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Background:Uveitis represents the most frightening extra-articular complication in juvenile idiopathic arthritis (JIA) and represents a significant cause of disability. In most cases, it occurs simultaneously with or after the diagnosis of arthritis, usually in the first 4 years from the onset of the joint disease.Objectives:The study aims to evaluate and describe cases of late-onset uveitis.Methods:The medical records of patients followed at our center suffering from JIA associated with uveitis from 1985 to 2022 were retrospectively reviewed.Results:114 patients suffering from JIA complicated by uveitis were included in the study (F 78%; n=89) with a mean follow-up time of 21 years (SD ± 10.9) from the joint or ocular disease onset. 99 patients (87%) belong to the oligoarticular JIA subgroup, 12 (11%) in the polyarticular RF - category, 2 (2%) in the psoriatic form, and 1 (1%) presented a form of acute anterior uveitis HLA B27 correlated with enthesitis-arthritis JIA. ANA antibodies were positive in 111 patients (97%). In 108 patients (95%), joint disease preceded ocular involvement, while in only 6 patients (5%), uveitis preceded arthritis. In the majority of cases, uveitis manifested itself within the first 4 years from diagnosis of arthritis, with a median arthritis-uveitis delta time of 12 months (IQR 37); however, in 25 patients (25/108; 23%), uveitis appeared after the first 4 years of the articular disease. In the latter subgroup, all patients had disease onset before 5 years of life and were classified as oligoarticular JIA ANA +, except for 4 patients diagnosed with polyarticular JIA RF -, ANA +. Clinical and demographic characteristics are summarized in Table 1. 19/25 patients (76%) were female. The median time between the onset of arthritis and uveitis was 7 years (IQR 3.5; range 4.5-23), with a mean number of visits equal to 19 (SD ±7.9) before the detection of uveitis. At the time of onset of uveitis, 10 patients were receiving methotrexate monotherapy and 2 were receiving methothrexate in combination with etanercept. In patients with onset over 5 years of age, the appearance of uveitis remained within 4 years of the onset of arthritis, unlike patients with onset in the first 5 years of life in whom uveitis also manifested itself later (p= 0.011). Furthermore, a negative correlation was found between age at onset of arthritis and age at onset of uveitis (r= -0.2; p=0.036) (Figure 1).Conclusion:The most significant risk of uveitis occurs in the first years after the onset of the joint disease. However, a non-negligible portion of patients with risk factors for uveitis appear even after many years of disease; therefore, long-term follow-up would appear to be the most prudent approach in this subgroup of patients.Table 1. Clinical and demographic characteristics of the cohortFigure 1.Correlation between age at onset of arthritis and age at onset of uveitis.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:D2T-RA definition offers a glimpse of multi-drug resistant patients presenting with evidence of inadequate disease control1. Even though data regarding the prevalence and characterization of D2T RA patients in real-life settings emerged, data regarding the maintenance of the condition over time and the principal drivers of the D2T status are absent.Objectives:Our study aimed to identify and characterize patients based on a time-based criterion of D2T status. Moreover, we sought to assess the rate of the definition criteria fulfillment to unveil any driver of the persistent (p)D2T status.Methods:In our 610 adult RA patients’ cohort, we identified 104 patients refractory to ≥2 b/tsDMARDs with different mechanisms of action. We collected demographic, clinical, and disease activity data for each patient at enrollment, as well as retrospectively from the medical records of the visits conducted bimonthly in the previous 12 months. Extrapolated the prevalence of D2T patients from each timepoint, we defined patients fulfilling the D2T definition for more than 6 months as pD2T patients and compared them to episodic D2T (eD2T, less than 6 months) patients with univariate and logistic regression analyses. Lastly, we assessed how the fulfillment rate of 3 definition criteria (the disease activity, CRP values, and inability to taper glucocorticoids criteria) would impact the persistence of the D2T status and evaluate whether one of such criteria would serve as the main driver of the pD2T definition through an ANOVA analysis and Tukey test.Results:At enrollment, 41.3% of the 104 refractory patients fulfilled the D2T definition criteria, while the prevalence of D2T patients in the previous 12 months ranged constantly between 29 to 31%. 29/104 patients (27.9%) fulfilled the pD2T definition, 32 (30.8%) were episodic D2T, while 43 (41.3%) never fulfilled the definition in the 12-month observation period. In univariate analysis, pD2T patients showed a higher frequency of male sex (p=0.01), higher HAQ (p=0.031) and SDAI scores (p<0.001), CRP values (p=0.004), a higher number of failed b/tsDMARDs (p=0.028), use of glucocorticoids (p<0.001) and the use of non-NSAID analgesics (p=0.039). Applying logistic regression analysis, higher SDAI scores (OR 1.23, p=0.001), CRP values (OR 2.22, p=0.035), and use of glucocorticoid (OR 24.29, p=0.004) were associated with pD2T, as well as more frequent use of analgesics (OR 4.5, p=0.046) (Table 1). The inability to taper glucocorticoid dosage appeared to be the most frequent criterion fulfilled across the entire population. The “at least moderate disease activity” criterion (p<0.001), the CRP criterion (p<0.001), and the glucocorticoids criterion (p<0.001) were all more fulfilled in the pD2T population compared to the eD2T population. Among the pD2T population, neither of the criteria emerged as a significant driver of the condition (ANOVA p=0.053). Nevertheless, a trend for a more frequent inability to taper glucocorticoids emerged (p=0.083 vs moderate disease activity; p=0.093 vs CRP) (Figure 1).Conclusion:In our cohort, the employment of a time-based criterion revealed a subset of refractory patients (27.9%) that persistently fulfilled the D2T-RA definition instead of patients that did so only episodically during the observation period. The application of a temporal criterion may thus increase the homogeneity of the D2T population for research purposes. Moreover, the inability to taper glucocorticoids appeared to be the main driver of D2T and pD2T status, suggesting that possibly different management strategies in real life could reshape this population.REFERENCES:[1] Nagy G, Roodenrijs NM, Welsing PM, et alEULAR definition of difficult-to-treat rheumatoid arthritisAnnals of the Rheumatic Diseases 2021;80:31-35.Table 1. Characteristics of persistent and non-persistent D2T patientsFigure 1.A) Rate of criteria fulfillment at each time point, either including all events (overall) or the rate of definition fulfillment for a single criterion (alone). B) Median rate of criteria fulfillment between pD2T and eD2T (excluding patients that never fulfilled the D2T definition) along the 12-month observation period.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Despite incredible progress in rheumatoid arthritis (RA) therapy, a substantial number of patients remain unresponsive to multiple treatments. These include patients who have high disease activity despite the use of two or more biotechnological or synthetic targeted DMARDs (b/tsDMARDs) with different mechanism of action (MOAs), identified as difficult-to-treat (D2T) patients.Objectives:The aim of the study is to analyse the clinical characteristics of RA patients who have failed at least two lines of b/tsDMARDs therapy and to understand whether D2T patients differ from multi-refractory patients with regard to the reasons for treatment failure.Methods:A retrospective analysis of data from patients with RA treated with b/tsDMARDs included in a single-centre Italian registry was performed. Four categories of patients were identified and analysed: non-refractory, refractory to at least 2 lines of therapy, refractory to drugs with at least 2 different MOAs, and D2T according to the 2021 EULAR definition. Four reasons for discontinuation were identified: primary inefficacy, secondary inefficacy, adverse event or malignancy. Comparison analyses were performed using the chi-squared test for categorical variables and analysis of variance (ANOVA) for continuous variables.Results:The study population included 610 patients with RA (83% female, median age [±SD] 59 years [±12.5], median disease duration 17.3 [±11.5] years). Seventy-five percent (458/610) of the patients had never failed first-line therapy. Among the refractory patients (149/610), 104 patients (17%) failed at least 2 drugs with different MOAs and 42 patients (7%) met the EULAR definition of ‘difficult-to-treat’ patients. Comparative analysis showed that D2T patients were statistically significantly different from the other patient categories in terms of younger age at disease onset (p=0.007) and longer disease duration (p<0.0005). It was also observed that the time from diagnosis to initiation of b/tsDMARDs drug therapy was significantly longer in D2T patients than in patients refractory to at least two MOAs (mean 120.6 [±105.9] months vs. 93.5 [±103.8] months, respectively [p=0.008]). With the exception of a higher prevalence of fibromyalgia in multi-refractory and D2T patients than in non-refractory patients, there were no significant differences in seropositivity, presence of erosions and comorbidities (Table 1). On average, the number of failed drug lines did not differ between the different categories of multi-refractory patients (p=0.249). Regarding the causes of failure, an average of 71.6% of treatments were discontinued due to inefficacy (24.3% primary and 47.3% secondary) and 28.4% due to an adverse event or malignancy, with no statistically significant differences between patient categories (p=0.25) (Table 2).Conclusion:Difficult-to-treat patients represent 7% of our cohort and are characterised by earlier disease onset and later initiation of targeted therapy. The main reason for discontinuation of the different therapeutic lines is inefficacy (primary or secondary) of the drug, regardless of the number of drug lines used or the number of MOAs the patient has undergone.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:EORA (Elderly-Onset Rheumatoid Arthritis) defines Rheumatoid Arthritis (RA) that arises after the age of 65 years, accounting for 10-33% of all cases of RA. Psoriatic arthritis (PsA), part of the seronegative spondyloarthritis group, can also manifest in later years, even if more rarely than RA. However, Elderly Onset Psoriatic Arthritis (EOPsA) lacks a clear age definition, reported variably between 50 and 60 years old. In older age, RA and PsA exhibit less typical clinical presentations leading to potential overlaps, complicating differential diagnosis.Objectives:Given the limited number of comparative reports, our study aims to comprehensively compare demographic, clinical and treatment characteristics of EORA and EOPsA patients undergoing methotrexate (MTX), and/or hydroxychloroquine (HCQ), and/or corticosteroid (CS).Methods:Within our Center, a retrospective analysis was conducted on our cohort of patients undergoing MTX, and/or HCQ, and/or CS therapy, comparing a subpopulation of EORA patients with a subpopulation of EOPsA (PsA onset > 55 years old). Patients were consecutively enrolled at our dedicated outpatient clinics during a 4-month period (Sep-Dec 2023). Patients treated with bDMARDs and axial PsA patients were not included. Assessment included demographic parameters, clinical manifestations, and treatment modalities.Results:During the observation period, 50 EORA patients and 31 EOPsA patients were enrolled. The demographic and clinical characteristics of the 81 enrolled patients are summarized in Table 1. Low disease activity is found in both groups, being median SDAI = 4,12 (IQR 6,07) and median DAPSA = 6,38 (IQR 8,38). Demographic characteristics reveal a gender difference, being EORA patients predominantly female (62%), while EOPsA patients predominantly male (64,5%), p = 0,02. EORA more often onsets with PMR-like symptoms (26%) compared to EOPsA (3,2%) (p = 0,008). No significant differences are noted in Charlson Comorbidity Index (CCI) or recurrent infections, but prior malignancies (p = 0,033) and stroke (p = 0,018) are more prevalent in EOPsA patients, while arterial hypertension is more common among EORA patients (p = 0,001). Notably, 56% of EORA patients but 80,6% of EOPsA patients receive MTX (p = 0,023). Conversely, EORA patients on CS, alone or with MTX, are 62%, compared to 32,2% of EOPsA patients (p = 0,009). Main differences between the two groups are shown in Graph 1. Among patients treated with MTX, the time between diagnosis and initiation of therapy does not statistically differ between groups, being 16,04 ± 15,07 months for EORA patients and 21,96 ± 19,02 months for EOPsA patients (p = 0,37). Among EORA patients, there is a statistically significant association between ACPA positivity (14 patients, 28%) and MTX therapy (p = 0,028). There is no association between treatment with MTX at any dose and increased incidence of recurrent infections (p = 0,64). Conversely, an association is found between CS therapy and recurrent infections (p = 0,011).Conclusion:Gender disparities and different onset characteristics exist between EORA and EOPsA patients. A different therapeutic attitude emerges between the two groups, EORA patients being more frequently on CS therapy and EOPsA patients on MTX. This could be explained by the fact that cutaneous psoriasis, present in the vast majority of EOPsA patients, benefits from treatment with methotrexate; furthermore, the higher frequency of PMR-like onset among EORA patients could explain the persistence of treating these patients with CS even after long disease course. It is useful to note, however, that there are no differences in terms of recurrent infections between the two groups, while patients under CS, but not MTX, more frequently suffer from recurrent infections. Furthermore, arterial hypertension is more common among EORA patients, who are treated more often with CS. These findings suggest a potential benefit for more EORA patients to receive MTX, in order to reduce or stop CS therapy.REFERENCES: NIL.Table 1. Demographic and clinical characteristics of EORA and EOPsA patients.Graph 1.Main differences between EORA and EOPsA patients.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA-U), occurring in up to 20% of children with JIA, especially in the mono-oligoarticular ANA+ subset. JIA-U typically presents as asymptomatic, chronic, bilateral anterior uveitis. Up to 38% of patients with JIA-U develop severe visual impairment or blindness, with cystoid macular edema as the most common cause. Chronic inflammation also leads to irreversible ocular complications like cataracts, glaucoma, and maculopathy, affecting the quality of life of these patients since young age. Early identification and aggressive treatment are critical to prevent sequelae in JIA-U.Objectives:This study aims to investigate the role of methotrexate (MTX) in the management of patients with JIA-U nd whether this can influence the course of ocular disease.Methods:A retrospective monocentric cohort analysis of JIA-U patients with a follow up of at least 6 months was carried out. Demographics and clinical characteristics were analyzed by standard descriptive statistical methods. Clinical variables and drug treatments were correlated by Spearman’s rank non-parametric test.Results:114 patients with JIA-U were analyzed. 89 patients (78%) were female, 99 were ANA positive (87%). The median disease duration was 17.59 years (IQR 13.89). 106 (93%) patients received MTX treatment and 76 (67%) biologic Disease Modified Anti-Rheumatic Drugs (bDMARDs) and/or target synthetic tsDMARDs (Table 1). Of these patients, 28 (25%) were already receiving MTX treatment (onMTX) at the time of uveitis diagnosis. In this group of patients, the presence of complications at onset (p=0.012), long-term complications (p=0.002) and surgical interventions (p=0.015) was significantly lower compared to the group of patients not receiving MTX at the time of diagnosis. Furthermore, the age at onset of uveitis (onMTX 4.7; offMTX 3.7; p=0.02), the number of flares (on MTX 9.6; offMTX 5.4; p=0.007) and surgical interventions (onMTX 0.25; offMTX 0.95; p<0.001) were significantly different between the two groups. In addition, onMTX patients had the most common risk factors for developing uveitis: 84% were female, 28 (100%) ANA+ and 27 (96%) had oligoarticular JIA.Conclusion:The preliminary data from this study demonstrate that MTX not only delays the onset of uveitis in JIA patients, but also plays a protective role by decreasing the number of disease flares, the development of short and long term sequelae, and the need for surgical referral. These data will need to be confirmed through studies on larger cohorts of patients and an experimental design.REFERENCES:[1] Ravelli, A.; Martini, A. Juvenile Idiopathic Arthritis. The Lancet 2007, 369, 767–778, doi:10.1016/S0140-6736(07)60363-8.[2] Thomas, J.; Kuthyar, S.; Shantha, J.G.; Angeles-Han, S.T.; Yeh, S. Update on Biologic Therapies for Juvenile Idiopathic Arthritis-Associated Uveitis. Ann Eye Sci 2021, 6, 19–19, doi:10.21037/aes-2019-dmu-10.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:The transition from pediatric to adult care of patients affected by juvenile idiopathic arthritis (JIA) represents a complex process. A recent retrospective study has shown that in an early adulthood cohort, one in four patients still had an active disease and one in two were in remission on medication. Ultrasound could provide support in the treatment management of patients with clinical inactive disease (CID); nevertheless, data about the prevalence and the prognostic role of ultrasound-detected subclinical synovitis are scarce and controversial.Objectives:Objective of this study is to evaluate the power of subclinical synovitis to predict flare in patients over 16 years old in CID. Secondary endpoints are to determine the prevalence of subclinical synovitis in a cohort of JIA in CID and possible clinical variables related to disease relapse.Methods:This monocentric study recruited JIA patients aged more than 16 years in clinical remission, according to Wallace criteria. Data about ultrasound assessment at baseline, demographic details, clinical features, ILAR category, disease activity status, flares, and ongoing/previous treatments were retrospectively reviewed for a 6-year follow-up. At baseline, 44 joints were scanned to detect the presence of synovial hyperplasia/joint effusion and Power-Doppler signal (PD).Results:The study included 16 patients with US evaluation at baseline (56% women with predominant oligoarticular/polyarticular JIA subtypes and a median disease duration of 12 years).6/16 (38%) patients displayed US-detected subclinical synovitis: abnormalities in grey scale examination were found in 6/6 (100%), whereas PD signal was detected in 4/6 (66%) cases. This data is consistent with previous studies: in literature, the prevalence of subclinical synovitis in JIA ranges from 23% to 67%. During the follow-up, a disease flare occurred in 11/16 (69%) subjects. 5/6 (83%) were US-positive and 6/10 (60%) were US-negative, without a statistically significant difference (p=0.58). Flare was not related to any demographic or clinical variable, except for treatment management. All patients undergoing bDMARDs tapering displayed a disease reactivation; conversely, flares occurred only in 4/10 (40%) patients taking methotrexate or no therapy (p=0.03).Conclusion:The present study provides a first evaluation of the prognostic role of US-detected subclinical synovitis in JIA during the transition phase. Although subclinical US-detected synovitis doesn’t show to predict disease relapse, a wider cohort and prospective studies are needed to determine the value of ultrasound in the challenging management of inactive JIA.REFERENCES:[1] Chhabra A, Robinson C, Houghton K, Cabral DA, Morishita K, Tucker LB, Petty RE, Larché M, Batthish M, Guzman J. Long-term outcomes and disease course of children with juvenile idiopathic arthritis in the ReACCh-Out cohort: a two-centre experience. Rheumatology (Oxford). 2020 Dec 1;59(12):3727-3730.[2] De Lucia O, Ravagnani V, Pregnolato F, Hila A, Pontikaki I, Gattinara M, Romano M, Gerloni V, Pieropan S, Murgo A, Rossini M, Cimaz R, Meroni PL. Baseline ultrasound examination as possible predictor of relapse in patients affected by juvenile idiopathic arthritis (JIA). Ann Rheum Dis. 2018 Oct;77(10):1426-1431.Acknowledgements:NIL.Disclosure of Interests:None declared.

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:Adalimumab (ADA) is frequently administered to pediatric patients with non-infectious uveitis (NIU). Given safety considerations, the quality of life of children, and cost implications, exploring the possibility of tapering/withdrawing ADA in patients experiencing a prolonged period of persistent remission has been suggested. However, few studies have investigated this in pediatric rheumatology, and none have specifically addressed how to taper/discontinue ADA in children with NIU.Objectives:To evaluate factors associated with the risk of NIU relapse in patients undergoing ADA tapering.Methods:A multicenter retrospective cohort study involving 18 international tertiary centers was conducted. Patients diagnosed with NIU, with or without an associated systemic disease, before age 18 and treated with ADA were included. ADA was administered subcutaneously every 2 weeks (20 mg for patients < 30 kg; otherwise, 40 mg). All patients underwent ADA tapering due to NIU inactivity. ADA tapering consisted of progressive injection spacing decided by the treating clinician. Time-to-event analysis was used to assess the risk of NIU recurrence after ADA tapering. Patients without recurrences were censored at their last follow-up visit. Hazard ratio (HR) and 95% confidence intervals (CI) were computed.Results:The cohort comprised 114 patients (57% female) with NIU treated with ADA. Demographic and clinical characteristics of the cohort are detailed in Table 1. Fifty-three patients (46%) experienced NIU recurrence after a median of 30 weeks (IQR 15-58 weeks) from the onset of ADA tapering.A noteworthy association was identified between ethnicity and recurrence status (Table 1; p = 0.04). Asian subjects exhibited a lower susceptibility to NIU relapse compared to patients of other ethnicities (8% vs. 50%; p = 0.00). Conversely, Caucasian patients experienced more frequent relapses than non-Caucasian subjects (54% vs. 32%; p = 0.03). The interval between ADA injections was increased by 1 week every month (n =1), 1 week every 2 months (n =2), 1 week every 3 months (n = 50), 2 weeks every 4 months (n = 1), 1 week every 4 months (n = 4), 1 week every 5 months (n = 5), 4 weeks every 6 months (n = 1), 2 weeks every 6 months (n =2), 1 week every 6 months (n = 24), 1 week every 12 months (n = 24).Considering the heterogeneity in the distribution of patients across the speed of tapering, ADA tapering was classified into two main groups based on the rate of drug reduction: faster (fast_t, comprising tapering speeds from 1 week every month to 2 weeks every 4 months, N = 54) and slower (slow_t, encompassing tapering speeds from 1 week every 4 months to 1 week every 12 months, N = 60). An association between the speed class and the incidence of uveitis relapse was observed, with 56% of recurrences in the fast_t group compared to 38% in the slow_t group (p = 0.06).Univariate Cox regression analysis (Table 2) indicated that Caucasian subjects had an increased risk of uveitis recurrence compared to non-Caucasian subjects [HR 2.2; 95% CI 1.2-4.2; p = 0.01]. In contrast, Asian patients had a reduced risk (HR 0.09; 95% CI 0.01-0.07; p = 0.02). The concomitant use of MTX was associated with a high risk of uveitis relapse (HR 2.1; 95% CI 1.1-4.1; p = 0.03). Additionally, a slower taper of ADA was linked to a lower recurrence rate (HR 0.49; 95% CI 0.28-0.87; p = 0.01). A multivariate Cox regression analysis was conducted to identify independent predictors of the recurrence rate. In the multivariate model, being Caucasian remained associated with more than a two-fold increase in the risk of developing uveitis relapse (HR 2.33; 95% CI 1.12-4.85; p = 0.02). Furthermore, the adjusted analysis confirmed that a slower ADA tapering is associated with a 50% lower risk of recurrence than a faster tapering (HR 0.49; 95% CI 0.26-0.95; p = 0.03) (Table 2).Conclusion:About half of the cohort experienced a NIU relapse after the initiation of ADA tapering. Caucasian race and fast tapering were associated with a higher risk of recurrences. Therefore, a strict follow-up for these patients should be advisable, and a gradual ADA taper is recommended.REFERENCES: NIL.Table 1. General features of the cohortAcknowledgements:NIL.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:Real-world evidence provides insights into treatment effectiveness, safety and PROs beyond clinical trials. FILOSOPHY (NCT04871919) and PARROTFISH (NCT05323591) are prospective, observational Phase 4 studies ongoing in Europe and France.Objectives:To report baseline characteristics, PROs, effectiveness and safety based on pooled data from the first 1,177 patients treated with filgotinib for up to 18 months.Methods:FILOSOPHY and PARROTFISH will enroll approximately 1,500 patients aged ≥18 years with moderate to severe active RA, who are prescribed filgotinib for the first time and as per the product label1 in daily practice.At Week 1, 2 and 3 and Month 1, 3, 6, 9, 12, 15 and 18, pain (visual analog scale [VAS]), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score, work productivity (Work Productivity and Activity Impairment questionnaire) and Rheumatoid Arthritis Impact of Disease (RAID) score were electronically assessed. The proportion of patients with a clinically meaningful change from baseline in VAS pain (reduction of ≥10 mm) and FACIT-Fatigue score (increase of ≥4) was assessed in advanced therapy (AT)-naïve and AT-experienced patients.At Month 1, 3, 6, 12 and 18, Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP), Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire–Disability Index (HAQ-DI) were assessed. The proportion of patients achieving DAS28-CRP of ≤2.6 or ≤3.2 and CDAI of ≤2.8 or ≤10 was determined.Treatment-emergent adverse events (TEAEs) on study were recorded.Results:As of July 2023, 1,177 patients had been treated, with a median follow-up of 322 days; baseline characteristics are shown in Table 1. 50.8% of patients received filgotinib monotherapy; 48.8% received filgotinib in combination with conventional synthetic disease-modifying antirheumatic drugs. 91.6% received filgotinib 200 mg; 8.4% received filgotinib 100 mg. 37.6% of patients were AT naïve; 62.4% were AT experienced. Pain and fatigue improved as early as Week 1. At Week 1, 39.2% and 46.6% of AT-naïve and AT-experienced patients, respectively, had a clinically meaningful improvement in VAS pain, and 42.9% and 44.4%, respectively, had a clinically meaningful improvement in FACIT-Fatigue score. Clinically meaningful changes were observed in patients followed up to Month 18 (Figure 1A and B). Work productivity and daily activity impairment improved from Week 1; improvements were observed in patients followed up to Month 18 (Figure 1C). Most patients initially had moderate to high disease activity. Improvements were seen as early as Month 1. By Month 18, DAS28-CRP of ≤2.6 was reported by 60.3% (82/136) while DAS28-CRP of >2.6 and ≤3.2 was reported by 15.4% (21/136) of patients; CDAI scores of ≤2.8 were reported by 36.8% (57/155) while scores of >2.8 and ≤10 were reported by 34.2% (53/155) of patients. Median (interquartile range) HAQ-DI was 1.4 (0.8, 1.8) at baseline (N=213), 0.8 (0.3, 1.4) at Month 1 (N=149) and 0.8 (0.3, 1.5) at Month 6 (N=97). Median (IQR) RAID score was 6.6 (5.0, 7.6) at baseline (N=142), 5.8 (4.1, 6.9) at Week 1 (N=300) and 3.9 (2.2, 6.0) at Month 6 (N=220). 618 patients (52.5%) had TEAEs on study, leading to treatment discontinuation in 91 (7.7%) cases. There were 6 deaths, 1 of which was considered related to study treatment (pneumonia and pulmonary embolism). TEAEs included COVID-19 (n=106), herpes zoster (n=16), fractures (n=20), opportunistic infections (n=3), stroke (n=6), transient ischemic attack (n=5), unstable angina (n=7), malignant/unspecified tumor (n=7) and pulmonary embolism (n=2).Conclusion:Interim data from patients treated with filgotinib in routine practice show pain, fatigue, work productivity and RAID score improved as early as Week 1. DAS28-CRP, CDAI and HAQ-DI improved as early as Month 1, the first timepoint these endpoints were assessed. Improvements were maintained up to Month 18 (Month 6 for RAID and HAQ-DI). Longer-term follow-up and completion of the studies will allow further evaluation of effectiveness and safety.REFERENCES:[1] Jyseleca SmPC. Galapagos NV, May 2022Acknowledgements:We thank the physicians and patients who participated in this study. The study was funded by Galapagos NV (Mechelen, Belgium). Medical writing support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV. Publication coordination was provided by Jo-Ann E. West, MSc, a consultant funded by Galapagos NV.Disclosure of Interests:Jérôme Avouac AbbVie, AstraZeneca, Biogen, BMS, Eli Lilly, Fresenius Kabi, Galapagos, MSD, Novartis, Pfizer, Sandoz and Sanofi, AbbVie, Fresenius Kabi, Galapagos and Sanofi, BMS, Fresenius Kabi, Galapagos, Novartis and Pfizer, Gerd R. Burmester AbbVie, BMS, Eli Lilly, Galapagos, MSD and Pfizer, AbbVie, BMS, Eli Lilly, Galapagos, MSD and Pfizer, Roberto F. Caporali AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer and UCB, AbbVie, Accord, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, Novartis, Pfizer and UCB, Thomas P. A. Debray Biogen, Daiichi Sankyo, Galapagos and Gilead, Francesco De Leonardis Galapagos, Galapagos, James Galloway AbbVie, Eli Lilly, Galapagos, Janssen, Pfizer and UCB, AbbVie, Eli Lilly, Galapagos, Janssen and Pfizer, AstraZeneca, Janssen and Pfizer, Neil Betteridge Amgen, ASIF, Edwards Lifesciences, Eli Lilly, EULAR Global Alliance for Musculoskeletal Health, Global Alliance for Patient Access, Grünenthal, Heart Valve Voice, Pfizer and Sanofi Genzyme, Karen Bevers Galapagos, Susana Romero-Yuste AbbVie, Biogen, BMS, Eli Lilly and Pfizer, Eli Lilly and Sanofi, Eli Lilly and MSD, Monia Zignani Galapagos, Galapagos, Patrick Verschueren Eli Lilly and Galapagos, AbbVie, Eli Lilly and Galapagos, Galapagos and Pfizer.