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BACKGROUND: Systemic lupus erythematosus (SLE) may result in great impact on patients' quality of life, social relationships, and work productivity. The use of patient-reported outcome measures (PROMs) in routine care could help capture disease burden to guide SLE management and optimize disease control. We aimed to explore the current situation, appropriateness, and feasibility of PROMs to monitor patients with SLE in routine care, from healthcare professionals' and patients' perspectives. METHODS: A scientific committee developed a Delphi questionnaire, based on a focus group with patients and a literature review, including 22 statements concerning: 1) Use of PROMs in routine care (n = 2); 2) PROMs in SLE management (n = 13); 3) Multidisciplinary management of patients with SLE (n = 4), and 4) Aspects on patient empowerment (n = 3). Statements included in Sects. 2-4 were assessed from three perspectives: current use, appropriateness, and feasibility (with currently available resources). For each statement, panellists specified their level of agreement using a 7-point Likert scale. A consensus was reached when ≥ 70% of the panellists agreed (6,7) or disagreed (1,2) on each statement. RESULTS: Fifty-nine healthcare professionals and 16 patients with SLE participated in the Delphi-rounds. A consensus was reached on the value of PROMs to improve SLE management (83%) and the key role of healthcare professionals (77%) and the need for a digital tool connected to the electronic medical record (85%) to promote and facilitate PROMs collection. PROMs most frequently used in clinical practice are pain (56%), patient's global assessment (44%) and fatigue (39%), all on visual analogue scales. Panellists agreed on the need to implement multidisciplinary consultation (79%), unify complementary tests (88%), incorporate pharmacists into the healthcare team (70%), and develop home medication dispensing and informed telepharmacy programmes (72%) to improve quality of care in patients with SLE. According to panellists, patient associations (82%) and nurses (80%) are critical to educate and train patients on PROMs to enhance patient empowerment. CONCLUSIONS: Although pain, fatigue, and global assessment were identified as the most feasible, PROMs are not widely used in routine care in Spain. The present Delphi consensus can provide a road map for their implementation being key for SLE management.
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OBJECTIVE: It has been documented that several major components of air pollution, including trace elements and polycyclic aromatic hydrocarbons, are associated with the prevalence of systemic lupus erythematosus (SLE). However, the impact of air pollution on the SLE disease activity is still elusive. In this paper, we review the current evidence investigating the link between air pollution, especially when measured as PM2.5, and SLE severity and activity. METHODS: A detailed literature search was applied a priori to the Ovid MEDLINE In-Process and Other Non-Indexed Citation 1986 to present. Presented abstracts from the European League Against Rheumatism and American College of Rheumatology (ACR)/Association for Rheumatology Health Professionals (ARHP) Annual Meetings (2011-2018) were also screened. RESULTS: Out of a total of 1354 papers retrieved from search and references list for detailed evaluation, data from 652 patients with SLE from three studies were analyzed. Two studies had an observational longitudinal design, counting for 348 patients with a follow-up of 24 months and 79 months. Retrieved studies differed for disease activity assessment and air pollution quantifications. CONCLUSION: Current evidence suggests that variations in air pollution may influence the disease activity in patients with SLE. However, the sample size, methodological biases, and differences across the studies make further research mandatory. Understanding the increased burden of SLE and its complications, not only from a medical, but also from a socio-demographic perspective, including an exposure to pollutants, should have implications for resource allocation and access to subspecialty care.
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OBJECTIVE: This article aims to analyse the rate of antiphospholipid antibodies (aPL) negativisation in patients with antiphospholipid syndrome (APS), and to evaluate potential new clinical manifestations after negativisation and/or aPL fluctuations in a long-term follow-up. METHODS: Inclusion criteria are (1) any patients with an APS diagnosis according to the current Sydney criteria and (2) patients in whom aPL negativisation occurred. aPL negativisation was defined as repeated aPL measurements on at least two consecutive occasions at least 12 weeks apart, with a follow-up of at least 1 year since aPL first turned negative. RESULTS: Out of 259 APS patients, a total of 23 patients (8.9%) met the inclusion criteria for persistent aPL negativisation. Patients were followed-up for 14.4 ± 8.1 years, experienced aPL negativisation after a mean of 5.3 ± 3.5 years and were followed-up after experiencing the aPL negativisation for a mean of 7.6 ± 5.8 years. Seventeen patients (73.9%) presented with thrombotic APS, 2 with pregnancy morbidity (8.7%) and 4 (17.4%) with both. Most of the patients (18; 78.3%) had a single aPL positivity, 5 (21.7%) double, while no triple aPL positivity was observed. At the time of data collection, after aPL negativisation, anticoagulation was stopped in 8 patients with previous thrombotic venous event (8/21, 38%) according to the treating physicians' judgements. None of the patients experienced any recurrent thrombotic event during the follow-up period after their aPL negativisation. CONCLUSION: In our patient cohort consisting of 259 patients with definitive APS, we observed over a mean observation period of > 5 years, that aPL negativisation occurred in approximately 9% of patients. Negativisation occurred most often in patients who were previously found to be positive for only one aPL.
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Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/terapia , Adulto , Idoso , Anticoagulantes/uso terapêutico , Feminino , Seguimentos , Humanos , Inibidor de Coagulação do Lúpus/imunologia , Masculino , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Índice de Gravidade de Doença , Trombose/diagnóstico , Trombose/terapiaRESUMO
The objective was to develop evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. Based on evidence from a systematic literature review and expert opinion, overarching principles and recommendations were formulated and voted. High-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS. Risk modification includes screening for and management of cardiovascular and venous thrombosis risk factors, patient education about treatment adherence, and lifestyle counselling. Low-dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with systemic lupus erythematosus without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin K antagonists (VKA) with a target international normalised ratio (INR) of 2-3. In patients with APS with first arterial thrombosis, treatment with VKA with INR 2-3 or INR 3-4 is recommended, considering the individual's bleeding/thrombosis risk. Rivaroxaban should not be used in patients with APS with triple aPL positivity. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3-4 or switch to low molecular weight heparin may be considered. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increase of heparin to therapeutic dose, addition of hydroxychloroquine or addition of low-dose prednisolone in the first trimester may be considered. These recommendations aim to guide treatment in adults with APS. High-quality evidence is limited, indicating a need for more research.
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Síndrome Antifosfolipídica , Guias de Prática Clínica como Assunto , Reumatologia/normas , Adulto , Anticorpos Antifosfolipídeos/sangue , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Feminino , Humanos , Masculino , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/imunologia , Fatores de Risco , Trombose Venosa/imunologiaRESUMO
OBJECTIVES: In this study we aimed to investigate foetal and maternal pregnancy outcomes from a large multicentre cohort of women diagnosed with MCTD and anti-U1RNP antibodies. METHODS: This multicentre retrospective cohort study describes the outcomes of 203 pregnancies in 94 consecutive women ever pregnant who fulfilled the established criteria for MCTD with confirmed U1RNP positivity. RESULTS: The foetal outcomes in 203 pregnancies were as follows: 146 (71.9%) live births, 38 (18.7%) miscarriages (first trimester pregnancy loss of <12 weeks gestation), 18 (8.9%) stillbirths (pregnancy loss after 20 weeks gestation) and 11 (5.4%) cases with intrauterine growth restriction. Maternal pregnancy outcomes were as follows: 8 (3.9%) developed pre-eclampsia, 2 (0.9%) developed eclampsia, 31 (15.3%) developed gestational hypertension and 3 (1.5%) developed gestational diabetes. Women with MCTD and aPL and pulmonary or muscular involvement had worse foetal outcomes compared with those without. Moreover, we report a case of complete congenital heart block (0.45%) and a case of cutaneous neonatal lupus, both born to a mother with positive isolated anti-U1RNP and negative anti-Ro/SSA antibodies. CONCLUSION: In our multicentre cohort, women with MCTD had a live birth rate of 72%. While the true frequency of heart block associated with anti-U1RNP remains to be determined, this study might raise the consideration of echocardiographic surveillance in this setting. Pregnancy counselling should be considered in women with MCTD.
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Autoanticorpos/sangue , Doença Mista do Tecido Conjuntivo/imunologia , Complicações na Gravidez/imunologia , Ribonucleoproteína Nuclear Pequena U1/imunologia , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/imunologia , Adulto , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/imunologia , Feminino , Retardo do Crescimento Fetal/imunologia , Bloqueio Cardíaco/congênito , Bloqueio Cardíaco/imunologia , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão Induzida pela Gravidez/imunologia , Recém-Nascido , Nascido Vivo/epidemiologia , Lúpus Eritematoso Sistêmico/congênito , Lúpus Eritematoso Sistêmico/imunologia , Doença Mista do Tecido Conjuntivo/complicações , Gravidez , Complicações na Gravidez/sangue , Resultado da Gravidez , Estudos Retrospectivos , Natimorto/epidemiologiaRESUMO
We aimed to identify the plasma miRNA profile of antiphospholipid syndrome (APS) patients and to investigate the potential role of specific circulating miRNAs as non-invasive disease biomarkers. Ninety APS patients and 42 healthy donors were recruited. Profiling of miRNAs by PCR-array in plasma of APS patients identified a set of miRNAs differentially expressed and collectively involved in clinical features. Logistic regression and ROC analysis identified a signature of 10 miRNA ratios as biomarkers of disease. In addition, miRNA signature was related to fetal loss, atherosclerosis, and type of thrombosis, and correlated with parameters linked to inflammation, thrombosis, and autoimmunity. Hard clustering analysis differentiated 3 clusters representing different thrombotic risk profile groups. Significant differences between groups for several miRNA ratios were found. Moreover, miRNA signature remained stable over time, demonstrated by their analysis three months after the first sample collection. Parallel analysis in two additional cohorts of patients, including thrombosis without autoimmune disease, and systemic lupus erythematosus without antiphospholipid antibodies, each displayed specific miRNA profiles that were distinct from those of APS patients. In vitro, antiphospholipid antibodies of IgG isotype promoted deregulation in selected miRNAs and their potential atherothrombotic protein targets in monocytes and endothelial cells. Taken together, differentially expressed circulating miRNAs in APS patients, modulated at least partially by antiphospholipid antibodies of IgG isotype, might have the potential to serve as novel biomarkers of disease features and to typify patients' atherothrombotic status, thus constituting a useful tool in the management of the disease.
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Síndrome Antifosfolipídica/complicações , Aterosclerose/diagnóstico , Biomarcadores/análise , MicroRNA Circulante/genética , Regulação Neoplásica da Expressão Gênica , Trombose/diagnóstico , Adulto , Idoso , Síndrome Antifosfolipídica/fisiopatologia , Aterosclerose/etiologia , Aterosclerose/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Trombose/etiologia , Trombose/patologia , Adulto JovemRESUMO
OBJECTIVE: Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients' prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q10 [Qred]) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial. APPROACH AND RESULTS: Thirty-six patients with APS were randomized to receive Qred (200 mg/d) or placebo for 1 month. Thirty-three patients with APS completed the intervention, which increased plasma coenzyme Q10. Qred improved endothelial function and decreased monocyte expression of prothrombotic and proinflammatory mediators, inhibited phosphorylation of thrombosis-related protein kinases, and decreased peroxides and percentage of monocytes with depolarized mitochondria; mitochondrial size was increased, and mitochondrial biogenesis-related genes were upregulated. Qred ameliorated extruded neutrophil extracellular traps in neutrophils and downregulated peroxides, intracellular elastase, and myeloperoxidase. Nanostring microRNA profiling revealed 20 microRNAs reduced in APS monocytes, and 16 of them, with a preponderance of cardiovascular disease-related target mRNAs, were upregulated. Monocytes gene profiling showed differential expression of 29 atherosclerosis-related genes, 23 of them changed by Qred. Interaction networks of genes and microRNAs were identified. Correlation studies demonstrated co-ordinated effects of Qred on thrombosis and endothelial function-associated molecules. CONCLUSIONS: Our results highlight the potential of Qred to modulate the overexpression of inflammatory and thrombotic risk markers in APS. Because of the absence of clinically significant side effects and its potential therapeutic benefits, Qred might act as safe adjunct to standard therapies in APS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02218476.
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Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/fisiopatologia , Ubiquinona/análogos & derivados , Vitaminas/uso terapêutico , Estudos Cross-Over , Endotélio Vascular/fisiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Inflamação/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias/fisiologia , Monócitos/patologia , Oxirredução , Estudos Prospectivos , Ubiquinona/uso terapêuticoRESUMO
BACKGROUND: Biological therapies represent a fundamental innovation for the management of inflammatory bowel diseases (IBD). However, many biological originators have reached, or are about to reach, patent expiry and long-term therapy costs have become progressively unsustainable. CT-P13, a biosimilar of the anti-tumor necrosis factor (anti-TNF) monoclonal antibody infliximab, might represent a significant alternative to its originator, with the potential to decrease medical care costs and, therefore, become available to a large number of patients. OBJECTIVES: In this systematic review, we analyzed the data from available clinical trials that recently investigated the validity of indication extrapolation of CT-P13 for the treatment of IBD in naïve patients and in patients who switched from its originator infliximab, focusing on clinical efficacy, safety and immunogenicity. METHODS: A detailed literature search was developed a priori to identify articles that investigated the validity of indication extrapolation of CT-P13 for the treatment of IBD in TNF inhibitor treatment-naïve patients and in patients who switched from the originator infliximab. This was applied to Ovid MEDLINE, In-Process and Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus for content from 2012 to September 2016. RESULTS: We based our review on the available data from 11 studies that included a total of 1007 IBD patients: 570 patients suffering from Crohn's disease (294 switched and 276 naïve), 435 patients suffering from ulcerative colitis (127 switched and 308 naïve), and two IBD unclassified patients (switched). Overall, no significant difference in efficacy and safety between the originator infliximab and its biosimilar CT-P13 was observed. When assessing the safety of CT-P13, we found that 9.2% of patients experienced adverse effects (4.1% infusion-related reactions and 4.3% infections). CONCLUSION: The analyzed studies did not report a significant difference in terms of efficacy, safety and immunogenicity when comparing the clinical experience with CT-P13 with the available literature data on the originator treatment in IBD. However, some debate is ongoing regarding interchangeability and immunogenicity.
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Anticorpos Monoclonais/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/metabolismo , Medicamentos Biossimilares/metabolismo , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Infliximab/imunologia , Infliximab/metabolismo , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The current treatment of thrombotic APS patients includes long-term anticoagulation with oral vitamin K antagonists (VKAs), with warfarin being the one most commonly used. However, the use of VKAs can be challenging, especially in patients with APS. VKAs monitoring in patients with aPL is complicated by the heterogeneous responsiveness to LAs of reagents used in the International Normalized Ratio test, potentially resulting in instability of anticoagulation. For decades, VKAs were the only available oral anticoagulants. However, non-VKA oral anticoagulants, including a direct thrombin inhibitor (dabigatran etexilate) and direct anti-Xa inhibitors (rivaroxaban, apixaban and edoxaban), are currently available. The use of these agents may represent a major step forward since, unlike VKAs, they have few reported drug interactions and they do not interact with food or alcohol intake, thereby resulting in more stable anticoagulant intensity. Most importantly, monitoring their anticoagulant intensity is not routinely required due to their predictable anticoagulant effects. In this review, we discuss the clinical and laboratory aspects of non-VKA oral anticoagulants, focusing on the available evidence regarding their use in patients with APS.
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Anticoagulantes/administração & dosagem , Síndrome Antifosfolipídica/tratamento farmacológico , Administração Oral , Anticoagulantes/efeitos adversos , Síndrome Antifosfolipídica/complicações , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Aleitamento Materno , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Interações Alimento-Droga/fisiologia , Hemorragia/induzido quimicamente , Humanos , Nefropatias/complicações , Hepatopatias/complicações , Inibidor de Coagulação do Lúpus/sangue , Gravidez , Complicações na Gravidez/tratamento farmacológico , Trombose/complicações , Trombose/tratamento farmacológico , Vitamina K/antagonistas & inibidoresRESUMO
Systemic lupus erythematosus (SLE) is a chronic autoimmune condition with unpredictable course, intermingled with flares and periods of remission. Although the prognosis of the disease has improved in the past decades, current therapies are still associated with treatment-related complications. Recently, there has been major progress in the understanding of the pathogenesis of SLE, paving the way for the development of new biological agents, potentially revolutionizing the treatment of SLE. This review summarizes available data on novel biological therapies for SLE, focusing on recent results from clinical trials. As a result of treatment strategies based upon an individualized therapeutic approach, it is hoped that the clinical view of SLE will change from a severe autoimmune disease to a condition in which significant damage, mortality and treatment related complications can be prevented in the majority of SLE patients.
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Produtos Biológicos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Animais , Terapia Biológica , HumanosAssuntos
Infecções Bacterianas/tratamento farmacológico , Imunoglobulinas Intravenosas/efeitos adversos , Imunoglobulinas Intravenosas/uso terapêutico , Vasculite/tratamento farmacológico , Adulto , Idoso , Infecções Bacterianas/complicações , Comorbidade , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/complicações , Infecções Oportunistas/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Vasculite/complicaçõesRESUMO
OBJECTIVE: Statins may have beneficial vascular effects in systemic lupus erythematosus (SLE) beyond their cholesterol-lowering action, although the mechanisms involved are not completely understood. We investigated potential mechanisms involved in the efficacy of fluvastatin in preventing atherothrombosis in SLE. METHODS: Eighty-five patients with SLE and 62 healthy donors were included in the study. Selected patients (n=27) received 20â mg/day fluvastatin for 1â month. Blood samples were obtained before the start and at the end of treatment. Monocytes from five patients were treated in vitro with fluvastatin. RESULTS: Increased prothrombotic and inflammatory variables were found in patients with SLE. SLE monocytes displayed altered mitochondrial membrane potential and increased oxidative stress. Correlation and association analyses demonstrated a complex interplay among autoimmunity, oxidative stress, inflammation and increased risk of atherothrombosis in SLE. Fluvastatin treatment of patients for 1 month reduced the SLE Disease Activity Index and lipid levels, oxidative status and vascular inflammation. Array studies on monocytes demonstrated differential expression in 799 genes after fluvastatin treatment. Novel target genes and pathways modulated by fluvastatin were uncovered, including gene networks involved in cholesterol and lipid metabolism, inflammation, oxidative stress and mitochondrial activity. Electron microscopy analysis showed increased density volume of mitochondria in monocytes from fluvastatin-treated patients, who also displayed higher expression of genes involved in mitochondrial biogenesis. In vitro treatment of SLE monocytes confirmed the results obtained in the in vivo study. CONCLUSIONS: Our overall data suggest that fluvastatin improves the impairment of a redox-sensitive pathway involved in processes that collectively orchestrate the pathophysiology of atherothrombosis in SLE.
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Aterosclerose/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Aterosclerose/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Estudos de Casos e Controles , Células Cultivadas , Comorbidade , Ácidos Graxos Monoinsaturados/farmacologia , Ácidos Graxos Monoinsaturados/uso terapêutico , Feminino , Fluvastatina , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Técnicas In Vitro , Indóis/farmacologia , Indóis/uso terapêutico , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Resultado do TratamentoRESUMO
BACKGROUND: Around 10% of all thrombotic cerebrovascular events (CVE) occur in young population and in a large proportion of those the trigger remains undetermined. Antiphospholipid antibodies (aPL) are recognised risk factors for ischaemic stroke and recurrent thrombotic events; however, the frequency of aPL in young people with CVE is still an unresolved issue. OBJECTIVES: To estimate the frequency of aPL in young adults with CVE and to determine whether aPL-positive young individuals are at greater risk of CVE when compared with individuals without aPL by systematically reviewing the literature. METHODS: Medline reports published between 1970 and 2013 investigating the presence of aPL in young patients (<50â years old) with CVE were included. The median frequency for positive aPL, including lupus anticoagulant, anticardiolipin antibodies (aCL) and antibodies against ß2Glycoprotein I (anti-ß2GPI), was calculated for stroke and transient ischaemic attacks. FINDINGS: This systematic review is based on available data from 5217 patients and controls from 43 studies analysing the frequency of aPL in young patients with CVE. The overall aPL frequency was estimated as 17.4% (range 5%-56%) for any CVE, 17.2% (range 2%-56%) for stroke and 11.7% (range 2%-45%) for transient ischaemic attack (TIA). The presence of aPL increased the risk for CVE by 5.48-fold (95% CI 4.42 to 6.79). Based on available data, the frequency of aPL in young patients with CVE can be estimated at 17%, rising up to 22% for aCL in patients with stroke. The presence of aPL seems to confer a fivefold higher risk for stroke or TIA when compared with controls. However, variability in test reproducibility and cut-off definition still represent an important methodological limitation for the current diagnostic testing for aPL. These observations should be confirmed by appropriately designed population studies.
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Anticorpos Anticardiolipina/imunologia , Ataque Isquêmico Transitório/imunologia , Inibidor de Coagulação do Lúpus/imunologia , Acidente Vascular Cerebral/imunologia , beta 2-Glicoproteína I/imunologia , Adolescente , Adulto , Anticorpos Antifosfolipídeos/imunologia , Autoanticorpos/imunologia , Humanos , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: This study was performed to prospectively and independently validate the Global Antiphospholipid Syndrome Score (GAPSS), a system derived from the combination of independent risk factors for thrombosis, including antiphospholipid antibodies (aPL) and conventional cardiovascular risk factors. METHODS: The GAPSS was applied to 51 consecutive systemic lupus erythematosus patients, all positive for aPL and prospectively followed up for mean ± SD 32.94 ± 12.06 months. Of them, 48 were women with a mean ± SD age of 37.35 ± 12.15 years at entry. The GAPSS was calculated yearly for each patient by adding together the points corresponding to the risk factors. RESULTS: An increase in the GAPSS (entry versus last visit) was seen in patients who experienced vascular events (n = 4, mean ± SD 7.5 ± 4.36 versus 10.0 ± 5.4; P = 0.032). No changes were observed in those without thrombosis (n = 47, mean ± SD 8.28 ± 4.88 versus 7.13 ± 5.75; P = 0.24). An increase in the GAPSS during the followup was associated with a higher risk of vascular events (relative risk 12.30 [95% confidence interval (95% CI) 1.43-106.13], P = 0.004), and an increase of more than 3 points showed the best risk accuracy for vascular events (hazard ratio 48 [95% CI 6.90-333.85], P = 0.0001). The cumulative proportion of thrombosis-free individuals was lower in patients whose GAPSS was increased by 3 or more points (P = 0.0027). CONCLUSION: We have prospectively demonstrated that GAPSS is a valid tool for accurate prediction of vascular events in SLE patients with aPL.
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Anticorpos Antifosfolipídeos/sangue , Lúpus Eritematoso Sistêmico/complicações , Trombose/etiologia , Adulto , Anticorpos Antifosfolipídeos/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Trombose/sangue , Trombose/imunologiaRESUMO
Antiphospholipid syndrome (APS) is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for antiphospholipid antibodies (aPLs). APS can be isolated (known as primary APS) or associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE; known as secondary APS). The kidney is a major target organ in APS and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal arteries, glomerular capillaries and renal veins); events reflect the site and size of the involved vessels. Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal prognosis is affected by the presence of aPLs in patients with lupus nephritis and can be poor. In patients with SLE and aPLs, biopsy should be performed because inflammatory and thrombotic lesions require different therapeutic approaches. Renal involvement in patients with definite APS is treated by anticoagulation with long-term warfarin. The range of renal manifestations associated with APS is broadening and, therefore, aPLs have increasing relevance in end-stage renal disease, transplantation and pregnancy.
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Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Nefropatias/etiologia , Adulto , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/patologia , Síndrome Antifosfolipídica/fisiopatologia , Feminino , Humanos , Infarto/etiologia , Rim/irrigação sanguínea , Falência Renal Crônica/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/complicações , Pessoa de Meia-Idade , Gravidez , Veias Renais , Trombose/complicações , Varfarina/uso terapêuticoRESUMO
OBJECTIVES: Some studies have shown efficacy of intravenous immunoglobulin (IVIG) in the treatment of systemic lupus erythematosus (SLE) but its use still lacks of confirmation in large cohorts. METHODS: This observational, retrospective, single-centre clinical study included 52 SLE patients who received at least one cycle of IVIG (400 mg/kg/day for 5 days) from January 2001 to February 2011. Twenty-seven SLE patients were treated with IVIG for active disease and concomitant infection, while 26 received the IVIG as resistant to standard therapy. The indications for IVIG in the SLE patients were mainly cutaneous, haematological, neuropsychiatric and heart involvements. RESULTS: In patients with active disease and concomitant infections, the response to IVIG treatment was a complete remission (n=9), partial remission (n=8), and no response (n=8). We recorded any response (total or partial) in 17 out of 27 patients (62.96%). In patients with active disease refractory to standard therapy, the response to IVIG treatment was a complete remission (n=6), partial remission (n=12), and no response (n=8). We recorded any response (total or partial) in 18 out of 26 patients (69.23%). Seven of these patients relapsed after a mean time of 8.9 months (3-23 months). CONCLUSIONS: In a long-term study in the largest published cohort of SLE patients, IVIG was found to be effective in selected manifestations such as haematological and cardiac involvement or when other therapeutic approaches are not available, such as in patients with active disease and concomitant infection.
Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Doenças Transmissíveis/complicações , Intervalo Livre de Doença , Resistência a Medicamentos , Feminino , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Fatores Imunológicos/efeitos adversos , Estimativa de Kaplan-Meier , Londres , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by abnormal autoantibody production and clearance. This immunological background has been suggested to play a role in the susceptibility of SLE patients to infection. Moreover, drugs (most of them immunosuppressive or immunomodulating agents) used in the treatment of moderate and severe lupus give rise to a tendency for infections, including opportunistic ones. Infections may mimic the exacerbations of SLE, leading to confusion over the diagnosis and appropriate treatment. Despite increased awareness of this problem, infections remain a major source of morbidity and mortality in SLE. There are various strategies which can be applied to try and reduce the risk of infection in SLE patients. Options include vaccinations, antibiotic/antiviral prophylaxis and intravenous immunoglobulins.
Assuntos
Lúpus Eritematoso Sistêmico/tratamento farmacológico , Infecções Oportunistas/tratamento farmacológico , Autoanticorpos/sangue , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/microbiologia , Infecções Oportunistas/imunologia , Infecções Oportunistas/microbiologia , Fatores de Risco , Vacinação , Vacinas/administração & dosagem , Viroses/tratamento farmacológico , Viroses/imunologia , Viroses/microbiologiaRESUMO
OBJECTIVE: To provide a reference to rheumatologists and other physicians involved in the treatment of systemic lupus erythematosus (SLE) who are using, or about to use biologic therapies. METHODS: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to a model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. RESULTS: We have produced recommendations on the use of belimumab, the only biological agent with approved indications for SLE, and other biological agents without an indication for SLE. The objective of treatment is to achieve a complete clinical response, taken as the absence of perceived or evident disease activity. Nuances regarding the use of biologic therapies in SLE were reviewed as well, such as the evaluation that should be performed prior to administration and the follow up of patients undergoing these therapies. CONCLUSIONS: We present the SER recommendations for the use of biological therapies in patients with SLE.
Assuntos
Terapia Biológica , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Humanos , Lúpus Eritematoso Sistêmico/diagnósticoRESUMO
The last two decades have witnessed a revolution in the treatment of autoimmune diseases due to the introduction of biological agents which, although now included as standard treatment in patients with autoimmune rheumatological, dermatological and gastrointestinal diseases. The use of biological agents is associated with greater costs compared with the mainly anti-inflammatory and immunosuppressant drugs used in the pre-biological era. Biosimilars are highly similar copies of biological drugs, but not identical to approved 'reference' agents. Biological agents are complex proteins involved in the immune response and their exact replicas are extremely difficult, if not impossible, to obtain. Three scenarios have converged to provide a specific opportunity for biosimilars in autoimmune diseases: growing demand for biologics due to successful clinical use; the nearing of patent expiry for the four top-selling biological brands; and the search to reduce health costs due to the financial crisis. We aimed to review the crucial topics of efficacy, safety and regulatory approach of upcoming biosimilars.