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1.
J Pain Res ; 13: 1925-1939, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821151

RESUMO

Cyclo-oxygenase (COX)-2 selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are important in managing acute and chronic pain secondary to inflammation. As a greater understanding of the risks of gastrointestinal (GI), cardiovascular (CV) and renal events with NSAIDs use has emerged, guidelines have evolved to reflect differences in risks among NSAIDs. Updated guidelines have yet to reflect new evidence from recent trials which showed similar CV event rates with celecoxib compared to naproxen and ibuprofen, and significantly better GI tolerability for celecoxib. This practice advisory paper aims to present consensus statements and associated guidance regarding appropriate NSAID use based on a review of current evidence by a multidisciplinary group of expert clinicians. This paper is especially intended to guide primary care practitioners within Asia in the appropriate use of NSAIDs in primary care. Following a literature review, group members used a modified Delphi consensus process to determine agreement with selected recommendations. Agreement with a statement by 75% of total voting members was defined a priori as consensus. For low GI risk patients, any nonselective NSAID plus proton pump inhibitor (PPI) or celecoxib alone is acceptable treatment when CV risk is low; for high CV risk patients, low-dose celecoxib or naproxen plus PPI is appropriate. For high GI risk patients, celecoxib plus PPI is acceptable for low CV risk patients; low-dose celecoxib plus PPI is appropriate for high CV risk patients, with the alternative to avoid NSAIDs and consider opioids instead. Appropriate NSAID prescription assumes that the patient has normal renal function at commencement, with ongoing monitoring recommended. In conclusion, appropriate NSAID use requires consideration of all risks.

2.
Arthritis Care Res (Hoboken) ; 72(12): 1820-1826, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31560454

RESUMO

OBJECTIVE: A project aimed at developing new classification criteria for systemic lupus erythematosus (SLE) is based on weighted criteria that include both laboratory and clinical items. Combinations of certain symptoms may occur commonly in SLE, which provides an argument against independently counting these items. The current study was undertaken to evaluate the interrelationship between candidate criteria items in the International Early SLE cohort and in the Euro-Lupus cohort. METHODS: The International Early SLE cohort included 389 patients, who were diagnosed within 3 years prior to the study. Data on the ACR's 1997 update of the SLE revised criteria, the Systemic Lupus International Collaborating Clinics 2012 criteria, and on 30 additional items were collected. To evaluate the interrelationship of the criteria, a tetrachoric correlation was used to assess the degree of association between different manifestations in the same organ system. The correlations identified in the International Early SLE cohort were validated in the Euro-Lupus cohort. RESULTS: A few relevant correlations were observed among specific clinical cutaneous manifestations (in particular, malar rash correlated with photosensitivity, alopecia, and oral ulcers) and serologic manifestations (anti-Sm and anti-double-stranded DNA and anti-RNA polymerase, anti-Ro and anti-La, and antiphospholipid antibodies), and these results were validated in the Euro-Lupus cohort. The associations within the mucocutaneous domain, hematologic and the specific autoantibodies suggest that within a single domain only the highest ranking item should be counted to avoid overrepresentation. CONCLUSION: Some of the candidate SLE criteria cluster within domains. Given these interrelationships, multiple criteria within a domain should not be independently counted. These results are important to consider for the structure of new SLE classification criteria.

3.
Rheumatology (Oxford) ; 59(2): 281-291, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302695

RESUMO

OBJECTIVE: This extension study of the Phase III, randomized, placebo-controlled Belimumab International SLE Study (BLISS)-52 and BLISS-76 studies allowed non-US patients with SLE to continue belimumab treatment, in order to evaluate its long-term safety and tolerability including organ damage accrual. METHODS: In this multicentre, long-term extension study (GlaxoSmithKline Study BEL112234) patients received i.v. belimumab every 4 weeks plus standard therapy. Adverse events (AEs) were assessed monthly and safety-associated laboratory parameters were assessed at regular intervals. Organ damage (SLICC/ACR Damage Index) was assessed every 48 weeks. The study continued until belimumab was commercially available, with a subsequent 8-week follow-up period. RESULTS: A total of 738 patients entered the extension study and 735/738 (99.6%) received one or more doses of belimumab. Annual incidence of AEs, including serious and severe AEs, remained stable or declined over time. Sixty-nine (9.4%) patients experienced an AE resulting in discontinuation of belimumab or withdrawal from the study. Eleven deaths occurred (and two during post-treatment follow-up), including one (cardiogenic shock) considered possibly related to belimumab. Laboratory parameters generally remained stable. The mean (s.d.) SLICC/ACR Damage Index score was 0.6 (1.02) at baseline (prior to the first dose of belimumab) and remained stable. At study year 8, 57/65 (87.7%) patients had no change in SLICC/ACR Damage Index score from baseline, indicating low organ damage accrual. CONCLUSION: Belimumab displayed a stable safety profile with no new safety signals. There was minimal organ damage progression over 8 years. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00424476 (BLISS-52), NCT00410384 (BLISS-76), NCT00732940 (BEL112232), NCT00712933 (BEL112234).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
4.
Clin Rheumatol ; 39(3): 697-702, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31691040

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of manifestations and potential to affect several organ systems. Complications arise from both disease and medications especially glucocorticoids, significantly contributing to overall morbidity and mortality. SLE predominantly affects patients during their prime productive years resulting in substantial economic burden on the patient, caregivers, and society due to direct, indirect, and intangible costs. This illness burden is compounded in developing countries with limited resources due to various disparities in healthcare delivery. Physician education and practical referral and endorsement guidelines adapted to the local setting reinforce continuity and coordinated care. Likewise, patient education, self-help programs, and shared decision-making are essential best practice in the clinics. Both physician education and patient education improve overall outcomes in chronic diseases like SLE. As a developing country with very few rheumatologists and/or lupus specialists, efficient healthcare delivery for most Filipino lupus patients remains elusive. We describe our experience in confronting these challenges through development of strategies which focus on physician and patient education. KEY POINTS: • Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a highly variable course, requiring specialized, individualized, and coordinated care by a healthcare team. • Health disparities and limited resources significantly contribute to illness burden on the patient, family, and society. • Physician education on SLE must commence at undergraduate medical school, be integrated in Internal Medicine and Pediatrics, and reinforced through specialized training in Rheumatology and related specialties. • Patient education and empowerment are integral to improving healthcare outcomes especially in a resource-limited setting.


Assuntos
Efeitos Psicossociais da Doença , Lúpus Eritematoso Sistêmico , Educação de Pacientes como Assunto , Reumatologistas/provisão & distribução , Reumatologia/educação , Países em Desenvolvimento , Mão de Obra em Saúde , Humanos
5.
Int J Rheum Dis ; 23(2): 197-202, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31692250

RESUMO

AIM: To identify clinical risk factors associated with herpes zoster (HZ) infections in systemic lupus erythematosus (SLE). METHODS: A case-control study of HZ infection was performed in SLE patients seen at the University of Santo Tomas Lupus Clinics from 2009-2014. Cases were matched 1:2 to SLE controls without HZ infection for age, sex, and disease duration. Clinical characteristics, SLE disease activity, and immunosuppressive use were compared. RESULTS: Sixty-five SLE patients (61, 93.8% female) who developed HZ were matched with 130 SLE patients without HZ. Mean age was 36.75 years (±1.35; P = 1.00) for the case group; mean SLE disease duration at first HZ infection was 6.1 years (±3.3; P = .919). Four patients had more than 1 episode of HZ. There was localized HZ in 63/65 (97%), and 2 (3%) disseminated HZ infections. The case group received higher doses of prednisone 64/65 (P = .012), mean prednisone dose 18.62 mg/d (±1.48, P < .001) and more were exposed to cyclophosphamide (Cyc) (19/65; P < .001) compared to the control group's mean prednisone dose of 11.73 mg/d (±1.16); there was Cyc use in 7/130 patients. Cyc in addition to mycophenolate mofetil (MMF) use among lupus nephritis patients conferred the highest risk for HZ infection occurrence. Hydroxychloroquine (HCQ) use reduced the risk for HZ by 87% (adjusted odds ratio 0.13, P = .003). CONCLUSION: Immunosuppressives and corticosteroid use are risk factors associated with the development of HZ in SLE. The risk for HZ increases among patients given intravenous Cyc and MMF for lupus nephritis. SLE disease activity did not show a direct association with HZ occurrence. HCQ use appeared to have a protective role against HZ infection.

6.
ACR Open Rheumatol ; 1(10): 649-656, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31872187

RESUMO

Objective: Quality of life (QOL) and quality of care (QOC) in systemic lupus erythematosus (SLE) remains poor. Satisfaction with care (SC), a QOC surrogate, correlates with health behaviors and outcomes. This study aimed to determine correlates of SC in SLE. Methods: A total of 1262 patients with SLE were recruited from various countries. Demographics, disease activity (modified Systemic Lupus Erythematosus Disease Activity Index for the Safety of Estrogens in Lupus Erythematosus: National Assessment trial [SELENA-SLEDAI]), and QOL (LupusPRO version 1.7) were collected. SC was collected using LupusPRO version 1.7. Regression analyses were conducted using demographic, disease (duration, disease activity, damage, and medications), geographic (eg, China vs United States), and QOL factors as independent predictors. Results: The mean (SD) age was 41.7 (13.5) years; 93% of patients were women. On the univariate analysis, age, ethnicity, current steroid use, disease activity, and QOL (social support, coping) were associated with SC. On the multivariate analysis, Asian participants had worse SC, whereas African American and Hispanic patients had better SC. Greater disease activity, better coping, and social support remained independent correlates of better SC. Compared with US patients, patients from China and Canada had worse SC on the univariate analysis. In the multivariate models, Asian ethnicity remained independently associated with worse SC, even after we adjusted for geographic background (China). No associations between African American or Hispanic ethnicity and SC were retained when geographic location (Canada) was added to the multivariate model. Canadian patients had worse SC when compared with US patients. Higher disease activity, better social support, and coping remained associated with better SC. Conclusion: Greater social support, coping, and, paradoxically, SLE disease activity are associated with better SC. Social support and coping are modifiable factors that should be addressed by the provider, especially in the Asian population. Therefore, evaluation of a patient's external and internal resources using a biopsychosocial model is recommended. Higher disease activity correlated with better SC, suggesting that the latter may not be a good surrogate for QOC or health outcomes.

7.
Int J Rheum Dis ; 22(10): 1933-1936, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31424178

RESUMO

INTRODUCTION: Serotonin syndrome is a potentially life-threatening condition characterized by the triad of mental status changes, autonomic instability, and neuromuscular changes. We report a case of serotonin syndrome masquerading as disease flare in a lupus nephritis patient with end-stage renal disease receiving linezolid for the treatment of infected pseudoaneurysm. CASE REPORT: A 36-year-old female lupus nephritis patient on maintenance hemodialysis for end-stage renal disease had been on multiple antibiotics, including anti-tuberculosis medications, over the past month for infected pseudoaneurysm complicating her arteriovenous fistula. Due to minimal response, she underwent pseudoaneurysmal ligation and given linezolid. Two days later, she developed chest pain, tachycardia, hypertension, tremors, later accompanied by high-grade fever, diarrhea, insomnia, and body weakness. Although fully awake and oriented, she was markedly agitated, mildly icteric, had hyperreflexia and asthenia with proximal muscle strength graded 3/5 in all extremities. Blood counts revealed anemia and thrombocytopenia; ancillary tests showed aspartate aminotransferase markedly higher than alanine aminotransferase, elevated serum lactate dehydrogenase and creatine kinase, and low C3 levels. Intravenous hydrocortisone was started for a suspected lupus flare. On the background of linezolid, isoniazid, and tramadol administration, serotonin syndrome with rhabdomyolysis was strongly considered. Offending drugs were discontinued, resulting in the dramatic improvement of symptoms and improved strength and well-being. The steroid was successfully tapered to 5 mg/day and a week later, she remained afebrile without recurrence of symptoms. CONCLUSION: Serotonin syndrome should be considered in patients on multiple serotonergic agents on the background of end-stage renal disease. Prompt recognition and distinction from lupus activity can significantly impact management decisions.


Assuntos
Falência Renal Crônica/complicações , Nefrite Lúpica/diagnóstico , Síndrome da Serotonina/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Diálise Renal , Síndrome da Serotonina/etiologia
8.
Kidney Int ; 95(1): 219-231, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30420324

RESUMO

Calcineurin inhibitors added to standard-of-care induction therapy for lupus nephritis (LN) may increase complete renal remission (CRR) rates. The AURA-LV study tested the novel calcineurin inhibitor voclosporin for efficacy and safety in active LN. AURA-LV was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial of two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) versus placebo in combination with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids for induction of remission in LN. The primary endpoint was CRR at 24 weeks; the secondary endpoint was CRR at 48 weeks. Two hundred sixty-five subjects from 79 centers in 20 countries were recruited and randomized to treatment for 48 weeks. CRR at week 24 was achieved by 29 (32.6%) subjects in the low-dose voclosporin group, 24 (27.3%) subjects in the high-dose voclosporin group, and 17 (19.3%) subjects in the placebo group (OR=2.03 for low-dose voclosporin versus placebo). The significantly greater CRR rate in the low-dose voclosporin group persisted at 48 weeks, and CRRs were also significantly more common in the high-dose voclosporin group compared to placebo at 48 weeks. There were more serious adverse events in both voclosporin groups, and more deaths in the low-dose group compared to placebo and high-dose voclosporin groups (11.2%, 1.1%, and 2.3%, respectively). These results suggest that the addition of low-dose voclosporin to mycophenolate mofetil and corticosteroids for induction therapy of active LN results in a superior renal response compared to mycophenolate mofetil and corticosteroids alone, but higher rates of adverse events including death were observed.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Ciclosporina/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Adulto , Inibidores de Calcineurina/efeitos adversos , Ciclosporina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Nefrite Lúpica/mortalidade , Masculino , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Indução de Remissão/métodos , Resultado do Tratamento , Adulto Jovem
9.
Arthritis Care Res (Hoboken) ; 71(12): 1647-1652, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-29693320

RESUMO

OBJECTIVE: Systemic lupus erythematosus (SLE) predominantly affects women. Clinical phenotype and outcomes in SLE may vary by sex and are further complicated by unique concerns that are dependent upon sex-defined roles. We aimed to describe sex differences in disease-specific quality of life (QoL) assessment scores using the Lupus Patient-Reported Outcome (LupusPRO) tool in a large international study. METHODS: Cross-sectional data from 1,803 patients with SLE on demographics, self-identified sex status, LupusPRO, and disease activity were analyzed. The LupusPRO tool has 2 constructs: health-related QoL (HRQoL) and non-HRQoL. Disease activity and damage were evaluated using the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, respectively. Nonparametric tests were used to compare QoL and disease activity by sex. RESULTS: A total of 122 men and 1,681 women with SLE participated. The mean age was similar by sex, but the damage scores were greater among men. Men fared worse on the non-HRQoL social support domain than women (P = 0.02). When comparing disease and QoL among men and women ages ≤45 years, men were found to have greater damage and worse social support than women. However, women fared significantly worse on lupus symptoms, cognition, and procreation domains with trends for worse functioning on physical health and pain-vitality domains. CONCLUSION: In the largest study of a diverse group of SLE patients, utilizing a disease-specific QoL tool, sex differences in QoL were observed on both HRQoL and non-HRQoL constructs. Although men performed worse in the social support domain, women (especially those in the reproductive age group) fared worse in other domains. These observations may assist physicians in appropriately addressing QoL issues in a sex-focused manner.


Assuntos
Nível de Saúde , Lúpus Eritematoso Sistêmico/epidemiologia , Psicometria/métodos , Qualidade de Vida , Adulto , Ásia/epidemiologia , Canadá/epidemiologia , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/psicologia , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de Doença , Distribuição por Sexo , Fatores Sexuais , Estados Unidos/epidemiologia
10.
Int J Rheum Dis ; 22(3): 425-433, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30398013

RESUMO

AIM: The aim of this manuscript is to describe the development of the Asia Pacific Lupus Collaboration (APLC) cohort. METHOD: The APLC cohort is an ongoing, prospective longitudinal cohort. Adult patients who meet either the American College of Rheumatology (ACR) Modified Classification Criteria for systemic lupus erythematosus (SLE), or the Systemic Lupus International Collaborating Clinics (SLICC) Classification Criteria, and provide informed consent are recruited into the cohort. Patients are routinely followed up at 3- to 6-monthly intervals. Information on demographics, clinical manifestations, treatment, pathology results, outcomes, and patient-reported quality of life (Short-form 36 version 2) are collected using a standardized case report form. Each site is responsible for obtaining local ethics and governance approval, patient recruitment, data collection, and data transfer into a centralized APLC database. RESULTS: The latest APLC cohort comprises 2160 patients with >12 000 visits from Australia, China, Hong Kong, Indonesia, Japan, Malaysia, Philippines, Singapore, Taiwan and Thailand. The APLC has proposed the Lupus Low Disease Activity State (LLDAS) as a treat-to-target (T2T) endpoint, and reported several retrospective and cross-sectional analyses consistent with the validity of LLDAS. Longitudinal validation of LLDAS as a T2T endpoint is currently underway. CONCLUSION: The APLC cohort is one of the largest contemporary SLE patient cohorts in the world. It is the only cohort with substantial representation of Asian patients. This cohort represents a unique resource for future clinical research including evaluation of other endpoints and quality of care.


Assuntos
Lúpus Eritematoso Sistêmico , Adolescente , Adulto , Idoso , Ásia/epidemiologia , Austrália/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Cooperação Internacional , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Gravidez , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
11.
Lupus Sci Med ; 4(1): e000214, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29214036

RESUMO

Objectives: Epstein-Barr virus (EBV) is considered an important environmental factor in SLE aetiology, but the relationship between SLE and EBV in the Filipino population is unknown. We tested associations between SLE, lupus-associated autoantibodies and seropositivity for EBV and other herpes viruses in the Filipino population. Methods: Sera from Filipino patients with SLE (n=233), unaffected first-degree relatives (FDRs, n=543) and unrelated controls (n=221) were tested for antibodies against EBV, cytomegalovirus (CMV) and herpes simplex viruses (HSV-1 and HSV-2) by standardised ELISAs. Humoral specificity against EBV nuclear antigen (EBNA)-1 was compared by solid-phase epitope mapping. Autoantibodies were detected by a bead-based multiplex assay. Results were analysed by Fisher's exact test, Student's t-test, χ2 test and one-way analysis of variance, as appropriate for the question. Results: Filipino patients with SLE had increased seroprevalence and elevated antibody concentrations against EBV viral capsid antigen (EBV-VCA), CMV, HSV-1 and HSV-2 compared with unrelated controls (p<0.05). Seropositivity for anti-EBV early antigen (EA), a marker of EBV reactivation, was dramatically increased in patients with SLE compared with unrelated controls (92.3% vs 40.4%; OR 17.15(95% CI 10.10, 30.66), p<0.0001) or unaffected FDRs (49.4%; OR 12.04(7.42, 20.74), p<0.0001), despite similar seroprevalence of EBV-VCA in patients and FDRs. In patients with SLE, EBV-EA seropositivity correlated with lupus-associated autoantibodies (p<0.001), most notably with autoantibodies against dsDNA, chromatin, Sm, SmRNP and RNP A (p<0.01). Patient and unrelated control sera reacted to the highly repetitive glycine and alanine domain of EBNA-1. An epitope spanning EBNA-1410-420 was identified in sera of patients with SLE and showed limited binding by FDR and control sera. Conclusions: Filipino patients with SLE have elevated prevalence and concentrations of antibodies against EBV, CMV, HSV-1 and HSV-2 antigens, along with altered anti-EBNA-1 specificities. EBV reactivation is more common among Filipino patients with SLE compared with healthy Filipinos and may contribute to SLE pathogenesis in this population.

12.
Ann Rheum Dis ; 75(9): 1615-21, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26458737

RESUMO

AIMS: Treating to low disease activity is routine in rheumatoid arthritis, but no comparable goal has been defined for systemic lupus erythematosus (SLE). We sought to define and validate a Lupus Low Disease Activity State (LLDAS). METHODS: A consensus definition of LLDAS was generated using Delphi and nominal group techniques. Criterion validity was determined by measuring the ability of LLDAS attainment, in a single-centre SLE cohort, to predict non-accrual of irreversible organ damage, measured using the Systemic Lupus International Collaborating Clinics Damage Index (SDI). RESULTS: Consensus methodology led to the following definition of LLDAS: (1) SLE Disease Activity Index (SLEDAI)-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity; (2) no new lupus disease activity compared with the previous assessment; (3) a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0-3) ≤1; (4) a current prednisolone (or equivalent) dose ≤7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents. Achievement of LLDAS was determined in 191 patients followed for a mean of 3.9 years. Patients who spent greater than 50% of their observed time in LLDAS had significantly reduced organ damage accrual compared with patients who spent less than 50% of their time in LLDAS (p=0.0007) and were significantly less likely to have an increase in SDI of ≥1 (relative risk 0.47, 95% CI 0.28 to 0.79, p=0.005). CONCLUSIONS: A definition of LLDAS has been generated, and preliminary validation demonstrates its attainment to be associated with improved outcomes in SLE.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Índice de Gravidade de Doença , Adulto , Feminino , Humanos , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Risco , Medição de Risco/métodos , Fatores de Tempo
13.
Int J Rheum Dis ; 18(2): 146-53, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25884458

RESUMO

Significant progress has been made in the development of therapies for systemic lupus erythematosus (SLE). These include agents which target interferons, cytokines, T lymphocytes and co-stimulatory molecules, B-lymphocytes and B stimulatory molecules. The latter are of special interest having the most robust efficacy data to date, ranging from clinical experience to clinical trials, with belimumab as the first Food and Drug Administration-approved biologic for the treatment of SLE. Given the wide disease heterogeneity, certain issues like clinical trial design and pharmacogenomics will continue to challenge drug development in SLE, there will always be a growing and compelling need for more of these drugs in order to alleviate the burden of illness in lupus patients.


Assuntos
Produtos Biológicos/uso terapêutico , Terapia Biológica/métodos , Imunidade Inata/fisiologia , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Anticorpos Monoclonais/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
15.
Int J Rheum Dis ; 17(3): 291-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24131578

RESUMO

AIM: To assess the potential risk of tuberculosis (TB) in patients treated with anti-tumor necrosis factor-alpha (TNF-α) agents in Asia. METHODS: Absolute risk increase (ARI) of TB was estimated for three widely used anti-TNF-α therapies using published standardized incidence ratios (SIR) from the French Research Axed on Tolerance of bIOtherapies registry and incidence (absolute risk [AR]) of TB in Asia. Assuming an association of increased TB risk with anti-TNF-α therapy and country TB AR (incidence), the ARI of TB by country was calculated by multiplying the SIR of the anti-TNF-α therapy by the country's TB AR. The numbers needed to harm (NNH) for each anti-TNF-α agent and numbers needed to treat (NNT) to reduce one TB event using etanercept therapy instead of adalimumab or infliximab were also calculated for each country. RESULTS: The ARI of TB with anti-TNF-α therapies in Asian countries is substantially higher than Western Europe and North America and the difference between etanercept versus the monoclonal antibodies becomes more evident. The NNH for Asian countries ranged from 8 to 163 for adalimumab, 126 to 2646 for etanercept and 12 to 256 for infliximab. The NNT to reduce one TB event using etanercept instead of adalimumab therapy ranged from 8 to 173, and using etanercept instead of infliximab therapy the NNT ranged from 13 to 283. CONCLUSION: Higher numbers of patients are at risk of developing TB with anti-TNF-α therapy in Asia compared with Western Europe and North America. The relative lower risk of TB with etanercept may be particularly relevant for Asia, an endemic area for TB.


Assuntos
Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Tuberculose/epidemiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Ásia/epidemiologia , Etanercepte , Europa (Continente) , Feminino , Humanos , Imunoglobulina G/efeitos adversos , Imunoglobulina G/uso terapêutico , Incidência , Infliximab , Masculino , América do Norte , Receptores do Fator de Necrose Tumoral/uso terapêutico , Sistema de Registros , Doenças Reumáticas/epidemiologia , Fatores de Risco
16.
Nephrology (Carlton) ; 19(1): 11-20, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23876069

RESUMO

Lupus nephritis (LN) is a common and important manifestation of systemic lupus erythematosus (SLE). Evidence suggests higher rates of lupus renal involvement in Asian populations, and maybe more severe nephritis, compared with other racial or ethnic groups. The management of LN has evolved considerably over the past three decades, based on observations from clinical studies that investigated different immunosuppressive agents including corticosteroids, cyclophosphamide, azathioprine, mycophenolic acid, calcineurin inhibitors and novel biologic therapies. This is accompanied by improvements in both the short-term treatment response rate and long-term renal function preservation. Treatment guidelines for LN have recently been issued by rheumatology and nephrology communities in U.S.A. and Europe. In view of the racial difference in disease manifestation and response to therapy, and the substantial disease burden in Asia, a panel of 15 nephrologists and rheumatologists from different Asian regions with extensive experience in lupus nephritis - the Steering Group for the Asian Lupus Nephritis Network (ALNN) - met and discussed the management of lupus nephritis in Asian patients. The group has also reviewed and deliberated on the recently published recommendations from other parts of the world. This manuscript summarizes the discussions by the group and presents consensus views on the clinical management and treatment of adult Asian patients with LN, taking into account both the available evidence and expert opinion in areas where evidence remains to be sought.


Assuntos
Nefrite Lúpica/terapia , Guias de Prática Clínica como Assunto , Ásia , Ciclofosfamida/uso terapêutico , Humanos , Imunossupressão , Nefrite Lúpica/classificação , Nefrite Lúpica/imunologia , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico
17.
Arthritis Rheum ; 65(8): 2143-53, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23754628

RESUMO

OBJECTIVE: To identify predictors of moderate-to-severe systemic lupus erythematosus (SLE) flare in 562 patients treated with standard therapy alone in phase III belimumab trials, and to evaluate the impact of standard therapies on preventing flares. METHODS: Post hoc analysis assessed baseline demographics, disease activity, and biomarkers in patients with and those without flare at treatment weeks 24 and 52. Severe flare was defined by the modified SLE Flare Index (SFI) and the development of any new British Isles Lupus Assessment Group (BILAG) A domain score. Severe and moderate flare was defined by development of 1 new BILAG A domain score or 2 new BILAG B domain scores. Baseline characteristics associated with a ≥10% absolute difference or a ≥50% increase in flare rates were considered predictive. RESULTS: Frequencies of flares over 52 weeks according to the SFI, any new BILAG A domain score, and 1 new BILAG A domain score or 2 new BILAG B domain scores were 23.7%, 23.1%, and 32.0%, respectively. Flare predictors by univariate analysis on all 3 indices at weeks 24 and 52 were a score ≥12 on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI); anti-double-stranded DNA (anti-dsDNA) positivity; proteinuria (≥0.5 gm/24 hours); BILAG renal, vasculitic, and hematologic scores; elevated C-reactive protein levels; and B lymphocyte stimulator (BLyS) levels ≥2 ng/ml. Independent predictors by multivariate analysis at week 52 were SELENA-SLEDAI and/or BILAG renal involvement and anti-dsDNA ≥200 IU/ml (on all 3 indices); SELENA-SLEDAI and/or BILAG neurologic and vasculitic involvement (on 2 indices: any new BILAG A domain score and 1 new BILAG A domain score or 2 new BILAG B domain scores); BLyS levels ≥2 ng/ml (on 2 indices: the SFI and 1 new BILAG A domain score or 2 new BILAG B domain scores); and low C3 level (on the SFI). Baseline medications did not significantly decrease or increase moderate-to-severe SLE flare risk. CONCLUSION: Patients who were receiving standard SLE therapy and had renal, neurologic, or vasculitic involvement, elevated anti-dsDNA or BLyS levels, or low C3 had increased risk of clinically meaningful flare over 1 year. Hydroxychloroquine use was not predictive.


Assuntos
Lúpus Eritematoso Sistêmico/patologia , Placebos/uso terapêutico , Adulto , Anticorpos Antinucleares/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , Fator Ativador de Células B/sangue , Complemento C3/análise , DNA/imunologia , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/complicações , Nefrite Lúpica/patologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Masculino , Valor Preditivo dos Testes , Prednisolona/uso terapêutico , Índice de Gravidade de Doença
18.
Int J Rheum Dis ; 16(6): 625-36, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24382275

RESUMO

Lupus nephritis (LN) is a common and important manifestation of systemic lupus erythematosus (SLE). Evidence suggests higher rates of lupus renal involvement in Asian populations, and maybe more severe nephritis, compared with other racial or ethnic groups. The management of LN has evolved considerably over the past three decades, based on observations from clinical studies that investigated different immunosuppressive agents including corticosteroids, cyclophosphamide, azathioprine, mycophenolic acid, calcineurin inhibitors and novel biologic therapies. This is accompanied by improvements in both the short-term treatment response rate and long-term renal function preservation. Treatment guidelines for LN have recently been issued by rheumatology and nephrology communities in U.S.A. and Europe. In view of the racial difference in disease manifestation and response to therapy, and the substantial disease burden in Asia, a panel of 15 nephrologists and rheumatologists from different Asian regions with extensive experience in lupus nephritis - the Steering Group for the Asian Lupus Nephritis Network (ALNN) - met and discussed the management of lupus nephritis in Asian patients. The group has also reviewed and deliberated on the recently published recommendations from other parts of the world. This manuscript summarizes the discussions by the group and presents consensus views on the clinical management and treatment of adult Asian patients with LN, taking into account both the available evidence and expert opinion in areas where evidence remains to be sought.


Assuntos
Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrologia/normas , Reumatologia/normas , Adulto , Ásia/epidemiologia , Grupo com Ancestrais do Continente Asiático , Consenso , Quimioterapia Combinada , Medicina Baseada em Evidências/normas , Fidelidade a Diretrizes , Humanos , Imunossupressores/efeitos adversos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/etnologia , Padrões de Prática Médica/normas , Índice de Gravidade de Doença , Resultado do Tratamento
19.
Ann Rheum Dis ; 71(11): 1833-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22550315

RESUMO

OBJECTIVE: To evaluate the effects of belimumab versus placebo, plus standard systemic lupus erythematosus (SLE) therapy, on organ domain-specific SLE disease activity. METHODS: Data obtained after 52 weeks of treatment from two phase III trials (BLISS-52 and BLISS-76) comparing belimumab 1 and 10 mg/kg versus placebo, plus standard therapy, in 1684 autoantibody-positive patients were analysed post hoc for changes in British Isles Lupus Assessment Group (BILAG) and Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ domain scores. RESULTS: At baseline, the domains involved in the majority of patients were musculoskeletal and mucocutaneous by both BILAG and SELENA-SLEDAI, and immunological by SELENA-SLEDAI. At 52 weeks, significantly more patients treated with belimumab versus placebo had improvement in BILAG musculoskeletal and mucocutaneous domains (1 and 10 mg/kg), and in SELENA-SLEDAI mucocutaneous (10 mg/kg), musculoskeletal (1 mg/kg) and immunological (1 and 10 mg/kg) domains. Improvement was also observed in other organ systems with a low prevalence (≤16%) at baseline, including the SELENA-SLEDAI vasculitis and central nervous system domains. Significantly fewer patients treated with belimumab versus placebo had worsening in the BILAG haematological domain (1 mg/kg) and in the SELENA-SLEDAI immunological (10 mg/kg), haematological (10 mg/kg) and renal (1 mg/kg) domains. CONCLUSIONS: Belimumab treatment improved overall SLE disease activity in the most common musculoskeletal and mucocutaneous organ domains. Less worsening occurred in the haematological, immunological and renal domains.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Fator Ativador de Células B/antagonistas & inibidores , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados , Fator Ativador de Células B/efeitos dos fármacos , Método Duplo-Cego , Feminino , Nível de Saúde , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Masculino , Índice de Gravidade de Doença , Resultado do Tratamento
20.
Ann Rheum Dis ; 71(5): 777-84, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22233601

RESUMO

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic multisystem genetically complex autoimmune disease characterised by the production of autoantibodies to nuclear and cellular antigens, tissue inflammation and organ damage. Genome-wide association studies have shown that variants within the major histocompatibility complex (MHC) region on chromosome 6 confer the greatest genetic risk for SLE in European and Chinese populations. However, the causal variants remain elusive due to tight linkage disequilibrium across disease-associated MHC haplotypes, the highly polymorphic nature of many MHC genes and the heterogeneity of the SLE phenotype. METHODS: A high-density case-control single nucleotide polymorphism (SNP) study of the MHC region was undertaken in SLE cohorts of Spanish and Filipino ancestry using a custom Illumina chip in order to fine-map association signals in these haplotypically diverse populations. In addition, comparative analyses were performed between these two datasets and a northern European UK SLE cohort. A total of 1433 cases and 1458 matched controls were examined. RESULTS: Using this transancestral SNP mapping approach, novel independent loci were identified within the MHC region in UK, Spanish and Filipino patients with SLE with some evidence of interaction. These loci include HLA-DPB1, HLA-G and MSH5 which are independent of each other and HLA-DRB1 alleles. Furthermore, the established SLE-associated HLA-DRB1*15 signal was refined to an interval encompassing HLA-DRB1 and HLA-DQA1. Increased frequencies of MHC region risk alleles and haplotypes were found in the Filipino population compared with Europeans, suggesting that the greater disease burden in non-European SLE may be due in part to this phenomenon. CONCLUSION: These data highlight the usefulness of mapping disease susceptibility loci using a transancestral approach, particularly in a region as complex as the MHC, and offer a springboard for further fine-mapping, resequencing and transcriptomic analysis.


Assuntos
Proteínas de Ciclo Celular/genética , Predisposição Genética para Doença , Cadeias beta de HLA-DP/genética , Antígenos HLA-G/genética , Lúpus Eritematoso Sistêmico/genética , Complexo Principal de Histocompatibilidade/genética , Estudos de Casos e Controles , Mapeamento Cromossômico , Estudos de Coortes , Grupos Étnicos/genética , Marcadores Genéticos , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Filipinas/epidemiologia , Polimorfismo de Nucleotídeo Único , Espanha/epidemiologia
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