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Background:Idiopathic Inflammatory Myositis (IIM) is a rare autoimmune systemic disease characterized by a wide spectrum of clinical manifestations mainly involving skin and muscles. Few data are available on literature exploring the gender differences in IIM patients.Objectives:To analyze the gender difference in IIM patients in clinical and autoantibody profiles as well as treatment strategies.Methods:We performed a cross sectional observational study including patients who fulfilled ACR/EULAR 2017 criteria for Dermatomyositis (DM), Polymyositis (PM), and Antisynthetasis Syndrome (ASS) (time frame Jan 2018-December 2023), referring to the Reference Center of “Tor Vergata” University Hospital in Rome (Italy). Demographic data, clinical manifestations, and treatment approaches were recorded. Additionally, an assessment of the antibody profile, encompassing Myositis Specific Antibodies (MSA) and Myositis Associated Antibodies (MAA), was conducted. Continuous variables were compared with T test, categorical variables by using Chi-square or Fisher’s exact test. P<0.05 values were considered statistically significant.Results:The study cohort included 51 patients (68.8% F). Median age at disease onset and diagnostic delay were similar in males and females, while disease duration was significantly longer in males (p 0.018) (Table 1). The diagnosis of DM and PM was equally distributed, while ASS was slightly prevalent in men. Accordingly, lung involvement occurred more frequently in males than females (Figure 1). No significant differences emerged between the groups according to comorbidities (Table 1). Joint involvement as well as upper limb muscle weakness affected more frequently female patients (p<0.05, Figure 1). A similar prevalence of ANA titer ≥ 1:160 resulted among males and females as well as for the distribution of MSA and MAA. Dual positivity of MSA was observed in one male (anti-Mi-2/anti-Pl7) and two females (anti-MDA5/anti-NXP2 and anti-MDA5/anti-EJ antibodies). Mycophenolate Mofetil (p<0.001) and Rituximab (p<0.05) were administrated with a higher prevalence in male patients than females.Conclusion:Our study documents for the first time gender differences in IIM, highlighting a different distribution of lung and joint involvement being prevalent mainly in males and females, respectively. Differences in clinical phenotypes, in the absence of a gender-related prevalence of specific autoantibodies, might affect treatment strategies. Our findings support the idea for a gender orientated approach which is crucial to improve decision making process in clinical practice.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Spondyloarthritis (SpA) and Psoriatic Arthrtis (PsA) are compelling causes of secondary osteoporosis. Low values of Bone Mineral Density (BMD) cause a high risk for fragility fractures, but other several determinants can play a role, such as smoking, alcohol, low BMI, corticosteroid medications, history of familiar or one’s own fractures. Nowadays, dual-energy X-ray absorptive densitometry (DXA) is the gold standard for osteoporosis diagnosis, but results could be biased when osteoproductive lesions of the spine are present. Therefore, algorithms like FRAX and the Italian DEFRAcalc have been developed to predict fracture risk in 10 years, even when BMD is not available. While FRAX includes Rheumatoid Arthritis and DeFRA includes PsA in calculation items, both of them do not consider other Spondyloarthritis, leading to a possibile underestimation of risk.Objectives:To compare FRAX and DeFRA assessment tools, with or without BMD, in patients affected by Axial Spondiloarthritis (axSpA) and axial Psoriatic Arthritis (axPsA). To compare FRAX and DeFRA estimation fracture risk in axSpA and axPsA patients with osteoporosis according to ESCEO guidelines.Methods:A monocentric, cross sectional, retrospective study was conducted in a cohort of patients referring to the Rheumatology Unit of the University of Rome Tor Vergata, from 1 July to 31 December 2023. We included patients with radiographic axSpA and axPsA who had performed at least one DXA since diagnosis. Demographic and clinical data, osteoporosis treatment, lumbar and femoral T-score values in total and single sites were collected. FRAX, for the entire population, and DeFRA, for postmenopausal women - with or without BMD - were estimated via online calculators. Patients were located in risk classes according to score values: low, intermediate, high (0-10%;11%-19%;>20%). Inter-groups comparisons were made with Wilcoxon signed rank test. Statistical analysis was conducted via GraphPad prism Version 9.5.1. p <.05 were considered statistically significant.Results:59 patients were enrolled (33 axPsA and 26 axSpA). Data are shown in Table 1. In the study population FRAX major and DEFRA values were significantly higher when estimated without BMD than those evaluated with BMD [respectively, 14 (2.2-66) vs 11 (1-52); p<.0001 and 14 (3-50) vs 13 (2.7-50); p<.0001]; FRAX at the hip were major with BMD than without BMD [2.4 (0-44) vs 2.2 (0.1-60); p<.0001]. FRAX major and DEFRA without BMD were higher in axPsA than in axSpA [respectively, 17 (2.2-51) vs 13 (3.4-66), p<.0001 and 14 (3-50) vs 7.3 (3.6-50); p<.0001]. FRAX major, FRAX hip and DEFRA with BMD were major in axPsA compared with axSpA [respectively 13 (2.1-52) vs 9.8 (1-45); p<.0001 and 3 (0-44) vs 1.6 (0-37); p<.0001 and 14 (2,7-50) vs 7.4 (3.4-50) p<.0001)]. In both groups of osteoporotic patients at lumbar spine, FRAX major, FRAX hip and DEFRA values were higher without than with BMD [respectively 21 (3,5-53) vs 17 (1-45); p<.0001 and 3,3 (0,1-44) vs 3,3 (0.8-37); p<.0001 and 18 (14.5-50) vs 15 (4.6-50) p<.001]. In osteoporotic patients at femoral neck FRAX major, FRAX hip and DEFRA with BMD were higher in both axPsA and axSpA than those without BMD [27 (6.6-52) vs 21 (3.5-66); p<.0.004 and 10 (3-44) vs 9.8 (0.3-60), p<.004 and 35 (11-50) vs 28 (6.6-50); p<.016].Conclusion:FRAX major and DEFRA without BMD in both axSpA and axPsA and in patients with lumbar spine osteoporosis, are higher than those with BMD. This issue confirms that DXA could underestimate fracture risk owing to syndesmophytes production, even in patients already affected by osteoporosis according to ESCEO guidelines. In axPsA we observed higher DEFRA with and without BMD than in axSpA, as expected since this comorbidity is excluded from the calculation. It is worth noting, however, that even FRAX major and hip, with and without BMD, were higher in axPsA than in axSpA. This suggests an increased fracture risk in axPsA, confirmed by a higher absolute number of fractures in axPsA patients (29 vs 20). In osteoporotic patients at femoral neck, DEFRA and FRAX were higher including BMD, possibly due to the absence of osteoproductive lesions at this level.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Osteoporosis is a systemic skeletal disease characterized by a high risk of fractures. Major osteoporotic fractures may affect different bone sites (as vertebrae, hip, forearm) and may cause disability. Given that, not only the BMD is fundamental to determine the fragility fracture risk, but also sarcopenia, inactivity and sedentary lifestyle seem to be relevant determinants. International recommendation (ESCEO) for the management of fragility fractures encourages patients to perform physical activity to improve muscle strength and reduce new incident fractures rate. Fragility fractures can be asymptomatic or provoke intense pain in the site of fractures, generally in the first 6 months. This can trigger irrational fear of movement due to the belief of susceptibility to injury that can be maintained up until several months after the injury. Indeed, having experienced fragility fractures without an adequate education program may lead to movement-avoidance beliefs due to an illogical fear of falls and related fractures.Objectives:To evaluate the prevalence of movement-avoidance behaviour in Osteoporotic patients after at least 6 months since the first fragility fracture occurred. To correlate the presence of fear of movement to the quality of life and to compare this data to a healthy control group.Methods:A monocentric case control study was conducted in 31 osteoporotic patients with and without a history of previous fractures, referring the Rheumatology Unit of the University of Rome Tor Vergata in Rome (Italy), (time frame July ‘23-Jenuary ‘24). Levels of Movement-Avoidance behaviour were measured using TSK1 (Tampa Scale Questionnaire 1 in the Italian version – questions 1,2,10,14,15,17). Disability was measured by HAQ-DI (Health assessment questionnaire – disability index). The incident fracture was detected at least 6 months earlier than the questionnaire submission. All the patients had no history of rheumatologic diseases. Demographic and clinical data were collected. Statistical analysis was performed by T-student, χ2 and ANOVA tests, by using GraphPad Prism 8.0.2 software. P-value<0.05 was considered significant.Results:Main results are shown in Table 1. The study consecutively enrolled 27 Controls without osteoporosis and 31 osteoporotic patients. Based on the occurrence of at least one fragility fracture, patients were divided into two groups: Osteoporotic patients with Fragility Fracture [n=16 (51.6%) – Group1] and Osteoporotic patients without fragility fractures [n=15 (48.4%) – Group 2]. All the groups exhibit a female-sex prevalence (Group 1: 81,3%; Group 2: 86,7%; Control Group:81,5%). Statistical difference in age and Body Mass Index (BMI) was recorded among the groups, in particular Group 1 showed a higher median age (p<0.05) and a lower BMI (p=0.001). No differences were noted in smoking habits, alcohol consumption, levels of education rate and occupational status. Statistically significant data were registered concerning the frequency of falls in the past 12 months and the familiarity of fractures between Group 1 and Group 2 (p<0.0001 and p<0.05). In group 1, vertebrae fractures, non-vertebral and non-femoral were prevalent (62.5% for both), instead, hip fractures were the 25% [Graphic 1]. A trend of significance with later menarche (12.4±0.98 vs 11.6±0.98) and earlier menopause (44.4±5.4 vs 48.6±6.2) was noticed for Group 1 vs Group2. Levels of movement avoidance behaviour measured by TSK1 score resulted statistically significant among all the groups (p=0,0001), despite HAQ-DI scoring exhibit no differences.Conclusion:Our analysis confirmed that older age, lower BMI, later menarche and earlier menopause are relevant risk factors for osteoporosis and fragility fractures, also the history of recent falls is an important determinant. Moreover, this study demonstrated that subjects with osteoporosis have higher levels of movement-avoidance behaviour compared to healthy subjects, in particular if a previous fracture has been occurred, suggesting the need for a multidisciplinary approach, that includes physical activity programs.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Kinesiophobia refers to the fear of physical activity and movement. It may promote chronic pain and sedentary lifestyle in patients affected by Psoriatic arthritis (PsA).Objectives:As physical activity has been included in treatment recommendations for spondyloarthritis, the aim of the present study was to evaluate the prevalence of kinesiophobia, depression and quality of life (QoL) in PsA patients compared to a sex- and age-matched controls group (CG).Methods:A case-control study was conducted in 72 PsA patients referring to PsA outpatient unit of University of Rome Tor Vergata, Italy, who fulfilled CASPAR classification criteria. Patients’ recruitment took place in April ‘23 and May ‘23. Anthropometric and demographic parameters, clinical features and treatment strategies were recorded. Levels of Kinesiophobia, depression and Quality of life were measured by: TAMPA Kinesiophobia Scale (TSK) divided into TSK1 (movement-avoidance behaviour) and TSK (movement causing pain), Beck’s Depression Inventory (BDI), Short-Form Health Survey (SF-36). Statistical analysis was performed by T-student, χ2 and ANOVA tests, by using GraphPad Prism 8.0.2 software. P-value<0.5 was considered significant.Results:Main results of the study are illustrated in Table 1. 72 PsA patients (37.5% male; 62.5% female) and 74 controls (31.1% male e 68.9% female) were enrolled. A higher prevalence of obesity, inactivity, cardiovascular comorbidities, hyperuricemia and lower education rate were observed in cases compared to Control Group. Statistically significant differences were observed between case and controls in:-Total TSK score (27.4±8.1vs23.0±7.3), TSK1 (12.3±4.3vs9.3±2.9), and TSK2 (15.1±4.3vs13.4±4.8).-BDI (8.3±7.2vs5.9±6.1).-SF-36: physical functioning (60.5±27 vs 91.9±13.1), physical health (51±43.5 vs 89.1±25), emotional problems (58.8±43.5 vs 77.6±37.6), emotion well-being (62.9±17.1 vs 72.2±21.8) vitality (47.2±18.8 vs 58.3±17.5), Social function (58.9±23.7 vs 72.2±21.8), bodily pain (51.2±23.9 vs 83.9±20.5), general health (42.7±19.2 vs 64.5±15.6).A further analysis in the group of patients revealed a relationship between disease activity (estimated by DAPSA-PCR) and higher scores in TSK (p=0.001), BDI (p<0.01) and lower results in SF36. By contrast, assessing VAS-pain alone denotes a trend of significance at higher TSK and BDI scores and lower SF-36 grade. Moreover, bDMARDs failure patients, who underwent at least three bDMARDs, showed higher TSK values with a trend of significance.Conclusion:This study highlights how kinesiophobia, related to depression and worse QoL, is more frequent in PsA, especially at higher disease activity. VAS-pain and DAPSA analysis suggests that kinesiophobia is not only determined to the painful experience of the patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Inflammatory Idiopathic Myositis (IIM) represents a specific group of rare rheumatologic diseases mainly characterized by skin and musculoskeletal involvement. However, interstitial lung disease (ILD) constitutes a key disease target in IIM, strongly affecting outcome and treatments.Objectives:We aimed at evaluating distribution and pattern of ILD in a selected cohort of IIM patients. Potential association between ILD and both the disease phenotype and the autoimmunity profile have been explored.Methods:We performed a cross sectional observational study including patients who fulfilled 2017 ACR/EULAR 2017 criteria for Dermatomyositis (DM), Polymyositis (PM), and Antisynthetasis Syndrome (ASS) (time frame June 2023-December 2023) referring to the Reference Centre of “Tor Vergata” University Hospital in Rome (Italy). Demographical data, including clinical and laboratory records, were collected. Concomitant ILD was defined based on chest computed tomography (chest CT) images: included patients were divided in two groups according to the presence of ILD. Continuous variables were compared with T test, categorical variables by using Chi-square or Fisher’s exact test. P<0.05 values were considered statistically significant.Results:The study cohort included 51 patients (68.6% women). Patients’ characteristics were summarized in Table 1. Patients with ILD were 51% (n=26; Group 1) while patients without were 49% (n=25 Group 2). Patients from Group 1 were older than those from group 2 at IIM diagnosis (p=0.04). ASS diagnosis resulted prevalent in Group 1 than Group 2 (p=0.01), while DM was significantly more frequent in Group 2 p=0.001). Patients in Group 1 showed a higher prevalence of dyspnoea (p<0.0001), arthralgias p=0.006), and arthritis (p=0.04) than those in Group 2. A significantly higher prevalence of Gottron papules and periorbital oedema has been registered in Group 2 than Group 1 (p<0.05). A diagnosis of malignancy occurred mainly in patients from Group 1 (p=0.02). Autoantibody profile resulted similar between two groups, excepted for anti-Jo1 patients who were mainly present in Group 1 (p=0.01) (Graphic 1).Conclusion:Our real-life data support the relevant association between concomitant ILD and specific IIM clinical pattern resulting mainly associated with joint involvement and IIM complicated by malignancy. Autoantibody profile might help in IIM patients’ stratification by potentially predicting ILD. Focusing on lung involvement in IIM represents a key tool to improve disease management and treatment strategies.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Mixed connective tissue disease (MCTD) is a rare complex syndrome with features of different autoimmune connective tissue diseases (CTDs) in patients with antibodies targeting the U1 small nuclear ribonucleoprotein particle. In MCTD, immune-system abnormalities and, thus, fibrosis may involve skin and other internal organs, including lungs, also leading to diffuse microangiopathy. Lung involvement in terms of interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are key manifestations strongly affecting morbidity and mortality in MCTD.Objectives:MCTD patients’ phenotypic pattern were analyzed according to the presence of concomitant lung involvement to explore potential association with microvascular damage.Methods:We performed a cross sectional observational study including patients with a defined diagnosis of MCTD, referring to the Reference Centre of “Tor Vergata” University Hospital in Rome (Italy). Recorded data included clinical and laboratory findings. Nail fold videocapillaroscopy (NVC) patterns and trans-thoracic echocardiographic PAPs value (PAPs>25 mmHg defined PAH) were analyzed. Concomitant ILD was defined based on chest computed tomography (chest CT) features: patients were thus divided in accordance with the presence of ILD. Continuous variables were compared with T test, categorical variables by using Chi-square or Fisher’s exact test. P<0.05 values were considered statistically significant.Results:The study cohort included 24 patients (95.8% women). Patients’ characteristics were shown in [Table 1]. Patients with ILD were 37.5% (n=9; Group 1) while patients without were 63.5% (n=15 Group 2). Disease duration was greater in Group 1 than in Group 2 (p=0.02). PAH has been revealed in a significantly higher percentage in Group 1 than Group 2 (P<0.01). Patients from Group 1 also exhibited a higher prevalence of telangiectasias, digital ulcers, pitting scars, and serositis than patients from Group 2 (p<0.02 for all the comparisons) along with a NVC late pattern (p<0.01) [Graphic 1]. A higher prevalence of cardiovascular and other respiratory comorbidities was observed in Group 1 than Group 2 (p<0.001 and p<0.05, respectively). A joint involvement showed a trend to be more frequent in Group 2. Patients from Group 1 showed a higher prevalence of both RoSSA-60 and -52 autoantibodies than those from Group 1 (p<0.01). Azathioprine resulted administered more frequently in Group 1 than in Group 2 (p<0.01).Conclusion:Our study documented in MCTD patients complicated with ILD a disease phenotype characterized by a more severe microvascular damage while confirming the role of specific autoantibodies profile in lung disease.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background: Despite the effectiveness of antiretroviral therapy, vertical HIV transmission continues. A potent, broadly neutralizing, monoclonal antibody (bNAb) administered to HIV-exposed infants might reduce transmission. VRC07-523LS is 5-fold more potent and has a prolonged half-life compared to VRC01. VRC07-523LS may provide therapeutic levels over the duration of breastfeeding with infrequent doses. Methods: This is an open-label study of VRC07-523LS administered to HIV-exposed infants. Non-breastfed infants receive 80 mg subcutaneous (SC) within 72 hrs of birth. Infants and mothers receive ART to prevent transmission. Infants have safety assessments and VRC07-523LS levels at 24 hrs, week 2, 4, 8, 12 and every 12 weeks through week 96. The target week 12 plasma level is 10 mcg/mL: the leve needed to neutralize > 90% of tier II viruses in a multiclade panel. Plasma VRC07-523LS levels are determined through week 12 and compared to previously reported levels of VRC01. Results: The non-breastfed cohort fully accrued (N = 11) from US sites Jan-Sep, 2019. All infants received 80 mg VRC07-523LS SC within 72 hours of birth (mean 1.5 days), resulting in an average dose of 28 mg/kg (range 23 to 32 mg/kg). Enrollees were 45% male, 73% Black, 18% Hispanic. One infant withdrew after 4 weeks. VRC07-523LS was well tolerated. Local reactions were rare and mild: 1 infant had injection site erythema of 0.5 cm and 1 had tenderness. Five infants developed Grade 3/4 events within 28 days of receipt of VRC07-523LS (vomiting [N = 2], neutropenia, hyperkalemia, and parainfluenza sepsis), none considered related to study treatment. Pharmacokinetic measures through week 12 show average levels of 68.7, 31.1, 16.3mcg/mL at weeks 4, 8, and 12, respectively. Mean VRC07-523LS levels exceeded those previously reported for VRC01 20 mg/kg SC at week 2, 4, and 8. Ongoing growth contributed to the fall in VRC07-523LS concentration but levels remain over the target of 10 mcg/mL at week 12. Conclusions: We identified no safety or tolerability findings when VRC07-523LS is administered to neonates. Week 12 is an appropriate time for a second dose in infants with ongoing breastmilk exposure. VRC07-523LS, with its enhanced potency and extended half-life, could achieve target levels for the duration of breastfeeding with dosing every 3 months.

BackgroundThe magnitude of infant antiretroviral (ARV) exposure from breast milk is unknown MethodsWe measured concentrations of nevirapine, lamivudine, and zidovudine in serum and whole breast milk from human immunodeficiency virus type 1 (HIV-1)–infected women in Botswana receiving ARV treatment and serum from their uninfected, breast-feeding infants ResultsTwenty mother-infant pairs were enrolled. Maternal serum concentrations of nevirapine were high (median, 9534 ng/mL at a median of 4 h after nevirapine ingestion). Median breast-milk concentrations of nevirapine, lamivudine, and zidovudine were 0.67, 3.34, and 3.21 times, respectively, those in maternal serum. The median infant serum concentration of nevirapine was 971 ng/mL, at least 40 times the 50% inhibitory concentration and similar to peak concentrations after a single 2-mg/kg dose of nevirapine. The median infant serum concentration of lamivudine was 28 ng/mL, and the median infant serum concentration of zidovudine was 123 ng/mL, but infants were also receiving zidovudine prophylaxis ConclusionsHIV-1 inhibitory concentrations of nevirapine are achieved in breast-feeding infants of mothers receiving these ARVs, exposing infants to the potential for beneficial and adverse effects of nevirapine ingestion. Further study is needed to understand the impact of maternal ARV treatment on breast-feeding HIV-1 transmission, infant toxicity, and HIV-1 resistance mutations among infected infants

BackgroundIn the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates.MethodsA ‘meta-model’ using NONMEM with 4894 concentrations from 1631 neonates was built and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming at reaching a target AUC0-24 of 400 mg*h/L at steady state in at least 80% of neonates.ResultsA two-compartment model best fitted the data. Current weight, post-menstrual age (PMA) and serum creatinine were the significant covariates for clearance (CL). After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg twice daily if < 35 weeks PMA and 15 mg/kg three times daily if ≥ 35 weeks PMA) achieved the AUC0-24 target earlier than a standard ‘Blue Book’ dosage regimen in more than 89% of the treated patients.ConclusionsThe results of a population meta-analysis of vancomycin data have been used to develop a new dosing regimen for neonatal use and assist in the design of the model-based, multinational European trial, NeoVanc.Disclosure(s)Nothing to disclose

New approaches to expedite the development of safe and effective pediatric dosing regimens and first‐in‐child doses are urgently needed. Model‐based approaches require quantitative functions on the maturation of different metabolic pathways. In this study, we directly incorporated a pediatric covariate model for the glucuronidation of morphine into a pediatric population model for zidovudine glucuronidation. This model was compared with a reference model that gave the statistically best description of the data. Both models had adequate goodness‐of‐fit plots and normalized prediction distribution errors (NPDE), similar population clearance values for each individual, and a Δobjective function value of 13 points (Δ2df). This supports our hypothesis that pediatric pharmacokinetic covariate models contain system‐specific information that can be used as semiphysiological functions in pediatric population models. Further research should explore the validity of the semiphysiological function for other UDP‐glucuronosyltransferase 2B7 substrates and patient populations and reveal how this function can be used for pediatric physiologically based pharmacokinetic models. CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e9; doi:10.1038/psp.2012.11; advance online publication 3 October 2012