Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 226
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-33547784

RESUMO

OBJECTIVES: Atacicept reduced SLE disease activity in the Phase IIb ADDRESS II study, particularly in patients with high disease activity (HDA; SLEDAI-2K ≥10) at screening. We assessed long-term safety and efficacy of atacicept in the long-term extension (LTE) of ADDRESS II. METHODS: In the 24-week, randomised, double-blind, placebo-controlled ADDRESS II study, patients received weekly atacicept (75 or 150 mg) or placebo. Atacicept was continued at the same dose in atacicept-treated patients in the LTE; placebo-treated patients switched to atacicept 150 mg. Long-term safety was the primary end point. Secondary endpoints included SLE responder index (SRI)-4 and SRI-6 response rates and flares. RESULTS: 253 patients entered the ADDRESS II LTE; 88 received atacicept 150 mg, 82 atacicept 75 mg and 83 placebo/atacicept 150 mg. Median active treatment duration in the LTE was 83.8 weeks. Frequencies of treatment-emergent adverse events (TEAEs) were similar across groups (90.4-93.2%). 12.5%, 14.6% and 21.7% of patients in the atacicept 150 mg, atacicept 75 mg and placebo/atacicept 150 mg groups reported serious TEAEs during the treatment period. The proportions of patients with TEAEs leading to discontinuation were 5.7%, 4.9% and 10.8%, respectively. SRI-4 and SRI-6 response rates were maintained with atacicept in the modified intent-to-treat and HDA populations and those on continuous 150 mg had a reduced risk of first severe flare and longer time to first severe flare vs those who initially received placebo. CONCLUSION: Long-term treatment with atacicept 150 mg in SLE patients had an acceptable safety profile, with durable efficacy. CLINICAL TRIAL REGISTRATION NUMBER: NCT02070978.

2.
Lupus ; : 961203320982668, 2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33459161

RESUMO

It is now two decades since Rituximab was first used in the treatment of patients with systemic lupus erythematosus. There have been many challenges but in spite of failing to meet its primary endpoints in two clinical trials it is widely used for many aspects of lupus, its side-effects and the possibility that combining it with Benlysta may be of value. We also consider the proposal that it may provide a useful initial therapy. In this review, we consider the place of Rituximab in the treatment of lupus and anticipate how developments in fully-humanized anti-CD20 monoclonals may well extend the "therapeutic life" of B-cell depletion as a viable treatment option.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33404639

RESUMO

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) have an increased risk of developing cardiovascular disease (CVD). Multiple studies have shown that these patients have increased numbers of carotid plaques and greater intima-media thickness (IMT) than healthy controls. Measures such as total plaque area (TPA) and plaque echogenicity may be more sensitive and more relevant to cardiovascular risk than presence of plaque and IMT alone. Our objective was to produce the first report of TPA and echogenicity in a population of. PATIENT: s with SLE. METHODS: One hundred patients with SLE and no history of clinical CVD were recruited. Clinical, serological and treatment variables were recorded and serum was tested for antibodies to apolipoprotein A-1 and high-density lipoprotein. Both carotid and both femoral artery bifurcations of each patient were scanned to determine IMT, TPA and echogenicity of plaques. Univariable and multivariable statistical analyses were carried out to define factors associated with each of these outcomes. RESULTS: Thirty-six patients had carotid and/or femoral plaque. Increasing age was associated with presence of plaque and increased IMT. Triglyceride levels were associated with presence of plaque. Mean (SD) TPA was 60.8 (41. 6) mm2. Patients taking prednisolone had higher TPA. Most plaques were echolucent but increased echogenicity was associated with prednisolone therapy and persistent disease activity. CONCLUSION: TPA and plaque echogenicity in patients with SLE are associated with different factors than those associated with presence of plaque and IMT. Longitudinal studies may show whether these outcome measures add value in the management of cardiovascular risk in SLE.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33216641

RESUMO

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease characterized by multiple pathologies in which sustained inflammatory activity leads to progressive tissue destruction and organ damage. One of the main proinflammatory cytokines playing a key role in autoimmune diseases such as rheumatoid arthritis (RA) or SLE, is tumor necrosis factor (TNF) alpha. AREAS COVERED: The introduction of TNF-alpha inhibitors revolutionized the treatment of RA and other conditions including psoriatic arthritis and ankylosing spodylitis. We review here the efficacy and safety of TNF-alpha blockers in SLE focussing on why it has not been more widely used since TNF-alpha was reported to be increased in SLE patients and to correlate with disease activity. EXPERT OPINION: We summarize the reported SLE cases that have received TNF-alpha blockers and the main results to date. We reflect on whether there is a case to reconsider the use TNF-alpha blockade in SLE.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33152181

RESUMO

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in SLE, but its association with hospitalizations has not been described. We estimated the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort. METHODS: Baseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in hospital. Multivariable models were adjusted for relevant baseline characteristics. RESULTS: The 1549 SLE patients eligible for this analysis were mostly female (88.7%) with mean (SD) age 35.7 (13.3) years and median (IQR) disease duration 1.2 (0.9-1.5) years at baseline. Mean (SD) baseline SLICC-FI was 0.17 (0.08). During mean (SD) follow-up of 7.2 (3.7) years, 614 patients (39.6%) experienced 1570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up (Incidence Rate Ratio 1.21; 95%CI 1.13-1.30), adjusting for baseline age, sex, corticosteroid use, immunosuppressive use, ethnicity/location, SLE disease activity index 2000 (SLEDAI-2K), SLICC/ACR damage index (SDI), and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (Relative Rate 1.09; 95%CI 1.02-1.16). CONCLUSION: The SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.

7.
Nat Rev Rheumatol ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33139947

RESUMO

The emergence of COVID-19 in early 2020 led to unprecedented changes to rheumatology clinical practice worldwide, including the closure of research laboratories, the restructuring of hospitals and the rapid transition to virtual care. As governments sought to slow and contain the spread of the disease, rheumatologists were presented with the difficult task of managing risks, to their patients as well as to themselves, while learning and implementing new systems for remote health care. Consequently, the COVID-19 pandemic led to a transformation in health infrastructures and telemedicine that could become powerful tools for rheumatologists, despite having some limitations. In this Viewpoint, five experts from different regions discuss their experiences of the pandemic, including the most challenging aspects of this unexpected transition, the advantages and limitations of virtual visits, and potential opportunities going forward.

8.
Clin Exp Rheumatol ; 38 Suppl 126(4): 85-94, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33095152

RESUMO

OBJECTIVES: To evaluate the systemic phenotype associated with the presence of isolated anti-La/SSB antibodies in a large international registry of patients with primary Sjögren's syndrome (pSS) fulfilling the 2002 classification criteria. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. Baseline clinical information from leading centres on clinical research in SS of the 5 continents was collected. Combination patterns of anti-Ro/SSA-La/SSB antibodies at the time of diagnosis defined the following four immunological phenotypes: double positive (combined Ro/SSA and La/SSB,) isolated anti-Ro/SSA, isolated anti-La/SSB, and immunonegative. RESULTS: The cohort included 12,084 patients (11,293 females, mean 52.4 years) with recorded ESSDAI scores available. Among them, 279 (2.3%) had isolated anti-La/SSB antibodies. The mean total ESSDAI score at diagnosis of patients with pSS carrying isolated anti-La/SSB was 6.0, and 80.4% of patients had systemic activity (global ESSDAI score ≥1) at diagnosis. The domains with the highest frequency of active patients were the biological (42.8%), glandular (36.8%) and articular (31.2%) domains. Patients with isolated anti-La/SSB showed a higher frequency of active patients in all ESSDAI domains but two (articular and peripheral nerve) in comparison with immune-negative patients, and even a higher absolute frequency in six clinical ESSDAI domains in comparison with patients with isolated anti-Ro/SSA. In addition, patients with isolated anti-La/SSB showed a higher frequency of active patients in two ESSDAI domains (pulmonary and glandular) with respect to the most active immunological subset (double-positive antibodies). Meanwhile, systemic activity detected in patients with isolated anti-La/SSB was overwhelmingly low. Even in ESSDAI domains where patients with isolated anti-La/SSB had the highest frequencies of systemic activity (lymphadenopathy and muscular), the percentage of patients with moderate or high activity was lower in comparison with the combined Ro/SSA and La/SSB group. CONCLUSIONS: Patients carrying isolated La/SSB antibodies represent a very small subset of patients with a systemic SS phenotype characterised by a significant frequency of active patients in most clinical ESSDAI domains but with a relative low frequency of the highest severe organ-specific involvements. Primary SS still remains the best clinical diagnosis for this subset of patients.


Assuntos
Síndrome de Sjogren , Estudos de Coortes , Feminino , Humanos , Fenótipo , Sistema de Registros , Síndrome de Sjogren/diagnóstico
9.
Lupus ; 29(12): 1571-1593, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33100166

RESUMO

Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive therapies (hydroxychloroquine, statins and vitamin D), targeted treatment including rituximab, belimumab, and anti-TNF agents, complement inhibition and drugs based on peptides of beta-2-glycoprotein I. In addition, the report summarises potential new players, including coenzyme Q10, adenosine receptor agonists and adenosine potentiation. In each case, the report provides recommendations for clinicians, based on the current state of the art, and suggests a clinical research agenda. The initiation and development of appropriate clinical studies requires a focus on devising suitable outcome measures, including a disease activity index, an optimal damage index, and a specific quality of life index.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33111137

RESUMO

OBJECTIVES: To characterize a LN cohort over 40 years, assessing its evolution, analysing two major outcomes: the development of end-stage renal disease and mortality rates in the first 5 years after LN diagnosis. METHODS: An observational retrospective study of patients with LN, followed up from 1975 at University College Hospital. Patients were divided into four groups, depending on the decade of LN diagnosis: 1975-1985 (D1), 1986-1995 (D2), 1996-2005 (D3) and 2006-2015 (D4). Comparison between groups was performed with respect to demographic, clinical, serological and histological characteristics and outcome. RESULTS: Two hundred and nineteen patients with LN were studied. There was a change in ethnic distribution, with a decreasing proportion of Caucasians (58.6% in D1 to 31.3% in D4, P = 0.018) and increase in African-ancestry (17.2% in D1 to 39.6% in D4, P = 0.040). Serological and histological patterns changed throughout time, with a reduction in class IV nephritis (51.7% in D1 to 27.1% in D4, P = 0.035), and increase in class II nephritis (10% in D2 to 18.8% in D4, P = 0.01) and anti-extractable nuclear antigen antibody positivity (17.2% in D1 to 83.3% in D4, P = 0.0001). The 5-year mortality rates decreased from D1 (24.1%) to D2 (4%), stabilizing for the next 30 years. The 5-year progression to end-stage renal disease remained stable over the decades. CONCLUSION: Despite the changes in treatment of LN in the past 20 years, we have reached a plateau in 5-year mortality and progression to end-stage renal disease rates, suggesting that new therapeutic and management approaches, and strategies to enhance adherence, are needed to improve outcomes further in LN patients.

12.
Curr Opin Rheumatol ; 32(6): 597-608, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32890026

RESUMO

PURPOSE OF REVIEW: Conventional approaches using hydroxychloroquine, corticosteroids and immunosuppressives have improved the prognosis for systemic lupus erythematosus (SLE) patients. Unfortunately, they have reached the limits of what they can achieve and patients still die prematurely and/or find their quality of life greatly impaired. Here, we discuss the problems of assessing activity in SLE, optimizing clinical trial design and more recent biologic approaches. RECENT FINDINGS: The success of B-cell depletion using Rituximab in open clinical studies, the approval of Belimumab (blocks the B-cell activating factor BAFF) and improvements in clinical trial design, gives cause for hope. Approaches including the use of fully humanized anti-CD20 and CD19 monoclonals, blocking interferons, inhibiting Bruton's tyrosine kinase (BTK), blocking the CD40 ligand (CD40L), utilizing an analogue of the Fc[Latin Small Letter Gamma]RIIB and an IL12-23 blocker and targeting the JAK-STAT pathway have met end points in phase II and III trials. SUMMARY: For 20 years, we hoped that the successes of the biologic therapies in rheumatoid arthritis and psoriatic arthritis would be replicated in SLE but we have been generally disappointed. However, the encouraging recent results with monoclonals that block interferon and fully humanized anti-CD20 in particular, offer the prospect of a real revolution in the treatment of SLE.

13.
Clin Exp Rheumatol ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32896257

RESUMO

OBJECTIVES: We aimed to characterise the frequency of thrombocytopenia in systemic lupus erythematosus (SLE) and determine its time of onset during the course of the disease, and its severity and impact on mortality. METHODS: This was a single-centre cohort analysis of 707 patients with SLE followed for up to 40 years. We reviewed the patients' clinical notes identifying the presence of thrombocytopenia, its time of onset and ascertained other clinical and serological features of the disease. Thrombocytopenia was classified as mild (100-149x109/L), moderate (31-99x109/L) or severe (≤30x109/L platelets). It was also classified as asymptomatic, with minor bleeding or with major bleeding. RESULTS: 22.9% of patients (n=162) had thrombocytopenia prior to or during the course of SLE. Twenty-three patients (14.2%) had isolated immune thrombocytopenia (ITP) before the diagnosis of SLE. Median follow-up time was 19 years (IQR=13). Most patients (n=67, 41.4%) had mild thrombocytopenia. More than half the patients (n=98, 60.5%) developed asymptomatic thrombocytopenia and only 6 patients (3.7%) had major bleeding events in the context of thrombocytopenia. The development of severe thrombocytopenia any time during the course of SLE was associated with an increased risk of death (HR=3.57, p=0.025). Anti-phospholipid syndrome was over twice as common in patients with thrombocytopenia in the cohort. There is an increased risk of death for male patients (HR=3.41, p=0.036) who develop thrombocytopenia and for those who present with concomitant haemolytic anaemia (HR=3.07, p=0.027). CONCLUSIONS: The presence of severe thrombocytopenia (platelets ≤30x109) in patients with SLE is associated with an increased risk of death, regardless of bleeding events. Male patients with SLE and thrombocytopenia have an increased mortality risk, as have those who develop concomitant thrombocytopenia and haemolytic anaemia.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32964932

RESUMO

OBJECTIVES: Risk factors for thromboembolism in SLE are poorly understood. We hypothesized a possible role for protein C, based on its dual activity in inflammation and haemostasis and on the evidence of an association between acquired activated protein C (APC) resistance (APCR) and high-avidity anti-protein C antibodies (anti-PC) with a severe thrombotic phenotype in venous thrombosis APS patients. METHODS: In a cross-sectional study of 156 SLE patients, the presence and avidity of IgG anti-PC was established by in house-ELISA, and APCR to exogenous recombinant human APC (rhAPC) and Protac (which activates endogenous protein C) was assessed by thrombin generation-based assays. Associations with aPL profile, thrombotic history and disease activity (BILAG and SLEDAI-2K) were also established. RESULTS: Anti-PC were detected in 54.5% of patients and APCR in 59%. Anti-PC positivity was associated with APCR to both rhAPC (P <0.0001) and Protac (P =0.0001). High-avidity anti-PC, detected in 26.3% of SLE patients, were associated with APCR in patients with thrombosis only (P <0.05), and with the development of thrombosis over time (range: 0-52 years; P =0.014). High-avidity anti-PC levels correlated with SLEDAI-2K (P =0.033) and total BILAG (P =0.019); SLEDAI-2K correlated inversely with APCR to Protac (P =0.004). CONCLUSION: Anti-PC occur in patients with SLE, independently of aPL profile, and are associated with APCR. High-avidity anti-PC are associated with thrombosis and with active disease and might prove a novel marker to monitor the risk of thrombosis and disease progression in SLE.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32813314

RESUMO

OBJECTIVE: To assess cancer risk factors in incident SLE. METHODS: Clinical variables and cancer outcomes were assessed annually among incident SLE patients. Multivariate hazard regression models (over-all risk, and most common cancers) included demographics and time-dependent medications (corticosteroids, antimalarial drugs, immunosuppressants), smoking, and adjusted mean SLE Disease Activity Index-2K. RESULTS: Among 1668 patients (average 9 years follow-up), 65 cancers occurred: 15 breast, 10 non-melanoma skin, seven lung, six hematological, six prostate, five melanoma, three cervical, three renal, two each gastric, head and neck, and thyroid, and one each rectal, sarcoma, thymoma, and uterine cancers. Half of cancers (including all lung cancers) occurred in past/current smokers, versus one-third of patients without cancer. Multivariate analyses indicated over-all cancer risk was related primarily to male sex and older age at SLE diagnosis. In addition, smoking was associated with lung cancer. For breast cancer risk, age was positively and anti-malarial drugs were negatively associated. Anti-malarial drugs and higher disease activity were also negatively associated with non-melanoma skin cancer (NMSC) risk, whereas age and cyclophosphamide were positively associated. Disease activity was associated positively with hematologic and negatively with NMSC risk. CONCLUSIONS: Smoking is a key modifiable risk factor, especially for lung cancer, in SLE. Immunosuppressive medications were not clearly associated with higher risk except for cyclophosphamide and NMSC. Antimalarials were negatively associated with breast cancer and NMSC risk. SLE activity was associated positively with hematologic cancer and negatively with NMSC. Since the absolute number of cancers was small, additional follow-up will help consolidate these findings.

16.
Lancet Rheumatol ; 2(8): e485-e496, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32818204

RESUMO

Background: Juvenile-onset systemic lupus erythematosus (SLE) is a rare autoimmune rheumatic disease characterised by more severe disease manifestations, earlier damage accrual, and higher mortality than in adult-onset SLE. We aimed to use machine-learning approaches to characterise the immune cell profile of patients with juvenile-onset SLE and investigate links with the disease trajectory over time. Methods: This study included patients who attended the University College London Hospital (London, UK) adolescent rheumatology service, had juvenile-onset SLE according to the 1997 American College of Rheumatology revised classification criteria for lupus or the 2012 Systemic Lupus International Collaborating Clinics criteria, and were diagnosed before 18 years of age. Blood donated by healthy age-matched and sex-matched volunteers who were taking part in educational events in the Centre for Adolescent Rheumatology Versus Arthritis at University College London (London, UK) was used as a control. Immunophenotyping profiles (28 immune cell subsets) of peripheral blood mononuclear cells from patients with juvenile-onset SLE and healthy controls were determined by flow cytometry. We used balanced random forest (BRF) and sparse partial least squares-discriminant analysis (sPLS-DA) to assess classification and parameter selection, and validation was by ten-fold cross-validation. We used logistic regression to test the association between immune phenotypes and k-means clustering to determine patient stratification. Retrospective longitudinal clinical data, including disease activity and medication, were related to the immunological features identified. Findings: Between Sept 5, 2012, and March 7, 2018, peripheral blood was collected from 67 patients with juvenile-onset SLE and 39 healthy controls. The median age was 19 years (IQR 13-25) for patients with juvenile-onset SLE and 18 years (16-25) for healthy controls. The BRF model discriminated patients with juvenile-onset SLE from healthy controls with 90·9% prediction accuracy. The top-ranked immunological features from the BRF model were confirmed using sPLS-DA and logistic regression, and included total CD4, total CD8, CD8 effector memory, and CD8 naive T cells, Bm1, and unswitched memory B cells, total CD14 monocytes, and invariant natural killer T cells. Using these markers patients were clustered into four distinct groups. Notably, CD8 T-cell subsets were important in driving patient stratification, whereas B-cell markers were similarly expressed across the cohort of patients with juvenile-onset SLE. Patients with juvenile-onset SLE and elevated CD8 effector memory T-cell frequencies had more persistently active disease over time, as assessed by the SLE disease activity index 2000, and this was associated with increased treatment with mycophenolate mofetil and an increased prevalence of lupus nephritis. Finally, network analysis confirmed the strong association between immune phenotype and differential clinical features. Interpretation: Machine-learning models can define potential disease-associated and patient-specific immune characteristics in rare disease patient populations. Immunological association studies are warranted to develop data-driven personalised medicine approaches for treatment of patients with juvenile-onset SLE. Funding: Lupus UK, The Rosetrees Trust, Versus Arthritis, and UK National Institute for Health Research University College London Hospital Biomedical Research Centre.

17.
Arthritis Rheumatol ; 72(10): 1734-1740, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32515554

RESUMO

OBJECTIVE: In previous studies, atherosclerotic vascular events (AVEs) were shown to occur in ~10% of patients with systemic lupus erythematosus (SLE). We undertook this study to investigate the annual occurrence and potential risk factors for AVEs in a multinational, multiethnic inception cohort of patients with SLE. METHODS: A large 33-center cohort of SLE patients was followed up yearly between 1999 and 2017. AVEs were attributed to atherosclerosis based on SLE being inactive at the time of the AVE as well as typical atherosclerotic changes observed on imaging or pathology reports and/or evidence of atherosclerosis elsewhere. Analyses included descriptive statistics, rate of AVEs per 1,000 patient-years, and univariable and multivariable relative risk regression models. RESULTS: Of the 1,848 patients enrolled in the cohort, 1,710 had ≥1 follow-up visit after enrollment, for a total of 13,666 patient-years. Of these 1,710 patients, 3.6% had ≥1 AVEs attributed to atherosclerosis, for an event rate of 4.6 per 1,000 patient-years. In multivariable analyses, lower AVE rates were associated with antimalarial treatment (hazard ratio [HR] 0.54 [95% confidence interval (95% CI) 0.32-0.91]), while higher AVE rates were associated with any prior vascular event (HR 4.00 [95% CI 1.55-10.30]) and a body mass index of >40 kg/m2 (HR 2.74 [95% CI 1.04-7.18]). A prior AVE increased the risk of subsequent AVEs (HR 5.42 [95% CI 3.17-9.27], P < 0.001). CONCLUSION: The prevalence of AVEs and the rate of AVE accrual demonstrated in the present study is much lower than that seen in previously published data. This may be related to better control of both the disease activity and classic risk factors.

18.
Immunotargets Ther ; 9: 105-110, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582577

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex pathogenesis, which presents a great variability in its presentation and can affect almost all organs and systems. Multiple therapeutic targets have been discovered recently, but there also have been failed attempts to treat SLE using biologic agents. Bruton's tyrosine kinase (BTK) is a cytoplasmic tyrosine kinase expressed in several types of cells of hematopoietic origin which participate in both innate and adaptive immunity. Ibrutinib, a BTK inhibitor, is approved for the treatment of several B cell malignancies, including some types of lymphoma and leukemia. As BTK is expressed on several immune cell types, the mechanism of action of BTK also suggests the use of BTK inhibitors in the treatment of autoimmune diseases. In this review, we will summarize what is known and what has been published so far about the treatment of mouse models of SLE and the human disease, using BTK inhibitors.

19.
Rheumatology (Oxford) ; 59(7): 1489-1494, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32359070

RESUMO

The antiphospholipid antibody syndrome (APS), a chronic autoimmune thrombophilia with an increased mortality and morbidity, has been recognized for more than three decades. Unlike other autoimmune rheumatic conditions such as systemic lupus erythematosus, myositis and Sjögren's syndrome, relatively few attempts have been made to develop activity, damage or disease-specific quality of life indices for APS. In this review of the literature, we consider those attempts that have been made to develop assessment tools for patients with APS, but also reflect upon the nature of the condition, to discuss, in particular, whether an activity index is appropriate for this disease.


Assuntos
Síndrome Antifosfolipídica/fisiopatologia , Qualidade de Vida , Tromboembolia/fisiopatologia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/psicologia , Humanos , Avaliação de Resultados em Cuidados de Saúde , Tromboembolia/etiologia
20.
Rheumatology (Oxford) ; 59(11): 3314-3323, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32303057

RESUMO

OBJECTIVES: To compare membranous lupus nephritis (MLN) and proliferative lupus nephritis (PLN) with respect to survival, demographic, clinical and laboratory characteristics; and to investigate predictors of renal and patient survival. METHODS: Single-centre retrospective observational study. Patients with biopsy-proven PLN, MLN and mixed lupus nephritis were included. Groups were compared using appropriate statistical tests and survival was analysed through the Kaplan-Meier method. Cox regression analysis was performed to investigate predictors of renal and patient survival. RESULTS: A total of 187 patients with biopsy-proven lupus nephritis (135 with PLN, 38 with MLN and 14 with mixed LN) were followed for up to 42 years (median 12 years). There was a higher proportion of MLN amongst Afro-Caribbeans than amongst Caucasians (31% vs 15%, P = 0.010). Patients with MLN had significantly lower anti-dsDNA antibodies (P = 0.001) and higher C3 levels (P = 0.018) at diagnosis. Cumulative renal survival rates at 5, 10, 15 and 20 years were 91, 81, 75 and 66% for PLN and 100, 97, 92 and 84% for MLN, respectively (P = 0.028). Cumulative patient survival at 5, 10, 15 and 20 years was 94, 86, 80 and 76%, with no difference between PLN and MLN. Urinary protein-creatinine ratio above 42 mg/mmol and eGFR below 76 ml/min/1.73 m2, one year after the diagnosis of LN, were the strongest predictors of progression to end-stage renal disease. eGFR below 77 ml/min/1.73 m2, at one year, development of end-stage renal disease and Afro-Caribbean ethnicity were associated with higher mortality. CONCLUSION: Patients with MLN and PLN differ significantly regarding serological profiles and renal survival, suggesting different pathogenesis. Renal function at year one predicts renal and patient survival.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA