Background: Data regarding the adoption of the treat-to-target (T2T) approach aiming at inactive disease (ID), or low disease activity (LDA) in axial (axSpA) and peripheral Spondyloarthritis (perSpA) in real-world clinical practice is scarce. Objectives: Our aims were to assess the level of disease activity of SpA patients in real-world practice, the extent of T2T strategy implementation and the reasons of possible non-implementation. Methods: Cross-sectional study of all consecutive patients with SpA who visited the outpatient department or the one-day infusions’ clinic of our hospital during a 7-month period. Detailed patient, disease and treatment characteristics were collected, as well as disease activity of axial (using ASDAS-CRP), peripheral (DAPSA) and extraarticular manifestations. Additionally, physicians filled in questionnaires regarding treatment intensification or not (and reasons) of patients not in target at the specific visit. Multivariable logistic regression analysis was employed to identify predictors of therapy intensifications in patients not in target. Results: We analyzed 243 patients (54% males; AxSpA:187, perSpA:56) with median (IQR) age of 52 (42-61) and disease duration 4.1 (2.1-12.3) years. The main therapy in the majority of the patients (83%) was a biologic (b-)DMARD. In patients with AxSpA, median (IQR) ASDAS-CRP was 2.4 (1.7-3.1), while in perSpA patients, median (IQR) DAPSA score was 26 (12.4-36.2). Low disease activity or inactive disease (LDA/ID), taking into account axial and/or peripheral as well as extraarticular manifestations was found in 26% and 25% of the patients in AxSpA and perSpA respectively. Of the patients not having at least LDA (N=181), 82 (45%) had their treatment intensified. Physician-documented reasons of non-intensification are shown in Figure 1. In multivariable logistic regression analysis, the type of patients’ main therapy [OR (95%CI) for non-bDMARD vs bDMARD:12.2 (4.8-41.4)], physician’s VAS score [OR:1.22 (1.10-1.27)] and patients’ VAS global score [OR:1.08 (1.02-1.12)] were predicting therapy intensifications in patients not in target. Conclusion: In this real-world study, the majority of SpA patients had high disease activity levels. T2T strategy was implemented in approximately half of those patients, especially those on non-biologic main therapy and high physician VAS score. The most common reason of non-implementation of T2T was a satisfactory clinical status according to physician in patients with long-standing disease and irreversible damage. REFERENCES: NIL. Acknowledgements: This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning» in the context of the project “Reinforcement of Postdoctoral Researchers - 2nd Cycle” (MIS-5033021), implemented by the State Scholarships Foundation (ΙΚΥ). Disclosure of Interests: Irini Flouri: None declared, Nestor Avgoustidis Abbvie, Pfizer, Argyro Repa Abbvie, Katerina Pateromichelaki: None declared, Sofia Pitsigavdaki: None declared, Eleni Marolachaki: None declared, Evgenia Emmanouilidou: None declared, Olga Dobysh: None declared, Eleni Kalogiannaki: None declared, Myrto Nikoloudaki: None declared, George K. Bertsias Novartis, Pfizer, Abbvie, Prodromos Sidiropoulos Lilly, Novartis, Pfizer, Abbvie.Figure 1Level of disease activity, type of therapy intensifications and reasons of non-intensification if patients not in target [N (%) of patients]

Background: Organ damage is a key determinant of unfavorable long-term prognosis and increased mortality, thus being reflective of disease severity in SLE patients. Objectives: To develop a clinical, machine learning based model for the prediction of early organ damage in SLE towards disease severity stratification. Methods: Using a cohort of 914 adults with SLE [1], panels of deconvoluted classification criteria [ACR 1997 (ACR), SLICC 2012 (SLICC) and EULAR/ACR 2019 (EULAR)] and non-criteria features present at any timepoint throughout the first five years since SLE diagnosis were assessed. Permanent organ damage was evaluated using the SLICC/ACR Damage Index (SDI). We randomly divided the patient cohort into a training (70%) and a test (30%) set. Employing feature selection algorithms, the smallest set of clinical features that most accurately predicted early organ damage accrual (defined as SDI increase within the first 5 years since SLE diagnosis) was selected. Five different prediction models (random forest (RF), logistic regression (glm), linear discriminant analysis (LDA), k-nearest neighbors (KNN), extreme gradient boosting (XGBoost)) were adopted. The best model in 10-fold cross-validation was tested in the test set. Accuracy, sensitivity, specificity, and area under (AUC) the receiver operating curve (ROC) were determined in the test set. Results: The LDA model demonstrated the highest performance in predicting early organ damage with an AUC of 0.831 (95% CI: [0.7817, 0.8739]) with sensitivity of 0.955 and specificity of 0.463. The leading predictors included synovitis, non-scarring alopecia, acute cutaneous lupus, SLICC 2012-based neurologic disorder, leukopenia, and the age at the time of SLE diagnosis. The XGBoost model exhibited the highest specificity (0.841) with an accuracy of 0.805 (95% CI: [0.7619 - 0.8241]) and sensitivity of 0.653. Age at the time of diagnosis, the presence of ACR 1997-based neurologic disorder, non-scarring alopecia, and low complement (2012 criteria) emerged as the strongest predictors in this model. Conclusion: Machine learning methods using standard disease features may identify SLE patients at risk for early damage accrual. Further validation in external cohorts is warranted. REFERENCES: [1] Adamichou C, Genitsaridi I, Nikolopoulos D, Nikoloudaki M, Repa A, Bortoluzzi A, Fanouriakis A, Sidiropoulos P, Boumpas DT, Bertsias GK. Lupus or not? SLE Risk Probability Index (SLERPI): a simple, clinician-friendly machine learning-based model to assist the diagnosis of systemic lupus erythematosus. Ann Rheum Dis. 2021 Jun;80(6):758-766. doi: 10.1136/annrheumdis-2020-219069. Epub 2021 Feb 10. PMID: 33568388; PMCID: PMC8142436. Acknowledgements: NIL. Disclosure of Interests: None declared.

Background Mental disorders such as anxiety and depression are highly prevalent in SLE patients,[1] yet their association with the underlying disease activity remains elusive and has been mostly evaluated at cross-sectional level.[2] This is further complicated by the often-increased rates of treatment non-adherence,[3] an important determinant of heightened lupus activity, among patients with depression.[4] Objectives To examine the relationship between longitudinal changes in anxiety (ICD-10-CM F41.9), depression (ICD-10-CM F32.x) and disease activity levels in adult SLE patients. Second, to test the association between the aforementioned mental disorders with treatment adherence and sociodemographic factors. Methods A prospective 6-month observational study of outpatients aged 18-65 years who fulfilled the EULAR/ACR 2019 classification criteria and had active disease ascertained by a SLEDAI-2K ≥3 and PGA (physician global assessment; scale 0–3) >1. Patients were enrolled by consecutive sampling technique during May-September 2021. Excluding criteria were overlap rheumatic diseases, active neuropsychiatric lupus, ongoing pregnancy or post-partum period, history of dementia or malignancy. Sociodemographic factors (age, disease duration, education level, working status) and comorbidities were collected. Anxiety and depression levels (assessed with the Hospital Anxiety and Depression Scale [HADS-A/D subscales]), disease activity (SLEDAI-2K, PGA), use of medications, and treatment adherence (Morisky Medication Adherence Scale-4 items scale) were monitored during the observation period. Results Forty SLE patients (39 females) with an average [standard deviation] age 50.5 (10.3) years and disease duration 10.3 (7.0) years, were enrolled. Baseline SLEDAI-2K was 6.0 (2.0) driven predominantly from the musculoskeletal and mucocutaneous domains. The prevalence of anxiety (HADS-A >11) and depression (HADS-D >8) were 42.5% and 45.0%, respectively. During follow-up, disease activity was significantly reduced (average [SD] reduction in SLEDAI-2K: 1.90 [2.80], p<0.001), however, anxiety and depression levels remained unchanged (average [SD] change in HADS-A -0.05 [3.76] and HADS-D 0.53 [3.25], respectively, p>0.300 for both). Accordingly, Spearman’s non-parametric test showed that longitudinal changes in SLEDAI-2K were not significantly correlated with the corresponding changes in the HADS-A ( rho = 0.13, p=0.417) or HADS-D ( rho = -0.05, p=0.781) scores. Treatment non-adherence was found in 19 patients (47.5%) but did not correlate with anxiety and depression (p>0.500 for both). Notably, mental disorders were not significantly associated with comorbidities (including fibromyalgia) but unemployment status predicted the presence of anxiety (odds ratio 7.73, p-value 0.018). Conclusion Anxiety and depression are frequent comorbidities in active SLE and do not correlate with short-term disease improvement, thus underscoring the need for adjunct treatment. Physician awareness in the detection of treatment adherence is necessary. Larger studies in early disease and with longer follow-up will be required to further explore the possible interaction between of mental disorder and lupus disease course. References [1]Zhang L, et al. BMC Psychiatry. 2017;17(1). [2]Tay SH, et al. Lupus. 2015;24(13):1392–9. [3]Costedoat-Chalumeau N, et al. Clin Pharmacol Ther. 2018;103(6):1074–82. [4]Alsowaida N, et al. Lupus. 2018;27(2):327–32. Disclosure of Interests None declared

BackgroundBelimumab has been introduced in the management of SLE for more than 10 years, however long-term efficacy and safety data are still limited and mostly derive from the extended phase of randomized clinical trials.ObjectivesTo evaluate the long-term survival of belimumab treatment, reasons for treatment cessation and associated predictors in routine care setting.MethodsMulticentre observational study of adult SLE patients who were treated with belimumab according to physician discretion and in line with the EULAR recommendations. Disease activity (Physician Global Assessment [PGA]: scale 0-3; SLE disease activity index-2000 [S2K]), flares (SELENA-SLEDAI Flare Index), organ damage (SLICC damage index [SDI]), co-administered treatments and dosage, adverse events and causes of belimumab discontinuation were monitored prospectively at 3–6-month intervals. Cox-regression analysis was performed to identify factors associated with reduced drug survival.ResultsA total 184 patients treated with belimumab for at least 3 months were included (women 95.6%; mean ± SD age 48.8 ± 13.4 years; disease duration 9.2 ± 11.3 years). Baseline S2K and PGA were 7.5 ± 3.0 and 1.64 ± 0.42, respectively, both demonstrating significant improvement at 6 months (4.5 ± 3.5 and 1.02 ± 0.69, respectively; p<0.001) and 12 months (3.5 ± 3.1 and 0.68 ± 0.55, respectively; p<0.001). Of patients receiving glucocorticoids at onset, 49.0% tapered the dose and 17.6% completely withdrew them. After a median (interquartile range) follow-up of 15.1 (16.9) months, 44.0% of patients discontinued belimumab due to suboptimal efficacy as judged by the treating physician (28.3%), adverse events (including infections) (9.8%) or other causes (e.g., pregnancy, patient decision). Accordingly, efficacy-related drug survival rates at 1 and 2 years were 70% and 61%, respectively, with corresponding safety-related survival rates of 94% and 87%, respectively. Baseline factors associated with belimumab discontinuation due to suboptimal efficacy included PGA >1.50 (hazard ratio [HR] 3.66; 95% confidence interval [95% CI] 1.14–11.73; p=0.029) and severe (RA-like) arthritis (HR 2.56; 95% CI 1.16–5.68; p=0.020) but not disease duration, use of glucocorticoids, active serology or organ damage. Notably, patients with early (3 months) improvement (i.e., any decrease in PGA) showed significantly lower risk for treatment cessation (HR 0.38; 95% CI 0.22–0.67; p=0.001) (Figure 1) and this effect was independent of the initial PGA level. Baseline use of hydroxychloroquine was associated with prolonged safety-related belimumab survival (HR 0.32; 95% CI 0.12–0.88; p=0.028).Figure 1.Efficacy-related survival of belimumab according to improvement or not of PGA at 3 months since treatment initiation.ConclusionIn real-life setting, about 28% of SLE patients discontinue belimumab due to suboptimal treatment response per physician judgement, especially those with moderate-to-high activity and severe arthritis. Improvement in PGA at 3 months predicts long-term drug maintenance, therefore suggesting its value for patient monitoring. Our data confirm the very good tolerability of belimumab and identify hydroxychloroquine co-administration as a predictor for prolonged safety-related drug survival.AcknowledgementsThe study was partly funded by the Greek Rheumatology Society and the Greek Association of Professional Rheumatologists (ERE-EPERE) and by Pfizer Global Medical GrantsDisclosure of InterestsMyrto Nikoloudaki: None declared, Dionysis Nikolopoulos: None declared, SOFIA KOUTSOVITI: None declared, Irini Flouri: None declared, Noemin Kapsala: None declared, ARGYRO REPA: None declared, PELAGIA KATSIMPRI: None declared, EVANGELOS THEOTIKOS: None declared, Sofia Pitsigavdaki: None declared, Katerina Pateromichelaki: None declared, Anastasios Eskitzis: None declared, ANTONIA ELEZOGLOU: None declared, Prodromos Sidiropoulos: None declared, Antonis Fanouriakis: None declared, Dimitrios Boumpas: None declared, George Bertsias Speakers bureau: GSK, AstraZeneca, Pfizer, SOBI, UCB, Novartis, AENORASIS, Abbvie, Grant/research support from: GSK, Pfizer

Background Early or pre-clinical forms of lupus encompass a broad range of presentations, spanning from asymptomatic individuals with immunological abnormalities to individuals with autoantibodies and some features suggestive of SLE who do not yet meet the classification criteria. Research on this topic could reveal predictive and diagnostic biomarkers for individuals at-risk for progression to SLE. Objectives To examine the rate of transition from at-risk to classified (ACR 1997 criteria) SLE, and identify demographic and clinical predictors. To prospectively evaluate the sensitivity and accuracy of the newer classification criteria (SLICC 2012, EULAR/ACR 2019) and the SLE Risk Predictive Index (SLERPI)[1] in patients at-risk who progress or not to classified SLE. Methods This is a single-centre analysis of individuals at-risk for SLE as part of an ongoing multicentric inception cohort study aiming to identify clinical, environmental and molecular prognostic factors for SLE onset. Enrolled individuals: a) were 18–55 years old; b) had clinical and/or serological features suggestive of SLE; c) had no clinical diagnosis of SLE or other autoimmune rheumatic disease; and d) did not fulfill the ACR 1997 classification criteria. Prospective monitoring at 6-month intervals was performed to determine accrual of classification and non-classification features, and ascertain the disease status (at-risk/undifferentiated connective tissue disease, SLE, other connective tissue disease). Results A total 124 subjects were included, all Whites, 94.4% women, with an average (standard deviation) age 36 (11) years. At first assessment, individuals fulfilled 2.25 (0.72) ACR 1997 criteria with ANA being the most prevalent feature (75.8%) followed by low complement (43.5%), arthritis (37.9%), photosensitivity (28.2%), malar rash (23.4%), and non-scarring alopecia (18.5%). After a median follow-up of 16 months, 27 participants (21.8%) fulfilled the ACR 1997 criteria, of whom 8 (6.5%) developed moderate or severe SLE. Multivariable-adjusted logistic regression identified anti-Ro/SSA (odds ratio [OR] 6.93; 95% confidence interval [95% CI] 1.75–27.5, p=0.006), combined low C3 and low C4 (OR 4.82; 95% CI 1.42–16.3, p=0.012) and photosensitivity (OR 3.25; 95% CI 1.17–8.99, p=0.023) as independent predictors for transition to classified SLE. The sensitivity of SLICC 2012, EULAR/ACR 2019 and SLERPI (>7) at baseline for detecting individuals who progressed to SLE (ACR 1997) was 40.7%, 25.9% and 40.7%, respectively, with corresponding specificities of 83.5%, 88.7% and 79.4%. Conclusion Among individuals at-risk for SLE, about 20% may evolve into classified disease after a medium follow up of 16 months which is predominantly of mild severity. Presence of anti-Ro/SSA, hypocomplementemia, and photosensitivity indicate subjects who at increased risk for transition to SLE. Newer classification systems may capture as many as 40% of progressors with acceptable specificity. References [1]doi: 10.1136/annrheumdis-2020-219069 Acknowledgements This work was funded by the Foundation for Research in Rheumatology (FOREUM). Disclosure of Interests None declared

BackgroundComparative data among rheumatoid arthritis (RA), spondylarthritis (SpA) and psoriatic arthritis (PsA) patients regarding long-term survival of etanercept (ETN) in clinical practice are limited.ObjectivesThe first aim of this study was to analyze the long-term (>3 years) ETN survival comparatively between its three main indications. We also aimed to analyze for predictors of long term ETN survival.MethodsWe analyzed data from the University of Crete Rheumatology Clinic Registry (UCRCR), a single center prospective cohort study. All patients with a diagnosis of RA, SpA or PsA starting treatment with a biologic DMARD are recorded prospectively based on a common follow-up protocol. For the first aim, ETN survival >3 years was compared among the 3 diseases. For the 2nd aim patients on ETN >3 years were compared to those stopping ETN during the first 2 years. We analyzed baseline and early on treatment (first 6 months) characteristics, comedications, comorbidities as predictors for long term survival applying univariate and multivariate models.ResultsA total of 711 patients who were started on ETN were analyzed (RA: 450, SpA: 177, PsA: 84). As expected, patients’ and disease characteristics at baseline differed significantly between the 3 diagnoses (Table 1). Patients’ function was compromised irrespective of the diagnosis, while inflammatory activity was significant across diseases.Table 1.Baseline parameters [Medians (IQR) unless otherwise specified]RA (n=450)SpA (n=177)PsA (n=84)pWomen N (%)370 (82)66 (37)46 (55)<0.001Age61.5 (53-70)44.5 (35-54)51 (41-62)<0.001Disease duration2.6 (0.9-6.5)0.8 (0.1-5.1)1.7 (0.6-4.9)<0.001Follow-up years1.0 (0.5-2.1)1.0 (0.4-3.1)1.1 (0.4-3.6)0.649Total comorbidities nr.3 (1-4)1 (0-3)2 (1-4)<0.001RDCI1 (1-2)0 (0-1)1 (0-1)<0.001Ever smokers N(%)124 (39)82 (67)30 (61)<0.001BMI31 (26-35)27 (25-32)29 (23-32)0.015Treatment line N (%): 1st264 (59)87 (49)43 (51)0.012 2nd119 (26)70 (39.5)24 (29) ≥ 3rd67 (15)20 (11)17 (20)Nr of previous csDMARDs2 (1-3)1 (0-2)1 (1-2)<0.001Co-administered MTX N(%)284 (63)65 (37)50 (60)<0.001Monotherapy, N (%)60 (13)100 (56.5)25 (30)<0.001Ongoing corticosteroids N(%)153 (34)25 (14)17 (20)<0.001DAS28 - ESR5.8 (5.0-6.5)3.7 (2.9-4.7)5.3 (4.5-6.4)<0.001ASDAS-ESR-3.4 (2.8-4.1)3.6 (3.2-4.7)0.067CRP (mg/dl)0.4 (0.3-1.1)1.1 (0.3-2.4)0.8 (0.4-2.0)<0.001During a follow-up of 1371 patient-years, 466 (65.5%) patients stopped therapy. The estimated percentage of patients persisting on ETN therapy for > 3 years was 28.4%, 42.8% and 44% of RA, SpA and PsA respectively. The main reason for therapy discontinuation was inefficacy (75% of stop reasons in RA vs. 58% in SpA vs. 69% in PsA).In multivariable Cox regression analyses the most important predictor for ETN survival was the achievement of LDA/remission at 6 months based on DAS28 for RA or ASDAS for SpA [Odds Ratio (OR) 1.98, p=0.008 and 3.02, p=0.001 respectively]. Prognostic factors for ETN discontinuation specifically due to inefficacy were comorbidities number and csDMARDs coadministration (p<0.05 for both), while older age and no co-therapy with MTX predicted ETN stop due to adverse events (p<0.05 for both).Logistic regression analysis indicated that male sex [OR: 2.08, p=0.004], calendar year of treatment start [OR per 3 years: 0.74, p=0.001], comorbidities’ number [OR: 0.82, p=0.045] and monotherapy [OR: 1.81, p=0.027] predict persistence on ETN therapy beyond 3 years, while the clinical diagnosis or other baseline parameters are not significant predictors.ConclusionIn this prospective cohort study, we found that ETN survival was higher for patients with SpA/PsA as compared to RA. Male sex, absence of comorbidities and no csDMARDs co-administration are independent predictors of long-term persistence to therapy, irrespectively of the clinical diagnosis. Notably, both in RA and SpA, 6-month response predicted ETN survival in the long term.AcknowledgementsThis study was funded by the Pancretan Health Association and Pfizer Global Medical Grants.Disclosure of InterestsNone declared

Background:Long-term observational studies of patients under biologic disease-modifying anti-rheumatic drug (bDMARD) therapies in routine clinical practice can provide us with important data regarding patients with comorbidities, who are usually excluded from randomized controlled studies.Objectives:To study the impact of comorbidities in the outcome (response and persistence to therapy) of patients with spondyloarthritis (SpA) receiving bDMARDs in real-world clinical practice.Methods:Prospective study of all patients who start a bDMARD in a tertiary centre University Hospital after their consent. All patient comorbidities [among a list of approximately 100 pre-specified major comorbidities] are registered by treating physicians at baseline and during follow-up.Comorbidities were studied as total Comorbidities Count (CC) and rheumatic disease comorbidity index (RDCI). Statistical analyses were performed using logistic and Cox regression models, adjusting for the potential confounding of age, sex, disease duration, diagnosis (axial vs. peripheral SpA), number of previous conventional synthetic and biologic DMARDs, year of therapy start, and co-administered methotrexate and corticosteroids (yes/no). Analyses of response to therapy also included baseline BASDAI or ASDAS indices as confounding variables.Results:A total of 603 biologic treatments (1st: 298, 2nd: 157, ≥3rd: 148) were analyzed. Half (51%) of the patients were female, 413 patients had axial SpA (AxSpA) and 190 peripheral SpA (perSpA). At baseline, median (IQR) age: 48 (38-57) years, disease duration: 11 (4-19) years, CC: 2 (1-4) and RDCI: 1 (0-2). Both comorbidity indices were significantly higher in perSpA compared to AxSpA (p<0.001).At 6 months of therapy, 31% of patients with AxSpA achieved BASDAI50 and 39% had ASDAS-ESR < 2.1. Higher CC was an independent predictor of insufficient response according to BASDAI50 [OR (95%) = 0.70 (0.52-0.94), p=0.019] and higher RDCI was predicting failure to achieve ASDAS-ESR < 2.1 [OR (95%) = 0.59 (0.37-0.94), p=0.027]. Other independent predictors of non-response were age, longer disease duration and (for ASDAS-ESR<2.1) higher baseline disease activity.During 1405 patient-years of follow-up, 349 (58%) treatments were discontinued. The adjusted hazard ratio for bDMARD discontinuation within the first 2 years of treatment due to insufficient response was doubled in patients with CC ≥2 versus those with CC ≤1 [HR = 2.27 (1.14-4.53), p=0.020] or with RDCI ≥1 (vs. RDCI = 0) [HR = 2.23 (1.22-4.07), p=0.009]. Comorbidities’ indices were not significant predictors of treatment discontinuations due to adverse events.Conclusion:The presence of comorbidities in patients with SpA is an independent predictor for insufficient 6-month response to bDMARDs and resultant treatment discontinuation due to failure.Acknowledgements:This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning» in the context of the project “Reinforcement of Postdoctoral Researchers - 2nd Cycle” (MIS-5033021), implemented by the State Scholarships Foundation (ΙΚΥ).Disclosure of Interests:None declared

Background:There is limited information on the burden of comorbidities in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) in real-world clinical practice and its impact on the incidence of serious adverse events (SAE) during biologic disease-modifying anti-rheumatic drug (bDMARD) therapy.Objectives:To evaluate the number of comorbidities in patients with RA and SpA initiating a bDMARD in everyday clinical practice and to explore its association with the occurrence of a SAE during therapy.Methods:Prospective study of all patients who start any bDMARD treatment in a tertiary centre University Hospital. All comorbidities and SAEs (AEs necessitating hospitalization or resulting in significant incapacity/death) are registered by treating physicians. Comorbidities’ number was evaluated using two different indices: total comorbidities count (CC) and Rheumatic Disease Comorbidity Index (RDCI). Statistical analysis was performed using multinomial logistic and Cox regression models.Results:A total of 799 patients were analysed, of which 428 (54%) had ≥3 comorbidities (Table 1). Comorbidity burden was higher in RA, however in multivariable analyses, comorbidities were not significantly associated with diagnosis, but mainly with increasing patient age. Patients received 1701 bDMARD treatments. During a follow-up of 4019 patient-years, 198 patients (RA:134, SpA:64) had a total of 295 SAE (RA: 217, SpA:78).Each one additional comorbidity in CC index was resulting in 16% increased adjusted risk for the first SAE [HR (95%CI) = 1.16 (1.12-1.20), p<0.001], and each additional comorbidity of the RDCI index was resulting in 28% increased risk [HR (95%CI) = 1.28 (1.20-1.37), p<0.001]. Other baseline independent predictors of the first SAE were greater age [HR=1.04, p<0.001] and use of corticosteroids [HR=1.42, p=0.006].Table 1.Biologic treatments and clinical characteristics at baselinePatients, ΝTotalRASpAp799501298Females, Ν (%)535 (67)404 (81)131 (44)<0.001Age, median (IQR) έτη55 (45-65)60 (51-68)46 (36-54)<0.001Disease duration, median (IQR) έτη6.0 (2.5-13)5.4 (3-11)7.4 (2.0-15)<0.001Comorbidities count, median (IQR)3 (1-5)3 (2-6)2 (1-4)<0.001Patients with no comorbidities, Ν (%)103 (13)43 (9)60 (20)<0.001Patients with 1 comorbidity, Ν (%)134 (17)77 (15)57 (19)0.172Patients with 2 comorbidities, Ν (%)134 (17)76 (15)58 (19,5)0.118Patients with ≥3 comorbidities, Ν (%)428 (54)305 (61)123 (41)<0.001RDCI, median (IQR)1 (0-2)2 (0-3)1 (0-2)<0.001Patients with RDCI = 0, Ν (%)267 (33)128 (25.5)139 (47)<0.001Patients with RDCI = 1, Ν (%)185 (23)119 (24)66 (22)0.665Patients with RDCI = 2, Ν (%)163 (20)113 (23)50 (17)0.057Patients with RDCI ≥ 3, Ν (%)184 (23)141 (28)43 (14)<0.001Total bDMARDs initiated by patients, Ν17011098603Co-administered methotrexate, Ν(%)946 (56)674 (61)272 (45)<0.001Co-administered corticosteroids, Ν (%)493 (29)397 (36)96 (16)<0.001DAS28, median (IQR) (in RA and perSpA)5.8 (4.9-6.6)5.8 (5.0-6.6)5.4 (4.2-6.3)<0.001BASDAI, median (IQR) (in axSpA)--5.6 (4.5-7.0)Conclusion:Patients with RA and SpA initiating a bDMARD treatment in real-world clinical practice have a significant comorbidity burden which increases with age and is an independent predictor for an SAE during therapy.Acknowledgements:This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning» in the context of the project “Reinforcement of Postdoctoral Researchers - 2nd Cycle” (MIS-5033021), implemented by the State Scholarships Foundation (ΙΚΥ).Disclosure of Interests:None declared

Background: Difficult-to-treat rheumatoid arthritis (D2T RA) was recently defined by a EULAR study group (1) and, as a disease category it is largely complicated and under-researched. Patient comorbidities may play a significant role in the response to therapy with biologic disease-modifying antirheumatic drugs (bDMARDs) and in the disease classification as D2T RA. Objectives: To evaluate the impact of comorbidities [studied as total Comorbidities Count (CC) and rheumatic disease comorbidity index (RDCI)] on 6-month response to therapy with the first bDMARD in real-world clinical practice and on eventual disease designation as D2T RA. Methods: Prospective study of all RA patients who start any bDMARD in a tertiary centre University Hospital after their consent. All patient comorbidities [among a list of approximately 100 pre-specified major comorbidities] are registered by treating physicians. Response to therapy was defined as achievement of low disease activity or remission (LDA/Rem) according to simplified disease activity index (SDAI) and health assessment questionnaire (HAQ) improvement of ≥ 0.25. D2T RA patient group was defined according to the EULAR definition of D2T RA and was compared to: a/ all other patients and b/ to a sub-group of patients designated as “well-controlled RA” (follow-up ≥2 years and ≥2 visits in the last year in LDA/Rem). Logistic regression models were used to adjust for the potential confounding of age, sex, disease duration, seropositivity, number of previous synthetic DMARDs, type of 1 st bDMARD initiated (TNF inhibitor vs. non-TNF inhibitor), co-administered methotrexate and corticosteroids (yes/no), baseline SDAI and HAQ and year of therapy start. Results: Analysis included 501 RA patients who received a total of 1098 bDMARD treatments. At 1 st bDMARD treatment start, patients (women: 81%) had a median (IQR) age: 60 (51-68) years, disease duration: 5.4 (3-11) years, SDAI: 36 (28-46), HAQ: 1.0 (0.5-1.5), CC: 3 (2-6) και RDCI: 2 (0-3). In adjusted analyses, total comorbidity count (CC) ≤1 (vs ≥ 2) was predicting LDA/Rem at 6 months of therapy [OR (95%CI) = 4.1 (1.5-11), p=0.005], while RDCI=0 (vs. ≥ 1) was predicting HAQ improvement ≥ 0.25 [OR (95% CI) = 2.6 (1.2-6.7), p=0.046]. During 2614 patient-years of follow-up, the disease in 98 patients could be classified as “D2T RA”, while 127 patients had “well-controlled RA”. Baseline independent predictors for D2T RA compared to all other patients were RDCI ≥ 1 (vs. 0) [OR = 3.3 (1.7-9.4), p = 0.024], female sex [OR =3.1 (1.01-9.5)] and age [OR = 0.97 (0.94-0.99)]. Multivariable analyses for predictors of “D2T” compared to “well-controlled” RA yielded similar results. Conclusion: In RA patients starting the first bDMARD treatment, a higher number of comorbidities at baseline is an independent predictor of lower 6-month response to therapy and final disease classification as “difficult-to-treat” RA. References: [1]Nagy G, Roodenrijs NM, Welsing PM, Kedves M, Hamar A, van der Goes MC, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 Jan;80(1):31–5. Acknowledgements: Pancretan Health Association and Special Account for Research Grants (ELKE) – University of Crete. Disclosure of Interests: None declared.

Background: Despite the increased incidence of influenza infection in rheumatoid arthritis (RA) patients, vaccination coverage has been shown to be suboptimal. Prospective data regarding the current rate and predictors of influenza vaccination adherence in RA patients are limited. Objectives: To calculate the current rate and predictors of influenza vaccination in a real-life, prospective, longitudinal RA cohort. Methods: Data regarding demographics, disease characteristics, treatments and co-morbidities from a multi-center, longitudinal cohort of Greek RA patients were collected at baseline and ~ 3 years later. Disease and patient characteristics were compared between patients with at least one influenza vaccine administration and non-vaccinated ones, during the 3 year follow-up period. Results: From a cohort of 1,569 RA patients, 1,406 with available vaccination data at baseline and 3 years later (mean interval: 2.9 years) were included; (women: 80.4%, mean age: 61.8 years, mean disease duration: 9.7 years, RF and/or anti-CCP positive: 50.4%, mean DAS-28 = 3.33, mean HAQ: 0.44, bDMARD use: 44.8%). At baseline, 54.2% of patients reported influenza vaccination in the past (31.8% during the previous season), while during the 3 year follow-up period, 81% had ≥1 influenza vaccinations (p=<0.001). Patients who received ≥1 influenza vaccine were older (63.5 vs. 54.7 years, p<0.001), were more likely to be seropositive (59.2% vs. 45.2%, p<0.001), had higher HAQ (0.46 vs. 0.36, p=0.02) and BMI (27.7 vs. 26.9, p=0.02) at baseline, more likely to be treated with bDMARDs (46.8% vs. 36.4%, p<0.001) and more likely to have chronic lung disease (9.7% vs. 5.3%, p=0.02), dyslipidemia (36.4% vs. 24.2%, p<0.001), hypertension (46.1% vs. 29.2%, p<0.001) and to report vaccination against influenza the previous season before baseline evaluation (34.9% vs. 18.2%, p<0.001). By multivariate analysis, history of influenza vaccination during the last season before baseline (OR=1.87, CI: 1.27-2.74, p=0.001), bDMARD treatment (OR=1.51, CI: 1.07-2.13, p=0.018) and age (OR=1.05, CI: 1.04-1.06, p<0.001) were independent predictors of influenza vaccination. Conclusion: In this ongoing, longitudinal, prospective, real-life RA cohort study, a significant increase in the influenza vaccination coverage was noted (from 53% to 81%). Influenza vaccination was independently associated with recent history of influenza vaccination, older age, and bDMARD treatment. Acknowledgments: Supported by grants from the Greek Rheumatology Society and Professional Association of Rheumatologists. Disclosure of Interests: Konstantinos Thomas: None declared, Argyro Lazarini: None declared, Evripidis Kaltsonoudis: None declared, Alexandros Drosos: None declared, ARGYRO REPA: None declared, Prodromos Sidiropoulos: None declared, Kalliopi Fragkiadaki: None declared, Maria Tektonidou Grant/research support from: AbbVie, MSD, Novartis and Pfizer, Consultant of: AbbVie, MSD, Novartis and Pfizer, Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Panagiota Tsatsani: None declared, Sousana Gazi: None declared, Pelagia Katsimbri: None declared, Dimitrios Boumpas: None declared, Evangelia Argyriou: None declared, Kyriaki Boki: None declared, Gerasimos Evangelatos: None declared, Alexios Iliopoulos: None declared, Konstantina Karagianni: None declared, Lazaros Sakkas: None declared, Konstantinos Melissaropoulos: None declared, Panagiotis Georgiou: None declared, Eleftheria Grika: None declared, PANAYIOTIS VLACHOYIANNOPOULOS: None declared, Theodoros Dimitroulas: None declared, Alexandros Garyfallos Grant/research support from: MSD, Aenorasis SA, Speakers bureau: MSD, Novartis, gsk, Constantinos Georganas: None declared, Periklis Vounotrypidis: None declared, Konstantinos Ntelis: None declared, Maria Areti: None declared, George D Kitas: None declared, Dimitrios Vassilopoulos: None declared

Background:Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder. In recent years biological disease modifying antirheumatic drugs (bDMARDs) are becoming increasingly important for its treatment.Objectives:To evaluate disease outcomes, treatment strategies and their long-term safety in a cohort of AOSD patients treated with bDMARDs.Methods:A single-center retrospective study of patients diagnosed with AOSD until 2019 was conducted. Patients were included if they: a) were 16 years old or older, b) met the Yamaguchi criteria and c) had received a bDMARDDemographics, clinical and laboratory parameters were collected at the time of diagnosis.Data regarding treatment lines included: the previous and concomitant conventional disease modifying antirheumatic drugs (cDMARDs), the type of initial bDMARD, switches, survival and corticosteroids discontinuation. Adverse events related to treatment and disease outcomes including death and amyloidosis were also recorded.Results:Sixteen patients with AOSD (Table 1) refractory to cDMARDs were administered biologics. The median duration of follow-up was 14 years (range 1-24). Consistent with recent literature1, two distinct disease patterns were recognized: the systemic form (SF) and the chronic articular form (CAF). In the SF the leading clinical symptoms were fever, pericarditis and pleuritis. In CAF the leading clinical symptom was persistent RA-like arthritis.Table 1.Some clinical and laboratory features of patients with FMF or MEFV mutations accompanied by demyelination diseaseCasesAge/SexDiseasesMEFV mutationsThe onset age/diagnostic age for FMFThe onset age for DD/MS/Presenting manifestations/MRI findingsTreatment for FMF /DD/MSCase 1(F1)17/FFMF+DDM694V homozygous3/515OB (-)Fusiform plaques in the cingulate gyrus; plaques in T4-6ColchicineIL-1 RAGlatiramer acetateCase 2(F1)46/FFMF+MSM694V homozygous8/928Optic nerve involvementOB(+)Plaques (+)ColchicineGlatiramer acetateCase 3(F1)17/FFMF+MSM694V heterozygous3/515Loss of the right eye, vertigoOB(+)PlaquesColchicinePulse steroidBeta-interferonTeriflunomideCase 4(F2)36/FMS+MEFV mutationM694V/R202Q-27Headache, blurred vision, optic nerve atrophyOB(+)Plaques (+)Glatiramer acetateCase 5(F2)16/FMS?+FMF+Cutaneous vasculitisM694V/R202Q16/1611Headache, blurred visionNo LP (denied by pt)Plaques-F: Female, F1: Family 1, F2: Family 2; DD: Demyelination disease;MS: Multiple sclerosis;MRI: Magnetic resonance imaging; OB:Oligoclonal band; LP: Lumbar punctionTable 1.Summary of patient characteristics at the time of diagnosisCharacteristicsResultsAge at the time of diagnosis median, (range) years32.5 (18-64)Sex (N)11 female, 5 maleFever14 (87.5%)Rash8 (50%)Lymphadenopathy2 (12.5%)Arthritis15 (93.75%)Pleuritis7 (43.7%)Pericarditis9 (56.25%)Hepatosplenomegaly2 (12.5%)Elevated liver enzymes2 (12.5%)Hyperferritinaemia4 (25%)Patients with the SF were treated with anakinra (n=4), tocilizumab (TCZ; n=3), canakinumab (n=1) and anti-TNFa (1 adalimumab, 1 etanercept) (n=2). Patients with the CAF received anti-TNFa (3 infliximab, 1 etanercept) (n=4) and TCZ (n=2). The median time from biologic initiation to corticosteroids discontinuation was 6.5 months, (range 2-32), (Table 2). 9 patients (56.25%) remained on treatment with the initial bDMARD, 4 patients (25%) received treatment with two and 3 patients (18.75%) with ≥ 3 bDMARDs. All patients with the CAF were on bDMARD at the end of follow-up, while 4/10 patients (40%) with the SF discontinued it. During follow-up only one serious adverse event was attributed to bDMARD (allergic reaction to infliximab infusion). There were no cases of amyloidosis or deathsConclusion:Dichotomous phenotype in AOSD can determine treatment strategy for initial biologic treatment. Inhibition of IL-1 and IL-6 was the preferred therapeutic option for systemic form while inhibition of TNF and IL-6 was the preferred option for the chronic articular form. All of the above bDMARDs have favorable long-term safety profile in patients with AOSD.References:[1]François Vercruysse et al. Adult-onset Still’s disease biological treatment strategy may depend on the phenotypic dichotomy Arthritis Research & Therapy. 2019Disclosure of Interests:Nikolaos Kougkas: None declared, Nestor Avgustidis: None declared, Sofia Pitsigavdaki: None declared, Katerina Pateromichelaki: None declared, ARGYRO REPA: None declared, Ainour Molla Ismail Sali: None declared, Anastasios Eskitzis: None declared, George Bertsias Grant/research support from: GSK, Consultant of: Novartis

Background:SLE onset is preceded by a preclinical phase evidenced by the presence of anti-nuclear and other autoantibodies (autoAbs), which however, have low predictive value for development of clinical SLE.Objectives:To define the subgroup of autoAbs-positive individuals who are at high risk for progression into SLE by integrating environmental, clinical/serological, genetic and transcriptome data.Methods:A multicenter, across five European countries, inception cohort of autoAbs-positive individuals or first-degree relatives (FDRs) of SLE patients who are monitored prospectively over five years for possible transition to SLE according to the classification criteria. Structured data collection on demographics, family and medical history, clinical (criteria and selected non-criteria manifestations) and serological parameters, use of medications, hydroxyvitamin D levels and lifestyle (tobacco, alcohol use, physical activity, adherence to Mediterranean diet). Blood samples are stored for RNA-sequencing and genotyping.Results:A total 254 at-risk individuals (93% women, 99% Caucasians, aged [mean ± standard deviation] 36 ± 12 years) have been included and enrolment/monitoring is still ongoing. Forty individuals (16%) have FDR with SLE and 88 individuals (35%) have FDR with another autoimmune disorder. The frequency of active and past use of tobacco was 28% and 20%, respectively. Sedentary lifestyle (moving only for necessary chores or outdoor activity 1-2 times/week) was reported by 54% and adherence to the Mediterranean diet was low (3.4 ± 2.3, maximum score: 9). At enrolment, individuals had 1.9 ± 1.1 ACR-1997 classification criteria, with anti-nuclear antibodies (ANA) being the most frequent (88%), followed by synovitis (39%), photosensitivity (33%) and immunologic disorder (30%) (Table 1). During follow-up of 15.2 ± 7.2 months, a total 15 individuals (5.9%) have progressed into classified SLE, including cases with severe hematological and neurological disease.Table 1.Baseline characteristics of the at-risk for SLE cohortN (%) or mean ± SDACR 1997 classification criteria1.9 ± 1.1 Malar rash68 (27%) Discoid rash29 (11%) Photosensitivity83 (33%) Mucosal ulcers49 (19%) Synovitis100 (39%) Serositis30 (12%) Renal disorder28 (11%) Neurologic disorder31 (12%) Hematologic disorder58 (23%) Immunologic disorder77 (30%) ANA222 (88%)SLICC 2012 classification criteria Clinical criteria1.0 ± 0.9 Immunological criteria1.3 ± 0.9Conclusion:Among individuals with positive autoAbs or FDRs with SLE, the short-term risk for transition into clinical SLE is low. Following the study completion, clinical and lifestyle data will be combined with blood transcriptome to define a high-risk subgroup of individuals for progression into SLE.Acknowledgments:The study is supported by the Foundation for Research in Rheumatology (FOREUM; preclin016)Disclosure of Interests:Christina Adamichou: None declared, Dionysis Nikolopoulos: None declared, Myrto Nikoloudaki: None declared, Zahra Rahme: None declared, Micaela Fredi: None declared, Antigoni Pieta: None declared, ARGYRO REPA: None declared, Alice Parma: None declared, Eleni Kalogiannaki: None declared, Nestor Avgustidis: None declared, Nikolaos Kougkas: None declared, Aggelos Banos: None declared, Anastasios Eskitzis: None declared, Alessandra Bortoluzzi: None declared, Søren Jacobsen: None declared, Prodromos Sidiropoulos: None declared, Emmanouil Dermitzakis: None declared, Marta Mosca: None declared, Luís Inês: None declared, Laura Andreoli: None declared, Angela Tincani: None declared, Antonis Fanouriakis Paid instructor for: Paid instructor for Enorasis, Amgen, Speakers bureau: Paid speaker for Roche, Genesis Pharma, Mylan, George Bertsias Grant/research support from: GSK, Consultant of: Novartis

Purpose To provide an updated, comprehensive assessment of the burden and severity of SLE manifestations at the community level. Methods Data were retrieved from the Cretan Lupus Registry, which includes adult patients with SLE who are regularly followed in Crete. SLE is defined as mild, moderate or severe, based on the BILAG glossary of the severity of disease manifestations and the use of potent immunosuppressive drugs. Organ damage was assessed through the SLICC/ACR Damage Index [SDI]. Results A total 737 SLE patients (98% with ≥4 ACR-1997 criteria, 74% fulfilling both ACR-1997 and SLICC-2012 criteria) were included in the present analysis, with a median (interquartile range) age at diagnosis of 43 (21) years and disease duration of 8 (7) years. Regarding disease severity, 49% of the patients had mild, 32% moderate and 19% severe lupus. Within the severe cases, most frequently afflicted systems were the haematological (4.6%), renal (3.6%), cardiovascular system (2.8%), and neurological (2.3%). Mycophenolate was administered in 0%, 2.7% and 8.5%, and rituximab in 0%, 7.1% and 15.3% of patients with mild, moderate and severe disease, respectively (p<0.01 for both). Disease severity did not differ according to age of SLE diagnosis (before or after 50 years), whereas female predominance was more pronounced in mild cases (31:1) as compared to moderate (12:1) or severe (5:1) (p<0.001). Notably, more severe disease correlated with shorter time interval from symptoms onset to SLE diagnosis (delay >12 months: 56% in mild, 39% in moderate, 27% in severe, p<0.001). Unemployment and smoking status (n=399 patients) tended to be higher in the moderate/severe group (54% versus 44% and 34% versus 28%, respectively). Regression analysis showed that moderate/severe as compared to mild disease is strongly associated (odds ratio 2.5, p<0.001) with organ damage accrual (SDI>0). Conclusions At the community level, more than half of SLE patients present with moderate or severe manifestations which may contribute to irreversible organ damage.

OBJECTIVES:Our primary objective was to study the long-term survival on drug (SOD) of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) treated with golimumab (GLM) in real life settings.METHODS:This was a retrospective, observational study of all patients treated with GLM in 4 Academic Centres in Greece during a 4-year period (09/2010-06/2014). SOD was analysed using Kaplan-Meier survival analysis, while Cox regression analysis estimating hazard ratios (HRs) for different baseline variables associated with drug discontinuation was performed for each disease.RESULTS:328 patients (RA: 166, PsA: 82, AS: 80) were included. The estimated SOD at 2 and 3 years was 68% and 62% overall and was better for AS (79% and 76%) compared to RA (69% and 60%, p=0.067) and PsA (58% and 53%, p=0.001) patients; no difference was noted between RA and PsA patients (p=0.204). There was no difference in SOD between biologic-naïve and experienced nor between non-biologic co-treated or GLM monotherapy treated patients. Seropositivity (rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) was associated with a lower risk for GLM discontinuation by multivariate analysis (HR=0.5, 95% CI=0.0.25-1.1, p=0.05) in RA patients. During 606 patient-years of follow-up, 11 (3.3%) patients discontinued GLM due to adverse events (AE), accounting for 11% of treatment discontinuations. The rates of serious AEs and serious infections were 2.3 and 1.0/100-patient-years, respectively.CONCLUSIONS:In this real-life study, GLM showed a high 3-year SOD in patients with inflammatory arthritides with a low rate of discontinuation due to AEs.

OBJECTIVES:Early arthritis clinics (EAC) aim to improve rheumatoid arthritis (RA) outcomes by tailoring treatment targeting to remission. Our aim was to analyse disease course and relevant predictors over 2 years in early arthritis; we also assessed the applicability of the "treat-to-target approach" in a real-life EAC.METHODS:Patients with early arthritis recruited at the EAC of the University Hospital of Heraklion were followed prospectively according to a follow-up protocol for two years, without implementing a pre-specified treatment protocol, to capture real-life practices. Early predictors of "suboptimal outcomes" (high disease activity or HAQ>1.0 at 2 years) and biologic DMARD (bDMARD) initiation were evaluated with multivariate logistic regression. Intensification of treatment at 3 and 6 months and subsequent long-term outcome were also assessed.RESULTS:251 patients [RA (n=188), undifferentiated arthritis (n=63)] were included. Although both DAS28 and HAQ at 2 years improved significantly compared to baseline in RA patients [mean (SD) DAS28 and median (IQR) HAQ 3.70 (1.32) and 0.44 (0.75) at 2 years, p<0.001 for both compared to baseline], 43.7% still had moderate and 18.8% high disease activity. The most powerful predictor of suboptimal outcomes or bDMARD initiation in RA was high disease activity at three months (adjusted odds ratio 2.22 and 2.62, respectively). At three and six months 72.8% and 62.4% of patients with medium/high disease activity received treatment intensification, which resulted in significant decrease in disease activity at 2 years (p<0.001 for ΔDAS28).CONCLUSIONS:DAS28 at three months was the most powerful predictor of suboptimal disease outcome during a 2-year follow-up in early RA. Despite significant DAS reductions, more than 50% of patients have active disease at two years. Failure to fully implement the treat-to-target strategy in our cohort could account for the low remission rates.

Introduction Rheumatoid arthritis (RA) develops upon aberrant activation of the immune system mainly due to failure of self-tolerance mechanisms. 1 Abatacept, approved for RA treatment, a recombinant fusion protein of the extracellular domain of human cytotoxic T lymphocyte antigen 4 (CTLA4), restricts T cell activation by blocking interaction of CD80/CD86 on dendritic cells (DCs) to CD28 on T cells. 2 In clinical practice, approximately 40–50% of RA patients treated with abatacept, respond to therapy in the first 6 months. 3 Development of a predictor of response is of clinical and immunological significance. Objectives Herein, we sought to investigate for early biomarkers of response to abatacept, based on a detailed immunological profile of peripheral blood cells and cytokines. Methods RA patients (ACR/EULAR 2010 criteria) who started abatacept due to highly active disease, were recruited to perform immunological studies at baseline, 3 and 6 months of therapy. Peripheral blood mononuclear cells (PBMCs) were isolated and pathogenic IL-17 and IFN-γ producing CD4+ T cells (Th1, Th17), regulatory (Tregs) T cell subsets as well as myeloid cell populations, like DCs and myeloid derived suppressor cells (MDSCs) were characterized using flow cytometry. Response to therapy (remission or low disease activity) was assessed based on the “Swollen joints” value. Results We studied 21 patients (mean age 60 years, 86% women, 48% rheumatoid factor or anti-citrullinated protein antibody positive). After 6 months of treatment, 45% of them attained remission or low disease activity. Notably, baseline levels of Th17 were statistically significant decreased in peripheral blood of patients in remission or low disease activity compared to those with active disease at 6 months of treatment (1.29±0.18% versus 2.44±0.41%, p=0.0482). Baseline levels of Th1 and Foxp3 + Tregs were comparable between responders and non-responders. No significant differences in CD14 int CD15 + CD33 + MDSCs or CD3 - HLADR + DCs were observed. Conclusions In this cohort of RA patients treated with abatacept (CTLA4Ig), low levels of IL-17 producing CD4 + T cells at baseline are associated with a better response to abatacept at 6 months. This novel finding (validation to a larger cohort in progress) may be used as an early biomarker to predict clinical responses to abatacept. References . McInnes, et al . The Lancet 2017. . Wing, et al. Science 2008. . Smolen, et al. Arthritis Res Ther 2015. Acknowledgements Project funded by BMS (Investigator initiated study, BMS PROTOCOL NUMBER: 2014-ORE-0033), “Pancretia” health organization.

Background For rheumatoid arthritis (RA) patients who discontinue the first biologic agent (bDMARD), most commonly being a TNF inhibitor (TNFi), there is little evidence supporting the next best choice between a second TNFi course or a non-TNFi bDMARD in clinical practice. Objectives To compare the effectiveness and the adherence to therapy with non-TNFi versus TNFi administered as the second-line bDMARD in RA patients with one prior TNFi use. Methods All patients starting a bDMARD in the Rheumatology Department of the University Hospital of Heraklion, Crete, are included in a prospective observational study after their written informed consent. Data concerning disease activity at pre-specified time-points, drugs, comorbidities and any adverse events are recorded. For the present study we analyzed patients with RA starting their second course of a bDMARD after discontinuation of a TNFi. We compared DAS28 difference at 6 and 12 months using linear regression analysis and treatment retention using Kaplan-Meier survival curves with log-rank test. Results A total of 384 patients started a 2nd (different) TNFi [N=213 (Infliximab: 26, Adalimumab: 77, Etanercept: 89, Golimumab: 13 and Certolizumab: 8)] or a non-TNFi [N=171 (Rituximab:71, Abatacept:66, Tocilizumab:34)]. Patients9 characteristics at baseline are described in the Table. Two-year drug survival was higher for non-TNFi (64% vs. 39%, log rank p<0.001) due to lower frequency of discontinuations for primary failure (p<0.001) and adverse events (p=0.019). δDAS28 was comparable between non-TNFi and TNFi patient groups both at 6 [mean (SD): -1.16 (1.29) and -1.07 (1.55) respectively, p=0.296] and at 12 months [-1.41 (1.29) and -1.39 (1.26) respectively, p=0.670]. In patients who did not receive co-therapy with methotrexate, significantly greater δDAS28 was observed with a non-TNFi (-1.25 (1.29) vs.-0.68 (1.61), p=0.006). When the first TNFi was discontinued due to primary failure, we observed a trend for greater δDAS28 in the non-TNFi patient group compared to the 2nd TNFi group (-1.4 vs. -1.0, p=0.12) while the opposite was observed in patients who have experienced secondary failure to the 1st TNFi (-0.81 vs -1.48, p=0.18), but this did not reach statistical significance, probably due to the low number of available patients. Conclusions In RA patients who need a 2nd bDMARD after discontinuation of a TNFi, administration of a non-TNFi results in similar clinical responses but higher treatment adherence compared to a second TNFi agent. In patients who do not receive methotrexate, responses are better with a non-TNFi bDMARD. Disclosure of Interest None declared