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Introduction: In the EXCEED head-to-head trial (NCT01752634), secukinumab (SEC) demonstrated higher simultaneous ACR50 plus PASI 100 response versus adalimumab (ADA) in patients (pts) with psoriatic arthritis (PsA) [ref:1]. We report a post-hoc analysis that investigated efficacy across various [for full text, please go to the a.m. URL]

Background To evaluate the influence of the disease activity on radiographic progression in axial spondyloarthritis (axSpA) patients treated with TNF inhibitors (TNFi). Methods The study included 101 axSpA patients from the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO), which had clinical data and radiographic assessment available. Patients were classified into 2 groups based on the duration of TNFi treatment at baseline: (i) long-term treatment (≥4 years) and (ii) no long-term treatment (< 4 years). Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. Disease activity differences between patients’ groups at each time point were assessed using a linear mixed-effect model. Results Radiographic progression was defined as an increase in ≥2 mSASSS units. At inclusion, approximately half of the patients (45.5%) were receiving long-term treatment with TNFi (≥4 years). In this group of subjects, a significant difference in averaged Ankylosing Spondylitis disease Activity Score (ASDAS) across follow-up was found between progressors and non-progressors (2.33 vs 1.76, p=0.027, respectively). In patients not under long-term TNFi treatment (54.5%) though, no significant ASDAS differences were observed between progressors and non-progressors until the third year of follow-up. Furthermore, no significant differences were found in progression status, when disease activity was measured by Bath Ankylosing spondylitis Disease Activity Index (BASDAI) and C reactive protein (CRP). Conclusions Patients on long-term TNFi treatment with a mean sustained low disease activity measures by ASDAS presented lower radiographic progression than those with active disease.

Supplemental material, sj-docx-1-tab-10.1177_1759720X221119246 for Uveitis in peripheral spondyloarthritis patients: an ancillary analysis of the ASAS-PerSpA study by Maria Llop, Jordi Gratacós, Mireia Moreno, Marta Arévalo, Joan Calvet, Maxime Dougados and Clementina López-Medina in Therapeutic Advances in Musculoskeletal Disease

Supplemental material, sj-docx-1-tab-10.1177_1759720X221119246 for Uveitis in peripheral spondyloarthritis patients: an ancillary analysis of the ASAS-PerSpA study by Maria Llop, Jordi Gratacós, Mireia Moreno, Marta Arévalo, Joan Calvet, Maxime Dougados and Clementina López-Medina in Therapeutic Advances in Musculoskeletal Disease

Background: COVID-19 pathophysiology and the predictive factors involved are not fully understood, but lymphocytes dysregulation appears to play a role. This paper aims to evaluate lymphocyte subsets in the pathophysiology of COVID-19 and as predictive factors for severe disease. Patient and methods: A prospective cohort study of patients with SARS-CoV-2 bilateral pneumonia recruited at hospital admission. Demographics, medical history, and data regarding SARS-CoV-2 infection were recorded. Patients systematically underwent complete laboratory tests, including parameters related to COVID-19 as well as lymphocyte subsets study at the time of admission. Severe disease criteria were established at admission, and patients were classified on remote follow-up according to disease evolution. Linear regression models were used to assess associations with disease evolution, and Receiver Operating Characteristic (ROC) and the corresponding Area Under the Curve (AUC) were used to evaluate predictive values. Results: Patients with critical COVID-19 showed a decrease in CD3+CD4+ T cells count compared to non-critical (278 (485 IQR) vs. 545 (322 IQR)), a decrease in median CD4+/CD8+ ratio (1.7, (1.7 IQR) vs. 3.1 (2.4 IQR)), and a decrease in median CD4+MFI (21,820 (4491 IQR) vs. 26,259 (3256 IQR)), which persisted after adjustment. CD3+CD8+ T cells count had a high correlation with time to hospital discharge (PC = −0.700 (−0.931, −0.066)). ROC curves for predictive value showed lymphocyte subsets achieving the best performances, specifically CD3+CD4+ T cells (AUC = 0.756), CD4+/CD8+ ratio (AUC = 0.767), and CD4+MFI (AUC = 0.848). Conclusions: A predictive value and treatment considerations for lymphocyte subsets are suggested, especially for CD3CD4+ T cells. Lymphocyte subsets determination at hospital admission is recommended.

Table S1. Baseline characteristics, subset with inflammatory biomarkers. Table S2. Baseline predictors of loss of low disease activity at 1 year in the logistic regression analysis. Table S3. Univariate methods for loss of low disease activity at 1 year– subset with inflammatory biomarkers. Table S4. Listing of infectious adverse events. (DOCX 38 kb)

Altres ajuts: This work is conducted under the umbrella of the Rheumatology Society of Catalonia and supported by Merck Research Laboratories. Background: Recent data suggest that anti-TNF doses can be reduced in ankylosing spondylitis (AS) patients. Some authors even propose withdrawing treatment in patients in clinical remission; however, at present there is no evidence to support this. Objective: To assess how long AS patients with persistent clinical remission remained free of flares after anti-TNF withdrawal and to evaluate the effects of treatment reintroduction. We also analyze the characteristics of patients who did not present clinical relapse. Methods: Multicenter, prospective, observational study of a cohort of patients with active AS who had received infliximab as a first anti-TNF treatment and who presented persistent remission (more than 6 months). We recorded at baseline and every 6-8 weeks over the 12-month period the age, gender, disease duration, peripheral arthritis or enthesitis, HLA-B27 status, BASDAI, CRP, ESR, BASFI, and three visual analogue scales, spine global pain, spinal night time pain, and patient's global assessment. Results: Thirty-six out of 107 patients (34%) presented persistent remission and were included in our study. After treatment withdrawal, 21 of these 36 patients (58%) presented clinical relapse during follow-up. Infliximab therapy was reintroduced and only 52% achieved clinical remission, as they had before the discontinuation of infliximab; in an additional 10%, reintroduction of infliximab was ineffective, obliging us to change the anti-TNF therapy. No clinical or biological factors were associated with the occurrence of relapse during the follow-up. Conclusions: Two thirds of patients in clinical remission presented clinical relapse shortly after infliximab withdrawal. Although the reintroduction of infliximab treatment was safe, half of the patients did not present the same clinical response that they had achieved prior to treatment withdrawal.

Objective: The objective was to determine if dose reduction is non-inferior to full-dose TNFi to maintain low disease activity (LDA) in patients already in remission with TNFi, in axial spondyloarthritis. Methods: Randomized, parallel, non-inferiority, open-label multicentre clinical trial. Patients were eligible if they had axial spondyloarthritis and had been in clinical remission for ≥ 6 months with any available TNFi (adalimumab, etanercept, infliximab, golimumab) at the dose recommended by product labelling. Patients were randomized by automated central allocation to continue the same TNFi dose schedule, or to reduce the dose by roughly half according to the protocol. The main outcome was the proportion of subjects with LDA after 1 year. Serious adverse reactions or infections were recorded. Results: The trial stopped due to end of the funding period, after 126 patients were randomized; 113 patients (84.1% male, mean age (SD) 45.6 (13.0) years) were included in the main per-protocol subset. Non-inferiority was concluded for LDA at 1 year (47/55 (83.8%) patients in the full-dose and 48/58 (81.3%) patients in the reduced-dose arm, adjusted difference (95% CI) - 2.5% (- 16.6% to 11.7%)). Serious adverse reactions or infections were reported in 7/62 patients (11.3%) assigned to full dose and 2/61 patients (3.3%) assigned to reduced dose (p value = 0.164). Conclusion: In patients with ankylosing spondylitis in clinical remission for at least 6 months, dose reduction is non-inferior to full TNF inhibitor doses to maintain LDA after 1 year. Serious adverse events may be less frequent with reduced doses. Trial registration: EU Clinical Trials Registry, EudraCT 2011-005871-18 and ClinicalTrials.gov, NCT01604629., The study was fully funded by grants from the Spanish Ministry of Health within the programme “Ayudas para el fomento de la investigación clínica independiente del Ministerio de Salud, Política Social e Igualdad - Orden SPI/ 2885/2011, de 20 de octubre” (project ID: EC11–229) and from the Ministerio de Economía y Consumo (MINECO)-Instituto de Salud Carlos III-Subdirección General de Evaluación and the European Fund for Regional Development (Project ID: PI13/02680).

Objective To assess HLA-B27 influence on the clinical phenotype of Ankylosing Spondylitis (AS) patients. Method An observational, cross-sectional and descriptive study of AS patients from the Spanish REGISPONSER database was performed. Demographic, clinical, disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)), and radiographic data (Bath Ankylosing Spondylitis Radiology Index (BASRI) score) were compared regarding HLA-B27 status. A univariate and multivariate analysis was performed to identify variables independently related to the presence of HLA-B27. Results Data from 1235 patients (74.8% male) were analyzed; 1029 were HLA-B27 positive (83%). HLA-B27-positive patients showed higher family aggregation and an earlier onset of disease compared with those who were HLA-B27 negative. HLA-B27-negative patients presented statistically higher BASDAI and BASFI scores and higher prevalence of arthritis, dactylitis, and extra-articular manifestations (psoriasis and inflammatory bowel disease (IBD)) but not anytime uveitis compared with those who were HLA-B27 positive. In the multivariate analysis, family history (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.27–3.49), younger age at diagnosis (OR 0.97, 95% CI 0.96–0.98), presence of peripheral arthritis (OR 0.53, 95% CI 0.32–0.89), dactylitis (OR 0.16, 95% CI 0.05–0.56), psoriasis (OR 0.45, 95% CI 0.26–0.78), and IBD (OR 0.22, 95% CI 0.12–0.40) were the main variables independently related to the presence or not of HLA-B27. Conclusion In Caucasian AS patients, the presence of HLA-B27 is related to an earlier disease onset and higher family aggregation. Absence of HLA-B27 is related to a higher frequency of peripheral arthritis, dactylitis, and extra-articular manifestations. Being HLAB27 positive is not related to a higher burden of disease or anytime uveitis.

Supplementary tables. (DOCX 54 kb)

More detailed description of statistical methods. (DOCX 13 kb)

Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socioeconomic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNF alpha and IFN gamma cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity.

En la tesi que presento s'avaluen les implicacions de la presencia de l'HLA-B27 en el fenotip i les comorbilitats de pacients amb Espondiloartritis Axial En la tesis que presento se evalúan las implicaciones de la presencia del HLA-B27 en el fenotipo y las comorbilidades de pacientes con Espondiloartritis Axial The present thesis assesses the implications of the presence of HLA-B27 in phenotype and comorbidities in Axial Spondyloarthritis patients Universitat Autònoma de Barcelona. Programa de Doctorat en Medicina

Les espondiloartritis axials (EspAax) han experimentat profunds canvis en la última dècada. Canvis que han condicionat modificacions en la conducta mèdica des de l’aproximació diagnòstica, passant pel maneig i acabant amb el tractament. Tots els canvis comporten períodes d’adaptació i apareixen incògnites a respondre mentre els implementem a la pràctica clínica. La implementació dels nous criteris ASAS de classificació de les espondilartritis ha suposat un profund canvi en el maneig d’aquests malalts. En aquesta tesis avaluem com els nous criteris de classificació ASAS han modificat el maneig dels malalts amb EspAax a la pràctica clínica. D’altra banda, l’aparició de la teràpia biològica (TB), ara fa dues dècades, ha modificat significativament el maneig farmacològic d’aquests malalts, i tot haver incorporat moltes novetats, encara a dia d’avui, hi ha moltes incògnites pendents de resoldre. La TB és un tractament crònic en aquests malalts? És possible reduir la dosis de la TB en els malalts que presenten bona resposta clínica? Què entenem per bona resposta clínica en aquests malalts? Està ben avaluada la seguretat de aquests tractament a llarg termini?. Aquests i altres aspectes que no estan del tot ben definits són els que a la tesis que presento intento abordar. Las espondiloartritis axiales (EspAax) han experimentado profundos cambios en la última década. Cambios que han condicionado modificaciones en la conducta médica desde el abordaje diagnóstico, pasando por el manejo y acabando con el tratamiento. Todos los cambios comportan periodos de adaptación y aparecen incógnitas para responder mientras implementamos dichos cambios en la práctica clínica. La implementación de los nuevos criterios de clasificación ASAS han modificado el manejo de los pacientes con EspAax en la práctica clínica. Por otro lado, la aparición de la terapia biológica (TB), hace ya dos décadas; ha modificado significativamente el manejo farmacológico de estos enfermos, y a pesar de haber incorporado múltiples novedades, todavía hay muchas incógnitas por resolver. ¿La TB es un tratamiento crónico en estos enfermos? ¿Es posible reducir la dosis de la TB en los pacientes que presenten una buena respuesta clínica? ¿Qué entendemos por buena respuesta clínica en estos enfermos? ¿Está bien evaluada la seguridad de estos tratamientos a largo plazo? Estos y otros aspectos que no están del todo bien definidos son los que intento abordar en esta tesis. Axial spondylarthritis have experienced a lot of changes in the last decade. The implementation of the new ASAS classification criteria of axial spondyloarhtritis (axSpA) had led a deep change in the vision and spectrum of axial spondylarthritis. In this thesis, we evaluate how the new ASAS classification criteria of axial spondylarthritis had modified the management of patients with axSpA in real world practice. On the other hand, the irruption of biological therapy (BT), as a new therapeutic strategy two decades ago, has significantly changed the pharmacological management of this patient however, several controversial issues remains to be elucidated. Is the BT a chronic therapy? Is it possible to reduce the doses in well controlled patients? How we can define well controlled patients? How about long-term safety of these therapies? My thesis is focused and try to evaluate some of these main concerns previously exposed. Universitat Autònoma de Barcelona. Programa de Doctorat en Medicina

L’objectiu principal d’aquest projecte és la confecció d’una guia de disseny d’instal·lacions destinada als enginyers industrials projectistes. Aquesta guia, de caràcter pràctic, es centra en un tipus concret d’establiment, el de restauració, i en dos de les principals instal·lacions que en aquest podem trobar, la de ventilació i la de protecció contra incendis. El present document és un projecte real realitzat al Col·legi d’Enginyers Industrials de Catalunya (en endavant COEIC), en concret l’Àrea Professional. Les raons principals d’aquesta guia són dues: la vocació del COEIC de servei vers l’enginyer projectista per a facilitar-li la seva tasca diària i una sèrie de canvis en l’àmbit normatiu que justifiquen la necessitat d’un document d’aquest tipus. La Guia de disseny per a enginyers projectistes. Instal·lacions en Establiments de Restauració: Ventilació i Protecció Contra Incendis està formada per dues guies clarament diferenciables i amb entitat independent, per una banda la Guia de Ventilació en Establiments de Restauració i per una altra la Guia de Protecció Contra Incendis en Establiments de Restauració. Degut a les peculiaritats de cadascuna de les guies s’han emprat metodologies de treball diferents per a obtenir un mateix resultat. La Guia de Protecció Contra Incendis en Establiments de Restauració s’ha confeccionat realitzant consultes puntuals a diferents experts en matèria de protecció contra incendis. Per a l’elaboració de la Guia de Ventilació en Establiments de Restauració s’ha creat un Grup de Treball, format per membres del COEIC, enginyers projectistes, enginyers de l’Administració i per personal tècnic d’empreses del sector de la ventilació. El resultat d’aquest treball i de l’esforç dipositat en aquest projecte no és altre que la publicació del la Guia de disseny per a enginyers projectistes. Instal·lacions en Establiments de Restauració: Ventilació i Protecció Contra Incendis dins la col·lecció dels Dossiers d’Acció Professional. Aquesta guia pretén esdevenir una eina útil per a l’enginyer projectista tot facilitant-li considerablement l’anàlisi normatiu i establint una metodologia projectual amb la inclusió de tots els continguts necessaris per tal de garantir la qualitat de les instal·lacions. Des del COEIC, seguint amb l’esperit de millora contínua, es promou la continuació d’aquest projecte confeccionant una guia de caire semblant però destinada als aparcaments.