Explore the vast range of titles available.

BackgroundJAK inhibitors (JAKi), small molecules that inhibit the Janus kinase enzymes, are increasingly used to treat children with rheumatologic diseases. Clinical experience of JAKi in the management of adult patients with pediatric-onset rheumatic conditions is still scarce.ObjectivesThe aim of this study consists in evaluating efficacy and safety of JAKi in a monocentric cohort of adult patients with juvenile idiopathic arthritis (JIA).MethodsClinical records of patients attending the rheumatology transition clinic at our centre were retrospectively reviewed; patients were included in case of: i) JIA diagnosis according to current classification criteria (1); ii) age ≥18 years and iii) treatment with JAKi for at least 3 months.Results17 patients that met the inclusion criteria were included in this study. Their demographics and clinical features are detailed in Table 1. 9 patients were treated with tofacitinib (52.9%) and 8 subjects (47.1%) received baricitinib. At 3 months, 4 patients (23.5%) achieved disease remission on JAKi: 3 patients achieving remission were treated with baricitinib and 1 with tofacitinib (37.5 vs. 16.7%, p=0.29). None of the patients with systemic JIA and enthesitis-related arthritis obtained remission; the remission rate at 3 months was higher, although not significantly, in the oligoarticular subset compared to the polyarticular subset (37.5 vs. 20%; p=1.0). Disease duration, age at onset and at JAKi start were similar between patients achieving remission and those with active disease (p=0.94, p=0.58 and p=0.72, respectively). Patients with ≤1 active joint involvement at JAKi start had higher remission rate (50 vs. 22.2%; p=0.58). Subjects who achieved remission on JAKi had a significantly lower pre-treatment DAS28 compared to those with still active disease (median DAS28 (IQR) 2.17 (1.9-2.4) and 4.54 (3.8-4.9), respectively; p=0.01, Mann-Whitney U=4). A pre-treatment DAS28 <3.76 predicted response to JAKi with 100% sensitivity and 84.6% specificity (AUC 0.88, p=0.02, 95%CI 0.71-1.05). Concomitant treatment with methotrexate did not significantly affect the remission rate (16.7 vs. 37.5%; p=1.0). This was lower among patients who had been treated with ≥2 biological drugs before JAKi start (9 vs. 66.7%; p=0.05). None of the patients developed side effects during JAKi treatment.ConclusionJAKi could represent an effective and safe treatment option for adult JIA patients with low/moderate disease activity, particularly in case of oligoarticular involvement.Reference[1]Petty RE, International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004;31:390–2.Table 1.Demographics and clinical features of enrolled JIA subjects.O-JIA (n=8)P-JIA (n=5)ERA (n=2)S-JIA (n=2)Total cohort (n=17)Age at JIA onset, median (IQR)4.5 (9)13 (6)15 (1)10 (6)10 (13)Age at JIA diagnosis, median (IQR)4.5 (10)14 (8)15 (1)10 (6)11 (13)Age at starting treatment with JAKi, median (IQR)28.8 (6.7)26 (12)40.8 (1.8)37 (10)31 (13.6)Gender (F, %)75% (6)100% (5)100% (2)50% (1)83.4% (14)ANA positivity, % (n)75% (6)60% (3)50% (1)0% (0)58.8% (10)Disease duration at JAKi start in years, median (IQR)27.1 (11.2)18 (3)26.25 (1.2)28 (4)25 (11.3)DAS28 at starting treatment with JAKi, median (IQR)3.76 (1.07)5 (1)4.86 (0.25)3.0 (1)4 (1.57)Iridocyclitis, % (n)50% (4)20% (1)0.0 (0)0.0 (0)29.4 (5)N of pre-JAKi sDMARDs, median (IQR)2 (1.0)2.0 (1.0)3.0 (2.0)4.5 (0.5)3 (2.0)Ongoing MTX, % (n)Median dose (IQR)12.5% (1)15mg/wk60%(3)10 mg/wk50%(1)7,5 mg/wk50%(1)7.5 mg/wk35.2 (6)15mg/wkOngoing LEF, % (n)Median dose (IQR)25%(2)20%(1)20mg die0% (0)0% (0)17.6% (3)Ongoing oral steroids, % (n)Median dose (IQR)0% (0)40%(2)10mg die0%(0)0% (0)11.7% (2)N of pre-JAKi bDMARDs, median (IQR)2.5 (2.25)3 (2)5 (1)2 (2)2 (2)N of involved joints at JAKi discontinuation, median (IQR)0.5(0)1 (2)4 (1)1 (1)1 (2)Days of duration of treatment with JAKi, median (IQR)324.5 (345)297(149)95 (5)574.5 (513.5)297 (315)Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundChronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease of bone primarily affecting children and adolescents. Although CRMO can be associated with inflammatory bowel disease (IBD)[1], the prevalence of subclinical bowel inflammation and its relationship with other autoimmune bowel disorders remains uncertain.ObjectivesThis study aims to evaluate the prevalence of subclinical bowel inflammation in CRMO patients and the potential association with celiac disease.MethodsClinical records of patients diagnosed with CRMO attending the Unit of Pediatric Rheumatology of Gaetano Pini Hospital were retrospectively reviewed. Fecal calprotectin and screening for celiac disease were performed in all patients within 2 years after diagnosis.ResultsComplete data from 24 patients were collected (83% female). The mean age at diagnosis was 10.1 (DS ± 2.7) and the median follow-up time was 68.5 months (IQR 97.5). The first symptom at onset was bone pain (100%), while only 4 patients (17%) complained of gastrointestinal symptoms (abdominal pain, weight loss, diarrhea). The patients in our cohort had no specific comorbidity, except for two patients suffering from hemophilia and pyoderma gangrenosum, respectively. 96% (23/24) of patients had polyostotic disease. During the follow-up period, 9 patients (38 %) received only non-steroidal anti-inflammatory drugs therapy, 10 patients (42%) received conventional disease-modifying antirheumatic drugs (methotrexate), 4 (17%) received anti-tumor necrosis factor (TNF) agents and 12 (50%) received intravenous bisphosphonates. Cumulative treatments are summarized in Figure 1. Two patients, both in clinical remission off medication, were lost to follow-up. Calprotectin levels were normal in 100% of patients, while 3 patients (13%) presented positive screening test for celiac disease with a positive test for IgA anti-tissue transglutaminase antibodies (Table 1). In one of these patients, the diagnosis of celiac disease was confirmed by duodenal biopsy. After a gluten-free diet, the patient, who was off medication, achieved complete clinical remission and a remarkable improvement in radiological lesions.ConclusionThe link between autoinflammatory bone disease and intestinal inflammation should be further investigated since it might open insight into bone inflammation and new therapeutic options. In our experience, controlling bowel disease may promote a better response to CRMO treatments. On the other hand, the percentage of unexplained bone pain in celiac disease is high, and, in this scenario, a possible inflammatory bone disorder should be ruled out.Reference[1] Audu GK, Nikaki K, Crespi D, Spray C, Epstein J. Chronic recurrent multifocal osteomyelitis and inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2015 May;60(5):586-91.Figure 1.Cumulative treatments during the follow-up time.MTX= methotrexate; TNF= tumor necrosis factor; NSAIDs= non-steroidal anti-inflammatory drugs.Table 1.Case series of CRMO in association with positive IgA anti-tissue transglutaminase antibodiesCase numberSexAge at onsetComorbidityPoly/monostotic diseaseDuodenal biopsyTreatment1F10NoPolyPositiveNSAIDs2F12NoPolyNot performed yetNSAIDs3F12Pyoderma gangrenosumPolyNot performed yetBisphosphonatesAcknowledgements:NIL.Disclosure of InterestsStefania Costi: None declared, Sabino Germinario: None declared, Maria Rosa Pellico: None declared, Andrea Amati: None declared, Maurizio Gattinara: None declared, Cecilia Chighizola: None declared, Achille Marino: None declared, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, UCB.

Background:Pneumologists do not routinely include screening for anti-neutrophil cytoplasmic antibodies (ANCA) in the evaluation of interstitial pneumonia (IP). Indeed, antibodies against myeloperoxidase (anti-MPO) and proteinase 3 (anti-PR3) are not encompassed in the classification of IP with Autoimmune Features (IPAF), However, anti-MPO antibodies have been reported in subjects with ILD or idiopathic bronchiectasis (percentage ranging from 7 to 23%), but only a few studies describe their clinical evolution.Objectives:To evaluate the prevalence of anti-neutrophil cytoplasmic antibodies (ANCA), anti-MPO antibodies and anti-proteinase-3 (ant-PR3) antibodies in patients with Idiopathic pulmonary fibrosis (IPF) and IPAF in a pneumologist setting.Methods:We retrospectively collected clinical charts of patients referred to a Pneumology Clinic specialized in IP, who received a diagnosis of IPF/IPAF from 31 March 2018 to 1 April 2023. None of the patients had Connective Tissue Disease (CTD) or vasculitis signs/symptoms at diagnosis. We re-tested all patients for IPAF-associated autoantibodies (ANA, ENA, anti-CCP, RF) and ANCA, anti-MPO or ant-PR3. Descriptive statistics were performed for demographic and disease characteristics. Comparisons were carried out by chi-square or one-way ANOVA test. Analysis of outcome predictors was performed by logistic multiple logistic regression. To identify the clinical subset of IP patients with baseline features at higher odds to progress to systemic vasculitis, unsupervised clustering with K-means fitted with all baseline covariates was performed.Results:103 patients were enrolled in the study whose demographics and clinical characteristics are showed in Table 1A. Of these, 37 patients were diagnosed with IPAF, and 64 with IPF. 21 patients were ANCA positive. We reclassified our patients into three groups: IP pANCA+ (n=21), IPF pANCA- (n=53), and IPAF pANCA- (n=27) (Table 1B). The IP pANCA+ group had a higher percentage of males (43%, p=0.04) and NSIP HRCT pattern (43%, p=0.02). At 6 and 12 months, IP pANCA+ patients showed higher frequency of bronchiectasis at 6 (71%, p=0.02) and 12 months (70%, p=0.04). None of the p-ANCA- patients developed vasculitis, but 29% and 38% of p-ANCA+ patients developed vasculitis at 6 and 12 months. No differences were observed in terms of HRTC progression, O2 therapy and death. Multiple regression models showed that disease duration was associated with HRCT progression (OR 1.28, p=0.03), smoke with death (OR 26.7, p=0.01), IPF with need of oxygen therapy (OR 6.33, p=0.04), ANCA positivity with the develop vasculitis (OR 1.22, p=0.04). None of the patients had full vasculitis at baseline, but some had extrapulmonary manifestations. Cluster analysis identified a subgroup of patients with higher odds to develop vasculitis (Figure 1).Conclusion:These findings suggest that in patients presenting with IP, testing for ANCAs should be performed routinely, as positive anti-MPO along with some systemic manifestation may identify a cluster of patients at high risk of vasculitis. Whether IP-ANCA+ disease should be considered a new pathological entity needs further investigation on prospective cohorts.REFERENCES:[1] Bridget A. Graney, Aryeh Fischer. Interstitial Pneumonia with Autoimmune Features. Ann Am Thorac Soc 2019, Vol 16, No 5, pp 525–533.[2] Sebastiani M, Manfredi A, Vacchi A, et al. Epidemiology and management of interstitial lung disease in ANCA-associated vasculitis. Clin Exp Rheumatol 2020; 38 (Suppl. 124): S221-S231.[3] Sebastiani M, Luppi F, Sambataro G, et al. Interstitial Lung Disease and Anti-Myeloperoxidase Antibodies: Not a Simple Association J. Clin. Med. 2021, 10, 2548 doi: 10.3390/jcm10122548.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:The negativization of antinuclear antibodies (ANA), defined as two consecutive negative determinations, is described in about 13% of patients with systemic lupus erythematosus (SLE). A single study assessed ANA negativization in juvenile-onset SLE (jSLE), reporting negative ANA seroconversion in 2.63% of patients, without significant associations with any demographic or clinical variable.Objectives:This study aims at determining the ANA negativization rate in a monocentric cohort of jSLE patients, evaluating all potential predictive factors of seroconversion and assessing the association between seroconversion and disease flare.Methods:Patients with SLE diagnosis formulated according to 2019 ACR/EULAR criteria before the age of 18 years, regularly attending our institution, were recruited in case of at least 3 available longitudinal ANA determinations. ANA were assessed by indirect immunofluorescence on HEp-2 and a titer ≥1:80 was considered positive. Demographic details, clinical and serological features of the disease, ongoing therapies, and disease activity (assessed through SLEDAI and BILAG) were retrospectively collected at each ANA determination. A flare was defined as a new BILAG A or two BILAG B in any disease domain. Univariate logistic regression analyses were performed.Results:35 patients (94% female, median age at diagnosis of 15 years) fulfilling the inclusion criteria were recruited. In 8 subjects (22.9%), isolated negativity was found in a single determination, without confirmation in the subsequent tests. ANA were negative in at least 2 consecutive determinations in 5 patients (14.3%). This seroconversion occurred on average 5.8 years after diagnosis and 1.5 years after the last disease relapse. Among the 5 patients with negative seroconversion, only one subject displayed a disease flare during follow-up (20%). A higher mean SLEDAI score, musculoskeletal and mucocutaneous involvements were associated with a lower frequency of ANA negativization (p=0.01, odds 36; p=0.02, odds 0.02; p=0.00, odds 0.03, respectively). No association was found with ongoing and/or previous therapy and the number of disease flares.Conclusion:The rate of ANA negative seroconversion in this cohort is higher than what reported for jSLE but consistent with literature data in SLE patients. Further studies with larger cohorts are needed to assess the association between ANA negativization and clinical features, as well as ongoing and/or previous therapies.REFERENCES:[1] Bao S, Huang H, Jin Y, Ding F, Yang Z, Xu X, et al. Autoantibody-based subgroups and longitudinal seroconversion in juvenile-onset systemic lupus erythematosus. Lupus Sci Med 2023;10(1).Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Rituximab, a pharmacological agent targeting B cells, is commonly employed in the treatment of rheumatoid arthritis, while its efficacy and safety in juvenile idiopathic arthritis (JIA) patients remain scarcely documented.Objectives:This study aims at assessing the efficacy and safety of rituximab within a single-center cohort of adult JIA patientsMethods:Patients were retrospectively recruited at the Rheumatology Transition Clinic of our institution in case of: i) a JIA diagnosis according to the International League of Associations for Rheumatology (ILAR) criteria [1], ii) age of at least 18 years, and iii) a minimum of 6 months of rituximab therapyEach course included two 1000 mg intravenous rituximab infusions 2 weeks apart, to be repeated based on clinical judgment every 24 weeks.Results:This study included 22 subjects (7 with oligoarticular (O-) JIA, 13 with polyarticular (P-) JIA, 2 with enthesitis-related arthritis [ERA]), whose demographics and clinical details are summarized in Table 1. All recruited patients had a recalcitrant disease, with a median of two failed biologics before starting rituximab. In 45% of cases, patients received rituximab in association with methotrexate. With rituximab, a similar improvement in DAS28 scores was observed across all JIA categories. In particular, after 12 months of rituximab therapy, remission was achieved by 86% of the patients, with a 100% remission rate in the O-JIA subgroup, 84% in patients with P-JIA and 50% in those with ERA. No significant differences in disease duration, age at JIA onset, age at start of rituximab, positivity for rheumatoid factor and/or antibodies against cyclic citrullinated peptides were observed between responders and non-responders. The overall median duration of treatment was 7.1 years, with a longer median retention in treatment in the O-JIA subgroup (9.71 years). Treatment with rituximab was complicated by seven major infections in the whole cohort, with only two patients requiring hospitalization because of lobar pneumonia and osteomyelitis due to Haemophilus influenzae.Conclusion:Rituximab allows controlling disease activity across different JIA categories, even in patients who have not responded to prior biological treatments. Rituximab demonstrates a tolerable safety profile.REFERENCES:[1] Petty RE, International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004;31:390–2.O-JIA(n=7)P-JIA(n=13)ERA- JIA(n=2)p-valueTotal cohort (n=22)Age at JIA onset, median (IQR)3.7 (9.3)14.6 (9.3)1.8 (0.8)0.43830.0 (6.82)Age at JIA diagnosis, median (IQR)3.8 (10.0)15 (10.2)2 (0.9)0.3518.7 (14.5)MTX monotherapy before bDMARDs treatment % (n)85.7 (6)69.2 (9)50 (1)0.55072 (16)LEF monotherapy before bDMARDs % (n)14.2 (1)15.38 (2)0 (0)0.83917 (3)Age at starting treatment with RTX, median (IQR)17 (12)19 (7)29.5 (7.5)0.75120.5 (7.75)Gender (F, %)85.7 (6)69.2 (9)100 (2)0.5177 (17)ANA positivity, % (n)57.4 (4)38.4 (5)50 (1)0.7245 (10)Disease duration at RTX start in years, median (IQR)11 (9)8 (5)27.5 (6.5)0.31810 (11.25)DAS28 at starting treatment with RTX, median (IQR)3.7 (0.5)3.8 (1.02)3.4 (0.4)0.6913.7 (0.79)DAS28 at 6 months with RTX treatment, median (IQR)1.7 (1.05)2.19 (1.4)2.1 (0.9)0.6062.0 (1.35)DAS28 at 12 months with RTX treatment, median (IQR)1.82 (1.0)2.10 (0.7)2.39 (0.6)0.6912.0 (0.90)Iridocyclitis, % (n)85.7 (6)30.7 (4)50 (1)0.06450 (11)Comorbidities, % (n)14.2 (1)46.1 (6)100 (2)0.07840.9 (9)Concomitant MTX, % (n)57.1 (4)38.4 (5)50 (1)0.71045.5 (10)N of pre-RTX bDMARDs, median (IQR)3 (1.5)2 (2.0)3 (2.0)0.5932 (2.0)Duration of treatment with RTX in years, median (IQR)9.71 (9.9)7.45 (3.4)4.79 (2.1)0.6237.2 (5.7)Number of major infections during RTX treatment, median (IQR)2 (1)2 (1)1.5 (0.5)0.8622 (1)Hospitalization during RTX treatment, % (n)14.3 (1)0 (0)50 (1)0.5299.1 (2)JIA: Juvenile Idiopathic Arthritis, IQR: Interquartile Range, MTX: Methotrexate, RTX: RituximabLEF: Leflunomide, bDMARDs: biological Disease-Modifying Antirheumatic Drugs, ANA: Antinuclear Antibodies, DAS28: Disease Activity Score 28Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Systemic Sclerosis (SSc) is a rare autoimmune disease characterized by an abnormal remodelling of tissue matrix, leading to fibrosis of skin and internal organs. Although progresses have been made in terms of knowledge of pathogenic mechanisms, disease biomarkers and therapeutic options are still limited. Lymphocytes, TGF-ß, PDGF- ß play a key role on fibroblast differentiation into activated apoptosis-resistant myofibroblast in SSc patients. Alpha smooth muscle actin (α-SMA) positive (+) myofibroblasts are the key effectors in the disease, being responsible for excessive synthesis, deposition, and remodelling of extracellular matrix proteins. Bcl2-associated athanogene 3 (BAG3) protein is a member of BAG family of co-chaperones that is constitutionally present in a few normal cell types and some tumors with large stromal component (i.e. pancreatic ductal adenocarcinoma), and may be induced by stressful stimuli in a wide variety of cells. Recent studies have demonstrated that BAG3 is a key player in fibrosis regulation; indeed, it is able to induce the transformation of cancer-associated fibroblasts to α -SMA+ myofibroblasts. These cells enhance the intra-tumoral deposition of collagen matrix making cancer more aggressive and drug-resistant.Objectives:To investigate BAG3 role in the pathogenesis of SSc and its contribution in the fibrotic processes.Methods:106 patients with SSc [59 diffuse (dc) and 47 limited (lc) SSc subset, according to the criteria of Le Roy et al.] and an equal number of age- and sex-matched healthy controls were enrolled. BAG3 serum levels measured by a sandwich ELISA assay were compared in three subgroups of SSc patients divided according to their clinical subset, nailfold videocapillaroscopic (NVC) patterns, presence and degree of interstitial lung disease (ILD). Mann-Whitney non-parametric test was used to compare the levels of serum BAG3 in the normal population and in the three subset of SSc patients. Correlations of BAG3 serum levels with modified Rodnan skin score (mRSS) and EUSTAR disease activity score (2017) have been evaluated through Spearman rank correlation test. Moreover, BAG3 expression in skin biopsies of 8 patients with dcSSc was investigated with immunohistochemistry and immunofluorescence. The unpaired t-test was used to compare the mean intensity of BAG3 between groups in the immunohistochemistry studies.Results:BAG3 serum levels were significantly higher in patients with SSc than in healthy controls, finding limited to dSSc subset (Figure 1 A). BAG3 serum levels were significantly higher in patients with scleroderma pattern late at NVC and ILD presence and extent but were not correlated with mRSS and global disease activity score (Figure 1 B-C). Finally, BAG3 was strongly expressed in the skin biopsies of patients with dSSc (Figure 2 A-B-C).Conclusion:To our knowledge, this is the first study showing BAG3 expression in SSc patients’ serum and skin. BAG3 levels are significantly higher in dcSSc, a clinical subset with a prevalent fibrotic signature. This finding was confirmed by BAG3 correlation with scleroderma pattern late and ILD extent. Unsurprisingly, no correlation was observed between BAG3 serum levels and EUSTAR disease activity score, an instrument expression of disease progression rather than fibrosis. The close correlation between serum BAG3 levels and major fibrotic manifestations of SSc suggests that BAG3 pathway may significantly contribute to the fibrotic process that involves both skin tissue and internal organs of SSc patients. Therefore, these promising data support our group to conduct further researches to promote BAG3 as a disease biomarker and therapeutic target in SSc.Acknowledgements:Next Generation EU (PNRR-MAD-2022-12376202 project).Disclosure of Interests:None declared.

Background:Calcinosis, or calcium deposits in skin and soft tissues, is a notable clinical feature of systemic sclerosis (SSc) occurring in around 20% of patients. However, its pathogenesis is unclear and likely involves microvascular injury and dysregulated calcification responses. Calcinosis can lead to painful nodules and ulcers, often on the fingers, and correlates with a history of ischemic digital loss affecting quality of life of patients with SSc. At present, no direct strong association with particular autoantibodies or specific clinical features of the disease has been demonstrated.Objectives:To evaluate prevalence of calcinosis in a Systemic Sclerosis cohort, association with other clinical manifestation and autoantibodies.Methods:A retrospective analysis was conducted on patients that met ACR/EULAR classification criteria for SSc. Clinical characteristics, comorbidities and commonly SSc-associated autoantibodies from these patients were collected. The association between categorical variables was assessed by chi-squared or Fisher exact tests as appropriate; Mann-Whitney test was applied to compare continuous variables between subgroups of patients, as appropriate. Correlation among variables was assessed using Pearson correlation coefficients.Results:The study cohort consisted of 331 SSc patients from our Scleroderma Unit. Of these, 46 (13.8%) presented with at least one calcinosis during the disease course, 27 (58.6%) were classified as limited cutaneous SSc, the other 10 (41,3%) as diffuse cutaneous SSc (dcSSc).Patients with and without calcinosis were compared. Limited cutaneous subtype was equally distributed between the groups. The two groups had comparable median age, age of onset, and female prevalence.Notably, other autoimmune conditions were more common in the calcinosis group (4.3% vs 0.7%, p=0.038). Pitting scars and acral ulcers were also more frequent in patient with calcinosis (54.3% vs 29.8%, p=0.001 and 58.7% vs 33%, p<0.001, respectively).Additionally, gastrointestinal involvement was more prevalent in calcinosis subgroup (56.5% vs 41.4%, p=0.048). In contrast, no significant differences existed between groups in myopathy, neuropathy, sicca symptoms, or autoantibody positivity. Arthralgia was instead less common in the calcinosis group (8.7% vs 22.8%, p=0.027).Positive correlations were confirmed between calcinosis and pitting scars, acral ulcers (coefficients of 0.168, and 0.173 respectively, p < 0.01), other autoimmune diseases, and GI involvement (coefficients of 0.117 and 0.119 respectively, p < 0.05) through Pearson correlation coefficients.Osteoporosis was also more prevalent in patients with calcinosis (43.5% vs 24.9%, p=0.009).Conclusion:The correlations between calcinosis, pitting scars, and acral ulcers highlight the need to better understand the pathophysiological mechanisms linking these manifestations in SSc. One hypothesized mechanism is that vascular injury and ischemia may contribute to dystrophic calcification in affected tissues, as ischemic digital loss is more common in SSc patients with calcinosis.Additionally, the association between calcinosis and osteoporosis suggests a possible connection related to calcium metabolism, though the exact biological mechanisms underlying this relationship remain to be elucidated.Overall, while no strong associations were found between calcinosis and a broader range of clinical features and autoantibodies, this reaffirms the complex, multifactorial nature of calcinosis in SSc. Further research into the pathophysiology, including vascular contributions, is critical to guide targeted treatment development and delineate the clinical implications of this debilitating manifestation for SSc patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Biologic drugs (bDMARDs) have dramatically changed the disease course in juvenile idiopathic arthritis (JIA). However, scarce evidence about their long-term efficacy and safety is available.Objectives:The aim of this study is to illustrate the long-term efficacy and safety of etanercept (ETN) and adalimumab (ADA) as first-line therapy in a monocentric cohort of JIA patients.Methods:Clinical data of patients with long-term AIG treated with ETN or ADA were retrospectively collected. The retention rate of the two bDMARDs was estimated by the Kaplan-Meier method.Results:Of the 118 patients included (72% female), 58 were treated with ETN and 60 with ADA. The most common diagnosis was oligoarticular JIA (55%), followed by polyarticular JIA (30%). The median age at disease onset was 3 years (1-7), with a median follow-up of 14 years. The median time to referral was 2 months (1-5 months). The median duration of treatment was 61.5 months for ETN and 49.5 months for ADA.At 1 year of treatment, the retention rate was 85% in patients treated with ADA and 91% in case of ETN therapy, at 2 years it was 70% in ADA and 73% in ETN, at 5 years it was 31% in ADA and 50% in ETN.In 62 cases (52%), bDMARD treatment was discontinued due to: sustained remission (17%; 4 in ADA group and 7 in ETN group), secondary non-response (19%; 4 in ADA and 8 in ETN), active uveitis (27%; 9 in ADA group and 8 in ETN group), while 19% of patients discontinued first-line bDMARD due to occurrence of adverse events (3 in ADA group and 9 in ETN), such as gastro-intestinal side effects (n=1 ADA, n=2 ETN) and development of anxious-depressive symptoms (n=2 ADA, n=1 ETN). Recurrent infectious events (n 3), occurrence of allergic reactions (n 2) and elevation of liver function tests (n 1) appeared more frequently in the ETN population.At the last follow-up, 44% of patients in ADA and 39% of patients in ETN were on methotrexate or leflunomide in combination with bDMARD. 85.9% of patients had achieved sustained clinical remission.Conclusion:Long-term treatment with ETN and ADA has been shown to be effective and safe for patients with JIA, as evidenced by the high retention rate recorded in our cohort. Most patients maintain current therapy for years to preserve remission status.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

BackgroundAlthough several studies report a high incidence of pulmonary manifestations in SLE, lung involvement is often underestimated in SLE clinical assessment [1]. This is also mirrored by the absence of pulmonary manifestations other than pleurisy in the old and new classification criteria for SLE [2]. Moreover, limited evidence on the management of SLE-related pulmonary manifestations is available.ObjectivesTo assess prevalence and clinical impact of the spectrum of SLE-related pulmonary manifestations and their association with patient autoantibody profiles in a large SLE cohort and to describe the effectiveness of different therapeutic approaches in distinct clinical settings.MethodsPatients followed at the Lupus Clinics of ASST G. Pini-CTO and San Raffaele Hospital (Milan, Italy) were enrolled. Data regarding demographics, disease characteristics, autoantibody profile, pulmonary manifestations, damage accrual and treatment were collected. The following types of lung involvement were recorded: pleurisy, acute lupus pneumonitis, interstitial lung disease (ILD), alveolar haemorrhage, pulmonary embolism, arterial pulmonary hypertension and shrinking lung syndrome.ResultsOf the 471 SLE patients enrolled, we identified 78 patients (16.5%) displaying at least one pulmonary manifestation. Epidemiological data on each manifestation are reported in Table 1. Pleurisy was the most common pulmonary manifestations and manifested at disease onset in most cases (56%).Patient home environment (urban vs countryside) did not seem to impact the risk of developing lung disease. Damage accrual was relevant, as 2/3 of patients displayed at least 1 point increase in SLICC Damage Index (SDI) after the onset of lung involvement in comparison to baseline. All patients received at least one steroid course. Immunosuppressive treatment choices and efficacy differed among distinct manifestations: only half of the patients with pleurisy received immunosuppression, mainly azathioprine, with 100% of improvement, while 80% of cases of ILD received immunosuppression, predominantly mycophenolate, with a 50% risk of non-response.By comparing demographics and clinical characteristics among cases and controls, we found a significantly lower median age at disease onset (p=0.002) and a higher frequency of male sex (18% vs 9%; p=0.07), joint involvement (p=0.02) and constitutional symptoms (p=0.02) in patients with lung involvement, while no differences were observed in the autoantibody profile, including anti-dsDNA and anti-ENA autoantibodies.ConclusionOur study confirms that, in addition to the known epidemiological burden of pleurisy, other types of pulmonary involvement can complicate the disease course and contribute to damage accrual. In particular, ILD can frequently occur and respond to immunosuppressants in only half cases. Consistent with the association of lung involvement with increased morbidity, higher-risk categories for severe disease such as males and subjects with early-onset SLE were more represented among patients with pulmonary manifestations.References[1] Amarnani R, et al. Front. Med. 2021; 7:610257.[2] Aringer M, et al. Ann Rheum Dis. 2019; 78:1151-1159.[3] Smith EMD, Clin Immunol. 2019; 209:108274.[4] Ryu S, et al. Lupus Sci Med. 2017;):e000221.Table 1.Demographic and disease characteristics of SLE patients with lung involvementDemographics and clinical characteristicsFemales, n (%)65 (83)Age at diagnosis (years): median (IQR)29 (22 – 39)Disease duration (years): mean ±DS19 ± 12Subjects with >0 and >1 point SDI increase from baseline: n (%)48 (61.5); 26 (33)Lung involvementN (%)immunosuppressive therapy, %Pleurisy61 (78)49Acute pneumonitis4 (5)100ILD15 (19)80PAH6 (8)50Pulmonary embolism4 (5)50Shrinking lung1 (1)100Alveolar hemorrage4 (5)100Acknowledgements:NIL.Disclosure of InterestsMaria Gerosa: None declared, Giuseppe Alvise Ramirez: None declared, Lorenza Maria Argolini: None declared, Isabella Scotti: None declared, Carolina Artusi: None declared, Luca Moroni: None declared, Enrica Bozzolo: None declared, Maria Rosa Pellico: None declared, Ludovica Cavallo: None declared, Lorenzo Dagna: None declared, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, and UCB,

Background:In addition to anti-SSA and anti-SSB antibodies, considered hallmarks of Sjogren Syndrome, recent studies described several other autoantibodies in the disease, but the clinical associations are not yet well known. Particularly, anti-centromere antibodies (ACA) have been increasingly studied in the context of primary Sjögren Syndrome (pSS). Approximately 3-5% of pSS patients show positivity for ACA. Different studies from national registries or data collections examined the clinical phenotype of ACA-positive SS patients with contrasting results, then definitive characterizations of this subgroup remain to be establishedObjectives:To describe the clinical characteristics of an Italian multicenter cohort of ACA positive (ACA+) pSS patients and compare them to a matched ACA-negative (ACA-) pSS cohort and an ACA+ Systemic Sclerosis (SSc) cohort.Methods:A retrospective analysis was conducted on patients meeting the ACR/EULAR SS classification criteria showing ACA positivity, referring to participating centers. Organ involvement and related clinical, instrumental and laboratory characteristics were evaluated.Results:The cohort comprised 55 ACA+ patients diagnosed with pSS, including 36 females, with a mean age of 69.15 years. Predominant clinical manifestations were Raynaud’s phenomenon (n=45), arthralgias (n=37), xerostomia (n=48), and xerophthalmia (n=39). Comparison to an ACA- pSS cohort revealed no significant demographic variance. However, the ACA+ cohort exhibited significantly higher incidence of Raynaud’s phenomenon, puffy fingers, scleroderma, telangiectasia, and gastrointestinal involvement (p<0.001, 0.0003, 0.0025, <0.0001, and 0.01, respectively) as shown in Table 1.In contrast to literature, no significant anti-Ro/SSA antibody prevalence or cancer development differences were observed between ACA+ and ACA- groups.We further compared the ACA+ pSS cohort to 96 ACA+ SSc patients. The latter demonstrated higher frequency of manifestations like scleroderma, puffy fingers, Raynaud’s, telangiectasias, calcinosis, pitting scars, and acral ulcers (p<0.0001, <0.0001, <0.0001, 0.003, 0.008, <0.0001, <0.0001, respectively). Conversely, the ACA+ pSS cohort exhibited more fibromyalgia, xerostomia, xerophthalmia, and anti-Ro/SSA positivity (p=0.002, <0.0001, <0.0001, <0.0001, respectively), as shown in Table 2.Conclusion:Our study shows that in a large cohort of Italian pSS patients, ACA positivity significantly influences disease clinical expression, with a more pronounced pSS-related extraglandular phenotype compared to ACA- pSS patients. However, when compared to SSc patients, ACA+ pSS patients display a less severe vascular profile, resulting in an intermediate clinical phenotype between limited cutaneous scleroderma and pSS. ACA presence in pSS patients may play a pivotal role in clinical features across disease settings.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.