclonal antibodies to SARS-CoV-2 proteins with tissue antigens: Implications for autoimmune diseases. Frontiers in Immunology, 11, 3679Disclosure of Interests:None declared

An increased risk of developing severe infections has been evidenced in rheumatic disease (RD) patients, and anti-COVID-19 vaccination is strictly recommended for RD patients. However, up to now, no data are available on safety, immunogenicity and efficacy of COVID-19 vaccinations in RD patients. The possible development of adverse events (AEs), including the flare-up of underlying RD, represents a matter of growing importance. The aim of our study is to assess, in RD patients, the safety profile of different types of approved vaccines and the possible influence of immunosuppressive therapies and clinical or demographic characteristics of RD patients on development of AEs. Participants (n = 185; 30.7%) received anti-COVID-19 vaccinations, 137 with autoimmune/chronic inflammatory RD (Au/cIn-RD) and 48 with nonautoimmune/chronic inflammatory RD (no-Au/cIn-RD). AEs were recorded in 42% of patients after the first dose of vaccine, and in 26% of patients after the second dose. The most common reported AEs after anti-COVID 19 vaccines were site injection pain (17%), headache (12%), fever (12%), myalgia (10%) and fatigue (10%). Relapses of the underlying Au/c-In-RD were recorded in 2.2% of patients after the first dose of vaccine. In Au/c-In-RD the risk of developing AEs after the first dose of vaccine was lower in older patients (OR = 0.95; p = 0.001), and in the group of patients with complete control of RD (OR: 0.2; p = 0.010). A lower percentage of AEs was observed in patients with complete control of their Au/cIn-RD (29%) compared to those with low (57%) or moderate-high disease activity (63%) (p = 0.002 and p = 0.006 respectively). In this study all types of COVID-19 vaccines in use in Italy seemed safe in RD patients. The results of this study might provide reassuring information for Au/cIn RD patients and clinicians and could strengthen the data on vaccine safety to guide the use of COVID-19 vaccines in Au/cIn-RD on immunosuppressive agents.

Background Limited data on myoglobin and infectious diseases are available. In this study, we evaluate the potential role of myoglobin in predicting poor outcome in patients with Sars-Cov2 pneumonia. Methods One hundred and twenty-one Sars-Cov 2 patients with an average age of 69.9 +/- 13.2 years, and symptoms duration of 8.8 +/- 7.9 days were enrolled in the study. At the admission, the serum levels of myoglobin, erythrocyte sedimentation rate, C reactive protein (CRP), procalcitonin, ferritin, creatine phosphokinase, creatinine, fibrinogen, d-dimers, lactic dehydrogenase, troponin (Tn-I), creatine kinase myocardial band (CK-MB), complement fractions C3 and C4, immunoglobulins, interleukin 6 were evaluated. We also assessed the patients' complete clinical history and performed a thorough physical examination including age, disease history, and medications. Results Twenty-four (20%) patients died, and 18 (15%) patients required intensive care. The mean time between symptoms onset and death was 12.4 days +/- 9.1. Univariate analysis of the patients' data highlighted some independent risk factors for mortality in COVID-19, including higher neutrophils rate (HR: 1.171), lower lymphocyte rate (HR: 0.798), high CK-MB serum levels (HR: 1.6), high Tn-I serum levels (HR: 1.03), high myoglobin serum levels (HR: 1.014), Alzheimer (HR 5.8), and higher CRP values (HR: 1.011). Cox regression analysis model revealed that higher serum values of myoglobin (HR 1.003; 95%CI: 1.001-1.006; p = 0.01), and CRP (HR 1.012; 95% CI: 1.001-1.023; p = 0.035) could be predictors of mortality in COVID-19 patients. The value of the myoglobin level for predicting 28 days-mortality using ROC curve was 121.8 ng/dL. Lower survival rate was observed in patients with serum levels of myoglobin>121.8 ng/dL (84% vs 20% respectively, p = 0.0001). Conclusion Our results suggest that higher serum levels of myoglobin could be a considerable and effective predictor of poor outcomes in COVID-19 patients; a careful follow-up in these patients is strongly suggested. The possibility of enhancing these findings in other cohorts of COVID-19 patients could validate the clinical value of myoglobin as a biomarker for worse prognosis in COVID-19.

Background Glucocorticoids (GC) modulate several regulators involved in the pathogenesis of bone changes in rheumatoid arthritis (RA). Trabecular bone score (TBS) allows the indirect assessment of bone quality. The aim of this study was to investigate the effects of GC on TBS and serum levels of bone turnover regulators in patients with recent-onset RA. Materials and methods Forty-seven subjects with recent-onset RA (< 6 months) were classified in two groups, low (lGC) and high (hGC) glucocorticoids, according to glucocorticoid dose regimens. Bone mineral density (BMD), TBS, and circulating Dickkopf-1 (Dkk1), sclerostin, osteoprotegerin (OPG), and RANK-L were evaluated at baseline and 6 and 12 months. Results BMD significantly declined after 12 months with no significant difference between the lGC and hGC group, whereas TBS decreased in the hGC group only. Circulating OPG decreased during the follow-up period, the reduction being significantly greater in hGC group; conversely, sclerostin and RANK-L serum increased, in a significantly greater extent in the hGC group. TBS inversely correlated with sclerostin, RANK-L, and Dkk1 circulating levels whereas directly correlated with OPG circulating levels. GC cumulative dose showed an inverse relationship with BMD in both the hGC and lGC groups; TBS values showed an inverse relationship with GC cumulative dose in the hGC group only. GC cumulative dose was associated to higher sclerostin and lower OPG serum levels. TBS did not correlate with disease activity whereas BMD was inversely related to disease activity. Conclusions In early RA, GC exposure contributes to the reduction of BMD and affects bone quality depending on dose regimens. TBS could be a useful tool to evaluate the negative effect of GC on bone microarchitecture. Trial registration This study was ancillary to a parallel-group observational prospective study which was approved by the medical local ethics committee (protocol number DDG 334/19-06-2019).

A decline in bone mass leading to an increased fracture risk is a common feature of age-related bone changes. The mechanisms underlying bone senescence are very complex and implicate systemic and local factors and are the result of the combination of several changes occurring at the cellular, tissue and structural levels; they include alterations of bone cell differentiation and activity, oxidative stress, genetic damage and the altered responses of bone cells to various biological signals and to mechanical loading. The molecular mechanisms responsible for these changes remain greatly unclear and many data derived from in vitro or animal studies appear to be conflicting and heterogeneous, probably due to the different experimental approaches; nevertheless, understanding the main physio-pathological processes that cause bone senescence is essential for the development of new potential therapeutic options for treating age-related bone loss. This article reviews the current knowledge concerning the molecular mechanisms underlying the pathogenesis of age-related bone changes.

Background: Little is known about effectiveness of certolizumab (CTZ) in clinical practice, especially in patients with inadequate response to prior biologics. Objectives: To estimate the survival rate of CTZ in RA, PsA or SpA cohorts from the registry BIOPURE. Secondary endpoint was the changes of clinical outcomes from baseline at 6 and 12 months for each disease. Methods: We analyzed longitudinal data of consecutive patients, affected with RA, PsA or SpA starting a treatment with CTZ recorded into the web-based Apulian registry BIOPURE. Demographic and disease related characteristics were collected at baseline, 6 and 12 months. Drug survival was evaluated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs, 95% confidence intervals (CI)) of drug discontinuation adjusted for patient’s demographics, disease characteristics and prior biologic treatments were computed by Cox-regression models. Differences of DAS28, DAPSA and BASDAI among baseline, 6 and 12 months were estimated by T-test. Results: 506 patients were included in this analysis (table 1). Global mean survival time (95% CI) was 58 (52-64) months. Drug survival rate was significantly higher in RA (71.1%) than in PsA (63.5%, p=0.001), while SpA showed 67.5% (Figure 1). Naïve-CTZ patients showed higher survival rates than biologic-inadequate responder (Bio-IR) patients in PsA (naïve 78.4% vs 56.9%, p=0.02), but not in RA (76.9% vs 64.1%, p=0.08), or SpA (73.7% vs 64.8%, p=0.84). The only weak predictor of drug discontinuation was age at baseline for SpA patients (HR 1.04 (95% CI:1.005-1.007) p=0.02) (Figure 1). No baseline covariate, including sex, cDMARDs co-therapy and biologic-naïve status, was found to be associated with CTZ discontinuation for RA and PsA cohorts. A significant improvement of clinical outcomes from baseline was seen at 6 and 12 months, regardless prior biologic therapies. In RA DAS28 dropped from 3.95 ±1.5 to 2.77 ±1.3 at 6 months (p=0.0001) and 2.55 ±1.3 at 12 months (p= 0.0001). In PsA DAPSA decreased from 19.1 ±10 to 10.8 ±8 at 6 months (p=0.0001) and 9.6 ±7 at 12 months (p=0.0001). In SpA DAS28 reduced from 3.66 ±1.4 to 2.85 ±1.3 at 6 months (p=0.0001) and 2.55 ±1.1 at 12 months (p=0.0001). Additionally, in SpA BASDAI dropped from 5.3 ±1.6 to 3.8 ±2.3 at 6 months (p=0.0001) and 2.8 ±1.8 at 12 months (p=0.0001). Conclusion: In real-life settings CTZ has shown a good effectiveness also in Bio-IR patients. Unlike other TNF-inhibitors, the clinical response and the survival rate were also meaningful in RA patients. Table: RA (nr. 180) PsA (nr.189) SpA (nr.137) Age (mean ± SD) 54.5 ±12 50.6 ±12 52.0 ±11 Female 82.9 % 74.6 % 56.3 % BMI (mean) 25.9 ± 5 28.4 ± 5 26.7 ± 5 Dis Durat months (mean ± SD) 46 ± 14 106 ± 82 97 ± 92 Naive 53.9 % 32.8 % 28.5 % Prior biologics 52.9 % 75.0 % 71.1 % Glucocorticoids 55.9 % 39.7 % 39.4 % DMARDs 72.4 % 52.4 % 43.8 % DAS28 (mean ± SD) 4.8 ± 1.5 3.6 ± 1.2 3.7 ± 1.3 BASDAI (mean ± SD) 5.2 ± 2 DAPSA (mean ± SD) 19.7 ±10 HAQ (mean ± SD) 1.2 ± 0.7 1.1 ± 0.6 1.2 ± 0.7 RF/ACPA + 72.4 % Disclosure of Interests: 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, Nicola Maruotti Speakers bureau: Pfizer, Angelo Semeraro Speakers bureau: Sanofi, Roche, AbbVie, BMS, MSD, Novartis, Romano Bucci Speakers bureau: Pfizer, Sanofi, MSD, BMS, Giorgio Carlino Speakers bureau: Pfizer, Janssen, AbbVie, MSD, BMS., Leonardo Santo Consultant of: AbbVie, MSD, Novartis UCB outside this work, Speakers bureau: AbbVie, MSD, Novartis UCB outside this work, Laura Quarta: None declared, Carmelo Zuccaro Consultant of: MSD, AbbVie, Novartis, Pfizer, Janssen outside this work, Speakers bureau: MSD, AbbVie, Novartis, Pfizer, Janssen outside this work, Giuseppina Santacesaria: None declared, Marco Fornaro: None declared, Francesco Paolo Cantatore: None declared