Background: Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease marked by various clinical features that significantly impact the quality of life for affected patients. While upadacitinib (UPA) has shown promising results in improving the signs and symptoms of PsA in two RCTs, real-world evidence on its effectiveness remains limited. Objectives: This study aims at assessing the real-world effectiveness of UPA in a large multicenter cohort of PsA patients by investigating its impact on key disease activity scores on both axial and peripheral engagement of the disease. Methods: Data of patients meeting CASPAR criteria for peripheral PsA and/or ASAS criteria for axial PsA were collected from 28 Italian rheumatology centers. The study included bio-naïve patients with a history of failure or intolerance to at least one conventional synthetic DMARD, as well as patients who had experienced failure with at least one biologic DMARD (bDMARD). Disease activity scores, such as LEI, DAPSA, MDA, VLDA, and ASDAS-CRP, were assessed at baseline and at 12, 24, 36, and 52 weeks. Adverse events were recorded at each visit. Paired t-tests were employed to compare disease activity indices at baseline and various follow-up times, while McNemar’s test was used to assess differences in the proportions of patients achieving MDA and ASDAS inactive disease at different follow-up intervals. Treatment persistence was estimated using the Kaplan-Meier method. Results: A total of 253 PsA patients, consisting of 181 females (71.5%) and 72 males (28.5%), underwent UPA treatment. The average age was 55.8±10.9 years, with a mean disease duration of 111.2±102.5 months. Peripheral joint involvement was observed in 161 individuals (63.6%), with 49 (33.6%) presenting an oligoarticular and 97 (66.4%) a polyarticular pattern (Table 1). Axial involvement was diagnosed in 92 patients (36.4%). Notably, 89 individuals (94.5%) had previously experienced treatment failure with at least one biologic DMARD (Table 1). Global treatment persistence was 77%, with a mean follow-up duration of 21.82 months. There were no differences observed between the axial and peripheral disease subsets or among the first line and further lines of treatment (Figure 1). Compared to baseline, a significant decrease in DAPSA (mean reduction 11.68; p<0.001) and ASDAS-CRP (mean reduction 1.00; p<0.001) was observed already at 3-month follow-up and throughout the observation period up to 52 weeks (Figure 1). The mean LEI score dropped from 0.64 at baseline to 0.36 at 12 weeks and 0.46 at 52 weeks (p<0.001). Additionally, a noteworthy increase in the percentages of patients achieving MDA (31.1%) and ASDAS-inactive disease (40.7%) was recorded at 52 weeks compared to baseline (Figure 1). During the follow-up period, 51 patients discontinued UPA [lack of efficacy (10 cases), loss of efficacy (25 cases), adverse events (4 cases), and infectious events (3 cases)]. The reasons for the remaining discontinuations were not specified. Conclusion: This study, conducted on a large cohort of PsA patients in a real-life setting, confirms the substantial benefits of UPA on both peripheral and axial disease involvement in the long term. It highlights UPA rapid onset of action, evident as early as the 3-month follow-up. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Giuseppe Lopalco: None declared, Eleonora Celletti: None declared, Maria Morrone: None declared, Fabiola Atzeni: None declared, Eleonora Bruschi: None declared, Antonio Carletto: None declared, Alberto Cauli declares consultation fee and meeting expenses from Abbvie, Massimiliano Cazzato: None declared, Maria Sole Chimenti: None declared, Francesco Ciccia: None declared, Francesco Cipollone: None declared, Fabrizio Conti: None declared, Addolorata Corrado: None declared, Francesca Cozzini: None declared, Lorenzo Dagna: None declared, Rosario Foti: None declared, Stefano Gentileschi: None declared, ELISA GREMESE: None declared, Roberto Gorla: None declared, Giuliana Guggino: None declared, Alberto Lo Gullo: None declared, Michele Maria Luchetti: None declared, Carlomaurizio Montecucco: None declared, Roberta Ramonda: None declared, Angelo Semeraro: None declared, Fausto Salaffi: None declared, Carlo Salvarani: None declared, Carlo Selmi: None declared, Emanuela Praino: None declared, Roberto F. Caporali: None declared, Florenzo Iannone: None declared.

Background: Nowadays, numerous therapeutic options are available for patients with rheumatoid arthritis (RA), and the number of patients achieving remission has significantly increased. However, some patients have a disease defined by EULAR as “difficult-to-treat”1 (D2T), which today represents a new challenge for rheumatologists. Objectives: The primary objective was to evaluate the characteristics of the D2T-RA population recorded in the Italian GISEA registry undergoing treatment with b/tsDMARDs. The secondary objective was to assess the effectiveness and changes at 6 and 12 months in disease outcomes, stratifying the analysis by different mechanisms of action. Methods: For this study, data from RA patients treated with b/tsDMARDs recorded in the Italian GISEA registry from January 2017 to December 2023 were analyzed. Disease activity scores and patient-reported outcomes (PROs) were recorded at baseline, and at six- and twelve-month follow-up. D2T-RA patients were defined by meeting these three criteria: 1) failure of ≥ 2 b/tsDMARDs (with different mechanisms of action); 2) signs suggestive of active/progressive disease (at least moderate disease activity according to disease activity scores and/or glucocorticoid treatment ≥ 7.5 mg/day prednisone or equivalent); 3) patient VAS (Visual Analogue Scale) pain and/or PtGA (Patient Global Assessment) and/or PhGA (Physician Global Assessment) > 20. The retention rates were estimated using the Kaplan-Meier method and compared with log-rank test, while repeated measures ANOVA (Analysis of Variance) was used to assess changes in disease activity and PROs during follow-up. Results: The GISEA cohort included 5251 treatment lines with b/tsDMARDs. We were able to assess the D2T category for 3439 cases at the start of a new treatment. Overall, 1060 (30.8%) patients met all three criteria for D2T-RA, while 2379 (69.2%) patients were not categorized as D2T. Table 1 reports the demographic and clinical characteristics of D2T-RA patients. Patients with D2T-RA showed higher disease activity and PRO scores at baseline. Notably, JAK inhibitors (JAKis) were used more frequently in D2T-RA patients (48.8%) compared to non-D2T-RA patients (33.3%, p<0.05).Globally, the 5-year survival rate was significantly lower for D2T-RA patients compared to those with non-D2T-RA (47.5% vs 62.5%, p<0.001). No significant differences in persistence were observed among the classes of b/tsDMARDs used in D2T-RA (log-rank test: 6.76, p=0.15), with a 5-year survival rate of 38.7% for abatacept, 41.2% for TNFi, 48.1% for IL6r inhibitors, 62.3% for anti-CD20, and 49.6% for JAK inhibitors. Figure 1 shows changes from baseline in disease activity scores and VAS pain in D2T-RA according to b/tsDMARD class. DAS28-ESR was reduced in all b/tsDMARD classes, except for TNFi. CDAI was reduced in all b/tsDMARD classes without any differences among the classes. VAS pain was reduced in all classes. For VAS pain, we observed a significant difference between abatacept and JAK inhibitors, with JAK inhibitors showing greater reduction in VAS pain (p<0.05). Also filgotinib, the latest JAK inhibitor approved onto the market, exhibited a significant decrease on pain perception at both time points. Conclusion: Our study provides a snapshot of D2T-RA patients within the GISEA registry. All currently used b/tsDMARDs appear to be effective in this patient cohort. The higher efficacy of JAK inhibitors, particularly in managing pain symptoms in these patients, warrants further investigation. REFERENCES: [1] Nagy G, Roodenrijs NMT, Welsing PM, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 Jan;80(1):31-35. Acknowledgements: We thank Ing. Massimiliano Dellisanti Fabiano Vilardi for his valuable contribution to database creation and management. Disclosure of Interests: None declared.Figure 1

OBJECTIVES:We aimed to investigate the effectiveness of tumour necrosis factor inhibitors (TNFi), anti-interleukin-17 or interleukin-12/23 monoclonal antibodies (anti-IL) on comorbidities in a cohort of patients with spondyloarthritis (SpA), using an average treatment effect (ATE) analysis. METHODS:SpA patients from the multicentre Italian GISEA Registry were divided into groups according to pharmacological exposure: no treatment (G0), TNFi (G1) and non-responders to TNFi switched to anti-IL (G2). In each group, we recorded the prevalence and incidence of infectious, cardiopulmonary, endocrinological, gastrointestinal, oncologic, renal and neurologic comorbidities. Each comorbidity was then fitted for ATE and baseline features were evaluated for importance. RESULTS:The main findings of this study comprising 4458 SpA patients relate to cancer, other gastrointestinal diseases (OGID) and fibromyalgia. ATE showed no increased risk of solid cancer in G1 (0.42 95% CI 0.20-0.85) and G2 (0.26 95% CI 0.08-0.71) vs. G0, with significantly higher incidence in G0 (14.07/1000 patient-years, p=0.0001). Conversely, a significantly higher risk of OGID and fibromyalgia was found in G1 (1.56 95% CI 1.06-2.33; 1.69 95% CI 1.05-2.68, respectively) and G2 (1.91 95% CI 1.05-3.24; 2.13 95% CI 1.14-3.41, respectively) vs. G0. No treatment risk reduction was observed in haematological malignancies, cardiovascular events and endocrinological comorbidities. CONCLUSIONS:Overall, our study confirms the safety of TNFi and anti-IL in SpA patients, albeit with some caveats pertaining to solid cancers, OGID and fibromyalgia. Furthermore, taking into consideration causality with observational data may yield more reliable and relevant clinical information.

Background: Cognitive deficits (CDs) are frequent and worsen the quality of life of Systemic Lupus Erythematosus (SLE) patients. The Montreal Cognitive Assessment (MoCA) is a feasible test used to screen the presence of cognitive deficits. Objectives: The aim of the study is to evaluate whether the MoCA is a valid test for identifying SLE patients who require a targeted neuropsychological evaluation for CDs and to discriminate which factors influence MoCA’s alterations (including subjective cognitive symptomatology). Methods: A cross-sectional study was conducted between April 2019 and November 2022 in which adult patients with SLE (ACR/EULAR 2019 criteria) and HC with similar demographic characteristics were recruited. Demographic, clinical, clinimetric, serological and therapeutic data were collected (Table 1). CDs were screened with the MoCA test performed by certified personnel (altered if<26/30). A neuropsychologist explored deficits in 8 cognitive domains with a battery of neuropsychological tests. Depressive symptoms were evaluated with the Center for Epidemiologic Studies Depression Scale CES-D, (altered if>15) and fatigue with FACIT-F (altered if<30). Results: Ninety-nine patients and 36 HCs were enrolled (Table 1). MoCA test was altered in 44 SLE and 7 HCs (44.4% VS 19.4%, p=0.008). MoCA values in SLE correlated significantly with the alterations found in the battery test in the domains of memory, executive functions, complex attention and problem solving (Rey Immediate Words p=0.014; Recognition p=0.043, Stroop Test p=0.010, FAB p =0.005, Digit Symbol p=0.018). High MoCA scores correlated with the absence of CDs (mean 26.86±1.86, p=0.012). At least one subjective cognitive symptom was reported by 31/57 SLE and 13/36 HC but no correlation was found with the MoCA alterations, while a correlation emerged with the CES-D values (p=0.002) and fibromyalgia (p=0.003). At multivariate analysis after correction for age, gender, level of education, disease duration, fibromyalgia, dyslipidemia, SLEDAI-2K, anti-RibP titre, the factors that influenced MoCA were male gender (β=-0.206, p=0.014), education <8 years (β=0.444, p<0.001), dyslipidemia (β=-0.205, p=0.016), and antiRib-P (β=-0.221, p=0.008). Conclusion: MoCA test is useful for screening but not for diagnosis of CDs in SLE patients. Low level of education, male gender, dyslipidemia and anti-Rib-P titer were factors independently associated with MoCA alterations. No correlation between subjective cognitive symptoms with MoCA alterations was found, while a correlation emerged with CES-D values and fibromyalgia. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Elisabetta Chessa: None declared, cristina serafini: None declared, Alberto Floris: None declared, Maria Maddalena Angioni: None declared, MATTIA CONGIA: None declared, Alessandro Mathieu: None declared, Alberto Cauli: None declared, Mauro Giovanni Carta: None declared, Matteo Piga AstraZeneca, GSK, Otsuka, Roche, AstraZeneca, GSK.Table 1Demographics, clinics, clinimetrics, serological, therapeutics characteristics of the cohortsVariablesSLE (N=99)HC (N=36)Gender, F (%)92 (92.9%)34 (94.4%)Age, mean (SD)43.6 (±12.36)40 (±14.2)Education ≤8 years, N (%)29 (29.3%)4 (11.1%)Disease duration years, median (IQR)10.3 (3.3-18.2)-Neuropsychiatric Lupus, N (%)19 (19.2%)-Dyslipidemia, N (%)22 (22.5%)9 (25%)Hypertension, N (%)33 (33.7%)4 (11.1%)Smoking, N (%)17 (17.5%)8 (23.5%)MoCA test, mean (SD)25.3 (±3.05)27 (±2.9)>=1 cognitive domain altered N (%)17 (53%)-CES-D altered (>15), N (%)46 (46.5%)14 (38.9%)CES-D, median (IQR)16 (9-21.8)13 (7-17.3)FACIT altered (<30), N (%)23 (44.2%)8 (22.2%)FACIT, median (IQR)33 (25-40)42.5 (33.8-47)Subjective cognitive symptoms N (%)31 (54.4%)13 (36.1%)Fibromyalgia, N (%)21 (21.2%)-SLEDAI-2K, median (IQR)2 (0-5.5)-PGA, median (IQR)0.2 (0-0.8)-SLICC-DI, median (IQR)0.0 (0-1)-LLDAS, N (%)58 (58.3%)-Anti-dsDNA, median (IQR)9.2 (2.2-36.8)-C3, median (IQR)89 (73-97.5)-Anti-phospholipids, N (%)29 (30.5%)-Anti Rib-P, N (%)20 (21.3%)-PDN dose mg/die, median (IQR)4.6 (2.5-7.5)-Hydroxychloroquine, N (%)78 (78.8%)-Immunosuppressors, N (%)80 (80.8%)-

Background: The efficacy of belimumab in reducing disease activity in Systemic Lupus Eythematosus (SLE) has been extensively explored across clinical trials and real-life studies (1, 2). However, few studies have evaluated its efficacy upon stratification for different skin and joint phenotypes. Objectives: To assess potential disparity in efficacy of belimumab on different skin and joint manifestations from a multicentre nation-wide cohort (BeRLiSS). Methods: Adult SLE patients treated with belimumab (intravenous 10 mg/kg monthly or subcutaneous 200 mg weekly) included in the pre-existing BeRLiSS cohort (1, 2) were retrospectively analysed. Participating centres were asked to enrich the old BeRLiSS database with these new variables: skin (acute, subacute, chronic, skin vasculitis, alopecia/lupus hair, livedo reticularis, ulcer/chilblain) and joint involvement (non-deforming non-erosive arthritis – NDNE -, Jaccoud's arthropathy, and rhupus). These different subtypes were assessed for variation in DAS28, CLASI-A (Cutaneous Lupus Erythematosus Disease Area and Severity Index - Activity), SRI-4 (SLE responder Index-4) and SLEDAI-2K scores at baseline, 12 and 24 months. Parametric and non-parametric tests were used as appropriate. Results: A total of 312 patients was recruited, 284 females and 28 males, F:M ratio 9.9:1, mean age at diagnosis 29.1±12.7 years, mean treatment duration 52.2±38.0 months. At belimumab initiation 213 patients with joint manifestations (68.3%) were identified: 174 NDNE (55.8%), 22 Jaccoud's arthropathy (7.1%) and 17 rhupus (5.5%). Skin manifestations were found in 167 patients (53.5%): 88 acute (28.2%), 46 subacute (14.7%), and 11 chronic (3.5%) phenotype, 38 skin vasculitis (12.2%), 17 livedo reticularis (5.4%), 62 alopecia/lupus hair (19.7%) and 46 ulcer/chilblain (14.7%). Achievement of response as measured by SRI-4 was significant in patients with either articular or cutaneous manifestations, albeit independent of joint (p = 0.75; p = 0.63) and skin subtype (p = 0.24; p= 0.37) at 12 and 24 months, respectively. Similarly, SLEDAI-2K reduction was significant in both groups (p < 0.001), regardless of joint (p=0.80) and skin phenotype (p=0.14). Organ-specific measures such as DAS28 and CLASI-A decreased from baseline at 12 and 24 months across all phenotypes (Table 1 and 2). A statistically significant decrease in DAS28 from baseline at 12 and 24 months was observed for NDNE (baseline-12 months: p < 0.001; baseline-24 months: p < 0.001), Jaccoud's arthropathy (baseline-12 months: p = 0.015; baseline-24 months: p = 0.006) and rhupus (baseline-12 months: p = 0.034; baseline-24 months: p = 0.045). However, by ANOVA rhupus did not show improvement, possibly due to insufficient sample size. Comparison of CLASI-A variation from baseline at 12 and 24 months for the acute (baseline-12 months: p = 0.001; baseline-24 months: p < 0.001) and subacute subtype (baseline-12 months: p < 0.001; baseline-24 months p < 0.001) resulted to be significant. On the other hand, for the chronic subtype it only appeared to become significant at 24 months (p = 0.033). Variation of CLASI-A was not significant among different timepoints in patients with SLE-nonspecific skin manifestations. Conclusion: In our cohort of SLE patients, belimumab was effective in patients with joint and skin manifestations with no significant difference in DAS28, SRI-4 or SLEDAI-2K variation across the various joint involvement subtypes. On the other hand, the acute and subacute skin phenotypes were associated with an earlier response to belimumab on CLASI-A than the chronic phenotype. Finally, a clear response to belimumab was not found in patients with SLE-nonspecific skin manifestations alone. REFERENCES: [1] Zen M, et al. J Pers Med. 2023;13(4):691. [2] Gatto M, et al. Arthritis Rheumatol. 2020;72(8):1314-1324. Acknowledgements: NIL. Disclosure of Interests: Luca Iaccarino LI received honoraria (speaker fee) from GSK., Marisol Bracalenti: None declared, Margherita Zen MZ received honoraria (speaker fee) from GSK., Martina Tizian: None declared, Elena Ruffato: None declared, Alberto Cauli: None declared, Rossella De Angelis: None declared, Roberto Gerli: None declared, Marcello Govoni: None declared, Renato Lo Gullo: None declared, Simone Negrini: None declared, Luca Quartuccio: None declared, Carlo Salvarani: None declared, Angelo Vacca: None declared, Andrea Doria AD received honoraria (speaker fee) from GSK.

Background: Anifrolumab (ANI) is a fully human monoclonal antibody against the type I interferon receptor that has recently been approved for the treatment of moderate to severe Systemic Lupus Erythematosus (SLE) as an add-on treatment to standard of care. Data from randomized controlled trials have demonstrated its efficacy and safety, but real-world data are still limited, especially regarding the impact of this new drug on patients' quality of life (QoL). Objectives: To evaluate the effect of ANI therapy on QoL and disease burden in a multicentric cohort of refractory SLE patients. Methods: Consecutive adult SLE patients (2019 EULAR/ACR criteria) were prospectively enrolled at ANI prescription. Data on demographic features, medical history, previous therapies and SLICC-DI were collected from clinical charts at enrolment. Patients' assessments were performed at the first ANI infusion and subsequently after one, three and six months of treatment. At each time-point, the clinical evaluation included SLEDAI-2K, SLE-DAS, Physician Global Assessment, number of tender and swollen joints and cutaneous activity and damage assessed using the Cutaneous LE Disease Area and Severity Index (CLASI-A for activity and -D for damage). Patients' perspective was assessed by self-administration of validated Patient Reported Outcomes (PROs): Lupus Impact Tracker (LIT) to assess the overall impact of SLE on patients' QoL, Functional Assessment of Chronic Illness Therapy – Fatigue scale (FACIT-F) to measure self-reported fatigue and its impact on daily activities and, in a subgroup of patients with mucocutaneous involvement, Skindex-16 which is a specific PRO to investigate the impact of the skin disease in symptom, emotional and functioning spheres. Results: Twenty-five patients (96% female, 92% Caucasian) with a median age of 45 years (IQR 37-58) and a median disease duration of 11 years (IQR 7.5-21.5) were enrolled. In the whole cohort, 24 patients (96%) had a history of articular involvement, 23 (92%) of mucocutaneous involvement, 16 (64%) of haematological involvement, 7 (28%) of lupus nephritis, 5 (20%) of serositis and 4 (16%) of neuropsychiatric involvement. At baseline, 23 patients (92%) were on concomitant steroid therapy (median prednisone daily dose 7.5 mg, IQR 5-10), 19 (76%) on hydroxychloroquine and 23 (92%) on immunosuppressive treatment (10 methotrexate, 9 mycophenolate mofetil, 3 azathioprine, 1 cyclosporine). Active disease manifestations at the time of ANI prescription were in most cases mucocutaneous (18/25, 72%), followed by articular (10/25, 40%) and haematological (5/25, 20%) involvement. As reported in Table 1, after ANI start, all the disease activity measures showed a progressive improvement over time. A significant correlation was observed between LIT and joint count and Skindex-16 and CLASI-A at baseline (r≥0.464, p≤0.026 for LIT; r≥0.731, p≤0.04 for Skindex-16). During follow-up, LIT and Skindex-16 exhibited progressively and significantly improved scores, while no changes were observed in FACIT-F scores. Notably, Skindex-16 was significantly improved as early as 4 weeks after the first drug infusion (symptoms p=0.028, emotions p=0.03, functioning p=0.05), while LIT reached statistical significance after 12 weeks of treatment (p=0.046), maintaining in both cases the result achieved over time (Figure 1). Conclusion: Our preliminary data show that ANI not only allows a rapid clinical improvement of SLE activity, but also of QoL as shown by the significant amelioration of PROs from the very first months of treatment. Further long-term studies on larger cohorts are needed to confirm and corroborate these results. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.

OBJECTIVES:The purpose of this study was to evaluate the performance of a dermatologist-filled-in 7-item questionnaire (called HERACLES) as a screening tool for psoriatic arthritis (PsA) in patients with psoriasis. METHODS:This study was performed in Italy in seven dermatology centres cooperating with rheumatology centres. Adults with psoriasis were consecutively recruited up to a calculated number of 750. They were invited to fill in the following questionnaires used for PsA screening: ToPAS, PASE, PEST, and EARP. The dermatologists, in addition to standard demographic and clinical data, scored each participant using a new 7-item questionnaire. All participants were later evaluated by the rheumatologists for a diagnosis of PsA. The performance of the various questionnaires was compared using receiver-operating-characteristic (ROC) area-under-the-curve (AUC) analysis. RESULTS:Of the 759 enrolled psoriatic patients, 524 (280 males and 244 females) were suitable for data analysis. PsA was diagnosed in 73 (13.9%) participants. PsA and non-PsA patient characteristics were comparable, except for arthritis-related features which were often more prevalent in the PsA group. The ROC AUC of the HERACLES instrument was 0.775 (CI: 0.722-0.828), similar to that of the other questionnaires (ToPAS 0.757; PASE 0.730; PEST 0.741; and EARP 0.739). For the HERACLES instrument, a score value of 2 yielded a sensitivity of 92% and a specificity of 47%. CONCLUSIONS:In this study, a dermatologist-filled-in questionnaire proved to be not inferior to patient-administered PsA screening tools and to be feasible. It might be an alternative (or additional) tool to screen psoriatic patients for rheumatology referral.

Objective We aimed to evaluate ixekizumab (IXE) effectiveness, drug survival and clinical response predictors in moderate-severe psoriatic arthritis (PsA) patients in different clinical scenarios. Methods This was a multicentre real-life observational study based on Gruppo Italiano Studio Early Arthritis (GISEA) registry of IXE treatment in PsA patients (January 2019-June 2023). Data were collected at baseline and every six months. Results 223 PsA outpatients were included. Statistically significant improvement was observed after 6 (T6), 12 (T12) and 24 (T24) months of therapy for tender and swollen joint count (TJC and SJC), Visual Analogue Scale (VAS)-pain and Disease Activity in PSoriatic Arthritis (DAPSA) score. DAPSA remission was reached at T12 in 22% and at T24 in 18.5% of patients. At baseline, higher fibromyalgia and combination therapy with conventional synthetic disease- modifying anti-rheumatic drugs (csDMARDs) in females with respect to males and higher Psoriasis Area Severity Index (PASI) in males than in females were observed. Therapeutic effectiveness showed in males higher DAPSA and VAS-pain reduction, higher percentage of males in DAPSA remission/low disease activity (LDA) at T6, and higher triangle PASI at T6 and T12 than in female patients. At multivariate analysis, male sex was predictive for treatment response at T6 [p=0.02, odds ratio (OR) 2.49 (95% confidence interval 1.11-5.54)], while it lost significance at T12. Conclusion IXE effectiveness was highlighted after 6 months at both joint and skin levels and lasted up to 24 months in different clinical scenarios, making IXE effective in the complexity of managing PsA in a real-life setting.

OBJECTIVE:To report real-world experience on the use of anifrolumab (ANI) in refractory systemic lupus erythematosus (SLE). METHODS:The present study is a multicenter, retrospective study involving 9 Italian SLE referral centers participating in a compassionate use program for the use of ANI in adult patients with active SLE in whom all the available treatment choices failed, were not tolerated, or were contraindicated. At baseline and 1, 3, 6, 9, and 12 months of treatment, overall and organ-specific disease activity, flares, daily glucocorticoid (GC) dose, and adverse events were recorded. RESULTS:A total of 26 patients were enrolled. At 4 weeks after starting ANI, a significant decrease in the Systemic Lupus Erythematosus Disease Activity Index 2000 (P = 0.01), Systemic Lupus Erythematosus-Disease Activity Score (P = 0.01), and physician global assessment (P = 0.001) was recorded, and the same trend was maintained over time. A significant reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index-activity (P < 0.001) and in tender (P = 0.03) and swollen (P = 0.02) joint counts was also recorded. At 3 months of follow-up, 33% of patients already achieved a remission state, whereas 46% were in Lupus Low Disease Activity State (LLDAS); at 6 months, 50% were in remission and 80% were in LLDAS. A significant reduction in the mean GC daily dose was observed, starting from week 4 (P = 0.04). A total of 4 disease flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index were recorded (3 mild-moderate and 1 severe). Overall, 4/20 patients with at least 24 weeks of follow-up (20%) were considered nonresponders. CONCLUSION:This study provides real-world experience on the use of ANI in patients with refractory SLE, confirming its rapid effectiveness and an overall acceptable safety profile.

Background Progression of radiographic damage in axial-spondyloarthropaties is related to higher functionality impairment in longstanding patients, resulting in poorer quality of life and autonomy. Its impact on gait has not been extensively studied yet. Time-up and go (TUG) test and GAIT analysis (GA) are currently used in neurological and musculoskeletal diseases to evaluate changes in patients gait and stance. Objectives The aim of this study is to evaluate with standardized procedures modifications of gait in patients with inactive longstanding axSpa with radiographic damage, comparing them with a cohort of sex, age and BMI matched healthy controls. Methods Patients followed at Rheumatology Unit of the University Hospital of Cagliari were enrolled. Inclusion criteria were: 1) having a diagnosis of axSpa, 2) having an inactive disease (BASDAI<4, PtGA<20, PhGA<20), 3) evidence of radiographic damage in the most recent spine x-ray available (mSASSS >20), 4) ability to walk autonomously. Exclusion criteria were: 1) deafness, 2) any medical condition that, according to investigators, could expose patients at any excess risk or interfere with the procedures of the study. Patients underwent a TUG test and a gait analysis at the Department of Mechanical, Chemical and Materials Engineering, University of Cagliari. For TUG Test the following parameters were recorded: TUG time, sit-to-stand time, first and second rotation time, stand-to-sit time, walking time. Walking speed and mean step length were recorded using GAIT analysis. Statistical analysis was performed with MANOVA (Pillai’s Trace, Wilk’s Lambda, Hotelling’s Trace, Roy’s Largest Roots). Level of statistical significance was set at<0,05. Results Fifteen patients and fifteen HC were enrolled in this study. Mean age was 60,1±7,8 years for patients and 61,3±7,8 for HC. Weight and height were similar in both groups (axSpa 76,7 ± 16,8kg vs HC 72 ±7,2kg; axSpa 169,33 ± 8,8cm vs HC 170,4 ± 5,2cm). Disease duration was 27.61±9,67 years, mean mSASSS was 46,33±16,84. All patients were inactive, but showed clinical signs of disease progression (BASMI 5,9±1,19). Thirteen patients were on treatment with bDMARDs (TNF inhibitors), while 2 were off treatment. MANOVA revealed differences between axSPa patients and HC for TUG test (p<0,05). TUG time and walking time were significant longer in axSpa (TUG time 12,88±1,92s vs 10,44±2,18s, p=0,003; walking time 5,69±1,17s vs 3,68±0,8, p<0,001), while other parameters were not different between groups. Finally, axSpa patients were slower (0,95±0,16 m/s vs 1,18±0,17 m/s; p<0,05), and had a shorter step (0,52±0,65 m vs 0,65±0,69 m; p<0,05). Conclusion Patients with longstanding axSpa showed a different gait when compared with matched HC: we found that axSpa patients walk slower than HC, and with shorter steps. This could be interpreted as a compensatory behaviour as walking speed slower than 1 m/s has been reported as a risk factor for falling in elderly. In conclusion, we found that disease progression in axSpa patients could interfere with walking speed. Clinical relevance of these findings should be confirmed in future studies, as well as if some medical intervention (e.g. physical therapy) could minimize the impact of disease progression on posture control and walking. Reference [1]Verghese et al. Quantitative Gait Markers and Incident Fall Risk in Older Adults. Gerontol, 2009. Vol. 64A, No. 8, 896–901 doi:10.1093/gerona/glp033 Acknowledgements: NIL. Disclosure of Interests None Declared.

Background Sex hormones have effects on the development, progression and severity of SLE, prevalently affecting women (F:M=9:1). The neuroprotective, neurotrophic and anti-inflammatory properties of a class of progesterone-derived NeuroActive Steroids (NASs), prompted numerous investigations about the potential of these GABAA receptor allosteric modulators. However, no data about NASs on neuropsychiatric SLE (NPSLE) are available. Objectives This exploratory pilot study aims to delve into a new unexplored landscape by assessing circulating NASs levels in NPSLE patients. Methods A cohort of 16 SLE patients without NP manifestations and 16 with new onset NP diffuse symptoms was enrolled. Mood disorders and cognitive dysfunction were defined according to the Center for Epidemiologic Studies Depression Scale (CES-D) and a battery of neuropsychological tests, respectively, interpreted by a neuropsychologist. A group of 8 healthy controls (HCs) matched for mean age and gender ratio was also recruited. Exclusion criteria: ongoing contraceptive or hormonal treatment; glucocorticoid pulse or treatment variations 6-month before blood collection; anxiolitic, anticonvulsivant, antiepilettic drug intake; gonadal-adrenal surgical intervention or pathologies. Data regarding demographics, SLEDAI andSLICC organ damage index (SDI) were collected. NASs serum levels and their precursor were measured by ELISA assay, as listed: Progesterone, Diidroepiandrosterone (DHEA), Diidroepiandrosterone-Sulphate (DHEA-S), Allopregnanolone. To appreciate differences between groups, women's fertile or menopausal subgroups were formed and p-value <0.05 has been set. Results Table 1 reports on data from the whole cohort. Progesterone levels in fertile women were significantly higher in the NPSLE versus HCs group (p=0.011). The Progesterone-direct metabolite, Allopregnanolone, was significantly increased in NPSLE compared to both groups of fertile SLE (p=0.026) and HCs females (p=0.027). Inversely, low levels of DHEA and DHEA-S in SLE patients versus HCs (p=0.025 and p=0.005) were found. Looking for NP symptoms, DHEA titer inversely correlates with cognitive deficit diagnosis (p=0.04), while depression diagnosis (62.5% of NPSLE cohort) correlates with Allopregnanolone levels (p=0.042). Moreover, depression severity measured by the CES-D score correlates with Progesterone (r=0.550, p=0.041) and Allopregnanolone (r=0.712, p=0.004; Figure 1). At multivariate analysis after correction for age, disease duration, SLEDAI and SDI, Allopregnanolone confirmed its independent correlation (β=0.712, p=0.004) with depression severity. Conclusion In this pilot study, we describe for the first time the unbalanced levels of the most potent neuroactive steroid Allopregnanolone in SLE fertile patients with new onset neuropsychiatric diffuse manifestations. Moreover, in NPSLE patients, the diagnosis of cognitive deficit associates with circulating DHEA low levels and that of depression associates with Allopregnanolone high levels, significantly correlated also with the severity of this manifestation. Since the appropriate NASs balance is needed for optimal brain and neuroimmune function, our preliminary observations – that needs to be validated in an extended cohort - open a new perspective in the field, where the circulating NASs assessment in NPSLE patient could be a new promising diagnostic and preclinical research strategy. Acknowledgements All staff of the Rheumatology Unit of the AOU of Cagliari, patients and volunteer donors. Disclosure of Interests Maria Maddalena Angioni: None declared, Elisabetta Chessa: None declared, alessandra perra: None declared, elisa pintus: None declared, Alberto Floris: None declared, MATTIA CONGIA: None declared, Mauro Giovanni Carta: None declared, Alberto Cauli: None declared, Matteo Piga Speakers bureau: GSK, Consultant of: GSK, GALAPAGOS, ASTRAZENECA.Figure 1Median value of NASs circulating levels on NPSLE/SLE/HCs fertile and menopausal female. *pvalue ≤ 0,05; ** pvalue ≤ 0,01Table 1Demographic and clinical characteristics of the participantsNPSLE (16)SLE (16)HC (8)Age mean (DS)48.2 (15.9)42.1 (10.8)49 (16)Gender (F, %)100100100Fertile (%)505050Menopausal (%)505050Disease duration, yrs median (IQR)6(2.3-9.3)6.7(3.0-10.4)-SLEDAI median (IQR)5 (1.8-11)2 (0-4)-Dose PDN mg/daily median (IQR)9.5 (5.1-14.6)3.8 (3.2-7)-Cognitive disorder (%)50--Major depression (%)62.5--

Background A remarkable variability in the clinical course of Behçet's Syndrome (BS) seems to arise by comparing cohorts from different geographical areas. However, no data are currently available on the possible variability of organ damage burden, although it is currently recognized as a major outcome in BS. Objectives To evaluate and compare the extent, characteristics, and associated factors of organ damage in patients from different World areas. Methods We analyzed demographic and clinical data of a multicenter cohort of 935 consecutive BS patients from 11 Countries clustered in 5 geographic areas: Europe (EU, n 345), North Africa (NA, n 278), Middle East (ME, n 227), Central Asia (CA, n 44), America (AM, 41). Organ damage was assessed by the BS organ damage index (BODI) [1]. Uni- and multivariate analysis was performed to evaluate the association between the geographical region and organ damage using demographic and clinical data as covariates. Results Demographics and clinical features are reported in the Table 1. The prevalence of any damage (BODI≥1) in the EU, ME, NA, CA, and AM areas was 47.0%. 54.6%. 91.7%. 97.6% and 77.3%, respectively, whereas the mean (SD) total BODI score was 1.1 (1.7), 1.2 (1.7), 3.5 (2.4), 4.5 (2.6), and 1.9 (1.9). The prevalence of different BODI domains is reported in the Table 1. Significant differences were recorded in NA vs. EU and ME cohorts (Figure 1) (CA and AM not included in the statistical analysis for the small sample size). In multivariate analysis, the geographical area was independently associated (p < 0.001) with damage (NA vs. EU OR 11.3; ME vs. EU OR 1.5). Male gender (OR 1.5; p = 0.004), age (OR 1.03 per year; p = 0.002), disease duration (1.03 per year; p = 0.003), ocular (OR 2.8; p <0.001), vascular (OR 5.3, p <0.001), and neuropsychiatric (OR 3.8, P<0.001) involvement were also associated with BODI≥1. Conclusion A variable prevalence of organ damage was observed in BS patients from different World areas. Further research is needed to understand the cause underlying such geographic variability, as it may unveil biological, environmental, or health-system factors driving damage accrual in BS. The BODI effectively captures damage independently from the studied cohort's geographical origin. Reference [1]Piga M. Floris A. Espinosa G. et al. Development and preliminary validation of the Behçet's syndrome Overall Damage Index (BODI). RMD Open 2020;6:e001192. Acknowledgements: NIL. Disclosure of Interests None Declared.Table 1Demographic and clinical characteristic of the patients form different geographical area.EuropeMiddle EastNorth AfricaCentral AsiaAmericaMales37.1%59.5%80.2%41.5%40.9%Age, yrs46.3 (14.1)37.4 (10.0)37.7 (11.1)36.2 (17.6)44.1 (14.5)Disease duration, yrs14.6 (11.4)12.1 (8.7)8.6 (7.2)11.6 (9.6)14.3 (10.1)Diagnosis delay, yrs4.1 (7.2)6.5 (7.4)2.4 (4.8)5.2 (6.1)4.5 (6.5)BODI domainsMucocutaneous13.0%14.5%46.8%92.7%4.5%Musculoskeletal3.2%0.4%1.4%7.3%6.8%Ocular22.0%31.3%54.3%68.3%31.8%Vascular10.7%12.3%36.0%7.3%18.2%Cardiovascular11.9%12.3%37.4%12.2%18.2%Neuropsychiatric11.3%4.8%18.3%46.3%36.4%Gastrointestinal0.6%1.3%1.4%0.0%0.0%Miscellaneous10.4%5.3%4.0%9.8%9.1%BODI score1.1 (1.7)1.2 (1.7)3.5 (2.4)4.5 (2.6)1.9 (1.9)In males1.6 (2.1)1.5 (1.8)3.7 (2.3)5.0 (2.9)2.9 (2.2)In females0.8 (1.3)0.9 (1.4)2.6 (2.4)4.2 (2.5)1.7 (1.8)Europe included patients from Italy. Portugal. Spain. Greece; North Africa: Morocco. Egypt; Middle East: Turkey. Iran; Central Asia: Kazakhstan; America: USA. Brazil. Continuous variables are reported as mean (SD).

BackgroundThe efficacy of Janus Kinase inhibitors (JAKis) in Rheumatoid Arthritis (RA) has been established in the last years through numerous randomized clinical trials. Recently, the safety profile of this drug class has come under the spotlight, questioning the actual use in clinical practice and making real-life data even more crucial.ObjectivesThe purpose of this study is to evaluate the long-term retention rate of JAKis and to estimate the influence of baseline population characteristics on treatment persistence.MethodsData of all RA patients who started a JAKi were prospectively collected in the Italian multicentric GISEA registry. The 3-year retention rate of JAKis was calculated by the Kaplan-Meier method and compared by a log-rank test after stratification according to different baseline population characteristics. A descriptive analysis of reasons for discontinuation was performed.ResultsThe study population included 1361 patients (females 83.5%, mean age [±SD] 57.3 [±12.3] years, over 65 years 30%, mean disease duration 12.7 [±9.7] years, mean baseline SDAI 20.6 [±11.7], ACPA positive 68%, RF positive 66%, current smokers 19%, past smokers 13%) who received a JAKi (baricitinib=763, tofacitinib=321, upadacitinib=151, filgotinib=126) as first (n=491) or subsequent line (n=870) targeted drug. The overall 3-year retention rate was 46%. Drug survival was significantly higher in ACPA positive compared with negative patients (51.6 vs 41.8%, p=0.0051) (Figure 1A) and in first-line versus second or further lines of therapy (50.6 vs 43.3%, p=0.0013) (Figure 1B). No difference was found according to age (< or ≥65 years), concomitant methotrexate, smoke, history of diabetes, or at least one cardiovascular comorbidity (hypertension, stroke, or heart failure). Therapy was discontinued in a total of 523 patients because of ineffectiveness (67.5%), adverse events (25.8%), or compliance/other reasons (0.3%). Of relevance, adverse events included cancer (0.7%), major adverse cardiovascular events (MACE) (0.4%), deep vein thrombosis (DVT) (0.6%), and herpes zoster virus (HZV) infections (1.5%).ConclusionOur data confirmed in a real-life setting a favorable 3-year retention rate of JAKis in RA. ACPA positivity and use as first-line targeted drug significantly improved persistence of JAKis. Discontinuations of JAKis because of adverse events (including MACE, DVT, HZV, and malignancy) were very uncommon, suggesting an overall favorable safety profile.AcknowledgementsWe thank the physicians and patients who participated in these studies.Disclosure of InterestsMartina Biggioggero Speakers bureau: Galapagos, Elisa Gremese: None declared, Serena Bugatti: None declared, Andreina Manfredi: None declared, Simone Parisi: None declared, Chiara Bazzani: None declared, Antonio Carletto: None declared, Carlo Garaffoni: None declared, Angelo Semeraro: None declared, Addolarata Corrado: None declared, Rosario Foti: None declared, Alberto Cauli: None declared, Francesca Romana Spinelli Speakers bureau: Amgen, AbbVie, Eli Lilly, Galapagos, Consultant of: Amgen, AbbVie, Eli Lilly, Galapagos, Florenzo Iannone: None declared, Ennio Giulio Favalli Speakers bureau: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB.

Background In the age of targeted-synthetic disease-modifying antirheumatic drugs (tsDMARDs), filgotinib represents the last JAK inhibitor available in Europe for rheumatoid arthritis (RA). Filgotinib is characterized by predominantly inhibition of JAK1 and its efficacy and safety have been highlighted by phase 2/3 studies, but no real-life data in RA are currently available. Objectives The aim of this study was to evaluate the effectiveness and safety profile of filgotinib in real-life setting in RA patients included in Italian GISEA (Group for the Study of Early Arthritis) registry. Methods For this study, data from RA patients treated with filgotinib recorded in Italian GISEA registry were analysed. Disease activity scores and patients reported outcomes (PROs) were compared at baseline and six months follow-up using paired t-tests. The retention rate was estimated by the Kaplan-Meier method, while a cox regression model was used to search for possible factors influencing drug survival. Results One hundred and seventy-nine patients (female 89.4%, age 57.8±12 years, FR/ACPA+ 64.3%, current/former smoker 31.8%) included in GISEA registry started filgotinib for active RA. Most patients were taking filgotinib as second (23.5%) or further (43%) b/tsDMARDs line of treatment. Filgotinib was used in monotherapy in 66.5% of patients, while 52% were not on treatment with glucocorticoids (GCs) at baseline. All demographic and clinical data are reported in Table 1. A follow-up visit was available for 122 patients (mean time of first follow-up visit: 4±2 months). As shown in table 1, we observed a decrease of all disease activity scores and PROs. At first follow-up visit, 67.8% of patients were in remission/low disease activity according to CDAI and 65.4% according to SDAI. Kaplan-Meyer analysis highlighted that drug persistence was similar either in monotherapy or combination therapy (Figure 1a), and irrespective of GCs at baseline (Figure 1b). However, a better persistence was observed in RA patients on first line treatment with filgotinib (Figure 1c). Thirty-five patients stopped filgotinib during follow-up, 10 for lack of efficacy, 4 for loss of efficacy, 4 for adverse events, while for the remaining cases the cause of drug discontinuation was unknown. No major cardiovascular events were reported. Finally, univariate Cox-regression model showed that b/tsDMARD naïve patients had a lower risk of drug discontinuation (naïve vs other lines: HR 0.37, 95%CI 0.20-0.86). Conclusion In Italian real-life setting, filgotinib confirms a good effectiveness and safety profile. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.Figure 1Survival analysis in RA patients treated with Filgotinib.Table 1Demographic and disease characteristics at baseline and at first follow-up visit (T1) of RA patients treated with Filgotinib.Variablesbaseline (n. 179)T1 (n. 122)Agemean (SD), years57.8 (12.7)58 (12.6)Gendern. (%), femalen. (%), man160 (89.4)19 (10.6)110 (90.2)12 (9.8)BMIn. (%), underweightn. (%), heathy weightn. (%), overweightn. (%), obese4 (3.8)50 (48.1)21 (20.2)29 (27.9)4 (5.3)36 (47.4)15 (19.7)21 (27.6)Smokersn. (%), currently smokern. (%), former smokern. (%), never smoker13 (13.8)17 (18)64 (68.1)8 (13.5)12 (20.3)39 (66.1)IgG RF/ACPA +n. (%)74 (64.3)54 (71.1)VAS painmean (SD)63.1 (29.1)35 (30.7)***VAS PtGAmean (SD)60 (26.7)35 (29)***VAS PhGAmean (SD)44 (25.4)20.9 (23)***TJC28mean (SD)5.4 (5)2.7 (3.8)**SJC28mean (SD)3.3 (3.5)1.3 (2.2)***DAS28-ESRmean (SD)4.6 (1.3)3.3 (1.4)**CDAImean (SD)19.1 (11.3)9.6 (9.5)**SDAImean (SD)20.5 (12)10.3 (10)**HAQ-DImean (SD)1.3 (0.7)0.9 (0.7)***glucocorticoidn. (%)86 (48)47 (38.5)**Prednisone (equivalent), mg/diemean (SD)5.8 (3.7)3.4 (2.6)*csDMARD (in corso)n. (%)60 (33.5)31 (25.4)b/tsDMARD linen. (%), 1^ linen. (%), 2^ linen. (%), 3^ line or others60 (33.5)42 (23.5)77 (43)/Mean time of first follow-up visit: 4±2 months*p<0.05, **p<0.01, ***p<0.001

Background Among the unmet needs in psoriatic arthritis (PsA), the discovery of molecular players and biomarkers of disease activity or clinical remission achievement, remains unsolved. Metabolomics is a valuable technology in identifying biomarkers, by the study of a set of small molecules produced by the catabolism or anabolism of an organism in response to physiological or pathological states, allowing to better understand the disease-related variations downstream of the genome and proteome. Objectives In this pilot study, we have compared the serum metabolomics profile of patients with psoriatic arthritis with active or clinically inactive disease state compared with healty controls, using Nuclear Magnetic Resonance Spectroscopy (1H-NMR). Methods From a cohort of 300 PsA patients according to CASPAR criteria, we selected 30 PsA with active disease state by DAPSA > 14 score (no bDMARDs ongoing) (A), 38 patients (peripheral arthritis subset) with >1-year remission by antiTNFα assessed by DAPSA ≤ 4 (B) and 32 healthy controls (C) matching for mean age and gender ratio. The sera metabolomics profile of 100 subjects was analyzed with a Varian UNITY INOVA 500 MHz NMR spectrometer, combined with Multivariate statistical Analysis (MVA). Principal Component Analysis (PCA) and Orthogonal Partial Least-Squares Discriminant Analysis (OPLS-DA) were applied. The model's goodness was evaluated using a permutation test (Q2 intercept value <0.005). Results The represented OPLS-DA models (Figure 1) exhibited a clear separation between subjects with active disease (red dots) and healthy controls (green dots), and patients with active disease or clinical remission state (blue dots), indicating significant differences in the serum metabolomics profile between all compared conditions. Interestingly, the OPLS-DA model shows how the PsA patients in the remission state have a profile which does not completely overlap with healthy subjects. The validity of the OPLS-DA models was evaluated through a permutation test using 500 times (Table 1) and indicate the great statistical validity of the OPLS-DA reported models. Conclusion The metabolomic profile of PsA patients with different disease state and healthy subjects reveal a high grade of dissimilarity between all compared conditions: remarkably, the metabolomic profile of patients with the drug-induced clinical remission appears still different from a healthy condition, perhaps reflecting molecular modifications induced by the great response to TNFalpha inhibition sustaining the clinical remission of PsA disease. Supplementary analysis of single-spectra is ongoing to obtain a list of metabolites differentially expressed in all conditions, and on this field further explorations are needed to validate metabolomics biomarkers that can accurately and reliably measure PsA disease activity or remission achievement, as well as to identify the metabolic fingerprint of antiTNFα-treatment success. Acknowledgements All staff of the Rheumatology Unit of the AOU of Cagliari, patients and volunteer donors. Disclosure of Interests None Declared.Figure 1OPLS-DA scores plots of 1H NMR spectra of sera samples. Red dots: (A) active PsA patients; blue dots: (B) remission PsA patients; green dots: (C) healthy controls.Table 1Parameters for OPLS-DA modelsOPLS-DA modelsPermutation (500 times)*active PsA patients vs healthy controlsComponentsaR2XcumbR2YcumcQ2cumdR2 interceptQ2 intercept1P+1O0.4060.6650.5170.330-0.336active PsA patients vs remission PsA patients1P+2O0.4810.8240.5040.461-0.424remission PsA patients vs healthy controls1P+1O0.3890.6110.4290.318-0.331aThe number of Predictive and Orthogonal components used to create the statistical models.b,c R2X and R2Y indicated the cumulative explained fraction of the variation of the X block and Y block for the extracted components.d Q2 cum values indicated cumulative predicted fraction of the variation of the Y block for the extracted components.*An Q2 intercept value less than 0.005 are indicative of a valid model.

Background Recurrent oral and genital ulcers are the most nagging clinical manifestations of Behcet's disease (BD) and colchicine should be used first for the treatment and prevention of ulcers relapse. In contrast, TNF-α inhibitors (TNFi) are helpful in resistant cases, leading to a rapid improvement of mucosal lesions [1]. More recently, the phosphodiesterase-4 inhibitor apremilast was evaluated in two RCTs showing a significant improvement of oral ulcers compared to placebo [2, 3]. Moreover, several observational studies also investigated the effectiveness of apremilast in BD patients with mucosal ulcers [4]. Objectives To date, there are no comparative data about the effectiveness between TNFi and apremilast in mucocutaneous involvement of BD. The present study aims to compare the effectiveness between TNFi and apremilast on oral ulcers of BD. Methods Data on patients classified as BD (according to International Criteria for BD and International Study Group criteria) who underwent apremilast or TNFi for refractory oral ulcers from March 2017 to January 2022 in 7 tertiary rheumatology centers (6 Italian and 1 Spanish) were retrospectively analyzed. Retrieved data including demographics and clinical characteristics were collected. We also recorded the presence of active oral aphtosis at either baseline, 3-month and 6-month follow-up as well as the occurrence of oral ulcers during the intervals between visits. Patients on TNFi were considered controls for nearest-neighbour propensity score (PS-)-matching (neighbours for replacement matching, minimum 1, maximum 4). PS is an epidemiological tool used for the adjustment of non-randomized longitudinal studies. It is a conditional probability of being exposed to a disease given an asset of covariates. In brief, this was carried out using the patients' age, disease duration and gender, with a selected calliper of 0.2. Chi-square test was used to test difference between proportions of patients with active aphtosis in both groups at different follow-up times. Results Among 159 patients with BD on TNFi or apremilast, the matching algorithm retrieved 84 patients. More in detail, 26 patients in the apremilast group and 58 patients in TNFi group. All had active aphtosis at treatment start. Clinical ad demographic characteristics of patients at baseline are reported in Table 1 and Figure 1 and 2. Concerning proportion of patients with active oral aphtosis, no difference was observed either at 3-month (p=0.60) and 6-month (p=0.66) follow-up visits (Figure 2). Consistently, the rate of flares in the time intervals between visits was not different between groups (46.15% vs 37.93% from month 0 to 3, p=0.47; 34.62% vs 34.48% from month 3 to 6, p=0.99). Conclusion The main limitations of our study are the small sample size and the short-term follow-up. Nevertheless, we provide evidence that apremilast and TNFi show similar effectiveness, inducing a meaningful and early benefit in BD patients with refractory oral ulcers. References [1]Hatemi G, Christensen R, Bang D, et al. 2018 update of the EULAR recommendations for the management of Behçet's syndrome. Ann Rheum Dis. 2018 Jun;77(6):808-818.[2]Hatemi G, Melikoglu M, Tunc R, et al. Apremilast for Behçet's syndrome—a phase 2, placebo-controlled study. N Engl J Med. 2015 Apr 16;372(16):1510-8.[3]Hatemi G, Mahr A, Ishigatsubo Y, et al. Trial of Apremilast for Oral Ulcers in Behçet'sBehçet's Syndrome. N Engl J Med. 2019 Nov 14;381(20):1918-1928.[4]Lopalco G, Venerito V, Leccese P, et al. Real-world effectiveness of apremilast in multirefractory mucosal involvement of Behçet'sBehçet's disease. Ann Rheum Dis. 2019 Dec;78(12):1736-1737. Acknowledgements: NIL. Disclosure of Interests None Declared.Figure 1Table 1ApremilastTNF-α inhibitorsAv.Obs.Av.ObsFemale, n(%)2617(65.38)5830 (51.72)Age at diagnosis, mean (SD)2631.15(14.05)5826.60(12.39)Age at baseline, mean (SD)2628.34(14.57)5840.84 (12.73)Disease Duration, mean (SD)267.19 (8.24)584.24(5.35)csDMARDs combotherapy, n(%)267(26.92)5837(63.79)Current bDMARD/tsDMARD treatment line, median (IQR)261 (1-2)581(1-2)

Purpose Glucocorticoids (GCs) are recommended in patients with systemic lupus erythematosus (SLE), in combination with hydroxychloroquine (HCQ) or immunosuppressant, but should be tapered or discontinued in the medium to long-term to minimize detrimental effects. A sub-analysis of the multicenter Early Lupus inception cohort was performed to investigate the real-world trajectory of Glucocorticoids (GCs) Use in newly diagnosed SLE Patients (the GULP study) and the associated outcomes. Methods The GULP study enrolled patients starting prednisone (PDN) ≥5mg/day and concomitant HCQ or immunosuppressant within 12 months of SLE classification. SLE core set variables were recorded at baseline and then every six months for 2 years, including changes in PDN dose, ECLAM and BILAG active domains. The SLICC/ACR Damage Index (SDI) and a 0–10 global health visual analog scale (GH-VAS) were also recorded. Regression models analyzed the damage accrual and GH-VAS in different GCs tapering and discontinuation trajectories. Results Overall, 127 SLE patients with a mean age of 36.7 (± 13.4) years and a median disease duration of 6.1 (1.3 - 11.5) months were included. At baseline 98 (77.2%) patients received HCQ, 81 (63.8%) received conventional immunosuppressants, and 57 (44.9%) received a combination of them. The median daily dose of PDN at baseline was 12.5 (6.3–25.0) mg/day and significantly decreased to 5.4 (4.3–9.4) mg/day at 12-month and 4.9 (2.5–6.6) mg/day at 24-month (p<0.001). At the end of follow-up, 73 (57.5%) successfully tapered PDN doses below 5 mg/day, and 17 (13.4%) discontinued GCs within a 2-year follow-up (Figure 1). Overall, 99 (78%) patients tapered the PDN dose below 5 mg/day: 34 (26.8%) within 6 months, 35 (27.6%) within 12 months, 22 (17.3%) within 18 months and 8 (6.3%) within 24 months of follow-up; 42.4% of patients who tapered PDN and 46.4% of those who never tapered PDN below 5mg/day required to increase the PDN dose within the end of the 2-year follow-up. A higher daily dose of PDN resulted in a greater probability (OR 1.4 per mg/day; 95%CI 1.3–1.5; p<0.001) of GCs tapering regardless of disease activity, whereas ECLAM (OR 1.6; 95%CI 1.2–2.3; p=0.004) and BILAG (OR 1.9; 95%CI 1.3–3.0; p=0.004) were independently associated with the risk of increasing GCs dose. In patients taking PDN <5mg/day, daily doses remained stable in 49.3% and 52.8% of visits despite, respectively, ECLAM=0 and no BILAG activity. Every month spent on PDN<5mg/day was associated with lower damage accrual (IRR 0.96; 95%CI 0.93–0.99; p=0.007) and better GH-VAS (beta 0.60; 95%CI 0.13–1.33; p=0.108), although the latter was statistically nonsignificant. Conclusion GCs are feasibly tapered to PDN <5mg/day maintenance dose with adequate control of disease activity and lowered damage in patients with newly diagnosed SLE, whereas physicians usually avoid GCs discontinuation in the early disease stage.

Background Cognitive dysfunction (CD) and mood disorders (MD) are among the most frequent neuropsychiatric (NP) events in Systemic Lupus Erythematosus (SLE), but their pathogenesis has not been clarified yet. Until now, an unquestionable correlation between the presence of specific autoantibodies, brain alterations and the presence of CDs and MDs in SLE is lacking. Objectives The primary aim of the study was to explore the effects of anti-NR2 (anti-DWEYS) and anti-ribosomal-P (anti-P) antibodies on CDs and MDs and their relation with functional brain connectivity in patients affected by SLE. Methods A cross-sectional study was conducted, between April 2019 and February 2020, including adult patients who fulfilled the ACR/EULAR 2019 SLE criteria. Demographics, ongoing medications, SLEDAI and SLICC/Damage Index were recorded. Serum level quantification for anti-P (normal values <18 U/ml) and anti-NR2 (normal values <0.5 OD) antibodies were performed using an ELISA. A battery of neuropsychological testing was interpreted by a neuropsychologist, exploring cognitive domains, depression and quality of life. A resting-state functional connectivity (rs-fc) MRI analysis was performed within 2 weeks since the neuropsychological status assessments. Two region of interest to region of interest (ROI-to-ROI) analyses with the graph theory was performed. Results Thirty-three SLE patients (9% male) were enrolled, mean age 43.5 (+-14) years, and median disease duration of 10.4 years (IQR 2.9-25.4) (Table 1). Anti-P were positive (range 0-255 U/ml) in 6 patients (18.2%) and anti-DWEYS (range 0-1.8 OD) in 14 (42.4%). Nineteen out of 33 patients (57.6%) showed at least a cognitive test alteration, but no significant association with antibodies was found. Depression was found in 14 (42.4%) patients using the Center for Epidemiologic Studies Depression Scale (CES-D) as screening instrument. In multiple regression backward models, after correction for age, disease duration, SLEDAI and SDI, the CES-D showed an independent association with anti-P titre (β= 0.32 per U/ml; p=0.049) and prednisone daily dose (β=0.38 per mg/day; p=0.023). The rs-fc MRI analysis revealed a statistically significant association between the titre of anti-P and many altered properties of the brain ROIs (Figure 1), but no effects of PDN daily dose on specific cerebral networks. Table 1. Demographic and clinical characteristics of the patients in total, Legend: PDN: Prednisone; LLDAS: Lupus Low Disease Activity State; OD: Optical density Demographic and clinical characteristics of the participants (N=33) Age, years mean (DS) 43.5 (14.0) Gender (M, %) 3 (9%) Disease duration, months median (IQR) 124.4 (34.7-305) SLEDAI-2k mediane (IQR) 4 (0-14) Dose PDN mg/daily median (IQR) 6.4 (3.8-13.5) LLDAS N, % 12 (36,4%) SLICC-DI mediane (IQR) 0 (0-1) Ongoing treatment 25 (75.8%) Hydroxychloroquine 30 (90.9%) Immunosuppressive 9 (27.3%) Biologics Education less than 8 years 13 (39.4%) Anti-Rib-P N, % 6 (18.2%) Anti-Rib-P (U/ml) mean (DS) 10.9 (5.7-13.3) Anti-DWEYS N, % 14 (42.4%) Anti-DWEYS (OD) mean (DS) 0.4 (0.25-0.67) Anti-phospholipids N, % 11 (33.3%) anti-dsDNA N, % 18 (54.5%) anti-dsDNA Titre mediane (IQR) 22.5 (2.9-74.5) Figure 1. Results of rs-fc MR Analysis 1 (effects of Anti-rib-P titre) on cerebral networks. The regions with decreased and increased property are shown in blue and red nodes, respectively (p< 0.01). The node size represents the significance of the between-group differences in the nodal degree. Conclusion Anti-P antibodies are associated with depressive symptoms and changes of brain network properties in SLE patients, which add knowledge on their pathogenetic effect. Disclosure of Interests None declared