Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

Searching for a prognostic index in lupus nephritis.

BACKGROUND: Currently we do not have an ideal biomarker in lupus nephritis (LN) that should help us to identify those patients with SLE at risk of developing LN or to determine those patients at risk of renal progression. We aimed to evaluate the development of a prognostic index for LN, through the evaluation of clinical, analytical and histological factors used in a cohort of lupus. We have proposed to determine which factors, 6 months after the diagnosis of LN, could help us to define which patients will have a worse evolution of the disease and may be, more aggressive treatment and closer follow-up. METHODS: A retrospective study to identify prognostic factors was carried out. We have included patients over 18 years of age with a clinical diagnosis of systemic lupus erythematosus (SLE) and kidney involvement confirmed by biopsy, who are followed up in our centre during the last 20 years. A multi-step statistical approach will be used in order to obtain a limited set of parameters, optimally selected and weighted, that show a satisfactory ability to discriminate between patients with different levels of prognosis. RESULTS: We analysed 92 patients with LN, although only 73 have been able to be classified according to whether or not they have presented poor renal evolution. The age of onset (44 vs. 32; p = 0.024), the value of serum creatinine (1.41 vs. 1.04; p = 0.041), greater frequency of thrombocytopenia (30 vs. 7%; p = 0.038), higher score in the renal chronicity index (2.47 vs. 1.04; p = 0.015), proliferative histological type (100%) and higher frequency of interstitial fibrosis (67 vs. 32%; p = 0.017) and tubular atrophy (67 vs. 32%; p = 0.018) was observed between two groups. The multivariate analysis allowed us to select the best predictive model for poor outcome at 6 months based on different adjustment and discrimination parameters. CONCLUSION: We have developed a prognostic index of poor renal evolution in patients with LN that combines demographic, clinical, analytical and histopathological factors, easy to use in routine clinical practice and that could be an effective tool in the early detection and management.

Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry).

BACKGROUND: Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. OBJECTIVES: This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. METHODS: This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. RESULTS: A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). CONCLUSION: SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).

OBJECTIVES: To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality. METHODS: This is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared. RESULTS: Mean age (years) ±â€¯S.D. at diagnosis was 14.2 ±â€¯2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ±â€¯S.D. was 1.27 ±â€¯1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons). CONCLUSIONS: In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement.

[Consensus document on pneumococcal vaccination in adults at risk by age and underlying clinical conditions. 2017 Update]. / Consenso sobre la vacunación anti-neumocócica en el adulto por riesgo de edad y patología de base. Actualización 2017.

Invasive pneumococcal disease (IPD) and pneumococcal pneumonia (PP) represent an important health problem among aging adults and those with certain underlying pathologies and some diseases, especially immunosuppressed and some immunocompetent subjects, who are more susceptible to infections and present greater severity and worse evolution. Among the strategies to prevent IPD and PP, vaccination has its place, although vaccination coverage in this group is lower than desirable. Nowadays, there are 2 vaccines available for adults. Polysacharide vaccine (PPV23), used in patients aged 2 and older since decades ago, includes a greater number of serotypes (23), but it does not generate immune memory, antibody levels decrease with time, causes an immune tolerance phenomenon, and have no effect on nasopharyngeal colonization. PCV13 can be used from children 6 weeks of age to elderly and generates an immune response more powerful than PPV23 against most of the 13 serotypes included in it. In the year 2013 the 16 most directly related to groups of risk of presenting IPD publised a series of vaccine recommendations based on scientific evidence regarding anti-pneumococcal vaccination in adults with underlying pathologies and special conditions. A commitment was made about updating it if new scientific evidence became available. We present an exhaustive revised document focusing mainly in recommendation by age in which some more Scientific Societies have been involved.

Resumen del Consenso sobre la Vacunación Antineumocócica en el Adulto por Riesgo de Edad y Patología de Base. Actualización 2017 / No disponible

En el año 2013 algunas de las Sociedades Científicas más directamente relacionadas con los grupos de riesgo para padecer enfermedad neumocócica publicamos un documento de Consenso con una serie de recomendaciones basadas en las evidencias científicas respecto a la vacunación antineumocócica en el adulto con condiciones especiales y patología de base. Se estableció un compromiso de discusión y actualización ante la aparición de nuevas evidencias. Fruto de este trabajo de revisión, en abril de 2017 se ha publicado una actualización del anterior documento junto a 4 nuevas Sociedades Científicas donde destaca, entre otras novedades, la recomendación de vacunación por criterio de edad. Se resumen algunas de las principales novedades que presenta la actualización del documento de Consenso

In the year 2013 some of the most directly related to groups of risk of presenting IPD Scientific Societies published a series of vaccine recommendations based on scientific evidence regarding anti-pneumococcal vaccination in adults with underlying pathologies and special conditions. A commitment was made about updating it if new scientific evidence became available. In april 2017 an exhaustive revision over the previous document was published focusing mainly in recommendation by age. We review some of the main changes in the new Consensus document

Analysis of disease activity and response to treatment in a large Spanish cohort of patients with systemic lupus erythematosus.

OBJECTIVES: The objectives of this paper are to study the impact of disease activity in a large cohort of patients with systemic lupus erythematosus (SLE) and estimate the rate of response to therapies. METHODS: We conducted a nationwide, retrospective, multicenter, cross-sectional cohort study of 3658 SLE patients. Data on demographics, disease characteristics: activity (SELENA-SLEDAI), damage, severity, hospitalizations and therapies were collected. Factors associated with refractory disease were identified by logistic regression. RESULTS: A total of 3658 patients (90% female; median SLE duration (interquartile range): 10.4 years (5.3-17.1)) were included. At the time of their last evaluation, 14.7% of the patients had moderate-severe SLE (SELENA-SLEDAI score ≥6). There were 1954 (53.4%) patients who were hospitalized for activity at least once over the course of the disease. At some stage, 84.6% and 78.8% of the patients received glucocorticoids and antimalarials, respectively, and 51.3% of the patients received at least one immunosuppressant. Owing to either toxicity or ineffectiveness, cyclophosphamide was withdrawn in 21.5% of the cases, mycophenolate mofetil in 24.9%, azathioprine in 40.2% and methotrexate in 46.8%. At some stage, 7.3% of the patients received at least one biologic. A total of 898 (24.5%) patients had refractory SLE at some stage. Renal, neuropsychiatric, vasculitic, hematological and musculoskeletal involvement, a younger age at diagnosis and male gender were associated with refractory disease. CONCLUSIONS: A significant percentage of patients have moderately-to-severely active SLE at some stage. Disease activity has a big impact in terms of need for treatment and cause of hospitalization. The effectiveness of the standard therapies for reducing disease activity is clearly insufficient. Some clinical features are associated with refractory SLE.

Manejo perioperatorio de los fármacos modificadores de la enfermedad en Reumatología: recomendaciones basadas en un metaanálisis / Peri-operative management of disease modifying anti-rheumatic drugs: Recommendations based on a meta-analysis

Con el objetivo de proponer recomendaciones para el manejo perioperatorio de los fármacos modificadores de la enfermedad (FAME) en pacientes con enfermedades reumáticas que van a ser sometidos a cirugía, se ha realizado una revisión sistemática de la literatura. Se realizó una búsqueda de todos los estudios publicados y de los resúmenes de congresos, recopilando 5.285 documentos, de los que finalmente se incluyeron 27 estudios que proporcionan información de 5.268 pacientes y 7.933 cirugías. La mayoría eran mujeres (edad media: 55 años), estaban diagnosticados de artritis reumatoide y el fármaco más estudiado fue el metotrexate (MTX). Las recomendaciones finales son las siguientes: mantener el tratamiento con MTX o leflunomida en el período perioperatorio en ausencia de otros factores de riesgo de complicaciones posquirúrgicas (Nivel de evidencia 1c; Grado de recomendación D) y con respecto a los FAME biológicos, suspenderlos momentáneamente o programar la cirugía lo más alejada posible a la última dosis, espaciando al menos 2 dosis si existieran otros factores de riesgo (Nivel de evidencia 2c; Grado de recomendación D) (AU)

The objective of this paper is make recommendations for the perioperative management of antirheumatic treatment based on the best available evidence. A systematic review was performed including studies in which patients with rheumatic diseases treated with biological and non-biological disease-modifying antirheumatic drugs (DMARDs) had undergone surgery. A total of 5,285 studies were recorded, of which 27 were finally included. These contained information on 5,268 patients and 7,933 surgeries. The majority were women (mean age 55 years) were diagnosed with rheumatoid arthritis, and the most studied drug was methotrexate (MTX). The final recommendations include: maintaining treatment with MTX or leflunomide in the perioperative period in the absence of other risk factors for postoperative complications (Level of Evidence 1c, Grade D recommendation). Biological DMARDs should be temporarily suspended, or the surgery scheduled as far as possible from the last dose, and, if there were other risk factors a space at least two doses (Level of Evidence 2c; Grade D recommendation) (AU)

[Peri-operative management of disease modifying anti-rheumatic drugs: recommendations based on a meta-analysis]. / Manejo perioperatorio de los fármacos modificadores de la enfermedad en Reumatología: recomendaciones basadas en un metaanálisis.

The objective of this paper is make recommendations for the perioperative management of antirheumatic treatment based on the best available evidence. A systematic review was performed including studies in which patients with rheumatic diseases treated with biological and non-biological disease-modifying antirheumatic drugs (DMARDs) had undergone surgery. A total of 5,285 studies were recorded, of which 27 were finally included. These contained information on 5,268 patients and 7,933 surgeries. The majority were women (mean age 55 years) were diagnosed with rheumatoid arthritis, and the most studied drug was methotrexate (MTX). The final recommendations include: maintaining treatment with MTX or leflunomide in the perioperative period in the absence of other risk factors for postoperative complications (Level of Evidence 1c, Grade D recommendation). Biological DMARDs should be temporarily suspended, or the surgery scheduled as far as possible from the last dose, and, if there were other risk factors a space at least two doses (Level of Evidence 2c; Grade D recommendation).