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Objective.Tofacitinib (TOF) is the first Janus kinase (JAK) inhibitor approved for psoriatic arthritis (PsA). It has shown efficacy in patients refractory to anti–tumor necrosis factor-α in randomized controlled trials (RCTs). Our aim was to assess efficacy and safety of TOF in clinical practice.Methods.This was an observational, open-label multicenter study of PsA patients treated with TOF due to inefficacy or adverse events of previous therapies. Outcome variables were efficacy, corticosteroid dose-sparing effect, retention rate, and safety. A comparative study of clinical features between our cohort of patients and those from the OPAL Beyond trial was performed.Results.There were 87 patients (28 women/59 men), with a mean age of 52.8 ± 11.4 years. All patients were refractory to biologic disease-modifying antirheumatic drugs (DMARDs) and/or to conventional synthetic DMARDs plus apremilast. TOF was started at 5 mg twice daily after a mean follow-up of 12.3 ± 9.3 years from PsA diagnosis. At first month, Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) decreased from median 4.8 (IQR 4.1–5.4) to 3.7 (IQR 2.8–4.7,P< 0.01), Disease Activity Index for Psoriatic Arthritis from median 28 (IQR 18.4–34.1) to 15.5 (IQR 10.1–25.7,P< 0.01), and C-reactive protein from median 1.9 (IQR 0.3–5.0) to 0.5 (IQR 0.1–2.2) mg/dL (P< 0.01). Also, TOF led to a significant reduction in prednisone dose. Mild adverse effects were reported in 21 patients (24.13%), mainly gastrointestinal symptoms. TOF retention rate at Month 6 was 77% (95% CI 65.2–86.3). Patients in clinical practice were older with longer disease duration and received biologic agents more commonly than those in the OPAL Beyond trial.Conclusion.Data from clinical practice confirm that TOF seems to be effective, rapid, and relatively safe in refractory PsA despite clinical differences with patients in RCTs.

To determine the potential impact of extra-articular manifestations (EAMs) on disease characteristics and cardiovascular (CV) risk in patients with axial spondylarthritis (axSpA).This is a cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Data on the history of CV events, subclinical carotid atherosclerosis, and disease-related features, including EAMs, were collected.888 axSpA patients were recruited. Concomitant acute anterior uveitis (AAU), psoriasis (PSO), and inflammatory bowel disease (IBD) were present in 177 (19.9%), 96 (10.8%), and 57 (6.4%) patients, respectively. When compared with axSpA patients without EAMs, a significant increase in past CV events was observed in patients with PSO (9% versus 4%, p = 0.048) and in those with at least one EAM (7% versus 4%, p = 0.032) or with more than one EAM (11% versus 4%, p = 0.022). The frequency of carotid plaques and the values of cIMT were higher in patients with EAMs than in those without EAMs, although only the univariable analysis for carotid plaques in patients with PSO (39% versus 30%, p = 0.038) and for cIMT in patients with AAU (665 ± 156 µm versus 637 ± 139 µm, p = 0.042) and those with at least one EAM (661 ± 155 µm versus 637 ± 139 µm, p = 0.024) showed significant results. In addition, patients with PSO or IBD were found to have specific disease-related features, such as higher ESR at diagnosis, and more frequent use of glucocorticoids and TNF inhibitors than those without EAMs. Also, PSO patients had more commonly peripheral involvement and those with AAU more severe radiographic damage than those without EAMs. The frequency of HLA B27 was higher in patients with AAU and lower in those with PSO or IBD compared to those without EAMs.Patients with axSpA and EAMs, in addition to displaying their own disease-related features, are likely to have an increased CV risk that appears proportional to the number of EAMs and could be related to proatherogenic factors other than traditional CV risk factors, such as the inflammatory load and the use of glucocorticoids.

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease characterized by a defective adaptive immune receptor repertoire (AIRR) that fails to distinguish self from non-self antigens. The AIRR is vast, encompassing four T cell receptor (TCR) and three B cell receptor (BCR) chains, each of which displays an extraordinary amino acid sequence variability in the antigen-binding site. How the concerted action of T and B cell clones is associated with the development and clinical evolution of immune-mediated diseases is still not known. Using a new immunosequencing technology that allows the unbiased amplification of the seven receptor chains, we conducted an in-depth quantitative analysis of the seven-receptor chain variability in RA. Compared to healthy controls, the AIRR in RA was found to be characterized by a lower BCR diversity, the depletion of highly similar BCR clones, an isotype-specific signature as well as a skewed IGL chain and gene segment usage. A predictor based on quantitative multi-chain AIRR information was able to accurately predict disease, including the elusive seronegative subset of RA patients. AIRR features of the seven immune receptor chains were also different between patients with distinct clinically relevant phenotypes. Incorporating HLA variation data, we were able to identify the TCR clones that are specifically associated with the main disease risk variants. The longitudinal analysis of the AIRR revealed that treatment with Tumor Necrosis Factor (TNF) inhibitors selectively restores the diversity of B cell clones in RA patients by reducing the frequency of clones with a similar biochemical profile. The biochemical properties of the TNFi-modulated clones were also found to differ between responders and non-responders, supporting a different antigenic reactivity in the B cell compartment of these two groups of RA patients. Our comprehensive analysis of the TCR and BCR repertoire reveals a complex T and B cell architecture in RA, and provides the basis for precision medicine strategies based on the highly informative features of the adaptive immune response.

Although several randomized clinical trials and observational studies have evaluated the effectiveness, safety and drug survival of etanercept (ETN) in the treatment of psoriatic arthritis (PsA), long-term data regarding these aspects are currently scarce. For this reason, we sought to investigate the long-term survival and safety of ETN in PsA patients in 4 tertiary care Spanish hospitals over a 13-year observation period (from 2004 to 2017). The records of 85 PsA patients were reviewed. ETN showed an excellent survival profile, with rates of treatment discontinuation at 1, 3, 5 and 10 years of 15, 37, 46 and 59%, respectively. In our cohort, a trend toward longer drug survival in patients with shorter disease duration and those who were treated with ETN as their first biologic agent was observed. On the other hand, combination therapy with conventional disease-modifying antirheumatic drugs did not provide greater improvement on the long-term drug survival. Only 12% of the patients reported adverse events (AEs) during therapy, being most of them of mild to moderate intensity, and in only 7% AEs led to drug discontinuation. To the best of our knowledge, the present study shows the largest follow-up period of ETN-treated population analyzed in a real-life setting, and these results demonstrate the positive safety profile and long-term effectiveness of this biologic agent in the management of PsA patients.

Background: X-Ray sacroiliitis is the cornerstone in the diagnosis of the ankylosing spondylitis (AS). It is clear that the presence of sacroiliitis is a specific lesion in long standing aS, but little evidence exists on the reliability of this image technique in early axial spondyloarthritis (axSpA), which associates with reduced structural damage. This is relevant because some rheumatologists and pharmacological authorities feel more confident with the diagnosis of aS rather than with non radiographic axial spondyloarthritis (nr-axSpA) forms. On the other hand, according to various research studies, clinicians are subject to potential bias when interpreting radiographs, influenced by their pretest clinical judgment Objectives: The main objective of this study is to determine the reliability of X-Ray sacroiliitis in the early diagnosis of axSpA. Methods: This study included 290 radiographs of the SI joints from patients of the Esperanza early spondyloarthritis cohort. Nine readers, blinded for the diagnosis, participated in the reliability exercise, all of them experienced rheumatologists and members of the Spanish spondiloarthritis working group (GRESSER). Patients with axSpa were classified as having aS if the radiographic criteria of the modified NY criteria (presence of radiographic changes in the SIJ of at least grade II bilaterally or at least grade III unilaterally) were fulfilled. The gold standard was the categorical opinion of at least five of the expert readers. For the statistical analysis, the Chi-square and Kappa tests were performed. Results: The table shows mean kappa values and the agreement reached by each reader. The mean kappa achieved was fair (0.375, range 0.146 - 0.652) and the mean agreement was 73.7% (range: 58.7% - 90%). When the categorical opinion of X-Ray sacroiliitis of at least 5 readers as gold standard was applied, 61 patients were classified as aS and 229, as nr-axSpa. Nevertheless, this scenario varied from 31 to 138 among the readers when the x-ray evaluation was performed by only one reader. Conclusion: Reliability of X-Ray SIJ in an early SpA cohort was weak among nine experimented readers and the diagnosis of aS was subject to a high variability. At least in doubtful cases, a central evaluation performed by highly qualified readers is advisable. Disclosure of interests: Carolina Tornero: None declared, Claudia Urrego-Laurin: None declared, Maria Luz Garcia-Vivar: None declared, Cristina Fernandez-Carballido: None declared, Xavier Juanola-Roura: None declared, Jose Francisco Garcia LLorente: None declared, Maria del Carmen Castro Villegas Paid instructor for: MSD, abbvie, Pfizer, Janssen, Lilly, Roche, Beatriz Joven-Ibanez Speakers bureau: Celgene, Novartis, MSD, Pfizer, abbVie, and Janssen, Eva Galindez: None declared, Eugenio de Miguel: None declared

Background X-Ray sacroiliitis is the cornerstone in the diagnosis of the ankylosing spondylitis (AS). It is clear that the presence of sacroiliitis is a specific lesion in long standing AS, but little evidence exists on the reliability of this image technique in early axial spondyloarthritis (axSpA), which associates with reduced structural damage. This is relevant because some rheumatologists and pharmacological authorities feel more confident with the diagnosis of AS rather than with non radiographic axial spondyloarthritis (nr-axSpA) forms. On the other hand, according to various research studies, clinicians are subject to potential bias when interpreting radiographs, influenced by their pretest clinical judgment. Objectives The aim of this study is to determine the value of X-Ray sacroiliitis in the early diagnosis of axSpA. Methods This study included 290 radiographs of the SI joints from patients of the Esperanza early spondyloarthritis cohort. Nine readers, blinded for the diagnosis, participated in the reliability exercise, all of them experienced rheumatologists and members of the Spanish spondiloarthritis working group (GRESSER). Patients with axSpa were classified as having AS if the radiographic criteria of the modified NY criteria (presence of radiographic changes in the SIJ of at least grade II bilaterally or at least grade III unilaterally) were fulfilled. The gold standard was the categorical opinion of at least five of the expert readers. For the statistical analysis, the Chi-square and Kappa tests were performed. Results The radiographic diagnosis, sensitivity, specificity, likelihood ratio, grade of agreement and mean K values compared to gold standard are showed in table 1. The concordance Kappa test was highly variable among the readers, ranging from fair to excellent. The agreement with the gold standard varied from 68 to 94% and the sensitivity and specifity, from 50-100% and 64-96%, respectively. Additionally, the number of AS was 61, with an inter-reader variability rate of 31 to 138. Larger discrepancies were observed when assessing sacroiliitis grade 2. Conclusion The diagnosis of AS in early axSpa is characterized by a marked variability. At least in doubtful cases, a second central evaluation performed by highly qualified experts should be advisable. Disclosure of Interests Eugenio de Miguel: None declared, Beatriz Joven-Ibanez Speakers bureau: Celgene, Novartis, MSD, Pfizer, AbbVie, and Janssen, Eva Galindez: None declared, Claudia Urrego-Laurin: None declared, Maria Luz Garcia-Vivar: None declared, Cristina Fernandez-Carballido: None declared, Jose Francisco Garcia LLorente: None declared, Maria del Carmen Castro Villegas Paid instructor for: MSD, Abbvie, Pfizer, Janssen, Lilly, Roche, Carolina Tornero: None declared, Xavier Juanola-Roura: None declared

Background:Longitudinal studies about the change from non-radiographic axial Spondyloarthritis (nr-axSpA) to r-axSpA (radiographic axial Spondyloarthritis) are scarce but show a 9-10% progression rate over 2 years (1-2) and a 24% progression rate over 10 years in another study (3). However, in early cohorts such as DESIR, this only represents a 5% over 5 years (4).Objectives:The aim of this study was to know the rate of progression from nr-axSpA to r-axSpA over 6 years in the early Esperanza cohort.Methods:This study included 94 patients of the Spanish early spondyloarthritis (SpA) Esperanza cohort, 60 fulfilled the ASAS classification criteria for SpA. Every patient had a baseline and a six years sacroiliac X-ray. Nine readers, blinded for the diagnosis, participated in the reliability exercise, all of them experienced rheumatologists and members of the Spanish spondyloarthritis working group (GRESSER). Patients with SpA were classified as having r-axSpA, at baseline or after 6 years of follow-up, if they fulfilled the radiographic item of the modified New York criteria (mNY) (presence of radiographic changes in the sacroiliac joints -SIJ- of at least grade II bilaterally or grade III or IV unilaterally). The gold standard of SIJ X-Ray was the categorical opinion of at least five of the expert readers. For the statistical analysis, the Chi-square and Kappa tests were performed.Results:Demographic data of the SpA patients were: mean age 33.4±7.5 years; 37 (61.7%) male; mean CRP 6.4±6.5 mg/dl and ESR 10.3±10.6. Present smokers 30.6%; and past smokers 16.3%. HLA-B27 (+) 56.7%. Regarding the presence of X-Ray sacroilitis: 20 patients had baseline sacroilitis and 18 at the final visit; 11 had sacroiliitis at both baseline and final visits; 9 patients changed from baseline sacroiliitis to no-sacroiliitis and 7 changed from baseline no-sacroiliitis to sacroiliitis at the 6 year visit. The reliability of the readers was fair with a mean inter-reader kappa test of 0.375 (range 0.146 - 0.652) and a mean agreement of 73.7% (range 58.7% - 90%).Conclusion:In this group of patients with early SpA no progression from nr-axSpA to r-axSpA over 6 years was observed. It appears that early diagnosis and standard treatment seem to reduce SIJ radiographic progression.References:[1]Poddubnyy D, Rudwaleit M, Haibel H, et al. Rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial spondyloarthritis. Ann Rheum Dis 2011;70:1369–74.[2]Sampaio-Barros PD, Conde RA, Donadi EA, et al. Undifferentiated spondyloarthropathies in Brazilians: importance of HLA-B27 and the B7-CREG alleles in characterization and disease progression. J Rheumatol 2003;30:2632–7.[3]Sampaio-Barros PD, Bortoluzzo AB, Conde RA, et al. Undifferentiated spondyloarthritis: a longterm followup. J Rheumatol 2010;37:1195–9.[4]Dougados M, et al. Ann Rheum Dis 2017;76:1823–1828.Disclosure of Interests:Carolina Tornero: None declared, María del Carmen Castro Villegas: None declared, Xavier Juanola-Roura: None declared, Maria Luz García-Vivar: None declared, Cristina Fernández-Carballido Consultant of: Yes, I have received fees for scientific advice (Abbvie, Celgene, Janssen, Lilly and Novartis), Speakers bureau: Yes, I have received fees as a speaker (Abbvie, Celgene, Janssen, Lilly, MSD, Novartis), Jose Francisco Garcia LLorente: None declared, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, E. Galindez: None declared, Claudia Urrego-Laurín: None declared, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi)

Background:There are few studies focused on the development of structural damage over time in patients with early SpAObjectives:The aim of this study is to analyze the mSASSS radiographic progression of spine in patients with early spondyloarthritis (SpA) in the Esperanza cohort.Methods:In this longitudinal study, 49 patients of the Spanish early spondyloarthritis (SpA) Esperanza cohort were included. Every patient had a baseline and a six years lateral X-Ray of the cervical and lumbar of spine. The assessment of spine structural damage was done by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Nine readers, blinded for the diagnosis, participated in the reliability exercise, all of them experienced rheumatologists and members of the Spanish spondyloarthritis working group (GRESSER). The mSASSS progression and development of new syndesmophytes was analyzed. The gold standard of every elemental lesion of the mSASSS and the total mSASSS score was the agreement achieved by the independent categorical opinion of at least five of the nine readers. For reliability, intraclass correlation coefficient (ICC) two-way mixed, absolute agreement was used.Results:Forty-nine patients were included, 69 % were males and 49%, HLA B27 positive. Mean ± SD baseline ESR, CRP, BASDAI, BASFI and mSASSS were 10.7±11.7, 5.4±7.1, 3.7±2.5, 2.1±2.0 and 0.326±0.85, respectively. Inter-reader ICC reliability of the 9 readers was 0.812 (CI 95%; 0.764-0.857). The mSASSS score at the six-year visit was 0.67 ± 1.6: thirty-nine patients did not present any changes in this score at the end of the follow-up, two patients had Δ mSASSS of – 1 and eight patients, an increase in this score (four patients, +1; three patients, +2 and one patient, +9 points).At baseline, five patients presented one syndesmophyte; at the six-year visit, seven had one syndesmophyte; one patient, two syndesmophytes and another one, one bone bridge. Only 2/5 patients (40%) with syndesmophytes at baseline showed an increase in Δ mSASSS; the two patients with a Δ mSASSS of -1 did not have syndesmophytes at baseline. Five out of eight patients (62.5%) with an increase of the Δ mSASSS presented this lesion at the six-year visit but only two of them showed syndesmophytes at baseline. On the other hand, two of the three patients who showed an increase of the ΔmSASSS without syndesmophytes at baseline presented an erosion in the anterior vertebral corner and the patient with the bone bridge had a previous syndesmophyte. Our results indicate that in early SpA much of the progression appears in patients without previous syndesmophytes.Conclusion:Spinal radiographic progression was very low in our early SpA cohort, with a mean progression of 0.3 mSASSS units. Only eight patients (16.3%) presented spinal structural progression, most of them not showing syndesmophytes at baseline. It is reasonable to consider that an early diagnosis and monitoring could result in a low radiographic progression.Disclosure of Interests:Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Jose Francisco Garcia LLorente: None declared, Claudia Urrego-Laurín: None declared, Maria Luz García-Vivar: None declared, Cristina Fernández-Carballido Consultant of: Yes, I have received fees for scientific advice (Abbvie, Celgene, Janssen, Lilly and Novartis), Speakers bureau: Yes, I have received fees as a speaker (Abbvie, Celgene, Janssen, Lilly, MSD, Novartis), María del Carmen Castro Villegas: None declared, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Xavier Juanola-Roura: None declared, Carolina Tornero: None declared, E. Galindez: None declared

Background Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. Objective The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. Methods Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. Results Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (?: ?0.303, 95% confidence interval: ?0.558 to ?0.047; P = .02). Conclusions RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT. This project has been supported by an unrestricted grant from Abbvie, Spain. The design, analysis, interpretation of results, and preparation of the article have been done independently of Abbvie. Dr González-Gay's studies have been supported by grants from “Fondo de Investigaciones Sanitarias” PI06/0024, PS09/00748, and PI12/00060 and RD12/0009/0013 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain).

Background Low back pain of mechanical origin is a major cause of disability and surgical intervention. The lumbar computed tomography (CT)-guided steroid infiltration can accelerate the recovery process and sometimes avoid the surgery. Objectives Our aim was to review the indications, efficacy and complications of this technique in a wide series of unselected patients. In addition a comparative study of efficacy was performed according to the lumbar underlying pathology, type of steroid and approach of injection. Methods Study of lumbar CT-guided steroid injections performed in a University Hospital between January 2012 and June 2015. The minimum follow-up was 3 months. The procedure was performed in patients with low back pain refractory to standard medical therapy and Lumbar Spine Rehabilitation. Efficacy was assessed at 1 and 3 months according to a semiquantitative scale as the pain response as a) total response, b) partially c) no or d) worsening pain. A comparative study of the efficacy and safety was performed, regarding: a) underlying pathology, b) approach of injection and c) the different types of steroids used. Fisher9s test and χ 2 and the SAS System for Windows V program 9.2.were used for statistical analysis. Results During the study period 258 procedures were performed in 171 patients (132 men/126 women) with a mean age ± SD of 58.24±13.45 years (range, 18–88). The indications for the injection were: a) disc herniation (44.57%), b) lumbar stenosis (34.11%), c) postoperative fibrosis and spondylolisthesis (20.15%) and d) facet joint synovial cysts syndrome (1.17%). Approaches used were: a) posterior epidural (24.42%), b) lateral recess (58.91%), and c) foraminal (16.67%). The chosen steroid was triamcinolone (74.81%), dexamethasone (23.64%) and methylprednisolone (1.55%). In a significant proportion of the procedures improvement in the patient9s sintomatology was reported at the first month, regardless of the indication, route of corticosteroid injection and steroid used (TABLE). Regarding the overall outcome, at 3 months 72.48% of the patients experienced clinical improvement. And only 21.71% of patients required a subsequent surgery. The clinical efficacy showed no statistically significant differences according to the indication of the procedure or the route used for the injection. However, the improvement of pain was significantly greater in patients treated with triamcinolone than those treated with dexamethasone (p=0.01). Regarding safety there were 6 (2.3%) local complications (puncture of the thecal sac) and 3 (1.16%) systemic complications (allergic reaction). None of these complicationes were of clinical relevance and they were not associated with the corticosteroid used. Conclusions CT-guided corticosteroid injection is an effective and safe treatment in low back pain refractory to standard medical therapy in patients with spinal stenosis, disc herniation and postoperative fibrosis. Triamcinolone infiltration seems to be more effective than dexamethasone. Disclosure of Interest None declared