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The presence of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) autoantibodies contributes to the current rheumatoid arthritis (RA) classification criteria. These criteria involve stratification on antibody levels, which limits reproducibility, and underperform in the RA patients without RF and anti-CCP. Here, we have explored if two anti-acetylated peptide antibodies (AAPA), anti-acetylated lysine (AcLys) and anti-acetylated ornithine (AcOrn), could improve the performance of the current criteria. The analysis was done in 1062 prospectively-followed early arthritis (EA) patients. The anti-AcOrn were more informative than the anti-AcLys, the conventional RA antibodies and the anti-carbamylated protein antibodies. The anti-AcOrn produced a classification that did not require antibody levels and showed improved specificity (77.6% vs. 72.6%, p = 0.003) and accuracy (79.0% vs. 75.8%, p = 0.002) over the current criteria. These improvements were obtained with a scoring system that values concordance between anti-AcOrn, RF and anti-CCP. No significant gain was obtained in sensitivity (80.2% vs. 78.8%, p = 0.25) or in improving the classification of the RA patients lacking RF and anti-CCP, although the anti-AcOrn ranked first among the analysed new antibodies. Therefore, the anti-AcOrn antibodies could contribute to the improvement of RA classification criteria by exploiting antibody concordance., This work was supported by the Instituto de Salud Carlos III (Spain) through grants [RD16/0012/0014 and PI17/01606 to AG; RD16/0012/0012 to AB; PI14/00442 and RD16/0012/0011 to IG-A]. These grants are partially financed by the European Regional Development Fund of the EU (FEDER). LRM was supported by Xunta de Galicia (Spain) through a Gain pre-doctoral fellowship. CR was supported by Ministerio de Educacion Cultura y Deporte (Spain) through a FPU pre-doctoral fellowship [FPU15/03434].

Introduction During the last years, regulatory agencies raised some relevant concerns with regard to the possibility of administrating biological therapy (BT) to non-SpA patients. Especially, the possibility of treating women with fibromyalgia as non-radiographic axSpA (nr-axSpA) was mentioned. Objectives To evaluate if the gender distribution and clinical pattern of patients with axSpA initiating biological therapy (BT) was modified in clinical practice after its approval for non radiographic-axSpA (nr-axSpA). Methods Baseline dataset from a prospective ongoing cohort including all patients with axSpA treated with BT at the Rheumatology Department of University Hospital La Paz, Madrid, Spain, was analysed. Patient's characteristics and disease activity parameters were collected. Based on the approval indication date of BT for nr-axSpA, patients were classified in two periods according to the starting date for the first BT: period 1 (before 2013) and period 2 (during or after 2013). Gender distribution and disease’ characteristics were compared between both groups using Chi-square and Student-t tests. Results In total, 385 patients initiated BT: 266 (69%) in period 1 and 119 (31%) in period 2. No significant differences between both periods were observed regarding gender distribution (38% and 39% of women; p = 0.8). Out of those patients with nr-axSpA initiating BT in period 2, the majority (60%) were men. Women starting BT in period 2 had significantly higher systemic inflammation and mobility restriction compared with women in period 1 [median (interquartile range) CRP 10.2 mg/l (3.0–24.9) vs 3.2 mg/l (2.0–9.4); p = 0.02 and BASMI 2.7 (1.8–3.5) vs. 2.0 (1.2–2.6); p = 0.01, respectively]. In addition, they also presented significantly higher disease activity [BASDAI 6.5 (5.4–8.0) vs. 5.8 (4.6–6.8); p = 0.02; ASDAS, mean (SD) 3.6 ± 3.4 vs. 3.2 ± 1.0; p = 0.02, respectively] and more functional limitation [BASFI 5.7 (3.8–6.7) vs. 4.3 (2.0–6.1); p = 0.01, respectively] than men treated in period 2. Conclusions In our clinical practice, the frequency of women who started BT did not increase since their approval for nr-axSpA. Women treated with BT after 2012 had more objective disease activity parameters than before their approval for nr-axSpA treatment.

Background: The aim of our study is to evaluate whether serum infliximab trough levels (ITL) during the early stages of treatment are predictive of long-term clinical failure in patients with axial spondyloarthritis (axSpA).Methods: Longitudinal observational study involving 81 patients with axSpA recruited from the SpA-Paz cohort and monitored during infliximab therapy. Serum ITL were measured at baseline, week 2 (W2), W6 and W12 of treatment. Disease activity was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline, W24 and W54, and every 6 months thereafter until therapy failure. Non-clinically important improvement was defined by ΔASDASResults: Out of the 81 patients, 45 (56%) did not achieve clinical improvement at W52. These patients had lower serum ITL at W12 compared to those who improved: ITL [median (IQR)]: 4.1(0.9-8.3) µg/ml vs 7.1(4.3-11.3)µg/ml, respectively; p=0.007). A cut-off of ITLConclusions: Serum ITL

The recent outbreak caused by a novel severe acute respiratory syndrome coronavirus 2 disease 2019 (COVID-19) has spread rapidly worldwide, and it has been declared a pandemic by the WHO.1 Elder people, male sex and some underlying comorbidities seem to be risk factors for morbidity and mortality, although an immunosuppressive status could favour the infection and the development of complications.2 However, as progress is made in the knowledge of the physiopathology of COVID-19, it has been observed that severe respiratory forms occur as a result of an hyperinflammatory status and an excessive production of cytokines.3 In this descriptive retrospective study, we aimed to characterise features related to severity and mortality in these patients and the influence of immune modulating drugs on the course of the infection. Patients were included from 25 February 2020 to 8 June 2020 with COVID-19 infection and rheumatic inflammatory diseases from Rheumatology Department of La Paz University Hospital. One hundred and twenty-two patients were included. One hundred (82.0%) were confirmed through nasopharyngeal swabs. Twenty-two patients (18.0%) exhibited compatible symptoms with compatible lung imaging and/or positive serology. Patients characteristics are shown in …

ObjectiveA novel population of B helper cells, phenotypically CD4+CXCR5−PD-1hi, has been described in the synovial tissues and peripheral blood of seropositive RA patients, and termed ‘peripheral helper T’ (Tph) cells. Contrary to CD4+CXCR5+PD-1hi follicular helper T (Tfh), Tph cells are not located in lymphoid organs but accumulate in inflamed tissues. Our objective was to study the frequency of circulating Tph (cTph) and circulating Tfh cell counterparts (cTfh) in patients with early RA (eRA).MethodsFreshly isolated peripheral blood mononuclear cells from 56 DMARD-naïve eRA patients and 56 healthy controls were examined by flow cytometry. Autologous cocultures of naïve or memory B cells were established with isolated peripheral blood Tph or Tfh cells.ResultsSeropositive (RF+ and/or ACPA+, n = 38) but not seronegative eRA patients (n = 18) demonstrated increased frequencies and absolute numbers of cTph and cTfh cells. cTph but not cTfh cells expressed CCR2. Those eRA patients who experienced a significant clinical improvement at 12 months demonstrated a marked decrease of their cTph cell numbers whereas their cTfh cell numbers remained unchanged. Both isolated Tph and isolated Tfh cells were able to induce maturation of memory B cells, whereas only Tfh cells could differentiate naïve B cells.ConclusionTwo populations of PD-1hiCD4 T cells with distinct phenotype and B cell helping capacity are increased in the peripheral blood of seropositive eRA patients. Whereas cTph cells are present only in patients with an active disease, cTfh cells seem to be constitutively elevated.

The initial management of rheumatoid arthritis (RA) has a high impact on disease prognosis. Therefore, we need to select the most appropriate treatment as soon as possible. This goal requires biomarkers of disease severity and prognosis. One such biomarker may be the presence of anti-carbamylated protein antibodies (ACarPA) because it is associated with adverse long term outcomes as radiographic damage and mortality. Here, we have assessed the ACarPA as short-term prognostic biomarkers. The study was conducted in 978 prospective early arthritis (EA) patients that were followed for two years. Our results show the association of ACarPA with increased levels of all the disease activity measures in the first visit after arthritis onset. However, the associations were more significant with the high levels in local measures of inflammation and physician assessment than with the increases in systemic inflammation and patient-reported outcomes. More notably, disease activity was persistently increased in the ACarPA positive patients during the two years of follow-up. These differences were significant even after accounting for the presence of other RA autoantibodies. Therefore, the ACarPA could be considered short-term prognostic biomarkers of increased disease activity in the EA patients.

Background Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular challenge to clinicians. Objectives This study aims to determine the percentage of rheumatoid arthritis (RA) patients who fail to respond to subsequent bDMARDs, describe their characteristics, and identify specific baseline and early features during the first bDMARD as possible predictors of consecutive multiple bDMARD failure. Methods This is a longitudinal study involving RA patients from the prospective biological cohort drawn from the La Paz University Hospital RA Registry (RA-Paz), starting a bDMARD during the years 2000 to 2019. Patients who presented insufficient response (due to primary or secondary inefficacy) to at least three bDMARDs or two bDMARDs with different mechanism of action were considered multi-refractory (MR-patients). Patients who achieved low disease activity or remission (by DAS-28) with the first bDMARD and maintained this over a follow-up period of at least 5 years were considered non-refractory (NR-patients). Results A total of 41 out of 402 (10%) patients were MR-patients and 71 (18%) NR-patients. In the multivariate analysis, the presence of erosions, younger age, higher baseline DAS-28 and mostly achieving delta-DAS Conclusions In our cohort, 10% of patients with RA were observed to have multi-refractoriness to bDMARDs. This study supports the contention that younger patients with erosive disease and especially the early absence of clinical response to the first bDMARDs are predictors of multi-refractoriness to consecutive biologics. Hence, patients with these characteristics should be monitored more closely and may benefit from personalized treatments.

ObjectivesTo determine the frequency of sustained remission (R) or low diseas activity (LDA) in patients with axial spondyloarthritis (axSpA) undergoing long-term biological therapy and to analyse predictive factors for achieving these outcomes.DesignProspective, observational cohort study.SettingSpanish hospital.ParticipantsPatients with axSpA who initiated biological treatment between 2003 and 2017.InterventionAssessment of demographic and clinical characteristics at the beginning of treatment and disease activity every 6 months up to a maximum of 2 years.Main outcome measuresDisease activity was measured by Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index and C reactive protein (BASDAI&CRP). Sustained R was defined as ASDASResultsIn total 186 patients (66.1% men and 75.3% with radiographic sacroiliitis) were included. Overall, 76.8% of patients achieved ASDAS R/LDA (R53.2%/LDA23.6%) in at least one visit. Forty per cent (R17.6%/LDA22.4%) of the patients fulfilled the sustained ASDAS R/LDA state, whereas only 30.8% maintained this status (R14.8%/LDA15.9%) according to BASDAI&CRP. In the multivariate analysis, male sex (OR=4.01), younger age at the beginning of biological therapy (OR=0.96) and an HLA*B27 positive status (OR=4.30) were associated with achieving sustained ASDAS R/LDA.ConclusionsIn clinical practice, around one-third of patients on biological disease-modifying antirheumatic drugs achieve a sustained R/LDA status, but these rates drop to less than one in five when targeting remission, preventing the use of the latter as a feasible target. Male sex, HLA*B27 positivity and younger age at the beginning of biological therapy are the main predictors for achieving sustained R/LDA.

Las nociones sobre Sentido Común y Sociedades Democráticas se abordan desde elementos comunicacionales que permiten interpretar la realidad social multidimensionada, deconstruirla, proponer su reconfiguración y articular la Comunicación como fuente de transformaciones sociales. Se desarrolla una diferenciación de matrices, abordajes y enfoques comunicacionales que permiten entender cada elemento comunicacional en función a metas y objetivos concretos de orden cuantitativo y cualitativo. Se proponen estrategias de gestión comunicacional inherentes a las diversas formas de organización popular que permiten perfeccionar la participación democrática a través de elementos comunicacionales, entendiendo que el Sentido Común de las sociedades se encuentra en permanente disputa, construcción y reconfiguración en torno al sentido de época y los momentos históricos particulares. Se brindan nociones de interpretación de la realidad social latinoamericana a partir de la Comunicación, pero también propuestas de transformación entendiendo que las sociedades latinoamericanas son heterogéneas muy diferentes a las sociedades europeo continentales y a las anglosajonas. La Comunicación es enfocada a través de sus estrategias comunicacionales como primaria para la interpretación y transformación social, no así accesoria como se teoriza desde el Pensamiento Crítico. A la vez, todo el trabajo devela que no son únicamente los medios hegemónicos de comunicación ni exclusivamente los políticos los únicos actores constructores de Sentido Común en las sociedades., The notions about Common Sense and Democratic Societies are approached from communicational elements that allow interpreting multidimensional social reality, deconstructing it, proposing its reconfiguration and articulating Communication as a source of social transformation. A differentiation of matrices, approaches and communicational approaches is developed that allow understanding each communicational element based on specific goals and objectives of a quantitative and qualitative order. Communication management strategies inherent to the various forms of popular organization are proposed that allow to improve democratic participation through communicational elements, understanding that the Common Sense of societies is in permanent dispute, construction and reconfiguration around the sense of time and the particular historical moments. Notions of interpretation of Latin American social reality are provided from the Communication, but also proposals for transformation, understanding that Latin American societies are heterogeneous and very different from continental European and Anglo-Saxon societies. Communication is focused through its communicational strategies as primary for interpretation and social transformation, not as accessory as it is theorized from Critical Thinking. At the same time, all the work reveals that it is not only the hegemonic means of communication, nor exclusively the politicians, the only common sense-building actors in societies., Facultad de Periodismo y Comunicación Social

Objective The protagonism of regulatory B cells seems to vary along the course of the disease in murine models of inflammatory conditions. Decreased numbers of circulating regulatory CD19+CD24hiCD38hi transitional (cTr) B cells have been described in patients with long-standing RA, thus our objective was to examine the frequency and evolution of cTr B cells in the peripheral blood of early RA (ERA) patients. Methods Freshly isolated peripheral blood mononuclear cells from 48 steroid- and DMARD-naïve ERA patients with a disease duration of Results As compared with HCs, ERA patients demonstrated an increased frequency of cTr B cells. cTr B cells of ERA patients and HCs displayed an anti-inflammatory cytokine profile and were able to downregulate T cell IFN-γ and IL-21 production, together with ACPA secretion in autologous B/T cell co-cultures. Basal frequencies of cTr B cells above the median value observed in HCs were associated with a good EULAR response to MTX at 12 months [relative risk 2.91 (95% CI 1.37, 6.47)]. A significant reduction of cTr B cells was observed 12 months after initiating MTX, when the cTr B cell frequency was no longer elevated but decreased, and this was independent of the degree of clinical response or the intake of prednisone. Conclusion An increased frequency of regulatory cTr B cells is apparent in untreated ERA and the baseline cTr B cell frequency is associated with the clinical response to MTX at 12 months.

The major environmental risk factor for rheumatoid arthritis (RA) is smoking, which according to a widely accepted model induces protein citrullination in the lungs, triggering the production of anti-citrullinated protein antibodies (ACPA) and RA development. Nevertheless, some research findings do not fit this model. Therefore, we obtained six independent cohorts with 2253 RA patients for a detailed analysis of the association between smoking and RA autoantibodies. Our results showed a predominant association of smoking with the concurrent presence of the three antibodies: rheumatoid factor (RF), ACPA and anti-carbamylated protein antibodies (ACarPA) (3 Ab vs. 0 Ab: OR = 1.99, p = 2.5 × 10–8). Meta-analysis with previous data (4491 patients) confirmed the predominant association with the concurrent presence of the three antibodies (3 Ab vs. 0 Ab: OR = 2.00, p = 4.4 ×10–16) and revealed that smoking was exclusively associated with the presence of RF in patients with one or two antibodies (RF+1+2vs. RF−0+1+2: OR = 1.32, p = 0.0002). In contrast, no specific association with ACPA or ACarPA was found. Therefore, these results showed the need to understand how smoking favors the concordance of RA specific antibodies and RF triggering, perhaps involving smoking-induced epitope spreading and other hypothesized mechanisms.

Background: The patients with RA benefit from early identification soon after the first clinical symptoms appear. The 2010 ACR/EULAR classification criteria were developed to fulfill this need and their application has been demonstrated to be effective. However, there is still room for improvement. Therefore, we aimed to evaluate the potential of the concordant presence of RF, anti-CCP and anti-carbamylated protein antibodies to improve current RA classification among early arthritis (EA) patients. Methods: Data from the first visit of 1057 patients in two EA prospective cohorts were used. The serological scores from the 2010 ACR/EULAR criteria and the concordant presence of the three RA autoantibodies were assessed relative to a gold standard consisting of the RA classification with the 1987 ACR criteria at the 2 years of follow-up. Results: The concordant presence of three antibodies showed predictive characteristics allowing for direct classification as RA (positive predictive value = 96.1% and OR = 80.9). They were significantly better than the corresponding to the high antibody titers defined as in the 2010 classification criteria (PPV = 88.8%, OR = 26.1). In addition, the concordant presence of two antibodies was also very informative (PPV = 82.3%, OR = 15.1). These results allowed devising a scoring system based only on antibody concordance that displayed similar overall performance as the serological scoring system of the 2010 criteria. However, the best classification was obtained combining the concordance and 2010 serological systems, a combination with a significant contribution from each of the two systems. Discussion: The concordant presence of RA autoantibodies showed an independent contribution to the classification of EA patients that permitted increased discrimination and precision., This work was supported by the Instituto de Salud Carlos III (Spain) through grants [PI17/01606 and RD16/0012/0014 to AG; RD16/0012/0011 to IG-A and RD16/0012/0012 to AB]. These grants are partially financed by the European Regional Development Fund of the EU (FEDER). CR was supported by Ministerio de Educacion Cultura y Deporte (Spain) through a FPU pre-doctoral fellowship [FPU15/03434]. LR-M was supported by a Xunta de Galicia predoctoral contract.

We read with great interest the publication entitled ‘EULAR definition of difficult-to-treat rheumatoid arthritis’, which sought not only to provide a uniform terminology, but also to formulate an adequate definition to classify those patients with difficult-to-treat rheumatoid arthritis (RA).1 Resolution of this issue promises to be very useful in clinical practice and in the design of studies for future research. Our group has recently published a study based on the clinical factors that could serve as possible predictors for identifying those patients with RA who are more susceptible to multiple failures to biological therapy.2 This study was designed and conducted prior to the publication of this paper establishing the definition of difficult-to-treat RA. Based on previous works published on this concept,3–8 we defined ‘multi-refractory’ patients as those who have received ≥2 biologic disease-modifying antirheumatic drugs (bDMARDs) with different mechanism of action or ≥3 bDMARDs with the same target. This definition seemed to us the most appropriate option for the classification of difficult-to-treat patients in terms of drug use. As the European League Against Rheumatism (EULAR) group of experts did, we did not include in our definition of multirefractory …

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background:CXCR5+PD-1hifollicular helper (Tfh) and CXCR5-PD-1hiperipheral helper (Tph) T cells play an important role in the pathogenesis of Rheumatoid Arthritis (RA) by providing help to autoantibody secreting B cells. Whereas Tfh cells typically dwell in the germinal centers of lymphoid organs, Tph cells accumulate at inflamed tissues. An increased frequency of Tph cells and of circulating counterparts of Tfh cells have been described in the peripheral blood of patients with seropositive RA.Objectives:To examine the effect of treatment escalation using biological agents (TNF blockers or abatacept), on the frequency of circulating Tfh (cTfh) and Tph (cTph) cells in RA.Methods:Peripheral blood was drawn from seropositive RA patients with an incomplete response to csDMARDS (n=29) who initiated biological therapy with TNF blockers (TNFb) (n= 17) or abatacept (n= 12), prescribed based on routine clinical practice. cTfh and cTph cell frequencies were determined by flow cytometry of freshly isolated PBMCs at the basal visit and 6 months after starting treatment escalation. For each patient, an age and gender-matched healthy control (HC) was also studied at both time points (n=29).Results:As compared with HC, active RA patients receiving csDMARDs demonstrated a baseline increased frequency of both cTfh and cTph cells. A significant improvement of disease activity as determined by the DAS28 score (ΔDAS28>2.0) was apparent in all of the patients 6 months after initiating biologicals. At that time point, a significant reduction of the previously elevated cTph cell frequency was observed in both treatment groups. However, cTfh cells remained elevated in patients receiving TNFb notwithstanding a good therapeutic response, whereas subjects receiving abatacept experienced a significant abatement of their cTfh cell frequency. Experimental variation of the cTfh and cTph cell numbers in HC was minimal.Conclusion:Abatacept but not TNFb, are able to bring down cTfh cell numbers in RA. This indicates that costimulation blockade can help attain an immunological remission, whereas TNF neutralization may allow a persistent pathogenic germinal center overactivity. At the same time, treatment with both abatacept and TNF blockers results in a downmodulation of the previouly elevated cTph cell numbers, in parallel with the remitting local joint inflammation.References:[1]Simpson N et al, Arthritis Rheum 2010; Craft J, Nat Rev Rheumatol 2012; Arroyo-Villa I et al., Arthritis Res Ther 2014; Rao DA et al., Nature 2017.Disclosure of Interests:Paula Fortea-Gordo Grant/research support from: BMS, Diana Peiteado: None declared, Alejandro Villalba: None declared, Maria-Jose Santos-Bornez Grant/research support from: BMS, Laura Nuño: None declared, Irene Monjo: None declared, Alejandro Balsa Grant/research support from: BMS, Roche, Consultant of: AbbVie, Gilead, Lilly, Pfizer, UCB, Sanofi, Sandoz, Speakers bureau: AbbVie, Lilly, Sanofi, Novartis, Pfizer, UCB, Roche, Nordic, Sandoz, Maria-Eugenia Miranda-Carus Grant/research support from: BMS, Roche

Background:The protagonism of regulatory B cells seems to vary along the course of the disease in murine models of inflammatory conditions. Decreased numbers of circulating regulatory CD19+CD24hiCD38hi transitional B cells (cTrB) have been described in patients with longstanding RA.Objectives:To examine the frequency and evolution of cTrB cells in the peripheral blood of early RA (ERA) patients.Methods:Freshly isolated PBMCs from 48 steroid and DMARD-naïve ERA patients with a disease duration below 24 weeks and 48 healthy controls (HC) were examined by flow cytometry. Cocultures of isolated memory B cells were established with autologous T cells, in the absence or presence of TrB cells.Results:As compared with HC, ERA patients demonstrated an increased frequency of cTrB cells. cTrBs of ERA and HC displayed an anti-inflammatory cytokine profile and were able to downregulate T cell IFNγ and IL-21 production, together with ACPA secretion in autologous B/T cell cocultures. Basal frequencies of cTrBs above the median value observed in HC were associated with a good EULAR response to MTX at 12 months (RR=2.91; 95% CI, 1.37-6.47). A significant reduction of cTrBs was observed 12 months after initiating MTX, when the cTrB cell frequency was no longer elevated but decreased, and this was independent of the degree of clinical response or the intake of prednisone.Conclusion:An increased frequency of regulatory cTrB cells is apparent in untreated ERA, and the baseline cTrB cell frequency is associated with the clinical response to MTX at 12 months.References:[1]Matsushita T, et al. J Clin Invest. 2008;118:342. Flores-Borja F, et al. Sci Transl Med. 2013;5:173ra23.Disclosure of Interests:Paula Fortea-Gordo Grant/research support from: BMS, Alejandro Villalba: None declared, Laura Nuño: None declared, Maria-Jose Santos-Bornez Grant/research support from: BMS, Diana Peiteado: None declared, Irene Monjo: None declared, Amaya Puig-Kröger: None declared, Paloma Sanchez-Mateos: None declared, Emilio Martín-Mola Grant/research support from: BMS, Roche, Alejandro Balsa Grant/research support from: BMS, Roche, Consultant of: AbbVie, Gilead, Lilly, Pfizer, UCB, Sanofi, Sandoz, Speakers bureau: AbbVie, Lilly, Sanofi, Novartis, Pfizer, UCB, Roche, Nordic, Sandoz, Maria-Eugenia Miranda-Carus Grant/research support from: BMS, Roche

Background Early treatment of rheumatoid arthritis (RA) improves longterm outcomes(1). However, at the beginning of the disease, some patients with RA fall within undifferentiated arthritis (UA) patients. Several studies have shown that almost half of patients with UA may experience spontaneous remission(2). So, in order to prevent overtreatment and poor outcomes, the identification of predictors of RA development is desirable. Objectives To determine the frequency of patients with UA evolving into RA after 2 years of follow-up and the factors contributing to predict this outcome. Methods A prospective analysis of an early arthritis cohort of 1377 patients from 1993 to 2017 was undertaken. For this study, 2 years follow-up data of patients who presented with UA were analysed. A detailed baseline assessment was completed including clinical features, physical examination and laboratory tests. Patients were stratified in two groups based on progression to RA (according to physician’s diagnosis) or to another disease (non-RA). First, differences between groups were tested using chi-squared and Student-t tests in the univariate analysis. Second, multivariate logistic regression models were employed to investigate the association between possible predictive factors and RA development. Results A total of 471 UA patients were included for analysis. Mean age was 48.7±17.5 years, 352 (74.9%) were females, and mean symptoms duration was 13.9±13.9 weeks. After 2 years of follow-up, 93 (19.7%) of UA patients evolved into RA. Meanwhile, 175 (37.2%) remained undifferentiated and 203 (43.1%) developed into other musculoskeletal diseases. In the univariate analysis, the presence of rheumatoid factor (RF) and anti-citrullinated peptides antibodies (ACPA), tender and swollen joint count, duration of morning stiffness, smoking, symmetry and ESR values were significantly associated with RA development. In the multivariate analysis, RF (OR=5,899; 95% CI 1,795–19,382), ACPA (OR=123,238; 95% CI 29,353–517,410) and swollen joint count (OR=1,233; 95% CI 1,048–1,450), remained significantly associated with RA development (table 1). Conclusions Approximately, 1 out of 5 patients with UA evolves into RA after 2 years of follow-up. Swollen joint count, and the presence of rheumatoid factor (RF) and anti-citrullinated peptides antibodies (ACPA) are independent predictors for the development of RA, supporting the early DMARDs initiation in such patients. References [1] Lard LR, Visser H, Speyer I, vander Horst-Bruinsma IE, Zwind- erman AH, Breedveld FC, et al. Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med2001;111:446–51. [2] Olivieri I, Sarzi-Puttini P, Bugatti S, Atzeni F, d’Angelo S, Caporali R. Early treatment in early undifferentiated arthritis. Autoimmun Rev2012;11:589–92. Disclosure of Interest None declared

Background A novel population of CD4 +T cells with B cell helping capacity has been described in the synovial tissues and peripheral blood of seropositive RA patients with an established disease, and termed ‘peripheral helper’ (Tph) cells. (Rao DA et al, Nature 2017) Tph cells are characterised by the lack of CXCR5 together with a bright expression of PD-1 (CD4 +CXCR5-PD-1hi T cells). As opposed to CD4 +CXCR5+PD-1hi follicular helper T cells (Tfh), Tph cells are not located in lymphoid organs but accumulate in inflamed tissues. Tph cell numbers have not been previously examined in early RA (eRA). Objectives To study the frequency of circulating CD3 +CD4+CXCR5-PD-1hi Tph cells (cTph), in patients with eRA. Methods Peripheral blood was drawn from DMARD-naive early RA patients (eRA) (2010 ACR criteria) with a disease duration 2 years), 45 patients with Spondyloarthritis (SpA), and their age and gender-matched HC (one HC per patient). In addition, synovial fluid from 7 patients with established RA and 3 patients with SpA was examined. Established RA patients were receiving low-dose oral methotrexate and were naive for biological agents. SpA patients were receiving NSAIDs, low-dose oral methotrexate and/or sulphasalazine and were naive for biologicals. After isolation by Ficoll-Hypaque gradient, PBMCs were stained with antibodies to CD3, CD4, CXCR5, ICOS and PD-1, and examined by flow cytometry. Results The frequency of circulating CXCR5- cells gated for CD4 +T cells was not different among the studied groups. In contrast, eRA patients demonstrated an increased frequency of circulating CD4 +CXCR5-PD-1hi Tph and CD4 +CXCR5-PD-1hiICOS+ T cells. When examining seropositive (RF +and/or ACPA+, n=25) and seronegative eRA patients (RF- and ACPA-, n=17) separately, it was evident that the above described alterations were only apparent in seropositive eRA. Likewise, increased cTph numbers were observed in seropositive (n=47) but not seronegative (n=19) established RA, and not in SpA patients (n=45), which is consistent with data reported by Rao et al. Interestingly, this increased cTph cell frequency was observed only in seropositive RA patients with an active disease (DAS28 >2.6, n=24), whereas the numbers of cTph cells in established RA patients who had achieved remission (DAS28 Conclusions Tph cells may play an important role in the pathogenesis of seropositive but not seronegative RA. An increased cTph cell frequency is a marker of active, seropositive RA. Reference [1] Rao DA, et al. Nature2017;542(7639):110–114. Disclosure of Interest None declared

Background Patients with psoriatic arthritis (PsA) may have predominant axial (axPsA) or peripheral (pPsA) manifestations. The development of TNF inhibitors (TNFi) has changed the course of PsA. However, most published data is focused on pPsA but almost no data is available for TNFi response in axPsA. Objectives to analyse the efficacy and the predictive factors of clinical response in patients with axPsA and pPsA starting treatment with TNFi in clinical practice. Methods An observational study analysing data from a prospective cohort including 93 patients (pts) with axPsA or pPsA treated with TNFi from 2002–2018 was conducted. Demographic information, disease activity indexes (ASDAS for axPsA and DAS28 for pPsA) and laboratory tests were collected before starting TNFi (baseline visit) and 6 months later (6 m visit). At 6 m, the percentage of pts achieving inactive disease (ASDAS 1.1 or delta-DAS28 >1.2) were determined. Baseline predictor factors of inactive disease/remission and clinical improvement at 6 m were identified using a univariable and multivariable binary regression models adjusted for confounder factors. Results Out of 93 included pts, 45 pts had predominant axPsA and 48 pPsA. Administered TNFi was etanercept for most pts (42%), infliximab in 29%, adalimumab in 22% and golimumab in 7%. Baseline characteristics are shown in table 1. Male sex was more frequent in axPsA vs pPsA (62% vs 42%; p=0.04, respectively). In axPsA, 55% clinically improved and 32% pts achieved inactive disease. After multivariable analysis, male gender (OR 25.8, p=0.01) and higher baseline ASDAS (OR 6.3, p=0.01) were associated as independent predictors of clinical improvement at 6 m. Also, male gender (OR 15.7, p=0.03) and lower BMI (OR 0.7, p=0.03) were associated as independent predictor factors for achieving inactive disease. In pPsA, 48% pts clinically improved and 33% pts were on remission at 6 m. The percentage of pts on remission tended to be higher in males than females (47% vs 20%; p=0.08, respectively). However, after running the regression analyses, none of the baseline predictor factors was significantly associated neither with clinical improvement nor with remission in patients with pPsA. Conclusions In clinical practice, 1 out of 3 pts with PsA is on remission 6 m after initiating a TNFi, and 1 out of 2 clinically improve; both proportions are similar for axPsA and pPsA. Male gender, higher baseline disease activity and lower BMI are associated with more probability to achieve inactive disease or an important clinical improvement in axPsA. Disclosure of Interest None declared

Background There are many pathologies and drugs that favour the development of Osteoporosis (OP). Although the prevalence of this secondary OP is very high, sometimes assuming a high risk of fracture, it remains an underdiagnosed and undertreated pathology. Objectives To assess the characteristics of the patients and bone metabolic pathology referred to a secondary OP consultation. Methods In order to optimise the management of bone metabolic pathology associated with Rheumatoid Arthritis (RA) and other inflammatory articular diseases, an inflammatory op consultation was founded in april/2012. Faced with the growing demand from other medical specialities, it became a secondary OP Consultation in 2014, 2 days per week. Sociodemographic, clinical, biochemical and densitometric data were collected. Results 418 patients with a mean age of 58.7±11.3 years were evaluated, 78.9% were women, 15.4% premenopausal. 57.4% of patients had densitometric OP and 25.8% Osteopenia. 22.4% had a fragility fracture (60.6% vertebral, 26.5% peripheral, 1.1% hip, 8.5% peripheral/vertebral). Vitamin D level was deficient in 71% of patients. The most frequent medical specialities who referred patients to our consultation were Rheumatology (18.9% from early RA Unit and 18.2% from Consultation or Rheumatol. Day Hospital), Gynaecology (12.7%) and Neumology (11.2%). But also, there were patient from Oncology, Endocrinology, Nephrology, Haematology and several more medical specialities. The most frequent underlying diseases were: breast cancer (22.5%, 77.6% in treatment with aromatase inhibitors, early RA (12.4%) and pulmonary disease (11.5%), 41.6% of them were sarcoidosis, other diseases are shown in table 1. The glucocorticoid-induced OP represented 30.1% of the sample, with a main age of 60.2±11.4 years, being 73% women, 20.6% premenopausal. The most frequent reasons for the use of corticosteroids were: early RA and pulmonary disease (23% respectively), rheumatic diseases (autoimmune dis.(13.5%), established RA (12%), other inflammatory articular disease(7.9%)), multifactorial (8.7%), haematological conditions and kidney transplantation(4% respectively). 42.8% of these patients had densitometric OP and 29.3% osteopenia We found 33 fragility fractures (26.1% of patients), 25 were vertebral (75.7%), peripheral 5 (15.1%) and 3 (9.1%)vertebral and peripheral. In 21.2% of cases, these fractures presented with BMD in the osteopenic range and in 6% with a normal BMD. Conclusions There are multiple processes that can associate bone metabolic pathology or a secondary OP, with a high prevalence of fragility fracture in these patients, being the rheumatologist a reference for the management of this comorbidity. A monographic consultation of secondary OP has been useful for other medical specialties and to optimise the management of OP associated with inflammatory/autoimmune diseases in Rheumatology Disclosure of Interest None declared

Background In patients with axial spondyloarthritis (axSpA), the use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), such as methotrexate (MTX) and sulfasalazine (SSZ), as well as the body mass index (BMI) have been associated with circulating TNFi levels. Recently, BMI has also been associated with TNFi clinical response but csDMARDs have not shown any significant clinical improvement for axial manifestations1. However, no study has assessed in the same population the influence of both factors -csDMARDs and BMI- on drug serum levels and clinical response Objectives To investigate the influence of csDMARD and BMI on circulating drug levels and clinical response to TNFi therapy in axSpA patients Methods A 1 year follow-up prospective observational study with two cohorts (Madrid and Amsterdam) including 180 axSpA patients treated with standard doses of infliximab (41%) or adalimumab (59%). Laboratory and clinical parameters were collected every 6 months. Patients were stratified by BMI: normal-weight (18.5–24.9 kg/m2) and overweight-obesity (>25.0 kg/m2). TNFi trough levels were measured by capture ELISA2. Clinical response to TNFi was defined as ▵BASDAI ≥2. The association between concomitant csDMARDs and BMI with drug levels and clinical response to TNFi at 1 year was analysed through multivariate log-regression models (odds ratio and 95% CI). The presence of significant interactions between covariates was tested and all models were adjusted for age, gender, HLA-B27, disease duration, TNFi-type (for drug levels) and baseline BASDAI and CRP (for clinical response) Results Seventy-nine out of 180 patients (44%) received concomitant csDMARDs (MTX 14%, SSZ 20% and MTX +SSZ 10%), 78 (43%) patients were normal-weight and 102 (57%) overweight-obese. Mean (SD) age and disease duration was 47(13) and 11(9) years respectively, 59% were males, 73% HLA-B27 +and 78% had r-axSpA. Concomitant csDMARDs (OR: 3.82; IC 95%: 1.06–13.84) and being overweight-obese (OR: 18.38; IC 95%: 2.24–150.63) were independently associated with serum TNFi drug presence. Furthermore, a significant interaction between csDMARDs and BMI with clinical response was found. While the use of concomitant csDMARD contributed positively to achieve clinical response in overweight-obese patients (OR: 7.86; IC 95%: 2.39–25.78), no association was found for normal-weight patients (OR: 1.10; 0.33–3.58). Additionally, sensitivity analysis using remission status and ASDAS were performed and showed results along the same line Conclusions In patients with axSpA, TNFi drug persistence is positively influenced by the use of concomitant csDMARDs and especially by being normal-weight. However, TNFi clinical response is associated with the use of concomitant csDMARDs only in overweight-obese, but not in normal-weight patients. Based on this, the use of concomitant csDMARDs in patients with axSpA could be beneficial in overweight patients References [1] van der Heijde D, et al. Ann Rheum Dis. 2017;76(6):978–991. [2] Pascual- Salcedo D, et al. Rheumatology (Oxford). 2011;50(8):1445–52. Disclosure of Interest None declared

Background Factors contributing to an early referral to Rheumatologist and DMARDs initiation following symptom onset in rheumatoid arthritis (RA) patients are unclear. Recent data suggest that ACPA/RF double seropositivity is associated with delayed presentation to primary care and DMARDs initiation. Identification of these factors is mandatory to faciliate an early diagnosis and treatment of RA patients. Objectives To determine whether time to DMARDs initiation and time to first visit at early arthritis clinic (EAC) following symptoms onset differs between RA patients according to autoantibody status. Methods A prospective analysis of an EAC cohort including 1377 referred patients from 1993 to 2017 was undertaken for this study. Patients diagnosed of RA (according to physician’s diagnosis) were selected. Based on the serological status, we clasified patients in 4 groups: RF+/ACPA+, RF-/ACPA+, RF+/ACPA-, RF-/ACPA-. A baseline clinical assessment was completed including time (months) from symptoms onset to first assessment at EAC and to DMARD initiation. First, differences between serotypes were tested using chi-squared and student-t tests. Second, univariable and multivariable logistic regression models taking into account confounding factors (age, smoking and baseline DAS28)were employed to evaluate the association between autoantibody status and both periods: time to first visit at EAC and to DMARDs initiation. Results A total of 463 RA patients were included for analysis, of whom 292 (63.1%) were RF/ACPA double-seropositive (RF+/ACPA+),35 (7.6%)RF-/ACPA+,39 (8.4%) RF+/ACPA- and 92 (19.9%)RF-/ACPA-. Demographic and clinical data are shown in table 1. In the univariate analysis, statiscally significant differences were observed for both periods when patients were stratified by autoantibody serotype, where RF+/ACPA +individuals experienced the longer delay to presentation at EAC compared with RF-/ACPA- (5.0±4.6 vs 3.5±3.4 months;p Conclusions In our EAC cohort, time to EAC presentation and DMARD initiation following symptom onset in early RA does not differ according to patients’ autoantibody status. However, more studies with greater sample size are necessary to confirm these results. Disclosure of Interest None declared

Background Calprotectin (CLP) is an important proinflammatory factor of innate immunity released from activated granulocytes and macrophages during inflammation, which has also been identified in synovial fluid. It is a potential pro-inflammatory biomarker reflecting joint damage. CLP levels in synovial fluid are well correlated with levels in plasma, which allows measuring it easily in patients with rheumatoid arthritis (RA). However, the additional value of CLP over other biomarkers is unclear Objectives To study the association of baseline CLP serum levels with the clinical response and serum drug levels in patients under biological therapy at 6 and 12 months after starting treatment. Methods Prospective observational study including 109 patients with RA who started biological treatment (Infliximab(Ifx);Adalimumab(Ada);Etanercept(Etn);Certolizumab(Ctz);Golimumab(Glm); Tocilizumab(Tcz) and Rituximab(Rtx) in a tertiary hospital since 1999 to 2016. Serum CLP levels were measured by ELISA with the commercial kit CALPROLAB (Lysaker, Norway). Levels of biological drug and ADA were measured by capture and bridging ELISA respectively, except Certolizumab which was measured by Sanquin Diagnostic Service. Clinical response was assessed by ΔDAS28. Serological and clinical parameters were evaluated at baseline, 6 and 12 months. For analysis, linear regression models adjusted for confounders (age, sex, BMI, DMARDs, smoking status) and with standardised beta as estimate were employed. Results Out of 109 studied patients, 22% patients received Ifx, 6% Ada, 16% Etn, 18% Ctz, 5% Glm, 25% Tcz and 9% Rtx. Most patients were woman (84%), with a median (IQR) age of 62 (52.3–73.1) and disease duration of 9.5 (4.8–15.3). At baseline, CLP levels directly correlated well with CRP and DAS28(r=0.411;p Conclusions In patients with RA initiating biological therapy, baseline CLP concentrations are inversely correlated with the circulating drug levels along the treatment. However, the additional value of CLP as a predictor of clinical response remains unclear. Acknowledgements This work has been supported by a SORCOM grant at 2016 Disclosure of Interest None declared

Background It has become increasingly clear that appropriate initial management of rheumatoid arthritis (RA) increases the chances of success and improves long-term prognosis. Therefore, rheumatologists need prognostic biomarkers to select patients requiring aggressive management. It is possible that anti-carbamylated protein antibodies (anti-CarPA) may serve as such biomarkers because they are associated with erosions and their progression, and with mortality in some studies. Recently, the possibility that they are also associated with disease activity in early arthritis (EA) has been examined by several studies with discordant results. Objectives We aimed to explore the relationship between variation in disease activity and anti-CarPA in EA patients. Methods EA patients from two prospective clinics, Hospital Universitario La Paz (n=492) and Hospital Universitario La Princesa (n=501), were included. DAS28 was available at baseline and at months 6 (M6), 12 (M12) and 24 (M24) of follow-up. Anti-CarPA were determined in baseline serum samples by ELISA using in vitro carbamylated fetal calf serum. Student t test and main effects general linear regression were used for analysis. Results The 27.4% of EA patients that were positive for anti-CarPA showed higher DAS28 at baseline than the negative patients (4.93 vs 4.31, p=1.6x10– 8 ). The difference persisted at all visits during follow-up (3.60 vs 3.19 at M6; 3.47 vs 3.09 at M12; and 3.31 vs 2.79 at M24; all with p≤0.001). These differences were independent of patient sex and age, smoking, time since symptoms onset, the specific EA clinic and the year of onset. In addition, they persisted after accounting for the presence of RF or ACPA at baseline (p=1.3x10– 5 , and p=5.7x10– 5 , respectively) and at later visits (p Conclusions Anti-CarPA were associated with high disease activity at presentation and with less improvement in the first 6 months of follow-up in EA patients. These results reinforce the possibility that anti-CarPA could be useful in the clinic as prognostic biomarkers. Acknowledgements Supported by grants PI14/01651 and RD16/0012/0014,/0011,/0012 of the Instituto de Salud Carlos III (Spain) that are partially financed by the ERDF Disclosure of Interest None declared

Background In patients with rheumatoid arthritis (RA), low disease activity (DA) overtime is associated with favourable outcomes. However, the progression of the disease is faster during the first years. Therefore, it is desirable to identify patients with a high probability of sustained DA in an early stage. Objectives To identify clinical predictor factors at diagnosis associated with sustained DA after 12 months of follow up in patients with early RA. Methods Baseline (at diagnosis) and 12 months follow-up data from an early arthritis clinic was analysed. At both visits, demographic, clinical, laboratory and treatment data were collected and clinical DA was assessed using DAS28 and SDAI. For this study, patients with RA according to physician’s diagnosis were selected. Sustained DA at 12 months was defined as DAS28 >3.2 and SDAI>11. Univariate and multivariable logistic regression models were employed to identify which factors are associated with sustained DA. Results In total, 566 patients were included. Out of these, 75.8% were women, 74.7% Caucasian, 77.7% RF +and 65.9% ACPA+. Mean (SD) age was 5417 years and mean symptoms duration was 1615 weeks. Regarding treatment, 89.8% patients received methotrexate as first line treatment and 81.1% received glucocorticoids. At baseline, 88.8% had moderate-high DA according to DAS28 (>3.2) and 77.6% with SDAI (>11). After one year of follow-up, 34% (DAS28) and 30.9% (SDAI) remained with moderate-high DA. Univariable logistic regression analysis results are shown in table 1. Sustained DA was significantly associated with baseline index and its individual components, HAQ, and GCs used for both indexes definitions, with smoking and MTX use for DAS28 definition and RF +for SDAI definition. In the multivariable analysis, sustained DA at 12 months remained significantly associated only with baseline DAS28 (OR 1.34; p Conclusions One out of three patients with RA maintains DA 12 months after diagnosis. The predictors for this status depend on the index employed: DAS28 at baseline is the best predictor for sustained disease activity when using DAS28-definition. Conversely, positive RF, impaired functionality and the need of glucocorticoids at baseline are associated with the SDAI-definition. Disclosure of Interest None declared

Background Inflammatory arthritis have a period of subclinical disease before the development of synovitis. It is necessary to know adequately the characteristics of this period to identify serological/imaging markers that recognise patients at risk of developing inflammatory arthritis. Objectives To describe the clinical characteristics and ultrasound (US) findings in ”pre-arthritis” phases. To investigate the association of the US parameters with clinical or laboratory parameters. Methods Prospective longitudinal study of a cohort of patients with suspicious joint pain (predominance in nights or mornings, improving at day or with movement, or with morning stiffness >30′) of less than 1 year of evolution and involvement of at least one small joint of hands or feet. Patients with clear synovitis, previously treated with DMARDs/steroids, or those with a diagnosis of fibromyalgia or osteoarthritis were excluded. The number of painful and swollen joints (PJC, SJC) and laboratory parameters were evaluated. A blind and extensive ultrasound examination (US) was performed with a MyLabTwice (Esaote) equip with a 5–13 MHz probe for grayscale (GS) and Power Doppler (PD). We assess the presence of synovitis in GS, PD (0–3) and erosions in 36 joints (radio- Carpal, Inter-carpal, 1 st −5th MCP and IPP, 2nd −5th MTP, elbow, shoulder and knee bilaterally) and 14 tendon compartments (2nd, 4th, 6th wrist extensor tendon compartments, 3rd and 4th finger flexor tendons, posterior tibial and fibularis tendons). In addition, an overall score of EG and PD in the cohort is calculated. Statistics analysis was made by mean ±SD or median (IQR), and comparison was made by t- Student test (quantitative parameters) and non parametric test (qualitative) (p Results 20 patients were included, 95% women (60% non-smokers). Symptoms duration was 8±3 months. PJC median was 6 (RIC 2–9), without swollen joints in any case. ACPA and/or RF were positive in 6 patients (30%). ESR and/or RCP were elevated in 6 patients (30%). In the following 12 months, 45% of patients improved clinically, and 6 patients (30%) developed rheumatoid arthritis (RA). US results are exposed in the table 1, showing the number and percentage of patients with presence [≥1] of synovitis in GS, PD and erosions at different locations. The mean overall PD score was significantly higher in patients who will evolve to RA (9.1±2.8 vs 2.7±1.9, p Conclusions In patients with pre-arthritis, Doppler scores were significantly higher among those with US erosions and those who evolve to RA. This results demonstrate the usefulness of US to predict the development of clinical arthritis in patients with inflammatory pain without synovitis Disclosure of Interest None declared

Background Several publications in rheumatoid arthritis (RA) have demonstrated a beneficial effect of concomitant methotrexate (MTX) use with TNF inhibitors (TNFi), mainly because of the MTX effect in reducing immunogenicity. In a previous work in the RA-La Paz cohort, we found that the concomitant use of MTX had a positive effect on the pharmacokinetics of serum TNFi levels, decreasing the immunogenicity of these drugs. Furthermore, the MTX effect was dose-dependent, being greater at high MTX dose. Currently, we investigate the effect of concomitant MTX use on the clinical response. Objectives To investigate the MTX influence on the clinical response in the RA-La Paz cohort treated with Infliximab (Ifx), Adalimumab (Ada) or Etanercept (Etn) at one year of treatment. Methods This is an observational study from a prospective cohort from the Biological Unit of the University Hospital La Paz, Madrid, Spain that analysed a total of 293 RA patients treated with Ifx (112 patients), Ada (71 patients) and Etn (110 patients). Patients were grouped according to the MTX dose: no MTX, low dose (LD: ≤12.5 mg/week), intermediate dose (ID: 15–17.5 mg/week) and high dose (HD: ≥20 mg/week). For this study, the clinical response was evaluated by DAS28-ESR and the clinical improvement byΔDAS28. Data were collected at baseline, 0.5 and 1 year of TNFi treatment. Statistical analysis was performed using GraphPad Prism 6.0 software. Results Out of 293 RA patients (pts) under TNFi treatment, 184 (71 with Ifx, 40 with Ada and 73 with Etn) were included. In this cohort, 128 (70%) pts used concomitantly MTX (91% oral administration) and 56 (30%) pts were in monotherapy. No differences in DAS28 were found at baseline between patients with or without MTX (p=0.8). After one year of treatment, pts with TNFi +MTX have a significantly lower DAS28 than patients without MTX (3.3±1.3 vs 3.9±1.1; p=0.004). When analyzing the DAS28 values in relationship to the MTX dose, statistical differences are observed with use of HD (≥20 mg/week) (3.1±1.3 with HD vs 3.9±1.1 without MTX; p=0.001) but not with intermediate (3.4±1.2 with ID vs3.9±1.1 without MTX; p=0.06) or low MTX dose (3.8±1.6 with LD vs 3.9±1.1 without MTX; p=0.4) at 1 year of therapy. Clinical improvement byΔDAS28 was higher in patients with TNFi +MTX than in patients without MTX (1.7±1.4 vs 1±1.3p=0.007). This effect was observed with all MTX doses (1.7±1.5 with HD vs 1±1.3 without MTX, p=0.01; 1.6±1.3 vs with ID 1±1.3without MTX, p=0.03; 1.8±1.3 with LD vs 1±1.3 without MTX, p=0.01). Conclusions In the RA-La Paz cohort under TNFi treatment, the concomitant use of MTX has a positive effect on the clinical activity, mainly when high dose of MTX is used. Moreover, we demonstrate a positive effect of any MTX dose on the clinical improvement at one year of treatment. Disclosure of Interest None declared

Background The treatment of Rheumatoid Arthritis (RA) has been transformed in the last decade with the introduction of biologic therapy. Nevertheless, a substantial proportion of patients (pts) are found to be primary or secondary nonresponders and will receive several biologics during the course of the disease. Evidence is lacking on the characterization of patients failing several agents and those who have adequate clinical response to their first biological treatment. Objectives To compare demographic, clinical and analytical characteristics in a cohort of RA pts who have failed treatment with at least two biological agents (“switchers”) and another cohort of RA patients showing a sustained clinical good response to their first therapy (“maintainers”). As a secondary objective, reasons for therapy discontinuation were also evaluated. Methods A total of 186 patients under biological therapy of the RA-PAZ cohort were included in this observational study. In this cohort, 63 pts were switchers and 123, maintainers. Baseline demographic data and clinical disease activity (DAS 28 -ESR), clinical improvement (delta-DAS 28) and serological data (CRP and ESR) were evaluated at baseline and sixth months after starting the first biological treatment.Serum anti-drug antibodies (ADA) were measured by bridging ELISA at the last visit available during the follow-up period under the first treatment. Reasons for discontinuation of the first therapy and the number of biologic treatments received during the course of the disease were also evaluated. Results Demographic and clinical characteristics of both groups are shown in Table 1.Mean Age (49,96±10,82 vs 53,77±12,91,p=0,046) and disease duration (6,79±6,19 vs 9,97±8,56,p=0,001) prior to biologic therapy initiation were lower in the switchers.Furthermore, a higher proportion of switchers had extraarticular manifestations in comparison to the maintainers (18/63 (28,6%) vs 16/121 (13,2%),p=0,016). Clinical activity at baseline (DAS28: 5,74±1,26 vs 5,01±1,14,p=0,01) and after 6 months of starting the first biological therapy (DAS28: 4,45±1,6 vs 3,22±1,1,p=0,001) were statistically significant higher in the switchers. At the last visit under the first biologic, there were also more ADA-positive pts in the switchers (6/25 (24%) vs 1/73 (1,4%), p=0,01).Moreover, duration under biologic treatment was higher in this group. In terms of the reason for discontinuation of the first biologic, 22,2% of pts showed primary lack of efficacy;38,1%, secondary loss of efficacy; 33,3%, adverse effects;4,8%interrupted because of other reasons and 1,6% because of remission. There was no association between reasons for discontinuation of the first therapy because of primary or secondary failure and adverse effects (3,4±0,9 vs 3,75±1,11vs 3,86±1,3, p=0,6) with the number of treatments received. Conclusions In our biologic therapy RA-PAZ cohort, we found a subgroup of younger pts, with a more systemic phenotype of the disease and a higher disease activity,who required a prompter biological therapy initiation. This subgroup of pts is more susceptible to biological treatment failures. The development of ADA after the first biological agent was also associated with the need to use more biologics. Disclosure of Interest None declared

Background IL-17-expressing FoxP3 regulatory T cells have been described, and their suppressive capacity has been questioned. An inflammatory environment seems to favor IL-17 secretion by regulatory CD4+CD25+FoxP3+ T cells. Objectives To assess the suppressive function and IL-17 producing capacity of CD4+CD25+CD127-FoxP3+ T cells in the synovial fluid of RA patients (RASFd). Methods Synovial fluid was drawn from 35 patients with established RA who were receiving methotrexate and low-dose oral prednisone. The frequency of CD4+CD25+CD127-FoxP3+ T cells was assessed by flow cytometry. Total CD4+ T cells, CD4+CD25+CD127- T reg cells and CD4+CD25- Tresp cells were isolated by Ficoll-Hypaque gradient, followed by sorting. After isolation, cells were stimulated for 5 hours with PMA+ionomycin or cultured for 5 days in flat-bottom 96-well plates coated with an anti-CD3 monoclonal antibody. Treg cell function was assessed using two different approaches: A.The regulatory function of natural proportions of Tregs was inferred by comparing the proliferative and cytokine responses of total CD4+ T cells (TCD4T) versus CD25+ depleted CD4+ T cells (CD4+CD25-T cells or Tresp cells); B. The per cell suppressor potency of Tregs was assessed in cocultures of isolated Tregs with Tresp, established at different Treg/Tresp ratios. Proliferation was determined by 3Hthymidine incorporation and CFSE dilution; cytokine secretion was measured by ELISA of culture supernatants. Results A high proportion of CD4+CD25+CD127- T cells was present in RASFd (mean ± SD, 21.1%±6.2), which is significantly higher than reported frequencies of this cell population in the peripheral blood of both RA and healthy subjects. These RASFd CD4+CD25+CD127- T cells expressed FoxP3 but did not express CD69. The proliferation rate, TNFα and IFNγ secretion were significantly higher for isolated Tresp as compared with TCD4T cells, indicating that natural proportions of Treg cells present in the synovial fluid of RA are funcionally suppressive. Surprisingly, TCD4T cells secreted higher amounts of IL-17 as compared with Tresp cells, although the difference did not reach statistical significance. On a per cell basis, RAPB Tregs were potent suppressors of Tresp proliferation, TNFα and IFNγ but not of IL-17 secretion; in fact IL-17 secretion did not decrease but was enhanced in the presence of increasing proportions of Treg cells. Isolated Treg cells did not proliferate or produce cytokines when cultured alone in anti-CD3 coated plates. However, in the presence of plate-bound anti-CD3 plus anti-CD28 and recombinant human IL-2, isolated Treg cells secreted significant amounts of IL-17 whereas no TNFα or IFNγ could be detected in supernatants. Conclusions CD4+CD27+CD127- FoxP3+ Treg cells present in the synovial fluid of RA patients are potent suppressors of Tresp proliferation, TNFα and IFNγ secretion, and at the same time produce significant amounts of IL-17. References Voo KS, et al. Proc Natl Acad Sci U S A. 2009;106:4793. Beriou G et al. Blood. 2009;113:4240. Wang T, et al. Ann Rheum Dis. 2015;74:1293. Komatsu N, et al. Nat Med. 2014;20:62. Yang BH, et al. Mucosal Immunol. 2016;9:444. Disclosure of Interest None declared

Background Biologic therapy has been a major change in Rheumatoid Arthritis (RA) prognosis, but around 40% of patients (pts) fail to respond. Part of this treatment failure can be explained by the development of anti-drug antibodies (ADA), but the ADA-associated secondary inefficacies rate is currently unclear Objectives To assess in our AR cohort treated with Adalimumab (Ada), Infliximab (Ifx), etanercept (Etn), certolizumab (Czp), Tocilizumab (Tcz) and Abatacept (Abt) as 1st biologic agent, the frequency of drug suspension as well as the main causes for discontinuation and the secondary inefficacy rate associated with the development of immunogenicity Methods From the RA cohort that initiated their 1st biologic agent at Hospital La Paz between 2005 and 2016, only those who had suspended those drugs were included, and causes for suspension were collected. Clinical activity was measured by DAS28 and Delta-DAS28 at 6 months of treatment to classify discontinuation by primary or secondary inefficacy. Drug levels (DL) and/or ADA were also measured by ELISA at 6 months since initiating the biologic agent in 43 pts and at drug discontinuation in 59 pts. Primary inefficacy was defined as DAS28>3.2 and delta-DAS28 3.2 plus delta-DAS28 1.2 or DAS28 Results From the 246 pts who started their first biologic therapy, 144 (58%) pts who had definitively discontinued were included. [Ifx (n 35, 24%), Ada (n 40, 28%), Etn (n 30, 21%), Czp (n 23, 16%), Tcz (n 10, 7%) y Abt (n 6, 4%)]. 116 (80,6%) were women. The mean age was 56.3±14.7 years. The mean time of biologic was 2.23±1.96 years. From the global cohort, 18 (12.5%) drop out the treatment due to primary inefficacy, 41 (28.5%) to secondary inefficacy, 57 (39.6%) to adverse effects (AE), 11 (7.6%) to remission and 17 (11.8%) to other causes (surgery, pregnancy, etc.). 12.5% pts who discontinued due to AE or other causes had also a primary or secondary inefficacy; by including those pts in these last causes for suspension, a total of 20 pts (14%) failed due to primary inefficacy and 57 pts (39.6%) to secondary inefficacy. The most frequent AEs were: infections (35%), cutaneous AEs (psoriasis, rash, etc. (10.5%), infusion reactions (9%) and neoplasia (9%). Of the 59 pts who had DL/ADA measured at drug discontinuation, 42.4% were ADA +. Within the group that failed due to secondary inefficacy and had DL/ADA determined, 50% were ADA+; nevertheless this rate was smaller in suspensions due to other causes. Likewise, in the ADA+ pts, 73% suspended due to secondary inefficacy Conclusions In our RA cohort, adverse effects were the main cause for discontinuation, with infections at 1st place. The 2nd cause conditioning interruption was the secondary inefficacy, in which 50% of our pts were ADA+ at drug discontinuation. These data suggest that the development of ADA is a frequent cause of secondary inefficacy in our RA pts Disclosure of Interest None declared

Background There is currently no consensus on selecting a therapeutic target in patients (pts) non-responsive to their first TNF-inhibitors (TNF-i). The development of anti-drug antibodies (ADA) is a frequent cause of secondary inefficacy in our pts with TNF-i and there is evidence that those who develop ADA at their 1st TNF-i achieve a higher degree of response to the second one, compared to ADA- pts. Thus ADA measurement can help in choosing a therapeutic target in pts who failed to respond to their 1st TNF-i Objectives To assess if development of ADA to the 1st TNF-i determines better response when switching to a 2nd TNF-i versus a nonTNF-i. As secondary objective, analyze whether the presence or absence of ADA to a 1st TNF-i influences the efficacy of a 2nd TNF-i Methods Of a total of 144 pts that switched from infliximab or Adalimumab to a 2nd biologic agent (Etanercept, Rituximab, Tocilizumab, Adalimumab, Abatacept, Certolizumab and Infliximab), only 60, who had measured drug levels (DL)/ADA at discontinuation of the 1st TNF-I, were included. Clinical response was evaluated with DAS28, Delta-DAS28 (ΔDAS28) and EULAR response (E-resp) at 6 (v-6) and 12 (v-12) months after initiating 2nd biologic agent and at the last visit prior to drug discontinuation or ending of the study for those who did not interrupt the biological therapy (v-end). DL/ADA levels were measured by ELISA. Statistical analysis was performed using SPSS version 20.0 Results Within the 60 pts who had measured DL/ADA at suspension of the 1st TNF-i, 26 (43%) were ADA- (i.e. DL +). In this ADA- subpopulation, 50% changed to a 2nd TNF-i; at v-6 there were no differences between switchers to a 2nd TNF-i and switchers to a nonTNF-i in DAS28 (3.7±2.1 TNF-i vs 4.2±1.1 nonTNF-i, p=0.286), ΔDAS28 (1,4±2 TNF-i, 1±1,2 nonTNF-i, p=0,374) and resp-E (75% good/moderate resp in TNF-I, 40% in nonTNF-i, p=0,064). At v-12, switchers to a 2nd TNF-i showed a lower DAS28 (2.5±0.6 TNF-i, 3.9±0.9 nonTNF-i, p=0.009) and a higher good E-resp rate with a marginally significant difference (80% in TNF-i, 22% in nonTNF-i, p=0.071). However, at v-end, pts with a 2nd nonTNF-i had better response (DAS28 >5,1 in 50% of TNF-i pts, 0% of nonTNF-i, p=0.044). Likewise ΔDAS28 at v-end was higher in the nonTNF-i group with trend to significance (0,7±1,7 TNF-i, 1,7±0,8 nonTNF-i, p=0,06). Along these lines, the good/moderate E-resp rate was higher in switchers to a nonTNF-i (70% in TNF-i, 8.3% in nonTNF-i, p=0.006). In ADA+ subpopulation (n=34), no differences were found in clinical response at v-end in DAS28 (3.7±1.2 TNF-i, 3.9±1.1 non-TNF-i, p=0.64), ΔDAS28 (0,63±1,6 in TNF-i, 1,4±1,4 in nonTNF-i, p=0,35) and good/moderate E-resp rate (30% in TNF-i, 91% in nonTNF-i, p=0,703). In pts who changed to a 2nd TNF-i, those with ADA to 1st TNF-i had a higher good response rate than ADA- pts (65% in ADA +, 30% in ADA-, p=0.07) Conclusions The development of ADA to the first TNF-i entails a better response when switching to a 2nd TNF-i, with a similar efficacy to the pts who switched to a nonTNF-i. In those pts who did not develop immunogenicity to the 1st TNF-I, there is a better response when changing therapeutic target. The ADA measurement can help to select the pts who can benefit from a 2nd TNF-i Disclosure of Interest None declared

Background There are many biological therapies for Rheumatoid Arthritis (RA) with different mechanisms of action and good efficacy rate; however, up to 40% of patients (pts) fail to respond to the 1st biologic agent, and it is still not clear what strategy to follow after showing inadequate response to tumor necrosis factor α inhibitors (TNF-i) Objectives To assess the clinical response and survival (SVV), in our cohort of RA pts that discontinued the 1st TNF-i, of a 2nd TNF-i vs a nonTNF-i, both in the global cohort and in the subpopulation that dropped out the 1st TNF-I due to inefficacy Methods This observational study included 110 pts in the RA-Paz cohort who previously suspended Ifx (68%) or Ada (32%) between 1999–2016. Two groups were established as they switched to a TNF-i or nonTNF-i. Clinical response was evaluated by DAS28, Delta-DAS28 (ΔDAS28) and EULAR response (E-resp). The assessments were performed at 6 (v-6) and 12 months (v-12) since initiating 2nd biological agent and during the last visit prior to drug discontinuation or ending of the study for those who did not interrupt the drug (v-end). Statistical analysis was performed using SPSS version 20.0 Results Of the 110 pts who had stopped Ifx or Ada as 1st TNF-i, 65% changed to a 2nd TNF-i. The 84% of the overall pts were women. The mean age was 64±14 years and the mean time of 2nd biologic drug was 3.71±3.51 years. 61% associated methotrexate at the beginning of 2nd biologic agent and 56% at the v-end, without differences between those who switched to TNF-i and those who did to nonTNF-i. At v-6 and v-12, there was no difference in ΔDAS28 [at v-6:1.3±1.4 in TNF-i and 1.2±1.2 in nonTNF-i (p=0.919), at v-12: 1.3±1.5 in TNF-I and 1.2±1.1 in nonTNF-i (p=0.852)]. In contrast, at v-end, pts with nonTNF-i showed a higher clinical improvement (ΔDAS28: 0.68±1.7 in TNF-i, 1.8±1.1 in nonTNF-i, p=0.002). At v-6, the TNF-i group achieved higher good E-resp rate (41% vs 18%, p=0.035), but there was no difference at v-12 (36% in TNF-I vs 23% in nonTNF-i, p=0.435). However, at v-end, the nonTNF-I group achieved better E-resp (good resp: 38% in nonTNF-i vs 25% in TNF-I, no resp 18% in nonTNF-i vs 50% in TNF-i, p=0.01). Likewise, 100% (n=7) of the pts that finished 2nd biologic agent by remission, had changed to a nonTNF-i (p Conclusions In our sample of RA patients who suspended Ifx/Ada as 1st TNF-i, switching to a 2nd biologic agent did not show relevant clinical differences between a TNF-i and a nonTNF-i within the 1st year of treatment. However, in the long-term, switching to a nonTNF-i shows enhanced clinical benefits with no impact on survival vis-a-vis a 2nd TNF-i. Despite the efficacy of TNF-i, new therapeutic targets are needed for those who fail to respond to these biological agents Disclosure of Interest None declared

Background The term spondyloarthritis (SpA) encompass a group of crhonic inflammatory disease with predominant axial involvement. Anti-TNF therapy (AT) has stirred up the management of these diseases. Nevertheles, according to nationwide registries of the drug continuation rate in several countries, the rate of treatment failure is considerable. Nowdays there are insufficient data to evaluate the differences between responders (Resp-AT) and non-responders (Nonresp-AT) to anti-TNF therapy. Objectives To compare the main sociodemographic, clinical and analytical features at baseline, after 6 months of treatment and at the end of the first anti-TNF therapy of responders to a first anti-TNF therapy and non-responders to several anti-TNF therapies form our cohort of patients diagnosed with SpA. We also analized the association between drug levels (DL) and antidrug antibody (ADA) in non-responders to several anti-TNF. Methods 181 patients were included, 155 (85%) kept receiving their first AT therapy (responders) and 26 (15%) had discontinued at least two different AT therapies. The main demographic features, disease activity (BASDAI, ASDAS, CRP and ESR) were measured at baseline, after 6 months (v-6) and when the first AT was discontinued. Serum drug levels and/or ADA were measured at drug discontinuation of anti-TNF treatment and last visit in non-responders and responders respectively. Results The mean age was 55.3±15 and 50±10.8 in the resp-AT and nonresp-AT groups, respectively. The demographic and clinical characteristics of both groups are shown in Table 1. At baseline, a lower BMI was observed in the resp-AT group (25.6±5 resp-AT, 28.7±5 nonresp-AT, p=0.013); 59% and 35% were in concomitant treatment with DMARDS at baseline in the resp-AT and nonresp-AT groups respectively (p=0.032); 33% of the resp-AT were in monotherapy in the last visit compared to 62% of the nonresp-AT when discontinued the 1st AT (p=0.008). There were no differences in BASDAI (5.6±2 resp-AT, 6.1±1.9 nonresp-AT, p=0.2) and ASDAS (3.3±1.1 resp-AT, 3.4±1.1 nonresp-AT, p=0.8) at baseline. In v-6, the resp-AT group had a better clinical response in terms of BASDAI (3.2±2.3 in resp-AT, 4.7±2.4 in nonresp-AT, p=0.004) and ASDAS (1.7±0.9 in resp-AT, 2.7±1.2 in nonresp-AT, p=0.00), as well as in the delta-ASDAS (ΔASDAS) (1.56±1.2 resp -AT, 0.7±0.9 nonresp-AT, p=0.04). However, delta-BASDAI (ΔBASDAI) showed no difference between the two groups (2.3±2.3 resp-AT, 1.5±1.6 nonresp-AT, p=0.1). 24% of the nonresp-AT were ADA + at drug discontinuation, while only 0.7% of the AT-resp (AT) were ADA + (p=0.00) at last visit. Conclusions In our cohort of patients with axial SpA, a significant improvement in BASDAI, ASDAS and ΔASDAS after 6 months of treatment is associated with a lower frequency of drop-out of the first AT. Moreover a lower BMI, DMARDS at baseline and absence of ADA determine a better response to AT treatment. Disclosure of Interest None declared

Background Golimumab (Glm) is a tumour necrosis factor (TNF) inhibitor used as Spondiloarthritis (SpA) treatment. There is more and more evidence of tapering therapies used in maintained low disease activity patients, avoiding overtreatments and adverse effects. Up to now, there are no studies concerning SpA patients with Glm tapering therapy and serum drug levels measured prior to tapering strategy. Objectives To analyze clinical and analytical course of SpA patients with Glm interval prolongation in SpA-Paz cohort. Associate pre-tapering Glm serum levels with flare occurrence along tapering treatment. Methods Observational prospective SpA-Paz cohort study of 22 patients treated with Glm that remained with low disease activity, so they started tapering strategy (Tap-S). We measured clinical activity with ASDAS and ΔASDAS at baseline, pre-tapering visit (v-pre)and at 6, 12, 18 and 24 months after tapering starting (v-end). All of them had a clinically important improvement determined as ΔASDAS≥191. We registered flares, defined as clinical worsening based on patient anamnesis and physical examination and on diverse activity indexes made from the beginning until the last visit. Drug serum levels in v-pre were measured by ELISA and classified following optimal concentration previously defined in our laboratory: 194 mg/L. We used the software Graph-Pad Prism 6 for statistical analysis. Results 22 of 79 patients from our cohort (28%) initiated Tap-S. The age range was between 25 and 70 years, 73% men and 27% women. 52% were non-smokers. 5 patients (23%) received another antiTNF drug previously (4 Infliximab, 1 Etanercept). All of them had a 6 months visit prior to tapering, 18 patients had 12 months visit, 8 had 18 months visit and 5 had 24 months visit. ASDAS and ΔASDAS were similar in v-pre and v-end (ASDAS: 193±094 v-pre vs 192±097 v-fin, p=093; ΔASDAS: 293±097 v-pre vs 294±099 v-end, p=096). 13 patients (59%) had 1 or 2 flares along tapering therapy. The occurrence of flare average was 14 months. In all the patients with flares, disease activity was controlled returning to previous tapering dose (4/13, 31%), to monthly schedule (6/13, 46%) or remaining tapering dose with symptomatic treatment adjustments (3/13, 23%). None of them discontinued the treatment. At v-end, ASDAS and ΔASDAS were similar between patients with and without flares along Tap-S (ASDAS v-end: 1±097 in patients without flares vs 193±097 in patients with flares, p=094, ΔASDAS v-fin: 297±097 in patients without flares vs 292±1 in patients with flares, p=093). All the patients (4/4, 100%) that were under optimal drug concentration ( Conclusions The tapering strategy in our SpA cohort treated with Glm results in similar disease activity control after 24 months of monitoring. The activity disease in patients with flares was controlled with symptomatic or biologic treatment adjustments avoiding therapy discontinuation. Flares incidence was more frequent in patients under optimal drug concentration in v-pre. Disclosure of Interest None declared

Background TNF inhibitors have become an important part of healthcare worldwide for inflammatory diseases such as RA1. Many publications show that responding patients have higher Adalimumab (Ada) serum trough levels (ATL) than non-responders. These factors are influenced by age, weight, gender or pharmacokinetics, which in turn depend on immunogenicity. Concomitant use of immunomodulators such as methotrexate (MTX) reduces immunogenicity and enhances therapy benefits1,3.Increasing drug dosage in patients with less response is the standard practice, while lowering dosage is advisable in patients achieving remission. Many recent publications2 assess serum trough levels that reflect optimal response and which could be used as benchmark for guidance to implement the Therapeutic Drug Monitoring. Objectives To establish an optimal Ada serum trough level (ATL) range in RA patients associated with good clinical response. Methods A prospective observational study with 40 RA patients under Ada treatment recruited in the Rheumatology Unit of Universitary Hospital La Paz was conducted. Demographic data, ATL and clinical activity of patients treated with 40 mg/kg every other week from 4 months up to 12 years of treatment were collected. A total of 206 samples were analyzed [χ=5 (3–13) samples/patient]. Disease activity was assessed using the DAS28 index and clinical improvement with ΔDAS28. ATL were measured with a capture ELISA3 [correlation with Promonitor (Derio, Vizcaya, Spain) k=1, r=0.91; and with Sanquin (Amsterdam, The Netherlands) k=1, r=0.86] and statistical analysis were performed with GraphPadPrism 5.0 software. Results Demographic data of our cohort were: mean age (±SD) 56.75±16.06, with 82.5% of females and 45% of patients treated with concomitant MTX. Sixty-five and 72% of patients were RF and ACPA positive, respectively. ATL were similar in patients treated with concomitant MTX (χ=3.82±2.42 μg/ml) or Ada monotherapy (χ=3.54±2.43 μg/ml) p=0.81. Consistent with previous studies1,2, low-disease activity patients (DAS28≤3.2) presented higher Ada circulating levels than patients with high-disease activity [3.7 μg/ml (IQR 2.97–5.48) vs. 1.71 μg/ml (IQR 0.23–4.51), p=0.01]. The median of Ada levels excluding the values (n=6) that showed immunogenicity was 3.42 μg/ml (IQR 1.55–5.03) where 3.50 μg/ml represented the most frequent value (15% of patients). Lack of clinical improvement (ΔDAS Conclusions ATL correlate with the disease activity and with the clinical improvement. The optimal range associated with good therapeutic response after the standard dose is 1.5–5 μg/ml. Higher circulating drug levels do not entail better response, which indicates they could be unnecessary. The knowledge of the optimal drug ranges can guide the Personalized Drug Therapy in order to maximise effectiveness and minimise costs. References Pouw, M.F., et al. ARD, 2013. Chen, D., et al. ARD, 2014. Pascual- Salcedo, D. Rheumatology (Oxford), 2011. Disclosure of Interest None declared

Classification of patients with rheumatoid arthritis (RA) as quickly as possible improves their prognosis. This reason motivates specially dedicated early arthritis (EA) clinics. Here, we have used 1062 EA patients with two years of follow-up to explore the value of anti-carbamylated protein (anti-CarP) antibodies, a new type of RA specific autoantibodies, for classification. Specifically, we aimed to determine whether the addition of anti-CarP antibodies to IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are helpful in RA classification, improves it or not. Our analysis showed that incorporation of the anti-CarP antibodies to combinations of the other two antibodies (all joint by the OR Boolean operator) produces a modest increase in sensitivity (2.2% higher), at the cost of decreased specificity (8.1% lower). The cost-benefit ratio was more favorable in the patients lacking the other autoantibodies. However, it did not improve by considering different titer levels of the anti-CarP antibodies, or after exhaustively exploring other antibody combinations. Therefore, the place in RA classification of these antibodies is questionable in the context of current treatments and biomarkers. This conclusion does not exclude their potential value for stratifying patients in joint damage, disease activity, disability, or mortality categories.