RESUMO
OBJECTIVE: To assess the economic burden of moderate to severe osteoarthritis (OA) management for patients and the health care system in Greece. DESIGN: A noninterventional, cross-sectional, prospective, epidemiological analysis of data from the medical records of patients with moderate to severe OA, recruited in a single visit from 9 sites in Greece. Outcomes included health care resource use (direct/indirect costs) associated with this patient population. RESULTS: A total of 164 patients were included in the analysis: mean age was 70.5 years, and the majority of participants were females (78.7%). The presence of comorbidities was reported by 87.2% of patients, with hypertension being the most frequently reported (53.7%). Paracetamol was the most commonly used analgesic treatment (96%), followed by systemic nonsteroidal anti-inflammatory drugs (NSAIDs) (75%) and opioids (50%). The mean overall annual direct costs per patient was estimated at 1,675.3, with approximately half incurred by the National Health Insurance Fund, whereas the mean overall annual indirect cost (absenteeism of patients and informal caregivers) was estimated at 3,501.4. Joint replacement (JR) procedures and paid care were the major drivers of annual direct costs in this patient population (4,326.3 and 9,360.0, respectively). CONCLUSIONS: This real-world analysis of direct and indirect costs confirmed the substantial economic burden imposed by moderate to severe OA to the health care system and the patients. Our findings emphasize the need for interventions to enhance disease management, to improve patients' health outcomes and reduce the global burden of OA on society.
RESUMO
BACKGROUND: Osteoarthritis (OA) represents a leading cause of disability with limited data available for the Greek patients. OBJECTIVES: To evaluate the impact of moderate to severe symptomatic hip/knee OA under treatment on physical performance and quality of life. METHODS: A non-interventional, cross-sectional, epidemiological study of patients with moderate/severe OA, recruited in a single visit from 9 expert sites in Athens, Greece. Assessments were based on commonly used outcome scales: the Hip disability and Osteoarthritis Outcome Score (HOOS), the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the EuroQol-5-Dimensions 3-levels questionnaire (EQ-5D-3L). RESULTS: One hundred sixty-four patients were included in the analysis. Most of the patients were females (78.7%), with a mean age of 70.5 ± 10.2 years. Comorbidities were reported by 87.2% of patients with hypertension being the most frequently reported (53.7%), followed by dyslipidemia (31.1%), obesity (24.4%) and diabetes mellitus (23.2%). Paracetamol was the most common treatment (96%), followed by NSAIDs (75%), opioids (50%) and locally applied medications (42.7%). Both hip and knee OA patients showed substantial deterioration in health-related quality of life (QoL) and health status as reflected by the HOOS/KOOS (Function in sport and recreation was the most impaired subscale, followed by Hip- or Knee-related QoL). The mean EQ-5D-3L index score was 0.396 ± 0.319 and the mean EQ-VAS score was 52.1 ± 1.9. When compared indirectly to the local population norms our OA population had worse QoL indices. CONCLUSION: Our findings suggest the functional disability and impaired QoL of Greek patients with moderate/severe hip/knee OA under treatment emphasizing the need for novel treatments that will reduce the burden of the disease.
Assuntos
Osteoartrite do Quadril , Osteoartrite do Joelho , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Qualidade de Vida , Estudos Transversais , Grécia/epidemiologia , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Quadril/diagnóstico , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Quadril/epidemiologia , Desempenho Físico FuncionalRESUMO
BACKGROUND: European data indicate that systemic sclerosis (SSc)-related death rates are increasing, thus raising concerns about SSc's optimal management. Herein, we describe current treatment modalities and drug survival in a real-life SSc cohort. METHODS: Details on immunosuppressive/antiproliferative (methotrexate, mycophenolate, cyclophosphamide, azathioprine, rituximab, tocilizumab) and vasoactive agent [(endothelin receptor antagonists (ERAs), sildenafil, iloprost, and calcium channel blockers (CCB)] administration during the disease course (11.8 ± 8.4 years, mean + SD) of 497 consecutive patients examined between 2016 and 2018 were retrospectively recorded. Drug survival was assessed by Kaplan-Meier analysis. RESULTS: Methotrexate was the most frequently administered immunosuppressive/antiproliferative agent (53% of patients), followed by cyclophosphamide (26%), mycophenolate (12%), and azathioprine (11%). Regarding vasoactive agents, CCB had been ever administered in 68%, ERAs in 38%, iloprost in 7%, and sildenafil in 7% of patients; 23% of patients with pulmonary fibrosis had never received immunosuppressive/antiproliferative agents, 33% of those with digital ulcers had never received ERAs, iloprost, or sildenafil, whereas 19% of all patients had never received either immunosuppressive/antiproliferative or other than CCB vasoactive agents. Survival rates of methotrexate, cyclophosphamide, and mycophenolate differed significantly, being 84/75%, 59/43%, and 74/63% at 12/24 months, respectively, with inefficacy being the most frequent discontinuation cause. Conversely, CCB, ERAs, and sildenafil had high and comparable retention rates of 97/91%, 88/86%, and 80/80%, respectively. CONCLUSIONS: Existing therapeutic limitations indicate that more evidence-based treatment is warranted for successful management of SSc. Vasculopathy seems to be managed more rigorously, but the low retention rates of immunosuppressive/antiproliferative drugs suggest that effective and targeted disease-modifying agents are warranted.
Assuntos
Preparações Farmacêuticas/administração & dosagem , Escleroderma Sistêmico/tratamento farmacológico , Adulto , Idoso , Azatioprina/uso terapêutico , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Antagonistas dos Receptores de Endotelina/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Preparações Farmacêuticas/classificação , Estudos Retrospectivos , Vasoconstritores/uso terapêuticoRESUMO
OBJECTIVE: This study aimed to analyse the phenotype of systemic lupus erythematosus (SLE) at first presentation and during follow-up in a newly established SLE cohort based at 'Attikon' University Hospital. The hospital combines primary, secondary and tertiary care for the region of Western Attica, Greece. METHODS: This study comprised a mixed prevalent and incident cohort of 555 Caucasian patients diagnosed with SLE according to American College of Rheumatology 1997 criteria and/or the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria. Demographic and clinical characteristics, patterns of severity, treatments and SLICC damage index were recorded for each patient at the time of diagnosis and at last evaluation. RESULTS: The mean age at lupus diagnosis was 38.3 years (standard deviation = 15.6 years), with a median disease duration at last follow-up of two years (interquartile range 1-11). At initial presentation, the most common 'classification' manifestations were arthritis (73.3%), acute cutaneous lupus (65%) and unexplained fever (25%), while among symptoms not included in any criteria set, Raynaud's phenomenon (33%) was the most common. Kidney and neuropsychiatric involvement as presenting manifestations were present in 10.3% and 11.5% cases, respectively. Irreversible damage accrual was present in 17.8% within six months of disease diagnosis, attributed mainly to thrombotic and neuropsychiatric disease. At last evaluation, 202 (36.4%) patients had developed severe disease, of whom more than half were treated with pulse cyclophosphamide. CONCLUSION: In this cohort of Caucasian patients, lupus nephritis is not as common as in older cohorts, while neuropsychiatric disease is emerging as a major frontier in lupus prevention and care. These data may help to document changes in the natural history and treatment of SLE over time and may have implications for its early recognition and management.
Assuntos
Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/epidemiologia , Nefrite Lúpica/epidemiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/epidemiologia , Reumatologia/normas , Adulto , Comorbidade , Feminino , Grécia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Índice de Gravidade de Doença , População Branca , Adulto JovemRESUMO
The study examined the hypothesis that hypoperfusion in brain areas known to be involved in emotional disturbances in primary psychiatric disorders is also linked to emotional difficulties in systemic lupus erythematosus (SLE) and that these are not secondary to the physical and social burden incurred by the disease. Nineteen SLE patients without overt neuropsychiatric manifestations (non-NPSLE), 31 NPSLE patients, and 23 healthy controls were examined. Dynamic susceptibility contrast MRI was used and cerebral blood flow and cerebral blood volume values were estimated in six manually selected regions of interest of brain regions suspected to play a role in anxiety and depression (dorsolateral prefrontal cortex, ventromedial prefrontal cortex, anterior cingulate cortex, hippocampi, caudate nuclei and putamen). NPSLE patients reported high rates of anxiety and depression symptomatology. Significantly reduced cerebral blood flow and cerebral blood volume values were detected in the NPSLE group compared to healthy controls in the dorsolateral prefrontal cortex and ventromedial prefrontal cortex, bilaterally. Within the NPSLE group, anxiety symptomatology was significantly associated with lower perfusion in frontostriatal regions and in the right anterior cingulate gyrus. Importantly, the latter associations appeared to be specific to anxiety symptoms, as they persisted after controlling for depression symptomatology and independent of the presence of visible lesions on conventional MRI. In conclusion, hypoperfusion in specific limbic and frontostriatal regions is associated with more severe anxiety symptoms in the context of widespread haemodynamic disturbances in NPSLE.
Assuntos
Ansiedade/etiologia , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular , Depressão/etiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico por imagem , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Adulto , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
BACKGROUND: Examining urban-rural differences can provide insights into susceptibility or modifying factors of complex diseases, yet limited data exist on systemic lupus erythematosus (SLE). OBJECTIVE: To study SLE risk, manifestations and severity in relation to urban versus rural residence. METHODOLOGY: Cross-sectional analysis of the Crete Lupus Registry. Demographics, residency history and clinical data were obtained from interviews and medical records ( N=399 patients). Patients with exclusively urban, rural or mixed urban/rural residence up to enrolment were compared. RESULTS: The risk of SLE in urban versus rural areas was 2.08 (95% confidence interval: 1.66-2.61). Compared with rural, urban residence was associated with earlier (by almost seven years) disease diagnosis - despite comparable diagnostic delay - and lower female predominance (6.8:1 versus 15:1). Rural patients had fewer years of education and lower employment rates. Smoking was more frequent among urban, whereas pesticide use was increased among rural patients. A pattern of malar rash, photosensitivity, oral ulcers and arthritis was more prevalent in rural patients. Residence was not associated with organ damage although moderate/severe disease occurred more frequently among rural-living patients (multivariable adjusted odds ratio: 2.17, p=0.011). CONCLUSION: Our data suggest that the living environment may influence the risk, gender bias and phenotype of SLE, not fully accounted for by sociodemographic factors.
Assuntos
Meio Ambiente , Lúpus Eritematoso Sistêmico/epidemiologia , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adulto , Idoso , Comorbidade , Estudos Transversais , Feminino , Grécia/epidemiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros , Características de Residência , Adulto JovemRESUMO
Systemic lupus erythematosus (SLE) is characterized by aberrant production of auto-antibodies and a sexual dimorphism both in the phenotypic expression and frequency of the disease between males and females. The striking female predominance was initially attributed primarily to sex hormones. However, recent data challenge this simplistic view and point more towards genetic and epigenetic factors accounting for this difference. More specifically, several SLE-associated single-nucleotide polymorphisms (SNPs) have been found to play an important role in the gender predilection in SLE. Their effect is mediated through their involvement in sex-hormone and immune system signalling and dysregulation of the expression of genes and miRNAs pertinent to the immune system. Additionally, the genetic factors are interchangeably associated with epigenetic modifications such as DNA methylation and histone modification, thus revealing a highly complex network of responsible mechanisms. Of importance, disturbance in the epigenetic process of X chromosome inactivation in females as well as in rare X chromosome abnormalities leads to increased expression of X-linked immune-related genes and miRNAs, which might predispose females to SLE. Microbiota dysbiosis has also been implicated in the sexual dimorphism by the production of oestrogens within the gut and the regulation of oestrogen-responsive immune-related genes. Sexual dimorphism in SLE is an area of active research, and elucidation of its molecular basis may facilitate ongoing efforts towards personalized care.
Assuntos
Cromossomos Humanos X/genética , Lúpus Eritematoso Sistêmico/genética , Fatores Sexuais , Metilação de DNA , Disbiose , Epigênese Genética , Feminino , Hormônios Esteroides Gonadais/fisiologia , Humanos , Sistema Imunitário , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , MicroRNAs/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Interferon regulatory factor 5 (IRF5) regulates type I interferon (IFN)-responsive genes, and has been one of the most consistently associated genes with systemic lupus erythematosus (SLE). We sought to investigate whether IRF5 haplotypes are associated with risk for SLE in the genetically homogeneous Greek population of the island of Crete, as well as whether these haplotypes are associated with increased type I IFN. 322 SLE patients and 247 healthy controls from Crete were genotyped for rs2004640, rs3807306, rs10488631 and rs2280714 SNPs of IRF5 gene by using Taqman primer-probe sets. Type I IFN levels were measured using a functional reporter cell assay. All IRF5 SNPs examined were found to be associated with SLE in univariate case-control analysis. The 4 SNPs formed 5 major haplotypes and the Neanderthal-derived TACA risk haplotype was present in Crete and enriched in the SLE cases (OR=2.01, P=0.0003). Serum IFN levels were measured in a subset of the SLE patients, and carriage of the TACA haplotype was associated with higher circulating type I IFN levels (P=0.037). This study demonstrates the association of IRF5 with an increased susceptibility for SLE in the population of Crete and emphasizes the association of the Neanderthal-derived IRF5 haplotype with SLE susceptibility. Patients carrying allele the Neanderthal allele C had greater type I IFN, supporting a functional consequence of this polymorphism.
Assuntos
Predisposição Genética para Doença , Fatores Reguladores de Interferon/genética , Lúpus Eritematoso Sistêmico/genética , Adulto , Animais , Estudos de Casos e Controles , Feminino , Grécia , Haplótipos , Humanos , Interferon Tipo I/sangue , Interferon Tipo I/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Homem de Neandertal/genéticaRESUMO
OBJECTIVES: Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). METHODS: Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. RESULTS: Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. CONCLUSIONS: Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.
Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Neoplasias dos Genitais Femininos/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Anticoncepcionais Orais Hormonais/uso terapêutico , Técnica Delphi , Detecção Precoce de Câncer , Terapia de Reposição de Estrogênios , Serviços de Planejamento Familiar , Feminino , Preservação da Fertilidade , Monitorização Fetal , Humanos , Menopausa , Cuidado Pré-Concepcional , Gravidez , Técnicas de Reprodução Assistida , Medição de RiscoRESUMO
OBJECTIVES: Several rheumatoid arthritis (RA) susceptibility loci have also been found to be associated with psoriatic arthritis (PsA), demonstrating that there is a degree of genetic overlap between various autoimmune diseases. We sought to investigate whether single nucleotide polymorphisms (SNPs) mapping to previously reported RA and/or PsA susceptibility loci, including PLCL2, CCL21, REL, STAT4, CD226, PTPN22, and TYK2, are associated with risk for the two diseases in a genetically homogeneous Greek population. METHOD: This study included 392 RA patients, 126 PsA patients, and 521 healthy age- and sex-matched controls from Greece. Genotyping of the SNPs was performed with Taqman primer/probe sets. Bioinformatic analysis was performed using BlastP, PyMOL, and Maestro and Desmond. RESULTS: A significant association was detected between the GC genotype of rs34536443 (TYK2) in both the PsA and RA cohorts. The C allele of this SNP was associated with PsA only. Evidence for association with PsA was also found for the GG genotype and G allele of the rs10181656 SNP of STAT4. The TC genotype of the rs763361 SNP of CD226 was associated with PsA only. CONCLUSIONS: Genetic overlap between PsA and RA was detected for the rs34536443 SNP of the TYK2 gene within a Greek population. An association of STAT4 (rs10181656) with PsA was confirmed whereas CD226 (rs763361) was associated with PsA but not with RA, in contrast to previous reports. The different findings of this study compared to previous ones highlights the importance of comparative studies that include various ethnic or racial populations.
Assuntos
Artrite Psoriásica/genética , Artrite Reumatoide/genética , População Branca/genética , Adulto , Idoso , Alelos , Antígenos de Diferenciação de Linfócitos T/genética , Estudos de Casos e Controles , Quimiocina CCL21/genética , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Técnicas de Genotipagem , Grécia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Proteínas Oncogênicas v-rel/genética , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Fator de Transcrição STAT4/genética , TYK2 Quinase/genéticaRESUMO
Analyses of the medical and economic burden of chronic disorders such as systemic lupus erythematosus (SLE) are valuable for clinical and health policy decisions. We performed a chart-based review of 215 adult SLE patients with active autoantibody-positive disease at the predefined ratio of 30% severe (involvement of major organs requiring treatment) and 70% non-severe, followed at seven hospital centres in Greece. We reviewed 318 patients consecutively registered over three months (sub-study). Disease activity, organ damage, flares and healthcare resource utilization were recorded. Costs were assessed from the third-party payer perspective. Severe SLE patients had chronic active disease more frequently (22.4% vs 4.7%), higher average SLE disease activity index (SLEDAI) (10.5 vs 6.1) and systemic lupus international collaborating clinics (SLICC) damage index (1.1 vs 0.6) than non-severe patients. The mean annual direct medical cost was 3741 for severe vs 1225 for non-severe patients. Severe flares, active renal disease and organ damage were independent cost predictors. In the sub-study, 19% of unselected patients were classified as severe SLE, and 30% of them had chronic active disease. In conclusion, this is the first study to demonstrate the significant clinical and financial burden of Greek SLE patients with active major organ disease. Among them, 30% display chronic activity, in spite of standard care, which represents a significant unmet medical need.
Assuntos
Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/economia , Adulto , Autoanticorpos/imunologia , Feminino , Grécia , Custos de Cuidados de Saúde , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Cyclophosphamide (CYC) is used in severe neuropsychiatric systemic lupus erythematosus (NPSLE), but long-term data regarding its efficacy and safety are lacking. We identified NPSLE cases who received CYC from two centres during the period 1999-2013 and had regular follow-up. General and neuropsychiatric outcome at last follow-up visit were determined, and major complications were documented. CYC was administered in 50 neuropsychiatric events. Median age was 45.0 years and 46% of patients were positive for antiphospholipid antibodies. Most frequent indications were psychosis (11 cases), polyneuropathy (six cases), and cerebrovascular disease, seizure disorder and cranial neuropathy (five cases). CYC was mainly administered as monthly pulses (median number: 8.0 (range 3-26), median cumulative dose: 7.2 g (range 2.4-33.8)). Cases were followed for a median of 46.5 months (range 5-408). At last follow-up, partial or complete response of NPSLE was observed in 84% of events; 10% had stable disease, whereas the remaining 6% failed to improve or worsened and were rescued with rituximab. In events that responded to CYC, maintenance therapy consisted of azathioprine in 31 events (65.9%), bimonthly or quarterly pulses of intravenous CYC in nine (19.1%), and mycophenolate mofetil in five (10.6%). Relapses were observed in six events (12%) at median eight months after initial response. No malignancies were observed, yet there were three cases of severe infections. Amenorrhea was recorded in three patients, who had not received gonadal protection. In conclusion, cyclophosphamide was efficacious and led to sustained response of severe NPSLE in a cohort with long follow-up.
Assuntos
Ciclofosfamida/administração & dosagem , Glucocorticoides/administração & dosagem , Imunossupressores/administração & dosagem , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Antifosfolipídeos/imunologia , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: We aimed to describe patterns of disease activity during infliximab plus methotrexate (MTX) treatment and explore C-reactive protein (CRP) as a potential marker of early response. METHODS: REMARK was a phase IV, open-label, observational study of infliximab-naïve adults with rheumatoid arthritis (RA) who received infliximab 3 mg/kg plus MTX for 14 weeks. Treatment response was evaluated in 3 subgroups: patients with <1 year disease duration who were TNF-inhibitor (TNFi)-naïve, patients with ≥ 1 year disease duration who were TNFi-naïve, and patients who had previous TNFi failure or intolerance. In post hoc analyses, CRP kinetic profiles were analysed by EULAR response (good, moderate, non-response) in REMARK and in an independent replication with data from the ASPIRE study. RESULTS: In the efficacy-evaluable population (n=662), median 28-joint disease activity score (DAS28) improved from baseline to Week 14 (5.2 vs. 3.6, p<0.0001). Regardless of disease history subgroup, most patients had good or moderate EULAR responses at Weeks 2 (64.9%), 6 (74.1%), and 14 (73.6%). DAS28 and its components did not differ across patient subgroups. Disease flare occurred in 16.2% of patients. CRP levels declined markedly at Week 2, but patients who were EULAR non-responders at Week 14 showed a CRP rebound at Weeks 6 and 14. This CRP pattern was independently replicated in data from ASPIRE. Adverse events were consistent with the known risk profile of infliximab. CONCLUSIONS: Infliximab plus MTX treatment in patients with RA rapidly diminished disease activity. A unique pattern of CRP rebound was found in non-responders early in treatment.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/metabolismo , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Quimioterapia Combinada , Feminino , Humanos , Infliximab , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , TerapêuticaRESUMO
Alleles of interferon (IFN) regulatory factor 8 (IRF8) are associated with susceptibility to both systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Although high-type I IFN is thought to be causal in SLE, type I IFN is used as a therapy in MS. We investigated whether IRF8 alleles were associated with type I IFN levels or serologic profiles in SLE and MS. Alleles that have been previously associated with SLE or MS were genotyped in SLE and MS patients. The MS-associated rs17445836G allele was associated with anti-double-stranded DNA (dsDNA) autoantibodies in SLE patients (meta-analysis odds ratio=1.92). The same allele was associated with decreased serum IFN activity in SLE patients with anti-dsDNA antibodies, and with decreased type I IFN-induced gene expression in peripheral blood mononuclear cell from anti-dsDNA-negative SLE patients. In secondary progressive MS patients, rs17445836G was associated with decreased serum type I IFN. Rs17445836G was associated with increased IRF8 expression in SLE patient B cells. In summary, IRF8 rs17445836G is associated with human autoimmune disease characterized by low-type I IFN levels, and this may have pharmacogenetic relevance as type I IFN is modulated in SLE and MS. The association with autoantibodies and increased IRF8 expression in B cells supports a role for rs17445836G in humoral tolerance.
Assuntos
Fatores Reguladores de Interferon/genética , Interferon Tipo I/sangue , Lúpus Eritematoso Sistêmico/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único , Autoanticorpos/imunologia , Estudos de Casos e Controles , DNA/imunologia , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Esclerose Múltipla/sangue , Esclerose Múltipla/imunologiaRESUMO
Renal podocytes and their slit diaphragms ensure the integrity of renal basement membrane and prevent urinary protein loss. We have previously reported that decreases of the podocyte slit diaphragm proteins nephrin and podocin represent early events in the podocytopathy of lupus nephritis (LN). We asked whether immunosuppressive agents such as glucocorticoids and cyclophosphamide may have direct effects on podocytes. We assessed in New Zealand Black/New Zealand White (NZB/W) F1 LN mice glomerular nephrin and podocin expression and localization by the use of Western blot and immunofluorescence; mRNA levels were measured by real-time polymerase chain reaction (PCR) and renal histology by light and electron microscopy. Early treatment with glucocorticoids and cyclophosphamide halted the histologic alterations associated with LN, preserving podocyte foot processes. Nephrin and podocin protein expression significantly increased in both glucocorticoid and cyclophosphamide groups as early as after three months of therapy. Real-time PCR revealed similar enhancement in nephrin and podocin mRNA levels after three to six months of treatment. This study documents that early treatment in experimental LN with glucocorticoids or cyclophosphamide preserves slit diaphragm proteins in podocytes and halts histological changes of the glomeruli, thus raising the possibility of a direct protective effect of these drugs on podocytes.
Assuntos
Ciclofosfamida/farmacologia , Glucocorticoides/farmacologia , Imunossupressores/farmacologia , Nefrite Lúpica/tratamento farmacológico , Animais , Western Blotting , Modelos Animais de Doenças , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Nefrite Lúpica/fisiopatologia , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos NZB , Podócitos/efeitos dos fármacos , Podócitos/patologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fatores de TempoRESUMO
BACKGROUND: Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD). METHODS: The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement. RESULTS: Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extra-articular manifestations of PsA. Five overarching principles and a research agenda were defined. CONCLUSION: These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Antirreumáticos/efeitos adversos , Comorbidade , Europa (Continente) , Medicina Baseada em Evidências/métodos , Glucocorticoides/uso terapêutico , Humanos , Cooperação Internacional , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVE: A patient-derived composite measure of the impact of rheumatoid arthritis (RA), the rheumatoid arthritis impact of disease (RAID) score, takes into account pain, functional capacity, fatigue, physical and emotional wellbeing, quality of sleep and coping. The objectives were to finalise the RAID and examine its psychometric properties. METHODS: An international multicentre cross-sectional and longitudinal study of consecutive RA patients from 12 European countries was conducted to examine the psychometric properties of the different combinations of instruments that might be included within the RAID combinations scale (numeric rating scales (NRS) or various questionnaires). Construct validity was assessed cross-sectionally by Spearman correlation, reliability by intraclass correlation coefficient (ICC) in 50 stable patients, and sensitivity to change by standardised response means (SRM) in 88 patients whose treatment was intensified. RESULTS: 570 patients (79% women, mean ± SD age 56 ± 13 years, disease duration 12.5 ± 10.3 years, disease activity score (DAS28) 4.1 ± 1.6) participated in the validation study. NRS questions performed as well as longer combinations of questionnaires: the final RAID score is composed of seven NRS questions. The final RAID correlated strongly with patient global (R=0.76) and significantly also with other outcomes (DAS28 R=0.69, short form 36 physical -0.59 and mental -0.55, p<0.0001 for all). Reliability was high (ICC 0.90; 95% CI 0.84 to 0.94) and sensitivity to change was good (SRM 0.98 (0.96 to 1.00) compared with DAS28 SRM 1.06 (1.01 to 1.11)). CONCLUSION: The RAID score is a patient-derived composite score assessing the seven most important domains of impact of RA. This score is now validated; sensitivity to change should be further examined in larger studies.
Assuntos
Artrite Reumatoide/reabilitação , Indicadores Básicos de Saúde , Adaptação Psicológica , Adulto , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/psicologia , Atitude Frente a Saúde , Métodos Epidemiológicos , Feminino , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor/métodos , Participação do Paciente , Psicometria , Transtornos do Sono-Vigília/etiologiaRESUMO
Autoimmune diseases affect approximately 5% of the population, but much work remains to define the genetic risk factors and pathogenic mechanisms underlying these conditions. There is accumulating evidence that common genetic factors might predispose to multiple autoimmune disorders. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune disorders with multiple susceptibility genes. The functional R620W (C1858T) polymorphism of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, a member of the PTPs that negatively regulate T-cell activation, has been recently associated with susceptibility to various autoimmune diseases. The aim of this study was to assess whether the C1858T polymorphism of PTPN22 also confers increased risk for SLE and RA in the genetically homogeneous population of Crete. It was found that the minor T allele of the PTPN22 C1858T SNP was more common in SLE patients than in control individuals (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.11 to 3.9, p = 0.017). No significant difference was observed in the frequency of this allele when RA patients were compared with controls (OR = 1.14, 95% CI = 0.65 to 1.9, p = 0.64). Although the PTPN22 1858 T allele is found at decreased frequency in Southern Europe, including Crete, an association was found between this allele and SLE in the population studied.
Assuntos
Artrite Reumatoide/genética , Lúpus Eritematoso Sistêmico/genética , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Renal podocytes and their slit diaphragms ensure the integrity of the renal basement membrane that forms the barrier to urinary protein loss. A putative disruption of the slit diaphragm and its main protein components, nephrin and podocin, may be implicated in the pathogenesis of lupus nephritis (LN). We studied the glomerular protein expression of nephrin and podocin in NZB/W LN mice by Western blot and immunofluorescence; mRNA levels were measured by real-time PCR. Human kidney biopsies of class II (n = 5), IV (n = 4), V (n = 7) LN were evaluated for nephrin expression by immunohistochemistry. Glomerular protein expression of nephrin and podocin were significantly reduced in NZB/W LN, starting from the earlier stages (mild mesangial LN) and becoming pronounced at advanced histological forms (focal and diffuse proliferative LN). Nephrin and podocin mRNA levels were substantially decreased in diffuse proliferative disease. Decreased expression of both proteins correlated with electron microscopy findings of distorted slit diaphragms. In patients with LN, nephrin was decreased particularly in diffuse proliferative LN. The main slit diaphragm proteins, nephrin and podocin, are affected from the earlier stages of LN and their expression correlates with disease histology. Our findings suggest a novel role of podocytes and their structures in immune-mediated nephritis.