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1.
BMC Musculoskelet Disord ; 22(1): 372, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882889

RESUMO

BACKGROUND: Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 50-60% of rheumatoid arthritis (RA) patients. However, there are yet no biomarkers to stratify patients for anti-TNF therapy. Rheumatoid factor (RF) and anti-cyclic-citrullinated antibodies (anti-CCP) have been evaluated as biomarkers of response but the results have shown limited consistency. Anti-carbamylated protein (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4) antibodies have been much less studied. Despite being linked to common immune processes, the interaction between these markers has not been evaluated yet. Our aim was to analyze the interaction between these four antibodies in relation to the response to anti-TNF therapy. METHODS: For this objective, a prospective cohort of n = 80 RA patients starting anti-TNF therapy was recruited. Serum determinations at baseline were performed for RF, anti-CCP, anti-CarP and anti-PAD4 antibodies using enzyme-linked immunosorbent assays (ELISA). The clinical response to anti-TNF therapy was determined at week 12 using the change in DAS28 score. Association was performed using multivariate linear regression adjusting for baseline DAS28, sex and age. RESULTS: The interaction between pairs of antibodies was tested by the addition of an interaction term. We found two highly significant antibody interactions associated with treatment response: anti-CarP with anti-PAD4 (p = 0.0062), and anti-CCP with RF (p = 0.00068). The latter antibody interaction was replicated in an independent retrospective cohort of RA patients (n = 199, p = 0.04). CONCLUSIONS: The results of this study suggest that antibody interaction effects are important factors in the response to anti-TNF therapy in RA.


Assuntos
Artrite Reumatoide , Autoanticorpos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Humanos , Peptídeos Cíclicos , Estudos Prospectivos , Estudos Retrospectivos , Fator Reumatoide
2.
Clin Exp Rheumatol ; 38(5): 973-977, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31969229

RESUMO

OBJECTIVES: The performance of many outcome measures for psoriatic arthritis (PsA) is almost unknown in real clinical practice. Our objective was to study the correlation and sensitivity to change of the Disease Activity in Psoriatic Arthritis (DAPSA) index and the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire in a real practice setting. METHODS: This was a prospective, open, non-controlled study that included 60 consecutive patients with PsA treated with ustekinumab. Most had been previously treated with one or more biologic therapeutic agents. The correlation (Spearman's rho coefficient) and the sensitivity to change [Standardized Mean Response (SMR)] of DAPSA and PsAID were studied. Effect size values of 0.20, 0.50 and 0.80 corresponded to low, moderate and high sensitivity to change, respectively. RESULTS: More than 70% of patients achieved therapeutic goals (21.7% were in remission and 50% in low disease activity according to DAPSA categories). Two out of three patients reached an acceptable symptomatic state (PsAID <4). The correlation between final values of both instruments was substantial (Spearman's rho: 0.62, p<0.0001). The SMR for the PsAID was 1.08 (0.95-1.21) and for DAPSA was 1.5 (1.37-1.63), both values corresponding to instruments with a high sensitivity to change (>0.80). The best PsAID cut-off value for identifying DAPSA remission was 3.32 with an area under the ROC curve of 0.82. CONCLUSIONS: DAPSA and PsAID seem to be useful instruments for a more comprehensive assessment of PsA in daily practice. Our results can help to disseminate the use of these instruments in the clinical practice of many rheumatologists.


Assuntos
Artrite Psoriásica , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Humanos , Estudos Prospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Ustekinumab
3.
J Clin Rheumatol ; 24(7): 381-384, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29509560

RESUMO

BACKGROUND/AIMS: Ustekinumab (UST) is a fully human immunoglobulin G1 monoclonal antibody approved for treating moderate to severe psoriasis and, more recently, psoriatic arthritis (PsA) as well. However, information regarding its clinical usefulness in a real-world setting is scarce. We aimed to evaluate the effectiveness and safety of UST in a real-world clinical setting. METHODS: This single-center observational study included PsA outpatients (n = 50) treated with UST from March 2015 to March 2017. Only patients who used at least 3 doses of UST were analyzed. The percentage of patients who achieved a minimal disease activity (MDA) response was collected. The impact of the disease was also evaluated according to the recently developed Psoriatic Arthritis Impact of Disease (PsAID) questionnaire. A binary logistic regression multivariate model was performed to look for variables predicting MDA. RESULTS: Twenty-seven patients (54%) reached an MDA state. Mean PsAID in MDA group was 3.5 ± 2.9 versus 6.8 ± 5.1 in non-MDA patients (p < 0.001). Among the patients who achieved MDA, 19 (70.4%) had a patient-acceptable symptom state according to the PsAID, whereas only 5 (21.7%) of the 23 patients who did not reach an MDA achieved a patient-acceptable symptom state (p < 0.001). Higher basal Psoriasis Area and Severity Index decreased the odds of achieving MDA (odds ratio [OR], 0.80; 95% CI, 0.65-0.99; p = 0.038), whereas a longer use of UST (OR, 1.52; 95% CI, 1.13-2.06; p = 0.015) and a previous failure to 1 anti-tumor necrosis factor α (OR, 18; 95% CI, 2.52-128.63; p = 0.004) increased this odds. We found no major safety problems. CONCLUSIONS: Ustekinumab was effective and safe in this PsA population. Minimal disease activity and PsAID may be useful tools in the evaluation of PsA therapeutic interventions in routine clinical practice.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Ustekinumab/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento
5.
Clin Dev Immunol ; 2013: 482691, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23690822

RESUMO

It has been shown that males with spondyloarthritis tend to suffer from more severe spinal disease while females are more likely to have peripheral joint involvement. Nevertheless, gender-related differences have not been thoroughly explored in psoriatic arthritis (PsA). In PsA, males accumulate more peripheral and axial joint damage compared to women. However, it is not clear whether these findings are secondary to differences in occupational physical activity, hormonal changes, or other factors. The present study analyzed the differences in clinical expression of PsA between men and women. We have also evaluated the possible existence of gender-linked differences in the distribution of genes and polymorphisms within the major histocompatibility complex and whether patients' age at the onset of psoriasis established any differences in these aspects. Women suffered more polyarthritis, greater functional impairment, and a larger number of swollen joints during followup. We appreciated a differential expression of certain MHC genes according to gender and age at onset of psoriasis. Our results point to the need to include patient's age at the onset of psoriasis and gender as key stratification elements in future studies of genetic associations in PsA.


Assuntos
Artrite Psoriásica/genética , Artrite Psoriásica/fisiopatologia , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos de Histocompatibilidade Classe I/genética , Articulações/fisiopatologia , Polimorfismo Genético , Adulto , Idade de Início , Artrite Psoriásica/epidemiologia , Artrite Psoriásica/imunologia , Feminino , Expressão Gênica/imunologia , Predisposição Genética para Doença , Antígenos HLA-B/imunologia , Antígenos HLA-C/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Teste de Histocompatibilidade , Humanos , Articulações/imunologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores Sexuais , Espanha/epidemiologia
6.
J Clin Rheumatol ; 19(1): 32-4, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23319021

RESUMO

Dropped head syndrome (DHS) occurs in patients with severe weakness of the neck extensor muscles, of diverse origin, but most frequently because of neuromuscular diseases. Exceptionally, DHS may be the first manifestation of a systemic autoimmune disease. This report describes the case of a patient with DHS as a presenting sign of scleromyositis. We analyze the clinical features of the case and discuss the most important aspects of its pathogenesis and differential diagnosis.


Assuntos
Debilidade Muscular/etiologia , Miosite/complicações , Músculos do Pescoço/fisiopatologia , Escleroderma Sistêmico/complicações , Quimioterapia Combinada , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Debilidade Muscular/diagnóstico , Miosite/diagnóstico , Miosite/tratamento farmacológico , Prednisona/uso terapêutico , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológico , Síndrome , Resultado do Tratamento
7.
Expert Rev Clin Immunol ; 19(12): 1469-1484, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37589128

RESUMO

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic, immune-mediated disease characterized by synovio-entheseal inflammation. It is estimated to affect around 30% of patients with psoriasis and significantly reduces patients' physical function and quality of life. There is a growing number of treatment options for PsA, but due to the heterogeneous clinical features of the disease and prevalence of comorbidities, managing PsA can be challenging. AREAS COVERED: In this article, we review current understanding of the disease and available pharmacological options. Based on published treatment guidelines, emerging evidence and clinical experience, we provide our expert opinion on treatment strategies, taking into consideration the predominant disease domain and the presence of comorbidities, which can impact treatment decisions and clinical outcomes. EXPERT OPINION: Biological and targeted synthetic disease-modifying agents are dramatically improving the lives of patients with PsA. Biosimilar TNF inhibitors offer a particularly versatile and cost-effective option, whilst newer biologics and targeted synthetic molecules that can be used to treat most domains of psoriatic disease are an attractive alternative to TNF inhibitors. Despite a lack of consensus on treatment sequencing and tapering, it is important that PsA patients, especially those with comorbidities, are looked after by a multidisciplinary team to optimize their care.


Assuntos
Antirreumáticos , Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/tratamento farmacológico , Antirreumáticos/uso terapêutico , Qualidade de Vida , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa , Psoríase/tratamento farmacológico
8.
J Clin Med ; 12(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36675395

RESUMO

Background and objectives: Information on the performance of ixekizumab (IXE) in patients with psoriatic arthritis (PsA) in clinical practice is scarce. We aimed to analyze the retention rate and safety of IXE in patients with PsA in routine clinical practice. Methods: A retrospective longitudinal observational single-center study of all patients with PsA who had received at least one dose of IXE. Adverse events (AEs) and drug retention rate were the main study focus. Survival was analyzed using Kaplan−Meier curves and predictive factors using multivariate Cox regression analysis. The hazard ratio (HR) was used as a measure of the association. Results: Seventy-two patients were included (52 women and 20 men). Median disease duration was 5 years (IQR 3−9). More than 90% received ≥2 biologic and/or targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) prior to IXE. Ixekizumab showed a 1-year retention rate of 65% and a 2-year retention rate of 57%. Regarding discontinuation due to AEs, 0.18 AEs per person-year were identified. The number of previous biologics did not influence drug survival but prior use of methotrexate (HR 2.31 (95% CI 1.05−5.10), p < 0.05) and depression (HR 2.40 (95% CI 1.07−5.41), p < 0.05) increased the risk of IXE discontinuation. Conclusions: Ixekizumab showed a good retention rate in a PsA population mostly refractory to biologic and targeted synthetic DMARDs. Drug survival was consistently good regardless of age, gender, metabolic comorbidities, smoking status, or prior number of biologic therapies. This information may be of interest to better position this drug in the PsA treatment algorithms.

9.
J Clin Med ; 12(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36902650

RESUMO

BACKGROUND AND AIMS: Breastfeeding is recognized as one of the most influential drivers of the gut microbiome. In turn, alterations in the gut microbiome may play a role in the development and severity of spondyloarthritis (SpA). We aimed to analyze different disease outcomes in patients with axial SpA (axSpA) based on the history of breastfeeding. PATIENTS AND METHODS: A random sample was selected from a large database of axSpA patients. Patients were divided based on history of breastfeeding and several disease outcomes were compared. Both groups were also compared based on disease severity. Adjusted linear and logistic regression statistical methods were used. RESULTS: The study included 105 patients (46 women and 59 men), and the median age was 45 years (IQR: 16-72), and the mean age at diagnosis was 34.3 ± 10.9 years. Sixty-one patients (58.1%) were breastfed, with a median duration of 4 (IQR: 1-24) months. After the fully adjusted model, BASDAI [-1.13 (95%CI: -2.04, -0.23), p = 0.015] and ASDAS [-0.38 (95%CI: -0.72, -0.04), p = 0.030] scores were significantly lower in breastfed patients. Forty-two percent had severe disease. In the adjusted logistic model for age, sex, disease duration, family history, HLA-B27, biologic therapy, smoking, and obesity, breastfeeding had a protective effect against the development of severe disease (OR 0.22, 95%CI: 0.08-0.57, p = 0.003). The selected sample size was sufficient to detect this difference with a statistical power of 87% and a confidence level of 95%. CONCLUSION: Breastfeeding might exert a protective effect against severe disease in patients with axSpA. These data need further confirmation.

10.
Clin Exp Rheumatol ; 30(4): 476-80, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22510299

RESUMO

OBJECTIVES: The age of psoriasis onset has an important impact on the clinical expression and heritability of psoriasis. Psoriasis characteristics according to the age at disease onset have been extensively studied. However, the impact of the age of psoriasis onset on psoriatic arthritis (PsA) features has not been analysed in depth. The aim of the present paper is to analyse whether the age of psoriasis onset may have an impact on the clinical and genetic characteristics in a cohort of PsA patients. METHODS: The study included 110 PsA patients classified in accordance with the CASPAR criteria. Patients were divided into early (onset age <30 years) and late (onset age >30 years) onset psoriasis, and clinical features were studied in accordance to this stratification. Distribution of several genes within the MHC region were analysed in accordance with the prior stratification, and their frequencies compared to that of 110 healthy matched blood donors. RESULTS: Compared to patients with late-onset disease, PsA patients with early-onset psoriasis showed more frequently: a longer psoriasis-arthritis latency period (9.9±6 years vs. 3.8±4 years, p=0.0001), a positive family history of disease (60.3% vs. 20.5%, OR 6.1, 95% CI: 2.5-15.0, p=0.0001), severe psoriasis (PASI 8.2±4 vs. 3.6±2.2, p=0.0001), clinical enthesitis (37.7% vs. 22.4%, OR 2.09, 95% CI: 0.9-4.9, p=0.08), and oligoarthritis (47.5% vs. 28.6%, OR 2.26, 95% CI: 1.02-5.02, p=0.04). MICA-A9 was associated with susceptibility in both early-onset (60.7% vs. 30%, p=0.0002) and late-onset patients (59.2% vs. 30%, p=0.0008). However, HLA-Cw*0602 was significantly increased in patients with early-onset psoriasis (73.8% vs. 17%, p<0.0001), whereas the allele 384 of the microsatellite C1_4_4, located 34 kb telomeric to HLA-C locus, was increased only in late-onset cases (49% vs. 21%, p=0.001). CONCLUSIONS: Clinical and genetic features of PsA may differ depending on the age at psoriasis onset. This type of stratification should be considered in future genetic and epidemiological studies of PsA.


Assuntos
Artrite Psoriásica/epidemiologia , Artrite Psoriásica/genética , Antígenos HLA-C/genética , Adulto , Distribuição por Idade , Idade de Início , Artrite Psoriásica/imunologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Glicoproteínas/genética , Glicoproteínas/imunologia , Antígenos HLA-C/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Teste de Histocompatibilidade , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/imunologia , Polimorfismo Genético/genética , Polimorfismo Genético/imunologia , Fatores de Risco , Telômero/genética
11.
Rheumatol Int ; 32(12): 3779-83, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22187056

RESUMO

The aim of this study was to investigate the cumulated incidence and clinical characteristics of the psoriasiform lesions seen in a wide cohort of rheumatic patients exposed to anti-TNFα drugs in a tertiary care hospital from northern Spain. The study population included 450 patients exposed to anti-TNFα agents from 2001 to 2007 and treated in a university hospital in northern Spain. Two hundred patients were exposed to infliximab (44%), 129 (29%) to etanercept, and 121 (27%) to adalimumab. The cumulated incidence (CI) of this skin reaction was calculated for each of the three agents studied. Psoriasis and psoriasiform lesions were documented in 7 patients diagnosed with different rheumatic inflammatory conditions (1.56%). Cases of this adverse effect were identified with all three anti-TNFα agents available at that time, but less frequently with infliximab (CI: 0.5%) compared with etanercept (CI: 2.3%) or adalimumab (CI: 2.5%). The most common lesion was palmoplantar pustulosis (71.3% of the cases), and the latency period to the development of the lesions ranged from 4 to 38 months (mean 9 months). In four of the 7 patients, treatment was suspended, while in the remaining three patients treatment was continued. The CI of this skin reaction in our setting is similar to that published by others. Infliximab was found to be less frequently associated with this adverse event. In our experience, it is not always necessary to stop anti-TNFα therapy for the skin lesions to improve.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Imunoglobulina G/efeitos adversos , Psoríase/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Etanercepte , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Incidência , Infliximab , Masculino , Pessoa de Meia-Idade , Psoríase/epidemiologia , Receptores do Fator de Necrose Tumoral/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Espanha , Atenção Terciária à Saúde , Resultado do Tratamento
12.
J Rheumatol ; 49(1): 8-15, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34393105

RESUMO

Spondyloarthritis (SpA) encompasses a group of inflammatory rheumatic diseases that share clinical and imaging characteristics as well as a common genetic basis. These diseases can affect 0.20-1.6% of the general population, limiting functioning and affecting the quality of life of patients. Considering the patient perspective in the management of the disease and ensuring patients are sufficiently prepared to participate in decision making is critical to treatment success, as well as for optimal health outcomes. The overall picture of impairments, limitations, and restrictions in activities or social participation for patients with SpA is not adequately assessed in SpA-specific instruments. Therefore, it is important to measure the broader range of impairments that can affect patients with SpA and integrate these into a single measure of overall functioning in daily life. The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is a recently introduced health instrument for evaluating SpA based on the International Classification of Functioning, Disability and Health (ICF) that could cover a good part of the health metric needs in SpA. This review addresses its origins, measurement properties, and use in routine clinical practice, as well as its prospects for future use.


Assuntos
Qualidade de Vida , Espondilartrite , Avaliação do Impacto na Saúde , Humanos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Espondilartrite/diagnóstico
13.
J Clin Med ; 11(20)2022 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-36294416

RESUMO

Background: Psychosocial health is a key driver of quality of life (QoL) in axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), but it is often overlooked in clinical practice. We aimed to analyze this aspect of QoL by using the Assessment of SpA International Society−Health Index (ASAS HI) in both SpA phenotypes. Patients and methods: One hundred and eleven patients with axSpA and 90 with PsA were consecutively recruited from two rheumatology centers. In both populations, the categories of stress handling (ASAS HI items #11 and 17) and emotional functions (ASAS HI item #13) were analyzed based on the International Classification of Functioning, Disability, and Health (ICF). A multivariate regression model was used to analyze the explanatory factors associated with positive responses to these items. Results: Thirty-four of the 90 PsA patients (37.8%) and 37/111 of the patients (33.3%) with axSpA reported a positive response to at least one of the stress-handling items. Compared to the patients with PsA, patients with axSpA were less likely to report stress-handling issues (OR 0.48, p < 0.05). Thirty-one of the 90 PsA patients (34.4%) and 44/111 of the patients (39.6%) with axSpA reported positive responses to item #13. In both groups of SpA patients, disease activity and severity (OR 6.6, p < 0.001) were independently associated with alterations in psychosocial health. Compared with those in the axSpA group, the psychosocial health items were better correlated with each other and with the ASAS HI sum score in the PsA group. Conclusions: Psychosocial health is frequently altered in SpA. Both disease activity and severity are associated with this issue. However, psychosocial factors seem to have a greater impact on QoL in PsA than in axSpA.

14.
Eur J Clin Nutr ; 75(9): 1368-1382, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33893449

RESUMO

BACKGROUND/OBJECTIVES: Immune-mediated inflammatory diseases (IMIDs) are prevalent diseases. There is, however, a lack of understanding of the link between diet and IMIDs, how much dietary patterns vary between them and if there are food groups associated with a worsening of the disease. SUBJECTS/METHODS: To answer these questions we analyzed a nation-wide cohort of n = 11,308 patients from six prevalent IMIDs and 2050 healthy controls. We compared their weekly intake of the major food categories, and used a Mendelian randomization approach to determine which dietary changes are caused by disease. Within each IMID, we analyzed the association between food frequency and disease severity. RESULTS: After quality control, n = 11,230 recruited individuals were used in this study. We found that diet is profoundly altered in all IMIDs: at least three food categories are significantly altered in each disease (P < 0.05). Inflammatory bowel diseases showed the largest differences compared to controls (n ≥ 8 categories, P < 0.05). Mendelian randomization analysis supported that some of these dietary changes, like vegetable reduction in Crohn's Disease (P = 2.5 × 10-10, OR(95% CI) = 0.73(0.65, 0.80)), are caused by the disease. Except for Psoriatic Arthritis and Systemic Lupus Erythematosus, we have found ≥2 food groups significantly associated with disease severity in the other IMIDs (P < 0.05). CONCLUSIONS: This cross-disease study demonstrates that prevalent IMIDs are associated to a significant change in the normal dietary patterns. This variation is highly disease-specific and, in some cases, it is caused by the disease itself. Severity in IMIDs is also associated with specific food groups. The results of this study underscore the importance of studying diet in IMIDs.


Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Lúpus Eritematoso Sistêmico , Humanos , Doenças Inflamatórias Intestinais/genética , Análise da Randomização Mendeliana , Índice de Gravidade de Doença
15.
Arthritis Rheumatol ; 73(6): 963-969, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33381897

RESUMO

OBJECTIVE: Previously, only the HLA-DRB1 alleles have been assessed in rheumatoid arthritis (RA). The aim of the present study was to identify the key major histocompatibility complex (MHC) susceptibility factors showing a significant association with anti-carbamylated protein antibody-positive (anti-CarP+) RA. METHODS: Analyses were restricted to RA patients who were anti-cyclic citrullinated peptide antibody negative (anti-CCP-), because the anti-CCP status dominated the results otherwise. Therefore, we studied samples from 1,821 anti-CCP- RA patients and 6,821 population controls from Spain, Sweden, and the Netherlands. The genotypes for ~8,000 MHC biallelic variants were assessed by dense genotyping and imputation. Their association with the anti-CarP status in RA patients was tested with logistic regression and combined with inverse-variance meta-analysis. Significance of the associations was assessed according to a study-specific threshold of P < 2.0 × 10-5 . RESULTS: The HLA-B*08 allele and its correlated amino acid variant Asp-9 showed a significant association with anti-CarP+/anti-CCP- RA (P < 3.78 × 10-7 ; I2 = 0). This association was specific when assessed relative to 3 comparator groups: population controls, anti-CarP-/anti-CCP- RA patients, and anti-CCP- RA patients who were positive for other anti-citrullinated protein antibodies. Based on these findings, anti-CarP+/anti-CCP- RA patients could be separated from other antibody-defined subsets of RA patients in whom an association with the HLA-B*08 allele has been previously demonstrated. No other MHC variant remained associated with anti-CarP+/anti-CCP- RA after accounting for the presence of the HLA-B*08 allele. Specifically, the reported association of HLA-DRB1*03 was observed at a level comparable to that reported previously, but it was attributable to linkage disequilibrium. CONCLUSION: These results identify HLA-B*08 carrying Asp-9 as the MHC locus showing the strongest association with anti-CarP+/anti-CCP- RA. This knowledge may help clarify the role of the HLA in susceptibility to specific subsets of RA, by shaping the spectrum of RA autoantibodies.


Assuntos
Artrite Reumatoide/genética , Autoanticorpos/imunologia , Antígeno HLA-B8/genética , Carbamilação de Proteínas/imunologia , Alelos , Anticorpos Antiproteína Citrulinada/imunologia , Artrite Reumatoide/imunologia , Ácido Aspártico/genética , Predisposição Genética para Doença , Antígeno HLA-B8/imunologia , Humanos
16.
Reumatol Clin (Engl Ed) ; 16(1): 56-58, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29463445

RESUMO

Pyle's disease (OMIN number 265900) is a metaphyseal dysplasia of benign course, inherited with an autosomal recessive pattern. Some 30 genuine cases have been described so far. The cause of this process has been known since 2016, when its relationship to mutations in the gene encoding the sFRP protein, a known inhibitor of the Wnt pathway, was discovered. We report the case of a 58-year-old man, diagnosed with Pyle's disease based on his clinical and radiographic characteristics, whose phenotype suggested a differential control of cortical and trabecular bone homeostasis.


Assuntos
Joelho/diagnóstico por imagem , Osteocondrodisplasias/diagnóstico por imagem , Clavícula/lesões , Fraturas Espontâneas/etiologia , Geno Valgo/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade
17.
Drugs Aging ; 37(2): 99-104, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31745833

RESUMO

OBJECTIVES: Elderly psoriatic arthritis (PsA) patients may show greater inflammatory activity and worse prognoses than patients of other ages. However, these patients may be at risk of receiving fewer systemic treatments. In this report, we have analysed disease outcomes in PsA by age groups. METHODS: This cross-sectional, multicentre study included 227 PsA patients under biological and non-biological systemic therapies. The study population was divided into four categories by age: < 40, 40‒49, 50‒65 and > 65 years. Physical functioning, disease activity, remission rates and disease impact were compared. RESULTS: Thirty-one patients (13.7%) were under 40 years, 26.9% (n = 61) were 40-49 years, 26.4% (n = 60) were 50-65 years and 33.0% (n = 75) were patients > 65 years. Compared with the other age groups, disease duration was significantly higher in subjects older than 65 years (p < 0.001). Only 8% of patients older than 65 years received corticosteroids compared with 29% of patients aged < 40 years, 13.1% of patients aged 40-49 years and 26.7% of patients aged 50-65 years (p = 0.007). Similarly, only 36% of patients over 65 years of age received a biological therapy compared with between 51.6 and 59% for the other age groups (p = 0.036). However, remission rates were not statistically different between groups. Disease-associated physical disability was similar among groups. Compared with patients aged < 40 years, more patients > 65 years achieved low disease impact (10.7% vs 37.7%, respectively; p < 0.05). CONCLUSIONS: Fewer older patients received corticosteroids and biological therapy. However, disease outcomes were similar or even better compared with those observed in younger patients. Therefore, treatment strategies for older patients with PsA should be similar to those offered to younger individuals.


Assuntos
Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Adulto , Fatores Etários , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
18.
J Rheumatol ; 47(10): 1483-1489, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32358161

RESUMO

OBJECTIVE: The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is a tool designed to assess disease impact in spondyloarthritis (SpA), but its clinical performance is barely known. We aimed to test the clinimetric properties of ASAS HI in a real clinical setting. METHODS: This cross-sectional study included 111 consecutive patients with SpA. The measurement properties of ASAS HI were tested against conventional assessment measures. Convergent validity was assessed by Spearman rho correlations, while discriminative validity was analyzed through receiver-operating characteristic (ROC) curves. A multivariate regression analysis was designed to identify ASAS HI items associated with active disease. RESULTS: The average ASAS HI was 5.4 ± 3.8 (interquartile range 3-8). ASAS HI showed high convergent validity against other SpA measures (rho ≥ 0.70, p < 0.0005). The optimal criteria for detecting high/very high disease activity Ankylosing Spondylitis Disease Activity Score (ASDAS) categories was an ASAS HI score > 6, area under the ROC curve 0.86 (95% CI 0.78-0.92), positive likelihood ratio 7.3 (95% CI 3.1-17.1), p < 0.0001. The ASAS HI items significantly associated with Bath Ankylosing Spondylitis Disease Activity Index active disease were "I often get frustrated" (OR 9.2, 95% CI 1.2-69.4, p = 0.032), and "I sleep badly at night" (OR 7.7, 95% CI 1.4-41.6, p = 0.018). As for ASDAS, it was "pain sometimes disrupts my normal activities" (OR 8.7, 95% CI 1.7-45.2, p = 0.010). CONCLUSION: The ASAS HI is a useful and simple instrument for its application in daily practice. Given its good clinimetric properties, it could be used as an additional instrument to evaluate SpA.


Assuntos
Espondilartrite , Espondilite Anquilosante , Estudos Transversais , Humanos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Espondilartrite/diagnóstico , Espondilite Anquilosante/diagnóstico , Inquéritos e Questionários
19.
Reumatol Clin (Engl Ed) ; 15(3): 156-164, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28789978

RESUMO

OBJECTIVE: The current guidelines in the treatment of rheumatoid arthritis (RA) include the early diagnosis and early use of disease modifying drugs to achieve remission or low disease activity level, known as "Treat to Target" (T2T). The objective of this study is to develop a composite indicator (CI) to evaluate the quality of care in the management of patients with RA, according to the T2T strategy and other general recommendations concerning the management of these patients. MATERIAL AND METHOD: The phases of the construction of the CI were: 1) selection of quality criteria through expert judgment; 2) prioritization of the criteria, according to relevance and feasibility, applying the Delphi methodology (two rounds) involving 20 experts; 3) design of quality indicators; and 4) calculation of the weighted CI, using the mean value in relevance and feasibility granted by the experts. The source of information for the calculation of the CI are the medical records of patients with RA. RESULTS: Twelve criteria out of 37 required a second Delphi round. Thirty-one criteria were prioritized. These criteria presented a median in relevance and feasibility greater than or equal to 7.5, with an interquartile range of less than 3.5, and a level of agreement (score greater than or equal to 8) greater than or equal to 80%. CONCLUSIONS: The constructed CI allows us to evaluate the quality of care of patients with RA following the T2T strategy in the rheumatology units of Spanish hospitals, offering a valid and easily interpretable summary measure.


Assuntos
Artrite Reumatoide/terapia , Ambulatório Hospitalar , Indicadores de Qualidade em Assistência à Saúde , Qualidade da Assistência à Saúde , Antirreumáticos/uso terapêutico , Técnica Delphi , Prova Pericial , Humanos , Prontuários Médicos , Espanha
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