Objective. To investigate the relationship between Krebs von den Lungen 6 (KL-6) and CCL18 levels and the severity and progression of systemic sclerosis (SSc)-related interstitial lung disease (ILD).Methods. Patients enrolled in the Scleroderma Lung Study II (cyclophosphamide [CYC] versus mycophenolate mofetil [MMF]) were included. Baseline and 12-month plasma samples were analyzed by enzyme-linked immunosorbent assay to assess CCL18 and KL-6 levels. The forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLco) were measured every 3 months. Joint models were created to investigate the relationship between baseline CCL18 and KL-6 levels and the course of the FVC and DLco over 1 year according to treatment arm.Results. Baseline KL-6 and CCL18 levels each correlated with the extent of radiographic fibrosis. Levels of both CCL18 and KL-6 declined significantly at 1 year. In both treatment arms (n = 71 for CYC, n = 62 for MMF), a higher baseline KL-6 level predicted progression of ILD based on the course of FVC (P = 0.024 for CYC; P = 0.005 for MMF) and DLco (P < 0.001 for CYC; P = 0.004 for MMF) over 1 year. A higher baseline CCL18 level predicted progression of ILD based on the course of the FVC (P < 0.001 for CYC; P = 0.007 for MMF) and DLco (P = 0.001 for CYC; P < 0.001 for MMF) over 1 year, as well as mortality (P = 0.0008 for CYC arm only).Conclusion. In a rigorously conducted clinical trial for SSc-related ILD, KL-6 and CCL18 levels correlated with ILD severity and declined with immunosuppression. Patients with higher baseline KL-6 and CCL18 levels were more likely to experience disease progression despite treatment. KL-6 and CCL18 levels could be used to identify patients with a progressive ILD phenotype who may benefit from a more aggressive initial treatment approach.
Background:The presence of inflammatory signals in sacroiliac joints (SIJ), using MRI, is used for early diagnosis of axial spondyloarthritis (axSpA)[1]. Some studies also demonstrate that this inflammation can be suppressed quite dramatically by TNF-α blockers. Different scoring methods to quantify inflammatory changes in SIJ using MRI have been defined and validated: SPARCC, Leeds, Berlin, and ASSpiMRI-a. However, its use is complex and subjective. Recently Zarco et al[2] developed a method to measure bone marrow edema (BME) in MRI images from SIJ. This method, in a semiautomatic procedure, allows to measure the area affected by inflammation and the signal intensity to produce an index: the SCAISS. A simplified version, the s-SCAISS, using only a semi-coronal slide, has been proposed with good validity and reliability results.Objectives:To assess responsiveness of inflammation in SIJ of axSpA patients, treated with TNF-α inhibitors, using a novel score method: the s-SCAISS.Methods:Two rheumatologists independently quantified SIJ images from axSpA patients by three methods (s-SCAISS, SPARCC and Berlin) on a single semi-coronal MRI slide (STIR). Patients were assessed before TNF-α therapy (PRE) and 3 months later (POST). Spearman correlations was used to analyze relationship between variables, Wilcoxon signed-rank test for significant differences and Cohen’s d for calculating the effect size of improvement. Figure shows MRI images of a patient before and after treatment.Results:9 axSpA patients were recruited from the COSPAR cohort (44% female, age 47±13 years, disease duration 18±14 years, BMI 29±4). Results PRE and POST are shown in Table: mean values (sd), statistical significance (NS, not significant; *, p<0.05; **, p<0.01), and Effect Size. In the first rows, different scoring system for MRI inflammation appears: Area analyzed by s-SCAISS, s-SCAISS, Berlin and SPARCC (using only a semi-coronal slide). Activity and functional indexes were lower with significant differences and a large effect size. Correlations of s-SCAISS with Berlin (rho=0.78;p<0.05) and SPARCC (rho=0.96;p<0.001) were good; with clinical disease activity outcomes were poor, except with BASDAS (rho=0.70;p<0.05). The best correlation according improvements appeared comparing reduction of ASDAS with reduction of s-SCAISS (rho=0.57) but this difference was not significant. Although improvements in BASMI was not significant, a good correlation was found between improvement in s-SCAISS and BASMI (rho=-0.72;p<0.05).PREPOSTSignE.S.Area71.33 (66.71)20.89 (39.02)**0.86-Larges-SCAISS118.67 (114.6)27.78 (51.09)**0.98-LargeBERLIN2.33 (1.66)0.67 (1.12)**1.14-LargeSPARCC3.11 (2.26)0.78 (1.39)**1.18-LargeCRP13.1 (9.4)4.1 (3.2)**0.90-LargeBASDAI6.5 (1.7)4.4 (2.7)*0.84-LargeBASFI6.3 (2.6)4.1 (3.4)*0.69-MediumASDAS3.6 (1.0)2.3 (1.2)**1.15-LargeBASDAS3.7 (1.1)2.6 (1.3)*0.96-LargeBASMI3.6 (1.5)3.3 (1.3)NSConclusion:Different methods exist for quantifying inflammation in MRI images of SIJ in axSpA patients. According to our preliminary results, all of them had significant improvements in axSpA patients treated with anti tnf-α. The s-SCAISS index show good responsiveness, with similar features to validated indexes, but with an accuracy assessment of the BME area.References:[1]Defining active sacroiliitis on MRI for classification of axial spondyloarthritis: update by the ASAS MRI working group. Annals of the Rheumatic Diseases 2016;75:1958-1963.[2]Development and validation of SCAISS, a tool for semi-automated quantification of sacroilitis by magnetic resonance in spondyloarthritis. Rheumatol Int. 2018 Oct;38(10):1919-1926.Disclosure of Interests:Cristina Garrido-González: None declared, María del Carmen Castro Villegas: None declared, MLourdes Ladehesa Pineda: None declared, Juan L. Garrido-Castro: None declared, Rafaela Ortega Castro: None declared, Cristina Gonzalez-Navas: None declared, Pedro Zarco-Montejo Speakers bureau: Abbvie, MSD, Novartis, Pfizer., RAQUEL ALMODOVAR Speakers bureau: Abbvie, Celgene, Janssen, Lilly, Novartis, Pfizer., Angel Bueno: None declared, Luis Miguel Molinero: None declared, Eduardo Collantes Estevez Grant/research support from: ROCHE and Pfizer, Speakers bureau: ROCHE, Lilly, Bristol and Celgene
Background:The ASAS Health Index (ASAS-HI) questionnaire, a tool that measures the impact of the disease on the health in patients with Spondyloarthritis (SpA), has been recently validated. However, there are still no studies evaluating the utility of this questionnaire in daily clinical practice.Objectives:The objective of this study is to evaluate the association of ASAS-HI with disease activity, functionality, mobility, and structural damage in patients with SpA.Methods:This is an observational, cross-sectional and single-center study in which 126 consecutive patients with SpA were included. Sociodemographic data, scores related to disease activity (BASDAI and ASDAS), functionality (BASFI), structural damage (cervical, lumbar and total mSASSS), mobility (BASMI and UCOASMI), quality of life (ASAS-HI) and the presence of concomitant fibromyalgia (evaluated with the FIRST questionnaire) were obtained from all patients. The ASAS-HI questionnaire was considered as the main outcome (scale from 0 to 17). Pearson’s correlation coefficient was used to evaluate the association of the different continuous variables with each other. Student’s t-test was used to compare the ASAS-HI between different subgroups of patients (men vs. women, ASDAS>2,1 vs. ASDAS≤2,1 and fibromyalgia + vs. fibromyalgia-). Finally, a multivariate linear regression was performed to determine which factors explain the variability of ASAS-HI in these patientsResults:Among the 126 patients included, 83 (65.9%) were men, with a mean age of 45.1±12.3 years and a mean disease duration of 18.7±14.5 years. The mean ASAS-HI score in all patients was 4.7±4.0, showing a “strong” positive linear correlation (r>0.60) with BASDAI and BASFI, and “moderate” positive (r=0.40 to 0.60) with Global VAS and ASDAS (Figure 1). Patients with fibromyalgia showed a significantly higher ASAS-HI score compared with patients without fibromyalgia (9.5±3.2 vs 3.7±3.4, respectively). In addition, patients with high disease activity (ASDAS>2,1) showed a higher mean score in ASAS-HI compared with those with low activity (ASDAS≤2,1) (5.8 ± 3.8 vs 2.0 ± 2.4, p<0,001).Figure 1.Simple linear correlation (Pearson’s r) between the different variables studied.Finally, multiple linear regression showed that 57,4% (R2=0,574) of the ASAS-HI variability is explained by the presence of concomitant fibromyalgia (β = 2.23, 95%IC 0.73 to 3.80, p=0.004), BASDAI (β = 0.62, 95%IC 0.25 to 0.97, p=0.001) and BASFI (β = 0.57, 95%IC 0.26 to 0.88, p=0.001).Conclusion:In our study, the impairment of the quality of life in patients with SpA was mainly associated with a high disease activity (BASDAI), worsening functionality (BASFI) and with the presence of concomitant fibromyalgia. Neither mSASSS nor UCOASMI was associated with a change in ASAS-HI; thus, in our patients neither structural damage nor mobility seem to influence the quality of life. In a patient with a high ASAS-HI we must evaluate the presence of concomitant fibromyalgia.Acknowledgments:The authors wish to thank all patients who participated in the study.Disclosure of Interests:María Ángeles Puche Larrubia: None declared, Clementina López-Medina: None declared, María del Carmen Castro Villegas: None declared, Rafaela Ortega Castro: None declared, MLourdes Ladehesa Pineda: None declared, Pérez Sánchez Laura: None declared, Gómez García Ignacio: None declared, José Miguel Sequí-Sabater: None declared, Maria del Carmen Abalos-Aguilera: None declared, Inmaculada Concepcion Aranda-Valera: None declared, Garrido Castro Juan Luis: None declared, Alejandro Escudero Contreras Grant/research support from: ROCHE and Pfizer, Speakers bureau: ROCHE, Lilly, Bristol and Celgene., Eduardo Collantes-Estevez: 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)
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