Damage in a large systemic lupus erythematosus cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER) with emphasis on the cardiovascular system: a longitudinal analysis

Objective To assess organ damage, with emphasis on the cardiovascular system, over the different stages of the disease in a large SLE cohort.Methods Multicentre, longitudinal study of a cohort of 4219 patients with SLE enrolled in the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We longitudinally analysed SDI (globally and for each domain) over time only in the 1274 patients whose dates of damage events had been recorded.Results During the first year after diagnosis of SLE, 20% of the 1274 patients presented with new damage manifestations. At years 2 and 3, new damage was recorded in 11% and 9% of patients. The annual percentage of patients with new damage after year 5 decreased to 5%. In the first year with the disease, most damage was accumulated in the musculoskeletal, neuropsychiatric and renal systems; in later stages, most damage was in the musculoskeletal, ocular and cardiovascular systems. Considering 'cerebrovascular accident' and 'claudication for 6 months' as cardiovascular items, the cardiovascular system was the second most affected system during the early stages of SLE, with 19% of the patients who presented with damage affected at first year after diagnosis. During the late stages, 20-25% of the patients presenting with new damage did so in this modified cardiovascular domain of the SDI.Conclusions New damage occurs mainly during the first year following diagnosis of SLE. Cardiovascular damage is relevant in both the early and the late stages of the disease. Strategies to prevent cardiovascular damage should be implemented early after diagnosis of SLE

Relevance of gastrointestinal manifestations in a large Spanish cohort of patients with systemic lupus erythematosus: what do we know?

SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. METHODS: We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil =4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. RESULTS: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. CONCLUSION: Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage. © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology

"Contributions to the characterization of the low disease activity state in systemic lupus erythematosus".

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune crónica que afecta a cualquier sistema corporal. Con el aumento de la supervivencia de los pacientes con LES en las últimas décadas, la prevención del daño orgánico se ha convertido en uno de los principales objetivos terapéuticos. Recientemente, han surgido conceptos para caracterizar el estado clínico del paciente, más allá de si el LES está activo o no. Estos son los estados de "baja actividad" o de "remisión clínica", que se asocian a un menor riesgo de acumular daño. Pues el daño se ha convertido en una medida de desenlace fundamental en los pacientes con LES, un mejor conocimiento de los factores implicados en su aparición, como la actividad de la enfermedad persistente, es útil para diseñar estrategias de prevención del mismo que contribuyan a mejorar el pronóstico de nuestros pacientes con LES. OBJETIVO El objetivo es analizar diferentes estados de remisión y baja actividad y como se relacionan con el daño acumulado en los pacientes con LES: influencia de la actividad de la enfermedad en el daño. MÉTODOS El plan de investigación se basa en un proyecto: 1) Estudio longitudinal prospectivo del “estado de baja actividad del lupus”: redefinición y comparación con la actividad del LES valorada por un experto. El estado de "baja actividad del lupus" se asocia a una reducción significativa del riesgo de acumular daño en los diferentes sistemas. Se pretende mejorar la definición de LLDAS (establecida por consenso de expertos de la región Asia-Pacífico) en los pacientes con LES de nuestro entorno geográfico y compararla con la actividad de la enfermedad evaluada por un experto. Para ello, diseñamos un estudio longitudinal prospectivo con pacientes en seguimiento en varios Departamentos de Reumatología españoles. Se recogen datos sobre el LES, manifestaciones de actividad y de daño, datos analíticos, comorbilidades, los tratamientos y la evolución de los pacientes. Creamos una plataforma web para la recogida de datos en las sucesivas visitas (basal y al cabo de 1 y 2 años).O lupus eritematoso sistémico (LES) é unha enfermidade autoinmune crónica que afecta a calquera sistema corporal. Co aumento da supervivencia dos pacientes con LES nas últimas décadas, a prevención do dano orgánico converteuse nun dos principais obxectivos terapéuticos. Recentemente, xurdiron conceptos para caracterizar o estado clínico do paciente, máis aló de se o LES está activo ou non. Son os estados de "baixa actividade" ou "remisión clínica", que se asocian a un menor risco de acumulación de danos. Dado que o dano se converteu nunha medida de resultado fundamental nos pacientes con LES, unha mellor comprensión dos factores que interveñen na súa aparición, como a actividade da enfermidade persistente, resulta útil para deseñar estratexias de prevención que contribúan a mellorar o prognóstico dos nosos pacientes con LES. OBXECTIVO O obxectivo é analizar os diferentes estados de remisión e baixa actividade e como se relacionan co dano acumulado en pacientes con LES: influencia da actividade da enfermidade sobre o dano. MÉTODOS O plan de investigación baséase nun proxecto: 1) Estudo lonxitudinal prospectivo do "estado de baixa actividade do lupus": redefinición e comparación coa actividade do LES avaliada por un experto. O estado de "actividade lúpica baixa" está asociado a unha importante redución do risco de acumulación de danos nos diferentes sistemas. O obxectivo é mellorar a definición de LLDAS (establecida por consenso de expertos da rexión Asia-Pacífico) en pacientes con LES no noso ámbito xeográfico e comparala coa actividade da enfermidade avaliada por un experto. Para iso, deseñamos un estudo lonxitudinal prospectivo con pacientes en seguimento en varios Servicios de Reumatoloxía españois. Recóllense datos sobre LES, manifestacións de actividade e danos, datos analíticos, comorbilidades, tratamentos e evolución do paciente. Creamos unha plataforma web para recoller datos sobre visitas sucesivas (base e despois de 1 e 2 anos).Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects any body system. With the increase in survival of patients with SLE in recent decades, the prevention of organ damage has become one of the main therapeutic objectives. Recently, concepts have emerged to characterize the clinical status of the patient, beyond whether SLE is active or not. These are the states of "low activity" or "clinical remission", which are associated with a lower risk of accumulating damage. Since damage has become a fundamental outcome measure in patients with SLE, a better understanding of the factors involved in its appearance, such as the persistent disease activity, is useful for designing prevention strategies that contribute to improving the prognosis of our patients with SLE. OBJECTIVE The objective is to analyze different states of remission and low activity and how they relate to accumulated damage in patients with SLE: influence of disease activity on damage. METHODS The research plan is based on a project: 1) Prospective longitudinal study of the "lupus low disease activity state ": redefinition and comparison with the activity of SLE assessed by an expert. The “lupus low disease activity state" is associated with a significant reduction in the risk of accumulating damage in the different systems. The aim is to improve the definition of LLDAS (established by consensus of experts from the Asia-Pacific region) in patients with SLE in our geographical setting and compare it with the activity of the disease evaluated by an expert. To do this, we designed a prospective longitudinal study with patients under follow-up in several Spanish Rheumatology Departments. Data on SLE, manifestations of activity and damage, analytical data, comorbidities, treatments and the evolution of the patients are collected. We created a web platform to collect data on successive visits (baseline and after 1 and 2 years)

Study of plasma anti-CD26 autoantibody levels in a cohort of treatment-naïve early arthritis patients

In rheumatoid arthritis (RA), the identifcation of biomarkers to adjust treatment intensity and to correctly diagnose the disease in early stages still constitutes a challenge and, as such, novel biomarkers are needed. We proposed that autoantibodies (aAbs) against CD26 (DPP4) might have both etiological importance and clinical value. Here, we perform a prospective study of the potential diagnostic power of Anti-CD26 aAbs through their quantifcation in plasmas from 106 treatment-naïve early and undiferentiated AR. Clinical antibodies, Anti-CD26 aAbs, and other disease-related biomarkers were measured in plasmas obtained in the frst visit from patients, which were later classifed as RA and non-RA according to the American College of Rheumatology criteria. Two diferent isotype signatures were found among ten groups of patients, one for AntiCD26 IgA and other for Anti-CD26 IgG and IgM isotypes, both converging in patients with arthritis (RA and Unresolved Undiferentiated Arthritis: UUA), who present elevated levels of all three isotypes. The four UUA patients, unresolved after two years, were ACPA and rheumatic factor (RF) negatives. In the whole cohort, 51.3% of ACPA/RF seronegatives were Anti-CD26 positives, and a similar frequency was observed in the seropositive RA patients. Only weak associations of the three isotypes with ESR, CRP and disease activity parameters were observed. Anti-CD26 aAbs are present in treatmentnaïve early arthritis patients, including ACPA and RF seronegative individuals, suggestive of a potential pathogenic and/or biomarker role of Anti-CD26 aAbs in the development of rheumatic diseasesOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by the European Union (Interreg V-A Spain-Portugal Cooperative Program (POCTEP), the Health Research Institute Carlos III (ISCIII/PI21/00370/Cofinanciado por la Unión Europea/FEDER), and 0227_CodigoMais_1_E, USC-SERGAS Cooperation 2018–2019S

Does remission in systemic lupus erythematosus according to the 2021 DORIS definition match the treating rheumatologist's judgement?

Objectives: To assess agreement between the 2021 Definition Of Remission In SLE (DORIS) and physician-judged lupus activity. Methods: A cross-sectional analysis was conducted of data from a Spanish prospective multicentre study of SLE patients. We applied the 2021 DORIS criteria and assessed whether remission status based on this definition agreed with remission as per physician clinical judgement and reasons for disagreement between them. Results: Out of 508 patients [92% women; mean age (s.d.): 50.4 years (13.7)] studied, 267 (54.4%) met the criteria for 2021 DORIS remission. Based on physicians' judgement, 277 (55.9%) patients were classified as in remission or serologically active clinically quiescent (SACQ). The overall rate of agreement between these assessments was 81.2% (95% CI: 79.9, 82.9%) with a Cohen's kappa of 0.62 (0.55-0.69). Overall, 46 (9.1%) patients were classified as in remission/SACQ by rheumatologists but did not meet the 2021 DORIS criteria for remission. The main reasons for discrepancies were a clinical SLE Disease Activity Index (cSLEDAI) score >0 in 39 patients, a Physician Global Assessment score >0.5 in five patients, and prednisone >5 mg/day in another five patients. Conclusions: The 2021 DORIS remission is an achievable target in clinical practice. There is substantial agreement between the DORIS definition and physician-judged remission. The discordance was mainly due to physicians classifying some patients with ongoing mild disease activity as in remission. Thus, the standardized DORIS definition should be used to define the target in a treat-to-target strategy for the management of SLE

Does expert opinion match the definition of Lupus Low Disease Activity State? prospective analysis of 500 patients from a Spanish multicentre cohort

Data de publicació electrònica: 12-08-2022Objectives: To apply Lupus Low Disease Activity State (LLDAS) definition within a large cohort of patients and to assess the agreement between the LLDAS and the physician's subjective evaluation of lupus activity. Methods: A cross-sectional analysis of a prospective multicentre study of Systemic Lupus Erythematosus (SLE) patients. We applied the LLDAS and assessed whether there was agreement with the clinical status according to the physiciańs opinion. Results: 508 patients (92% women; mean age (±SD): 50.4 years (± 13.7)). A total of 304 (62.7%) patients were in LLDAS. According to physician assessment, 430 patients (86,1%) were classified as remission or low activity. Overall agreement between both evaluations was 71.4% (95% CI: 70.1-70.5%) with a Coheńs kappa of 0.3 (0.22-0.37). Most cases (96.1%) in LLDAS were classified as remission or low activity by the expert. Of the patients that did not fulfill LLDAS, 126 (70.4%) were classified as having remission/low disease activity. The main reasons for these discrepancies were the presence of new manifestations compared with the previous visit and a SLEDAI 2-K > 4, mainly based on serological activity. Conclusions: Almost two thirds of SLE patients were in LLDAS. There was a fair correlation between LLDAS and the physician's evaluation. This agreement improves for patients fulfilling the LLDAS criteria. The discordance between both at defining lupus low activity, the demonstrated association of LLDAS with better outcomes and the fact that LLDAS is more stringent than physician's opinion imply that we should use the LLDAS as a treat to target goal

Does expert opinion match the definition of lupus low disease activity state? Prospective analysis of 500 patients from a Spanish multicentre cohort.

To apply the lupus low disease activity state (LLDAS) definition within a large cohort of patients and to assess the agreement between the LLDAS and the physician's subjective evaluation of lupus activity. We conducted a cross-sectional analysis of a prospective multicentre study of SLE patients. We applied the LLDAS and assessed whether there was agreement with the clinical status according to the physician's opinion. A total of 508 patients [92% women; mean age 50.4 years (s.d. 3.7)] were recruited and 304 (62.7%) patients were in the LLDAS. According to physician assessment, 430 (86.1%) patients were classified as remission or low activity. Overall agreement between both evaluations was 71.4% (95% CI: 70.1, 70.5) with a Cohen's κ of 0.3 [interquartile range (IQR) 0.22-0.37]. Most cases (96.1%) in the LLDAS were classified as remission or low activity by the expert. Of the patients who did not fulfil the LLDAS, 126 (70.4%) were classified as having remission/low disease activity. The main reasons for these discrepancies were the presence of new manifestations compared with the previous visit and a SLEDAI 2K score >4, mainly based on serological activity. Almost two-thirds of SLE patients were in the LLDAS. There was a fair correlation between the LLDAS and the physician's evaluation. This agreement improves for patients fulfilling the LLDAS criteria. The discordance between both at defining lupus low activity, the demonstrated association of the LLDAS with better outcomes and the fact that the LLDAS is more stringent than the physician's opinion imply that we should use the LLDAS as a treat-to-target goal

Relevance of gastrointestinal manifestations in a large Spanish cohort of patients with systemic lupus erythematosus: what do we know?

Objective: SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. Methods: We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil ?4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. Results: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. Conclusion: Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage.Funding: The RELESSER Registry was partially funded by GlaxoSmithKline (GSK), Roche, Union Chimique Belge (UCB), Lilly and Novartis

Thorough assessment of the effectiveness of belimumab in a large Spanish multicenter cohort of systemic lupus erythematosus patients

To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles.Funding was received from GlaxoSimthKline to support the statistical analysis of this work. Disclosure statement: I.A-G.: received payments for educa- tional talks from: GSK, AstraZeneca. J.M.P-R.: member of speakers’ bureau: Advisory boards for GSK, Otsuka, Astrazeneca, Gebro. Received grants/research support: Investigator Sponsorized Study Grant from GSK. Research support from Pfizer International (Competitive International Grants for Learning and Change). T.C.S-M.: received payments for educational talks and consulting activities from: GSK, Otzuka, Vifor. Received grants/research support: Investigator Sponsorized Study Grant from GSK. J.A.G-P.: received payments for educational talks from Abbvie, Astra Zeneca, GSK, Janssen, Lilly, Pfizer, Gala´ pagos and Otsuka. B.F-S.: received payments for educational talks from Abbvie, Astrazeneca, MSD and BMS for presentations. I.J.R-F.: received honoraria as speaker in GSK scientific meetings and as a member of advisory boards.Medicin