Background Nowadays, rheumatoid arthritis (RA) patients can benefit from several drugs classified as biologic (b) or JAK inhibitors (JAKi). Four JAKi are now available, whose two JAKi, with predominantly JAK1 selectivity (JAK1i), came onto the market in 2020. Objectives The aim of this study was to compare the effectiveness among RA patients included in BIOPURE registry on treatment on TNF inhibitors (TNFi) JAK1i, other JAKi (oJAKi), and other mechanisms of action (oMOA) bDMARD. Methods Data of RA patients who started a new line of treatment with a b/tsDMARD were prospectively collected from October 2020, when JAK1i was first prescribed, to May 2022. Demographics and disease characteristics were evaluated using standard descriptive statistics. Patients were divided in four groups: patients on TNFi therapy, patients on JAK1i (upadacitinib and filgotinib), patients on oJAKi (tofacitinib and baricitinib) and patients on oMOA (abatacept, tocilizumab and sarilumab). The drug survival was evaluated by Kaplan– Meier analysis. Estimated hazard ratios (HRs) of discontinuing therapy were assessed by multivariate regression models. Results Since October 2020, 580 RA patients started a new line treatment with b/tsDMARDs (171 TNFi, 192 oMOA, 88 oJAKi and 120 JAK1i). Overall cohort characteristics are reported in Table 1. As expected, monotherapy was more used in patients treated with JAK1i (73.6%), oJAKi (63.6%) and oMOA (54.7%) compared to TNFi (30.4%). Patients treated with JAK1i and oJAKi were more likely to be refractory to previous b/tsDMARDs, 76% of JAK1i and 76.2% of oJAKi had received prior treatment with ≥2 bDMARDs or other tsDMARDs. Patients treated with JAK1i presented higher disease activity compared to other b/tsDMARD and higher grade of disability at baseline compared to TNFi. Drug survival was similar between the four groups, being 66.7% for TNFi, 71.9% for oMOA, 64.8% for oJAKi and 69.8% for JAK1i (log-rank test:4.69, p=0.19) (Figure 1a). Multivariate cox regression model and K-M analysis (Figure 1b) showed that the main predictor of b/tsDMARDs discontinuation was a previous treatment with >2 b/tsDMARDs (HR: 1.85, 95% CI 1.21-2.85)Finally, a comparable number of adverse events causing drug discontinuation was observed: 10 (5.8%) in TNFi, 12 (6.3%) in oMOA, 9 (10.2%) in oJAKi and 10 (8.3%) in JAK1i. Conclusion Our study highlighted good effectiveness and safety of new and old b/tsDMARDs in Apulian cohort of RA patients included in BIOPURE registry. Of note, despite more than half patients starting JAK1i or oJAKi were multi-failure, they showed a similar drug survival compared to those on TNFi who were predominantly biologic-naïve. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.Table 1Characteristics of RA patients treated with b/tsDMARDsVariablesTNFi (171 pt.)Other MOA (192 pt.) (84 ABA, 88 TCZ, 20 sarilumab)Prevalent JAK1i (129 pt.) (78 upadacitinib, 51 filgotinib)Other JAKi (88 pt.) (55 baricitinib, 33 tofacitinib)Age, mean (SD)56 (13)58 (12)55 (12)58 (11)Female, n(%)143 (83.6)156 (81.3)114 (88.4)71 (80.7)Seropositivity, n. (%)108 (74)123 (81.5)100 (90.9)*^50 (67.6)Erosive arthritis80 (46.8)99 (51.6)69 (53.5)48 (54.5)Comorbidities count, median (IQR)0 (0-1)1 (0-2)*1 (0-2)*0 (0-2)csDMARD, n. (%)119 (69.6)87 (45.3)*34 (26.4)*32 (36.4)*°Glucocorticoid, n. (%)99 (57.9)132 (68.8)87 (67.4)55 (62.5)Glucocorticoid dose daily, mean (SD)5.9 (3.3)6.2 (4.0)6.2 (3.9)5.5 (2.0)Biologic line, n. (%)12other99 (57.9)29 (17)43 (25.1)83 (43.2)*34 (17.7)75 (39.1)*31 (24)*°32 (24.8)66 (51.2)*21 (23.9)*°16 (18.2)51 (58)*°DAS28-ESR, mean (SD)4.2 (1.3)4.1 (1.5)4.5 (1.5)°^4 (1.2)CDAI, mean (SD)17 (10)18 (11)20 (12)^16 (8)VAS-pain, mean (SD)56 (25)53 (24)61 (25)57 (26)VAS-phGA, mean (SD)35 (18)41 (22)44 (22)*37 (22)VAS-pGA, mean (SD)56 (23)55 (24)61 (22)56 (21)HAQ-DI, mean (SD)1 (0.7)1.3 (0.8)*1.3 (0.7)*1.1 (0.8)phGA: physician global assessment; pGA: patient global assessment; VAS: visual analogue scale*p<0.05 vs TNFi; °p<0.05 vs other MOA, ^p<0.05 vs other JAKi

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

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

OBJECTIVESWe aimed to evaluate the baseline characteristics, the reasons for prescription, and the effectiveness/safety profile of real-life apremilast for the treatment of psoriatic arthritis (PsA).METHODSPsA patients treated with apremilast were retrospectively extracted from an Italian multicentric cohort. Baseline population characteristics and reasons for apremilast prescription were analysed. Clinical response was defined as the proportion of patients achieving Disease Activity in PSoriatic Arthritis (DAPSA) remission/low disease activity (LDA), minimal disease activity (MDA), and very low disease activity (VLDA). Six-month retention rate was computed by the Kaplan-Meier method, with a detailed analysis of reasons for discontinuation. Univariate and multivariate models were developed to examine predictors of clinical response and persistence.RESULTSThe study population included 131 patients mainly with oligoarticular PsA (58%), carrying at least one comorbidity (64.1%, in particular history of malignancies [25.9%] and latent tuberculosis [16.3%]) treated with apremilast as first-line targeted therapy (47.7%) or in biologics failures (52.3%). Contraindication to biologics (60.3%) and lack of poor prognostic factors (27.5%) were the most frequent reason for apremilast prescription. The 6-month retention rate was 72.1%. Inefficacy (n=7), diarrhoea (n=10), nausea (n=3), and headache (n=7) were the most frequent reasons for discontinuation. At 3 months DAPSA LDA/remission, MDA, and VLDA were observed in 40.3, 6.7, and 5.6% of patients, respectively. Female sex was a negative predictor of both retention rate and clinical response.CONCLUSIONSIn our real-life analysis apremilast was mainly used in oligoarticular PsA carrying comorbidities leading to contraindications to biologics. Effectiveness and safety profiles were consistent with clinical trials.

We performed a retrospective analysis to evaluate the survival on first line biologic drug of rheumatoid arthritis (RA) patients with potential occult HBV infection (pOBI). We analysed longitudinal data of 486 consecutive RA patients starting a first biological drug in a time frame from 1st January 2008 to 31st December 2014. Demographic and disease related characteristics were collected at baseline and at the last observation visit. Baseline serological markers of HBV infection and causes of treatment discontinuation were also recorded. Primary endpoint was the influence of pOBI on drug survival, estimated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs) of drug discontinuation, adjusted for disease characteristics, biological drug class and HBcAb status were computed by Cox-regression models. The retention rate was significantly lower in pOBI positive patients (58.2%) when compared to pOBI negative ones (67.8%) and this data was confirmed also when only discontinuation due to ineffectiveness was considered (pOBI positive 66.4% vs pOBI negative 75.3%, long rank 7.93, p=0.005). Cox regression models showed a significant association between HBcAb-neg (HR 0.58, 0.41-0.84), higher ESR-DAS28 at baseline (HR 1.07, 1.03-1.11) or RF/ACPA-neg (HR 1.46, 1.04-2.06) and drug discontinuation. Occult HBV infection seems to influence negatively the effectiveness of biological therapies in RA patients.

Background There are no real-world data for the profiling of patients with psoriatic arthritis (PsA) receiving the phosphodiesterase-4 inhibitor apremilast. Objectives To retrospectively evaluate the baseline characteristics and the reasons for apremilast prescription in a large Italian multicenter cohort of PsA cases (Real-life APremilast for Psoriatic arthritis Evaluation Registry, RAPPER). Methods Data were retrospectively extracted from the RAPPER registry which includes all PsA cases treated with apremilast in 11 Italian tertiary rheumatology centres between January 2017 and December 2017. Descriptive analysis of baseline characteristics of study population included demographics, previous treatments before apremilast, pattern of PsA involvement, disease activity indices, and prevalence of comorbidities (computed by the Rheumatic Disease Comorbidity Index [RDCI]1). Reasons for apremilast choice were also analysed. Results We studied 97 patients with PsA (61% women; mean [±standard deviation, SD] age 56.7±11.9 years; mean disease duration 10±13.1 years) who received apremilast as first-line targeted disease modifying drug (51.5%) or after the failure of at least one biologic agent (48.5%). In 75%, 33%, 11%, and 63% of patients there were articular (57% asymmetric oligoarthritis; mean Disease Activity in PSoriatic Arthritis [DAPSA] 22.55±11.55), entheseal (mean Leeds Enthesitis Index [LEI] 2.63±1.42), axial (mean Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] 6.02±2.40), and skin/ungueal (mean body surface area [BSA] 1.71±3.44) involvement, respectively. Two thirds (64%) of patients had at least one comorbidity (mean RDCI 1.20) and the prevalence of conditions is reported in table 1. The main reasons for apremilast prescription were contraindication to biologic agents (66%), lack of poor prognostic factors (35%), comorbidities (34%), risk of infections (33%), and history of malignancy (22.6%), whereas a preference for an oral drug drove the choice only in 7% of patients. Conclusions Based on our analysis, apremilast is mainly used in PsA with oligoarthritis, enthesitis, mild skin involvement, and low risk of disease progression, carrying comorbidities (especially history of infections and malignancies) with contraindications to the use of biologic drugs. Reference [1] England BR, Sayles H, Mikuls TR, et al. Validation of the rheumatic disease comorbidity index. Arthritis Care Res2015;67(6):865–72. Disclosure of Interest None declared

Background In BIO.PU.RE. Registry are collected data from patients being treated with Biologics from rheumatologic centres in Apulia (Southern Italy). Methods We analysed longitudinal data of consecutive patients, affected with RA, PsA or axial-SpA starting a treatment with certolizumab (CTZ) in the time frame from 1st January 2011 to 30th June 2017. Demographic and disease related characteristics were collected at baseline and at last observation visit. Primary endpoint was the persistence on CTZ, and secondary endpoint was the search of baseline predictors of drug survival and clinical outcomes. Drug survival was evaluated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs, 95% confidence intervals (CI)) of drug discontinuation or achievement of low-disease/remission in RA, and minimal disease activity (MDA) in PsA at last visit, adjusted for patient’s demographics, disease characteristics and prior biologic treatments were computed by Cox-regression stepwise backward models. Results 345 patients were included in this analysis (table 1). Global median survival time (95% CI) was 30 [23–36] months. Drug survival rate was significantly higher in SpA (63.9%, p=0.009) than in RA (54.0%) or PsA (54.5%). Within each disease, naïve-CTZ patients showed higher survival rates than biologic-experienced patients in RA (63.4% vs 45.7%, p=0.0001), but not in PsA (59.1% vs 52.3%, p=0.60), or SpA (62.5% vs 64.4%, p=0.94). In the whole cohort, the only negative predictor of drug discontinuation was the CTZ-naïve status (HR 0.62, 95 CI 0.40–0.96, p=0.03). This association was even stronger for RA (HR 0.45, 95 CI 0.26–0.77, p=0.004). In SpA, patient’s age at baseline was weakly correlated to CTZ stopping (HR 0.96, 95 CI 0.93–0.99, p=0.02), but no predictor of CTZ discontinuation was detected in PsA. No factor did correlate to the achievement of low disease/remission in RA, while co-medication with MTX was significantly associated to the achievement of MDA (HR 3.82, 95 CI 1.26–11.54, p=0.01) in PsA. Globally, the causes of discontinuation were: ineffectiveness (nr 94, 27.2%), adverse event (nr. 40, 11.6%), pregnancy (nr.1, 0.3%), remission (nr. 3, 0.9%), others (nr.13, 3.8%). Conclusions In our real-life experience CTZ seems to have better drug survival in PsA rather in RA and SpA; in all these polyarthritis was observed CTZ-naïve status as negative predictor of drug discontinuation. Disclosure of Interest None declared

Background There is evidence that autoimmunity, namely RF and ACPA antibodies, may influence disease activities and impact the clinical outcomes in RA. Objectives There is evidence that autoimmunity, namely RF and ACPA antibodies, may influence disease activities and impact the clinical outcomes in RA. Methods We analysed longitudinal data of consecutive RA patients from the Italian registry GISEA, starting a treatment with golimumab (GOL) and tested for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Demographic and disease related characteristics were collected at baseline, 6 months, 12, and 24 months or at last observation visit. Primary endpoint was the persistence on GOL in RF/ACPA +ve and RF/ACPA patients. Secondary endpoint was the search of baseline predictors of drug survival and clinical outcomes n the two RA subsets. Drug survival was evaluated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs, 95% confidence intervals (CI)) of drug discontinuation or achievement of low-disease adjusted for patient’s demographics, disease characteristics and prior biologic treatments were computed by Cox-regression stepwise backward models. Results 345 patients had data on RA and ACP testing and were included in this analysis. No significant difference in terms of age, BMI, disease activity, co-therapy with glucocorticoids or methotrexate (MTX) was detected between RF/ACPA+ve and RF/ACPA-ve patients, but the former had significantly higher disease duration (10.6±vs 8.2±6 years) and frequencies of comorbidities (60.6% vs 44.2%). The 2 years global drug retention was 64.5%, and it was almost identical in RF/ACPA+ve 64.2% and in RF/ACPA-ve 65% RA patients. Drug survival was not influenced by the gender or cause of discontinuation (adverse or inefficacy). To note, in 31% of the patients GOL was not associated to MTX. The only predictor of drug discontinuation was the lack of MTX at baseline (HR 1.62, 95 CI 1.07–2.46, p=0.02), and the GOL-naïve status (HR 0.62, 95 CI 0.39–0.99, p=0.04). At two years, 44.4% achieved the state of low-disease activity (DAS28 <3.2) with no difference between RF/ACPA+ve (45.4%) and RF/ACPA-ve (42.0%) patients, and none baseline factor correlating with low disease activity. No safety issues were raised during the study. Conclusions In this study, we demonstrated that RF/ACPA positivity does not negatively impact on drug survival on golimumab. This may aid rheumatologists in their clinical decisions. Disclosure of Interest None declared

Background Several studies showed a close relationship between Rheumatoid Arthritis (RA) and accelerated atherosclerosis [1,2]. At the best of our knowledge, no such study has been carried out in a large Italian series. Objectives To investigate the prevalence of presence of subclinical atherosclerosis and history of cardio-cerebrovascular events (CVEs), in 1266 patients consecutively admitted to Rheumatology Units throughout the whole Italy. Methods From 01/01/2015 to 31/12/2015, 1266 consecutive patients admitted to GIRRCS centres, satisfying ACR/EULAR criteria for RA were investigated for: i. traditional cardiovascular risk factors: gender, age, smoking habit, cholesterol, triglycerides, glycemia, systemic arterial hypertension (SAH), metabolic syndrome (MS), type 2 diabetes (T2D); ii. RA aspects: disease duration as assessed from the first symptom, disease activity as evaluated by DAS28, radiographic damage by joint X-ray, and joint surgery; iii. subclinical atherosclerosis, as assessed by ultrasound technique and/or atherosclerotic peripheral lesions; iv. history of CVEs. Results We evaluated 1176 patients out of 1266, that were investigated for both CVEs and subclinical atherosclerosis. They were mostly females (80.52%), with a median age of 60 years (range 18–91 years), a median disease duration of 12 years (range 0.8–25 years), seropositive in 69.21%. Nineteen percent were in remission; 17.51% presented low disease activity; 39.45% moderate disease activity, 22.61% high disease activity. Out of 1176 patients, 217 (18%) showed evidence of subclinical atherosclerosis: a figure lower than that reported worldwide (32.7%) [2]. Eighty-two patients (6.9%) had a history for CVEs (58 myocardial infarction, 38 heart failure, 10 ischemic transitory attack, 7 Stroke), too this figure is lower than that reported worldwide (8.5%) [3,4]. In multivariate analysis, older age (p=0.0001, OR:1.069, CI95%:1.05–1.09), MS (p=0.0001, OR:3.417, CI95%:2.16–5.40) and SAH (p=0.0001, OR:3.714, CI95%:2.23–6.17) and high disease activity (p=0.001, OR:2.117, CI95%:1.35–3.32) were significantly associated with the presence of subclinical atherosclerosis. Male gender (p=0.0001, OR:3.465, CI95%:1.94–6.185), MS (p=0.005, OR:2.542, CI95%:1.29–4.52), T2D (p=0.007, OR:2.324, CI95%:1.29–4.29) and SAH (p=0.001, OR:4.921, CI95%:2.14–11.45) and higher disease activity (p=0.003, OR:1.316, CI95%:1.15–1.68) were significantly associated with a history of CVEs. Conclusions This is the first Italian multicenter study on subclinical and clinical atherosclerosis in patients with RA. We pointed out a low prevalence of both subclinical atherosclerosis and history of CV events. Nonetheless, a high disease activity and presence of cardiovascular risk factors were found to play a role, similarly to other countries. References Ruscitti P, et al. PLoS One. 2017;12:e0170108. Ambrosino P, et al. Thromb Haemost. 2015;113:916–30. Solomon D et al. Ann Rheum Dis. 2010;69:1920–5. Avina-Zubieta JA, et al. Ann Rheum Dis. 2012;71:1524–9. Disclosure of Interest None declared

Background In real-life world settings, failure of a first TNF-inhibitor (TNFi) put rheumatologists against a crossroad to choose a further TNFi or a biologic drug with a different mechanism of action. Objectives Aim of this study was to assess effectiveness of golimumab (GOL) as second line drug after failure of a first TNFi as treatment of patients affected with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or axial-spondyloarthritis (Ax-SpA). Methods GOAREL is a prospective cohort of patients starting GOL in community-based care rheumatology centers in Apulia (south Italy) since 2013. Of 494, we selected 368 patients (RA n.73, PsA n.168, and n. Ax-SpA 127) commencing GOL as first ever biological (n.206, 56%) or second treatment (n.161, 44%) after inadequate response to a first TNFi (adalimumab (ADA, n.51), etanercept (ETA, n.81), or infliximab (IFX, n.29). Three patients failing certolizumab were excluded. Primary endpoint was to compare the drug retention rate of biological naïve and TNFi inadequate responders (TNFi-IR) patients on treatment with GOL. In addition, drug retention of second line GOL patients according to the firs TNFi was assessed. Drug survival was estimated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs) of 2- years drug discontinuation adjusted for demographics, type of disease, disease characteristics, body mass index, co-therapy with glucocorticoids or methotrexate, and prior TNFi were computed by backward selection Cox-regression model. Results 2-year drug survival on GOL of naïve and TNF-IR patients was not significantly different (Figure 1). Mean survival time was 20.0 months (95% CI 18.9–21.0) for naïve and 20.4 months (95% CI 19.3–21.6) for TNFi-IR patients. Likewise, drug retention rates on GOL of TNFi-IR patients subdivided by previous TNFi was not significantly different and similar to naïve patients (Figure 1). Mean survival time was 19.0 months (95% CI 16.7–21.4) for prior-ADA, 20.5 months (95% CI 18.9–22.1) for prior-ETA, and 22.0 months (95% CI 19.6–24.3) for prior-IFX. Multiple Cox-regression model showed gender female as the only independent factor positively associated to the risk of GOL discontinuation (HR 2.5, 95% CI 1.5–4.2, p 0.0001). Conclusions In real-life setting effectiveness of GOL seems to be similar in naïve or TNFi-IR patients with RA, PsA, and Ax-Spa. Furthermore, clinical outcomes were not influenced by the previous TNFi. Disclosure of Interest None declared

Background The occurrence of hepatitis B virus (HBV) infection may be a concern during the treatment of patients with Rheumatoid Arthritis (RA). We wondered whether a state of HBV occult infection (anti-HBcAg-pos, HBsAg-neg, HBV-DNA-neg) might influence the effectiveness of biological drugs in RA patients in real-world settings. Objectives We performed a retrospective analysis to evaluate the survival on first line biologic drug of RA Apulian patients with HBV occult infection. Methods We analyzed longitudinal data of 384 consecutive RA patients starting a first biological drug in a time frame from 1st January 2008 to 31st December 2014. Demographic and disease related characteristics were collected at baseline and at last observation visit. Baseline serological markers of HBV infection and causes of discontinuation of treatment were also recorded. Primary endpoint was the influence of anti-HBcAg-pos on drug survival, estimated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs) of drug discontinuation or achievement of Clinical Disease Activity Index (CDAI) based remission at last visit, adjusted for disease characteristics, biological drug class and anti-HBcAg-pos were computed by Cox-regression models. Results No baseline demographic and disease characteristics difference between anti-HBcAg-pos and anti-HBcAg-neg RA patients were detected, except for DAS28 that was significantly higher in anti-HBcAg-pos group. Drug survival rate was significantly lower in anti-HBcAg-pos (57.6%, median survival time (95% CI) 54 months (38–69)) than in anti-HBcAg-neg patients (67.8%, median survival time (95% CI) 77 months (59–94)). Median survival time for ineffectiveness was 15 months (12–17) for anti-HBcAg-pos and 24 months (18–30) for anti-HBcAg-neg patients (p=0.04). Cox regression models showed a significant association between anti-HBcAg-neg (HR 0.60, 0.39–0.92) or RF/ACPA-neg (HR 1.69, 1.16–2.46) and drug discontinuation, while co-therapy with MTX (HR 2.14, 1.01–4.58) or with steroids (HR 0.38, 0.16–0.91), and RF/ACPA neg (HR 0.45, 0.21–0.95) were independently associated with the achievement of CDAI based remission. Conclusions HBV occult infection seems to influence negatively the effectiveness of biological therapies in RA patients. However, being a real-life setting, unknown confounding factors might generate an apparent association or mask a true correlation between the HBcAb status and clinical outcomes. Disclosure of Interest None declared

Background Since the introduction of biologics many concerns about the increased risk of infections, have been reported [1]Available data from randomized controlled trials, national registries and open label studies do not fully clarify the magnitude of this risk [2]. To date, the real impact of infections in the daily practice in the rheumatologic centers is still largely unknown. Objectives To evaluate the infection rates associated with the use of biologics in a large cohort of patients enrolled in 3 tertiary referral rheumatologic units in Italy. In addition, the risk of infections, including serious infections, was correlated with different clinical features. Methods A retrospective study, between January 2010 and December 2013, enrolled 731 rheumatic patients: 332 with rheumatoid arthritis (RA), 308 with psoriatic arthritis (PsA), 85 with ankylosing spondylitis (AS), 16 with primary Sjogren syndrome (pSS). Demographic and disease characteristics, therapies, comorbidities and infectious events were recorded and statistically analysed by multivariate analysis. Results All patients received at least 1 biologic, 82 patients 2 biologics, 30 patients 3 biologics, 6 patients 4 biologics and 4 patients 5 biologics. Two-hundred-thirty-five infectious episodes were observed in 208 (28.4%) patients. About total infections, bacteria were identified in 70.6% out of total cases, and viruses in 18.3%. The most common site of infection was the urinary tract (39.1%). Duration of disease (p=0.02), longer follow-up (p=0.0001), concomitant steroid therapy (p=0.001), comorbidities (p=0.015), treatment with infliximab (p=0.001), etanercept (p=0.029), golimumab, (p=0.004), abatacept (p=0.0001) and tocilizumab (p=0.0001) were significantly associated with any infection. In our cohort, 17 episodes fulfilled the criteria of serious infection, and occurred in 17 different patients (2.3%), the majority involving the lower respiratory tract (41.2%). Serious infections were associated with the beginning of biologics in older age (p=0.002), the use of i.v. therapy with infliximab (p=0.02), rituximab (p=0.05) and tocilizumab (p=0.01). Conclusions Surprisingly, our study shows that, in daily practice, a lower rate of infections was observed in our patients, when compared with previous reports. Duration of disease, concomitant steroid therapy and comorbidities may be considered risk factors for the occurrence of infections in treated patients. Of note, serious infections seem to be associated with older age of patients and i.v. treatments. References Singh JA. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD008794. Ruderman EM. Overview of safety of non-biologic and biologic DMARDs. Rheumatology (Oxford). 2012;51:vi37–43. Disclosure of Interest None declared

Background TNFa plays a key role in the pathogenesis of both rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Recent data support the hypothesis that TNFa is involved in the regulation of carbohydrate and lipid metabolism and it is well know that patients with RA and PsA present a high prevalence of metabolic syndrome and insulin resistance. Objectives The aim of this study is to evaluate the effects of three different anti TNFa drugs on lipid profile, insulin resistance and circulating levels of various adipokines in a cohort of patients with RA and PsA and the possible relationship with activity disease Methods We evaluated 25 consecutive patients fulfilling the 2010 revised American College of Rheumatology criteria for RA and 66 consecutive patients age and sex matched fulfilling the CASPAR criteria for PsA. At time of recruitment all patients were treated with methotrexate (10 – 15 mg/weekly) and low dose of prednisone (up to 7,5 mg/day). PsA and RA patients were randomly assigned to receive adalimumab (ADA), infliximab (IFX) or etanercept (ETN). For each group we evaluated the effect of treatment on body mass index (BMI), lipid profile, atherogenic index, insulin resistance index (HOMA2-IR), insulin sensitivity index (QUICKI), circulating levels of adipokines (resistin, leptin, adiponectin) and Framingham cardiovascular risk score at baseline (T0) and after 3 (T1) and 6 (T2) months and we correlated these data with disease activity (DAS28). Results At baseline we found that compared to PsA, RA patients presented a significantly higher disease activity (p<0,01), atherogenic index and insulin resistance (p<0,05 and p<0,01 respectively), whereas serum levels of adiponectin were significantly lower (p<0,05). No differences in BMI, insulin sensitivity index, Framingham cardiovascular risk score, serum lipid profile and circulating levels of resistin and leptin were observed between AR and PsA patients. Both in RA and in PsA patients the activity disease at baseline positively correlated with atherogenic index and circulating levels of leptin and resistin (r=0,62, p<0,01); conversely, a negative correlation was observed at baseline between disease activity and circulating levels of adiponectin (r=-0,58, p<0,01). Both in RA and PsA patients ADA, IFX and ETN induced a significant reduction of atherogenic index (p<0,05 both at T1 and T2), insulin resistance (p<0,05 both at T1 and T2) and serum levels of leptin and resistin (p<0,01 both at T1 and T2); this reduction positively correlated with the reduction of disease activity. On the other hand, circulating levels of adiponectin and insulin sensitivity index significantly increased after treatment with ADA, IFX and ETN (p<0,05 at T1, p<0,01 at T2) and presented an inverse relationship with the disease activity. No differences were found between different anti TNFa treatments in the two group of patients. Conclusions These preliminary data confirm the hypothesis that treatment with anti TNFa biologic drugs can positively affect the lipid metabolism, the atherogenic index and the insulin resistance profile in RA and PsA patients. References Costa L et al. Clin Rheumatol. 2014 Jun;33(6):833–9 Derdemezis CS et al. Fundam Clin Pharmacol. 2009 Oct;23(5):595–600 Disclosure of Interest None declared

AIM In the last years there is an increasing interest for the question of whether patients treated with antitumour necrosis factor-α (TNF-α) agents are at increased risk of infections. We aim to assess the possible role of anti-TNF-α treatment in the increase of the risk of infections in a population of patients affected by rheumatoid arthritis or psoriatic arthritis. METHODS We analyzed data of patients affected by chronic arthritis treated with anti-TNF-α to investigate the risk of infections. Statistical analysis was done using STATA software. RESULTS The odds ratio for patients treated with anti-TNF-α who developed infections was 1.61 (CI: 0.88, 2.92, P<0.11). We found an odds ratio of 1.41 (CI: 0.74, 2.68, P<0.29) in patients treated with anti-TNF-α who developed urinary tract infection, and an odds ratio of 2.63 (CI: 0.31, 22.19, P<0.37) in patients treated with anti-TNF-α who developed herpes zoster. DISCUSSION These results seems to indicate a role of anti-TNF-α treatment in the risk of infection. Nevertheless, our results are not statistically significant probably because the sample sizes are too small and the time of observation among patients is variable. Moreover, other confounding factors may be gender, age and the different degrees of disease activity and comorbidity. In conclusion, limitations in the study size and design preclude definitive conclusions about the question of whether patients treated with anti-TNF-α agents are at increased risk of infections. The performance of additional research are needed to answer this question.

In psoriatic arthritis, swelling and pitting oedema may be caused by different pathogenic mechanisms: on one hand, the involvement of tenosynovial structures; on the other hand, the involvement of lymphatic vessels, which may be rarely implicated by the inflammatory process. This different involvement is responsible for a different response to therapy and a different clinical outcome. In fact, patients with inflammation of the tenosynovial structures and normal lymphatic drainage have a more favourable clinical outcome and response to pharmacologic treatment, whilst patients affected by psoriatic arthritis with chronic lymphatic vascular damage are characterized usually by resistance of oedema to therapy. In this study, we report two cases of psoriatic arthritis with distal extremity swelling and pitting oedema. In the first patient, the swelling and pitting oedema were associated with lymphatic obstruction, as detected by lymphoscintigraphy. In the second, the predominant involvement of the tenosynovial structures, as shown by magnetic resonance, with normal lymphatic flow, may have been the cause of arthritis with oedema. These different pathogenetic mechanisms were associated with different response to therapy. Nevertheless, oedema was resistant to therapy in both patients probably because of other unknown factors, which influence therapy and clinical outcome.

Because of the increased incidence of tuberculosis (TB) in recent years, infective spondylitis is still a major problem in the world. In skeletal TB the spine is the most often involved and lumbosacral spine involvement is rare. Nowadays early diagnosis and new medical treatment can reduce the incidence of the serious skeletal sequelae and the number of surgery procedures in spinal TB. We present a case of TB spondylodiscitis characterized by a rapid and progressive clinical and radiological improvement after treatment with Neridronate and chemotherapic drugs. Our data suggest that in the treatment of the TB spondylodiscitis the combined use of these drugs is a good alternative to stimulate bone reparative process to the chemotherapy alone. To our knowledge this is first case of a patient with TB discitis treated with Neridronate. Further studies are necessary to confirm the effectiveness of Neridronate treatment added to antiTB drugs in spondylodiscitis