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1.
Front Med (Lausanne) ; 9: 933884, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091689

RESUMO

Objectives: To classify patients with rheumatoid arthritis (RA) in an earlier stage of the disease, the ACR/EULAR classification criteria were updated in 2010. These criteria might have led to an increased incidence of RA in the rheumatology clinic. Since a higher incidence increases the socio-economic burden of RA, it is worthwhile to evaluate whether there is a time effect. Materials and methods: A systematic review was conducted using Embase, Medline Ovid, Cochrane Central, and Web of Science from database inception to February 2021. Included were only articles that addressed incidence rates of rheumatoid arthritis from rheumatology outpatient clinics. Results: Of the 6,289 publications only 243 publications on RA were found eligible for full-text review. Nine studies were included reporting incidence. The pooled incidence for RA was 11% (95% CI 6-16%) per year. Over time the incidence increased after the introduction of the 2010 ACR/EULAR classification criteria. Overall there was a high intragroup heterogeneity (I 2 = 97.93%, p < 0.001), caused by geographical area, study design and differences in case definitions. Conclusion: Although the incidence seems to increase after the introduction of the 2010 ACR/EULAR criteria, no conclusions can be drawn on this time effect due to heterogeneity.

2.
Rheumatology (Oxford) ; 60(8): 3617-3627, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-33484138

RESUMO

OBJECTIVES: Management of early arthritis is based upon early recognition of individuals at high risk of developing persistent arthritis. Therefore, this study investigates whether the number of risk factors for persistent disease or treatment determines the clinical course of early arthritis by comparing the chance at (sustained) DMARD-free remission ((S)DFR) after 2 years follow-up. METHODS: Data from the tREACH trial, a stratified single-blinded multicentre strategy trial with a treat-to-target approach were used. We selected all patients with ≥1 swollen joint who did not fulfil 1987 and/or 2010 criteria for RA. The number of risk factors present; autoantibody-positivity, polyarthritis (>4), erosive disease and elevated acute phase reactants, determined risk group stratification. Multivariate logistic regression analyses were performed with (S)DFR as dependent variables and baseline disease activity score (DAS), treatment, symptom duration and number of risk factors present as independent variables. RESULTS: In total, 130 early arthritis patients were included and respectively 31, 66 and 33 had 0, 1 and ≥2 risk factors present. DFR rates were respectively 74%, 48% and 45% for early arthritis patients with 0, 1 and ≥2 risk factors present. In accordance SDFR rates were 61%, 32% and 30%. In our logistic model (S)DFR was not influenced by the initial treatment strategies when stratified for risk groups. CONCLUSION: The chance at (S)DFR in early arthritis diminishes when more risk factors are present, which is irrespective of the given initial treatment. Our data point out to a stratified management approach in early arthritis based on their risk profile, but validation is needed. TRIAL REGISTRATION: ISRCTN registry: ISRCTN26791028 (http://www.isrctn.com/ISRCTN26791028).


Assuntos
Artrite/epidemiologia , Adulto , Antirreumáticos/uso terapêutico , Artrite/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Remissão Espontânea , Fatores de Risco
3.
Drugs ; 80(16): 1699-1722, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32852745

RESUMO

BACKGROUND: Inflammatory autoimmune diseases are chronic diseases that often affect women of childbearing age. Therefore, detailed knowledge of the safety profile of medications used for management of inflammatory autoimmune diseases during pregnancy is important. However, in many cases the potential harmful effects of medications (especially biologics) during pregnancy (and lactation) on mother and child have not been fully identified. OBJECTIVE: Our aim was to update the data on the occurrence of miscarriages and (major) congenital malformations when using biologics during pregnancy based on newly published articles. Additionally, we selected several different secondary outcomes that may be of interest for clinicians, especially information on adverse events in the use of a specific biologic during pregnancy. MATERIAL AND METHODS: A search was conducted from 1 January 2015 until 4 July 2019 in Embase.com, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar with specific search terms for each database. Selection of publications was based on title/abstract and followed by full text (double blinded, two researchers). An overview was made based on outcomes of interest. References of the included publications were reviewed to include and minimize the missing publications. RESULTS: A total of 143 publications were included. The total number of cases ranged from nine for canakinumab to 4276 for infliximab. The rates of miscarriages and major congenital malformations did not show relevant differences from those rates in the general population. CONCLUSION: Despite limitations to our study, no major safety issues were reported and no trend could be identified in the reported malformations.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Aborto Espontâneo/epidemiologia , Doenças Autoimunes/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Inflamação/tratamento farmacológico , Troca Materno-Fetal , Aborto Espontâneo/induzido quimicamente , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Infliximab/efeitos adversos , Gravidez
4.
Hum Reprod Update ; 26(6): 961-1001, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32743663

RESUMO

BACKGROUND: Information regarding the possible influence of immunosuppressive drugs on male sexual function and reproductive outcomes is scarce. Men diagnosed with immune-mediated diseases and a wish to become a father represent an important neglected population since they lack vital information to make balanced decisions about their treatment. OBJECTIVE AND RATIONALE: The aim of this research was to systematically review the literature for the influence of paternal immunosuppressive drug use on many aspects of male sexual health, such as sexual function, fertility, pregnancy outcomes and offspring health outcomes. SEARCH METHODS: A systematic literature search was performed in the bibliographic databases: Embase (via Elsevier embase.com), MEDLINE ALL via Ovid, Cochrane Central Register of Trials (via Wiley) and Web of Science Core Collection. Additionally, Google Scholar and the Clinical trial registries of Europe and the USA were searched. The databases were searched from inception until 31 August 2019. The searches combined keywords regarding male sexual function and fertility, pregnancy outcomes and offspring health with a list of immunosuppressive drugs. Studies were included if they were published in English and if they included original data on male human exposure to immunosuppressive drugs. A meta-analysis was not possible to perform due to the heterogeneity of the data. OUTCOMES: A total of 5867 references were identified, amongst which we identified 161 articles fulfilling the eligibility criteria. Amongst these articles, 50 included pregnancy and offspring outcomes and 130 included sexual health outcomes. Except for large Scandinavian cohorts, most of the identified articles included a small number of participants. While a clear negative effect on sperm quality was evident for sulfasalazine and cyclophosphamide, a dubious effect was identified for colchicine, methotrexate and sirolimus. In three articles, exposure to tumour necrosis factor-α inhibitors in patients diagnosed with ankylosing spondylitis resulted in improved sperm quality. The information regarding pregnancy and offspring outcomes was scant but no large negative effect associated with paternal immunosuppressive drug exposure was reported. WIDER IMPLICATIONS: Evidence regarding the safety of immunosuppressive drugs in men with a wish to become a father is inconclusive. The lack of standardisation on how to evaluate and report male sexual function, fertility and reproduction as study outcomes in men exposed to immunosuppressive drugs is an important contributor to this result. Future research on this topic is needed and should be preferably done using standardised methods.


Assuntos
Fertilidade/efeitos dos fármacos , Hormônios Gonadais/metabolismo , Imunossupressores/uso terapêutico , Exposição Paterna/efeitos adversos , Resultado da Gravidez/epidemiologia , Comportamento Sexual/efeitos dos fármacos , Adulto , Feminino , Fertilidade/fisiologia , Humanos , Recém-Nascido , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/epidemiologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fatores de Risco , Disfunções Sexuais Fisiológicas/induzido quimicamente , Disfunções Sexuais Fisiológicas/complicações , Disfunções Sexuais Fisiológicas/epidemiologia , Adulto Jovem
5.
RMD Open ; 6(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32669451

RESUMO

OBJECTIVES: Methotrexate (MTX) is currently the recommended first-line therapy for treating psoriatic arthritis (PsA), despite lacking clear evidence. No estimates of efficacy of MTX in usual care and no clear MTX responsive clinical or laboratory variables are currently available. This study describes the response to MTX monotherapy in newly diagnosed patients with PsA in usual care. Second, we compared clinical variables and cytokine profiles in patients responding and not responding to MTX monotherapy. METHODS: We used data collected in the Dutch southwest Early Psoriatic Arthritis cohoRt study to select patients with PsA with oligoarthritis or polyarthritis, and at least 1 year follow-up. We analysed disease activity at 6 months of patients who started MTX monotherapy and still used MTX monotherapy 1 year after diagnosis. Cytokine profiles were determined at baseline and after 3 and 6 months with a bead-based multi-immunoassay. RESULTS: We identified 219 patients of which 183 (84%) patients started MTX monotherapy within 6 months after diagnosis. 90 patients used MTX monotherapy throughout the first year of which 44 patients (24%) reached minimal disease activity(MDA) at 6 months, decreasing to 33 patients (18%) after 1 year. Non-responders had significantly higher concentrations of interleukin (IL) 23 and IL-10 before and during MTX therapy. CONCLUSIONS: Our results showed that only 18% of patients with PsA are in sustained MDA after 1 year of MTX monotherapy and non-responders more often had IL-23-driven disease. Our results indicate the need for more treat-to-target and personalised therapy strategies in PsA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/sangue , Artrite Psoriásica/tratamento farmacológico , Interleucina-23/sangue , Metotrexato/uso terapêutico , Adulto , Idoso , Antirreumáticos/administração & dosagem , Artrite Psoriásica/diagnóstico , Biomarcadores , Citocinas/sangue , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Resultado do Tratamento
6.
RMD Open ; 6(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32646954

RESUMO

OBJECTIVE: To describe parenting disability postpartum in patients with rheumatoid arthritis (RA) using the Parenting Disability Index and to determine early in pregnancy which patients will face parenting problems postpartum. METHODS: Data were collected from a prospective study on pregnancy and RA (Pregnancy induced Amelioration of Rheumatoid Arthritis study). Postpartum visits were performed at 6, 12 and 26 weeks after delivery. Domains causing parenting difficulties were identified. A multivariate logistic regression model to identify which patients develop parenting disabilities postpartum with patient characteristics in the first trimester as covariates was performed. RESULTS: 148 patients were eligible for this study. The domains carrying, hygiene, feeding, getting up and down, and household/shopping were frequently scored as difficult. Maintaining discipline, taking care of the children when sick, listening and having other children over caused the least problems. 30.1% of patients with RA report low parenting disability, 30.9% reports intermediate disability and 39.0% reports high disability. Patients with a low Health Assessment Questionnaire (HAQ)-score in the first trimester (OR 9.2, 95% CI 3.0 to 27.7, p<0.001) and low disease activity in the first trimester (Disease Activity Score 28-joint count C reactive protein<3.2) (OR 4.8, 95% CI 1.8 to 12.9, p=0.002) were likely to report low parenting disability postpartum. Patients with a longer disease duration (OR 0.87, 95% CI 0.79 to 0.95, p=0.003) were less likely to report low parenting disability postpartum. A high HAQ-score in the first trimester (OR 4.54, 95% CI 1.99 to 10.34, p<0.001) and erosive disease (OR 2.32, 95% CI 1.00 to 5.35, p=0.049) increased the risk of high parenting disability postpartum. CONCLUSION: Physical domains of parenting postpartum are most commonly affected in patients with RA. When counselling patients with RA, a HAQ-score in the first trimester is the most reliable marker to identify patients that develop parenting disability after delivery.


Assuntos
Artrite Reumatoide/psicologia , Avaliação da Deficiência , Pessoas com Deficiência , Indicadores Básicos de Saúde , Poder Familiar/psicologia , Adulto , Artrite Reumatoide/fisiopatologia , Feminino , Humanos , Modelos Logísticos , Análise Multivariada , Países Baixos , Período Pós-Parto , Gravidez , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Índice de Gravidade de Doença
7.
Semin Arthritis Rheum ; 50(3): 423-431, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32224045

RESUMO

OBJECTIVES: To determine the impact of a disease flare on patient reported outcome measures (PROMs) in rheumatoid arthritis (RA) patients, who are tapering treatment. METHODS: Data were used from the TARA trial; a multicenter, randomized controlled trial in which RA patients, with a well-controlled disease (DAS≤2.4 and SJC≤1) for at least 6 months, gradually tapered their DMARDs. PROMs of patients with a flare (DAS>2.4 and/or SJC>1) were compared every three months before and after a flare with their own norm values. Linear Mixed Models were used to investigate whether a disease flare influenced functional ability (HAQ-DI), fatigue (BRAF-MDQ), quality of life (EQ-5D and SF36), anxiety and depression (HADS), morning stiffness, general health (GH) and worker productivity, and if so, the duration was determined. For unemployment and sick leave we used descriptive statistics. RESULTS: A flare negatively influenced GH, morning stiffness, HAQ-DI, EQ-5D, BRAF-MDQ, and the SF36 physical component scale and this effect lasted >3 months. Except for the HAQ-DI, effect sizes exceeded the minimum clinically important differences (MCIDs). For the physical outcomes effects lasted >6 months. Worker productivity was not significantly affected by a flare. CONCLUSION: A disease flare influenced patients' lives, the largest effect was seen in the physical outcomes, and lasted 6 months. Although on a group level effect sizes for the separate PROMs were not always significant or larger than specific MCIDs, a disease flare can still be of great importance for individual patients.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Redução da Medicação/métodos , Exacerbação dos Sintomas , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diferença Mínima Clinicamente Importante , Medidas de Resultados Relatados pelo Paciente , Desempenho Físico Funcional , Qualidade de Vida , Fatores de Tempo
8.
Semin Arthritis Rheum ; 50(3): 557-573, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32165034

RESUMO

BACKGROUND: Information about the possible effect of rheumatic diseases on male sexual function and reproduction (sexual health) is scarce and difficult to summarize. Factors known to impair sexual health, such as inflammation, medication use and hypogonadism can be present in a significant proportion of male patients with rheumatic diseases. OBJECTIVES: The objective of our study was to systematically review the literature for the influence of paternal rheumatic disease on sexual health, such as sexual function, reproductive hormones, male fertility, pregnancy and offspring outcomes. DATA SOURCES: English language articles identified through Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Google Scholar and the Clinical trial registries of Europe and the USA published until February 2019. STUDY APPRAISAL AND SYNTHESIS METHODS: Literature was synthesized in narrative form and in summary tables. Outcomes were categorized as: sexual function, reproductive hormones, fertility and pregnancy and offspring outcomes. Results are presented per category and per disease. RESULTS: 9735 articles were identified with our search strategy. After removal of duplicates, excluding articles by screening titles and abstracts and assessing eligibility by reading 289 fulltext articles, 87 articles fulfilled the eligibility criteria. All included studies enrolled patients diagnosed with a rheumatic disease and had results at least on one of the outcome categories. Sexual function was the most common category, followed by reproductive hormones, fertility and pregnancy and offspring outcomes. Sexual function is impaired in a high proportion of patients with rheumatic diseases. This was statistically significant in most of the studies where a control group was available. Clinically relevant abnormalities in reproductive hormones were mainly identified in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and a positive correlation with disease activity were reported. Semen quality in men with rheumatic diseases can be impaired in patients with SLE, SpA, sarcoidosis, BD and MWS. Sperm count and motility were the most common semen quality parameters affected. No negative effect of paternal RA and vasculitis on pregnancy outcomes were reported in 3 studies. No studies reporting the effect of paternal disease on offspring outcomes were identified. LIMITATIONS: Most of the studies included in this review suffer from an inconsistent methodological quality, definitions of outcomes varied in several studies, a wide variety of screening questionnaires and/or diagnostic tools were used and results might only apply to the specific populations that were studied. CONCLUSIONS: This systematic review suggests that sexual health is impaired in men with rheumatic diseases. The degree and extent of sexual health impairment vary per disease. More research is needed to fully understand the link between rheumatic diseases and impaired male sexual health. Meanwhile, rheumatologists should be aware of this association and discuss it with their patients. IMPLICATIONS OF KEY FINDINGS: Sexual health of men with rheumatic diseases can be impaired by the disease itself. Especially in men trying to conceive, information on sexual function, reproductive hormones and sperm quality are needed to identify these problems. Treatment resulting in lower disease activity can improve overall sexual health in man with rheumatic diseases and facilitate their journey to fatherhood. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO 2018 CRD42018099845.


Assuntos
Infertilidade Masculina/etiologia , Doenças Reumáticas/complicações , Disfunções Sexuais Fisiológicas/etiologia , Saúde Sexual , Adulto , Humanos , Masculino , Pessoa de Meia-Idade
9.
Br J Clin Pharmacol ; 86(3): 580-590, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31633830

RESUMO

AIMS: The effects of biologics on reproduction/lactation are mostly unknown although many patients that receive biologics are women of reproductive age. The first objective of this study was to investigate the publicly available data on pregnancy/lactation before and after marketing authorization in Europe of biologics for the indications of rheumatologic inflammatory autoimmune diseases and inflammatory bowel disease. Secondary objectives included the assessment of the clinical relevance of the provided data and comparison of initial and post-authorization data. METHODS: Initial and post-authorization data were extracted from the European Public Assessment Reports and the latest versions of Summary of Product Characteristics using publicly available documents on the European Medicines Agency's website. Four sections were categorized regarding pregnancy outcomes: pre-clinical/animal studies, human female fertility, pregnancy-related outcomes and congenital malformations in the human fetus. Three sections were categorized regarding lactation outcomes: pre-clinical/animal studies, excretion in human breast milk and absorption in children through breastfeeding. The clinical applicability of each category was scored by specified criteria, based on scientific literature, and further as defined by the authors. RESULTS: For the 16 included biologics, post-authorization data were delivered only for adalimumab, certolizumab pegol, etanercept and infliximab. For the 12 remaining biologics limited data on pregnancy and lactation during the post-marketing period of 2-21 years were available. CONCLUSIONS: In this article several suggestions are provided for improving a multidisciplinary approach to these issues. The initiation of suitable registries by marketing authorization holders and data transparency for clinicians and academics are highly endorsed.


Assuntos
Produtos Biológicos , Aleitamento Materno , Adalimumab , Animais , Criança , Europa (Continente) , Feminino , Humanos , Lactação , Gravidez
10.
ACR Open Rheumatol ; 1(2): 97-103, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31777786

RESUMO

OBJECTIVE: Disease Activity Score 28 (DAS28)-using the C-reactive protein (CRP) level has been validated to determine disease activity in rheumatoid arthritis (RA) patients during pregnancy. A self-administered questionnaire like Rheumatoid Arthritis Disease Activity Index (RADAI) has practical advantages over DAS28-CRP, and in this study, we aimed to validate the RADAI for use during pregnancy. METHODS: Patients were derived from a prospective cohort on RA and pregnancy (Pregnancy-induced Amelioration of Rheumatoid Arthritis study). To validate the RADAI as a disease activity measure, the disease course over time and the disease activity states were compared with the DAS28-CRP. Furthermore, the RADAI was compared with DAS28-CRP in predicting fertility and pregnancy outcomes. Finally, to test construct validity, correlation of both RADAI and DAS28-CRP with a biomarker (galactosylation of immunoglobulin G [IgG]) were determined and compared. RESULTS: In total, 269 patients were analyzed in this study. Mean RADAI scores showed a great decline in disease activity in the first trimester compared with DAS28-CRP (mean RADAI, -1.13; mean, DAS28-CRP, -0.04). Correlations between DAS28-CRP and RADAI scores were moderate to good (0.44 < ρ < 0.71). Agreement in disease states was low (0.26 < κ < 0.51). Time to pregnancy was different between disease states according to DAS28-CRP (P = 0.03), but not according to RADAI (P = 0.56). Only DAS28-CRP could predict birthweight (DAS28-CRP ß-0.17, P = 0.04; RADAI ß-0.09, P = 0.10). Both DAS28-CRP and RADAI were associated with galactosylation of IgG at specific time points, but only change in DAS28-CRP was correlated with change in galactosylation of IgG from preconception to pregnancy. CONCLUSION: The RADAI could not be validated as a disease activity measure during pregnancy. DAS28-CRP remains the gold standard of measuring disease activity in pregnancy.

11.
Osteoarthritis Cartilage ; 27(8): 1148-1151, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31108225

RESUMO

OBJECTIVE: To compare direct evaluation of cartilage with high resolution MRI (hrMRI) to indirect cartilage evaluation using MRI inter-bone distance in hand OA patients and healthy controls. DESIGN: 41 hand OA patients and 18 healthy controls underwent hrMRI of the 2nd and 3rd metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. The images were read by two independent readers using OMERACT hand OA MRI inter-bone distance score (0-3 scale) and a new hrMRI cartilage score with direct evaluation of the cartilage (0-3 scale). Inter-reader and intra-reader reliability was calculated using exact and close agreement and kappa values. The prevalence of abnormal scores and agreement between methods was assessed in both hand OA patients and healthy controls. RESULTS: The intra- and inter-reader reliability of both scores was comparable, with exact agreement in 73-83% and close agreement in 95-100%. In hand OA patients 27% of 161 joints had both cartilage damage and loss of inter-bone distance, cartilage damage by hrMRI only was present in 20% of joints and reduced inter-bone distance only in 4% of joints. In the healthy controls, 1 of 71 joints were scored as abnormal by both hrMRI and inter bone distance scoring, 1 joint was scored as abnormal using the hrMRI cartilage score only, whereas 15% of joints had only reduced inter bone distance. CONCLUSIONS: Direct cartilage evaluation of MCP and PIP joints using hrMRI has a good reliability, and the higher prevalence of hrMRI cartilage damage in hand OA patients and the lower prevalence in healthy controls in comparison to evaluation of inter-bone distance suggests a better validity.


Assuntos
Cartilagem Articular/diagnóstico por imagem , Articulações dos Dedos/diagnóstico por imagem , Osteoartrite/diagnóstico por imagem , Adolescente , Adulto , Cartilagem Articular/patologia , Estudos de Casos e Controles , Feminino , Articulações dos Dedos/patologia , Humanos , Imageamento por Ressonância Magnética , Articulação Metacarpofalângica/diagnóstico por imagem , Articulação Metacarpofalângica/patologia , Osteoartrite/patologia , Adulto Jovem
12.
PLoS One ; 13(12): e0208534, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532219

RESUMO

OBJECTIVE: The objective was to predict insufficient response to 3 months methotrexate (MTX) in DMARD naïve rheumatoid arthritis patients. METHODS: A Multivariable logistic regression model of rheumatoid arthritis patients starting MTX was developed in a derivation cohort with 285 patients starting MTX in a clinical multicentre, stratified single-blinded trial, performed in seven secondary care clinics and a tertiary care clinic. The model was validated in a validation cohort with 102 patients starting MTX at a tertiary care clinic. Outcome was insufficient response (disease activity score (DAS)28 >3.2) after 3 months of MTX treatment. Clinical characteristics, lifestyle variables, genetic and metabolic biomarkers were determined at baseline in both cohorts. These variables were dichotomized and used to construct a multivariable prediction model with backward logistic regression analysis. RESULTS: The prediction model for insufficient response in the derivation cohort, included: DAS28>5.1, Health Assessment Questionnaire>0.6, current smoking, BMI>25 kg/m2, ABCB1 rs1045642 genotype, ABCC3 rs4793665 genotype, and erythrocyte-folate<750 nmol/L. In the derivation cohort, AUC of ROC curve was 0.80 (95%CI: 0.73-0.86), and 0.80 (95%CI: 0.69-0.91) in the validation cohort. Betas of the prediction model were transformed into total risk score (range 0-8). At cutoff of ≥4, probability for insufficient response was 44%. Sensitivity was 71%, specificity 72%, with positive and negative predictive value of 72% and 71%. CONCLUSIONS: A prognostics prediction model for insufficient response to MTX in 2 prospective RA cohorts by combining genetic, metabolic, clinical and lifestyle variables was developed and validated. This model satisfactorily identified RA patients with high risk of insufficient response to MTX.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Área Sob a Curva , Artrite Reumatoide/patologia , Estudos de Coortes , Feminino , Ácido Fólico/análise , Ácido Fólico/sangue , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Fatores de Risco , Resultado do Tratamento
13.
Rheumatol Int ; 38(9): 1643-1650, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30014260

RESUMO

Fatigue has a large impact on quality of life and is still unmanageable for many patients. Study aims were describe (1) the prevalence and pattern of fatigue over time in patients with early rheumatoid arthritis under a treat-to-target strategy and (2) identify predictive factors for worsening and recovering of fatigue over time. Data from the tREACH study were used, comparing different treatment strategies with fatigue as secondary objective. Patient outcomes on fatigue, quality of life, depression, and coping were obtained every 6 months and clinically assessed every 3 months. Prediction of fatigue at 12 months was investigated with an ROC curve. Analysis was stratified into non-fatigue and fatigue at baseline. Logistic regression was used for the evolution of fatigue in relation with the covariates over time. Almost half of all patients (n = 246) had high fatigue levels at baseline, decreasing slightly over time. At 12 months, 43% of patients were fatigued; while 23% of the initially fatigued patients showed lower levels of fatigue, the fatigue level had increased in 15% of the initially non-fatigued patients. The strongest predictor of fatigue was the previous fatigue levels (AUC 0.89). Higher score on the depression scale and coping with limitations was associated with developing fatigue over time in the initially non-fatigued group. Despite a strict treat-to-target strategy, fatigue remained an overall problem during the first year of treatment, and was mainly predicted by its baseline status. In subgroups, a small additional effect of depression was seen. Monitoring fatigue and depression may be important in managing fatigue.


Assuntos
Artrite Reumatoide/epidemiologia , Fadiga/epidemiologia , Qualidade de Vida , Índice de Gravidade de Doença , Artrite Reumatoide/psicologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC
14.
Arthritis Rheumatol ; 70(10): 1557-1564, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29745059

RESUMO

OBJECTIVE: To evaluate, from a societal perspective, the incremental cost-effectiveness of withdrawing tumor necrosis factor inhibitor (TNFi) treatment compared to continuation of these drugs within a 1-year, randomized trial among rheumatoid arthritis patients with longstanding, stable disease activity or remission. METHODS: Data were collected from a pragmatic, open-label trial. Cost-utility analysis was performed using the nonparametric bootstrapping method, and a cost-effectiveness acceptability curve was constructed using the net-monetary benefit framework, where a willingness-to-accept threshold (WTA) was defined as the minimal cost saved that a patient accepted for each quality-adjusted life year (QALY) lost. RESULTS: A total of 531 patients were randomized to the stop group and 286 patients to the continuation group. Withdrawal of TNFi treatment resulted in a >60% reduction of the total drug cost, but led to an increase of ∼30% in other health care expenditures. Compared to continuation, stopping TNFi resulted in a mean yearly cost saving of €7,133 (95% confidence interval [95% CI] €6,071, €8,234]) and was associated with a mean loss of QALYs of 0.02 (95% CI 0.002, 0.040). Mean saved cost per QALY lost and per extra flare incurred in the stop group compared to the continuation group was €368,269 (95% CI €155,132, €1,675,909) and €17,670 (95% CI €13,650, €22,721), respectively. At a WTA of €98,438 per QALY lost, the probability that stopping TNFi treatment is cost-effective was 100%. CONCLUSION: Although an official WTA is not defined, the mean saved cost of €368,269 per QALY lost seems acceptable in The Netherlands, given existing data on willingness to pay.


Assuntos
Antirreumáticos/economia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Custos de Medicamentos/estatística & dados numéricos , Suspensão de Tratamento/economia , Adulto , Idoso , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Ensaios Clínicos Pragmáticos como Assunto , Anos de Vida Ajustados por Qualidade de Vida , Estatísticas não Paramétricas , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
15.
Arthritis Res Ther ; 20(1): 15, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29382379

RESUMO

BACKGROUND: At present, there are no prognostic parameters unequivocally predicting treatment failure in early rheumatoid arthritis (RA) patients. We investigated whether baseline ultrasonography (US) findings of joints, when added to baseline clinical, laboratory, and radiographical data, could improve prediction of failure to achieve Disease Activity Score assessing 28 joints (DAS28) remission (<2.6) at 1 year in newly diagnosed RA patients. METHODS: A multicentre cohort of newly diagnosed RA patients was followed prospectively for 1 year. US of the hands, wrists, and feet was performed at baseline. Clinical, laboratory, and radiographical parameters were recorded. Primary analysis was the prediction by logistic regression of the absence of DAS28 remission 12 months after diagnosis and start of therapy. RESULTS: Of 194 patients included, 174 were used for the analysis, with complete data available for 159. In a multivariate model with baseline DAS28 (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.2-2.2), the presence of rheumatoid factor (OR 2.3, 95% CI 1.1-5.1), and type of monitoring strategy (OR 0.2, 95% CI 0.05-0.85), the addition of baseline US results for joints (OR 0.96, 95% CI 0.89-1.04) did not significantly improve the prediction of failure to achieve DAS28 remission (likelihood ratio test, 1.04; p = 0.31). CONCLUSION: In an early RA population, adding baseline ultrasonography of the hands, wrists, and feet to commonly available baseline characteristics did not improve prediction of failure to achieve DAS28 remission at 12 months. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01752309 . Registered on 19 December 2012.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Índice de Gravidade de Doença , Ultrassonografia/métodos , Adulto , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/patologia , Estudos de Coortes , Feminino , Mãos/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Punho/diagnóstico por imagem
16.
Arthritis Res Ther ; 19(1): 202, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28915847

RESUMO

BACKGROUND: To decrease the burden of disease of rheumatoid arthritis (RA), patients at risk for RA need to be identified as early as possible, preferably when no clinically apparent synovitis can be detected. Up to now, it has been fairly difficult to identify those patients with arthralgia who develop inflammatory arthritis (IA), but recent studies using ultrasound (US) suggest that earlier detection is possible. We aimed to identify patients with arthralgia developing IA within 1 year using US to detect subclinical synovitis at first consultation. METHODS: In a multi-centre cohort study, we followed patients with arthralgia with at least two painful joints of the hands, feet or shoulders without clinical synovitis over 1 year. Symptom duration was < 1 year, and symptoms were not explained by other conditions. At baseline and at 6 and 12 months, data were collected for physical examinations, laboratory values and diagnoses. At baseline, we examined 26 joints ultrasonographically (bilateral metacarpophalangeal joints 2-5, proximal interphalangeal joints 2-5, wrist and metatarsophalangeal joints 2-5). Scoring was done semi-quantitatively on greyscale (GS; 0-3) and power Doppler (PD; 0-3) images. US synovitis was defined as GS ≥ 2 and/or PD ≥ 1. IA was defined as clinical soft tissue swelling. Sensitivity and specificity were used to assess the diagnostic value of US for the development of IA. Univariate logistic regression was used to analyse the association between independent variables and the incidence of IA. For multivariate logistic regression, the strongest variables (p < 0.157) were selected. Missing values for independent variables were imputed. RESULTS: A total of 196 patients were included, and 159 completed 12 months of follow-up. Thirty-one (16%) patients developed IA, of whom 59% showed US synovitis at baseline. The sensitivity and specificity of US synovitis were 59% and 68%, respectively. If no joints were positive on US, negative predictive value was 89%. In the multivariate logistic regression, age (OR 1.1), the presence of morning stiffness for > 30 minutes (OR 3.3) and PD signal (OR 3.4) were associated with incident IA. CONCLUSIONS: The presence of PD signal, morning stiffness for > 30 minutes and age at baseline were independently associated with the development of IA. Regarding the value of US in the diagnostic workup of patients with early arthralgia at risk for IA, US did perform well in ruling out IA in patients who did not have US synovitis.


Assuntos
Artralgia/etiologia , Artrite Reumatoide/diagnóstico por imagem , Diagnóstico Precoce , Ultrassonografia/métodos , Adulto , Idoso , Artralgia/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Inflamação/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Sinovite/diagnóstico por imagem
17.
Ann Rheum Dis ; 75(12): 2119-2123, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27283332

RESUMO

OBJECTIVES: With early and intensive treatment many patients with early RA attain remission. Aims were to investigate (1) the frequency and time to sustained remission and subsequent tapering in patients initially treated with conventional synthetic disease modifying anti-rheumatic drug ((cs)DMARD) strategies and (2) the frequency and time to flare and regained remission in patients tapering csDMARDs and biological (b)DMARDs during 2 years of follow-up. METHODS: Two-year follow-up data from the treatment in the Rotterdam Early Arthritis Cohort (tREACH) cohort were used. Patients were randomised to initial treatment with triple DMARD therapy (iTDT) with glucocorticoid (GC) bridging or methotrexate monotherapy (iMM) with GC bridging. Patients were evaluated every 3 months. In case Disease Activity Score (DAS) was >2.4 treatment was switched to a TNF-blocker. In case DAS<1.6 at 2 consecutive time points, tapering was initiated according to protocol. Outcomes were rates of sustained remission (DAS<1.6 at 2 consecutive time points), flare (medication increase after tapering) and remission after flare (DAS<1.6). Data were analysed using Kaplan-Meier analyses. RESULTS: During 2 years of follow-up, sustained remission was achieved at least once by 159 (57%) of patients, of whom 118 and 23 patients initiated tapering of csDMARDs and bDMARDs, respectively. Thirty-four patients achieved drug-free remission. Flare rates were 41% and 37% and within 1 year, respectively. After flare, 65% of patients tapering csDMARDs re-achieved remission within 6 months after treatment intensification. CONCLUSIONS: Regardless of initial treatment strategy, 57% of patients achieved sustained remission during 2 years of follow-up. Flare rates were 41% and 37% within 12 months in patients tapering csDMARDs and bDMARDs, respectively. TRIAL REGISTRATION NUMBER: ISRCTN26791028; Post-results.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/administração & dosagem , Metotrexato/administração & dosagem , Adulto , Idoso , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Exacerbação dos Sintomas , Fatores de Tempo
19.
Rheumatol Int ; 35(8): 1325-33, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25724472

RESUMO

Glucocorticoids (GC) are widely used in rheumatoid arthritis (RA). Ongoing active disease due to GC resistance may unfavorably influence long-term disease outcome in RA. We studied the association between the presence of glucocorticoid receptor (GR) and glucocorticoid-induced transcript 1 (GLCCI1) gene polymorphisms, which modulate GC sensitivity, and baseline disease activity score (DAS) and efficacy of GC bridging therapy in RA. We prospectively studied in vivo GC sensitivity in 138 patients with recent-onset or longstanding RA. In vivo GC sensitivity was expressed as the relative decrease in DAS following 2 weeks of standardized GC therapy. All patients were genotyped for the GR polymorphisms BclI (rs41423247), N363S (rs6195), 9ß (rs6198), ER22/23EK (rs6189 + rs6190), and the GLCCI1 variant rs37972 and subsequently divided in groups carrying a polymorphism associated with increased GC sensitivity (BclI-G allele, N363S-G allele, GLCCI1-C allele) or decreased GC sensitivity (9ß-G allele, ER22/23EK-A/A allele, GLCCI1-T allele). Differences in baseline DAS and relative decrease in DAS in the different genotype groups were analyzed using analysis of covariance and linear regression. Baseline DAS was higher in patients who carried polymorphisms of the GR and GLCCI1 genes associated with decreased GC sensitivity. GLCCI1 genotype, but not GR genotypes, was associated with improvement in DAS in male patients with RA. The GLCCI1 gene minor allele (rs37972) may be associated with less efficient GC bridging therapy in male RA patients. Carriers of the BclI-G, N363S-G, or GLCCI1-C alleles had lower levels of baseline disease activity, suggesting a role for the GLCCI1 and GR gene in regulation of GC sensitivity to endogenously produced cortisol.


Assuntos
Artrite Reumatoide/genética , Receptores de Glucocorticoides/genética , Adulto , Idoso , Artrite Reumatoide/tratamento farmacológico , Estudos de Coortes , Feminino , Glucocorticoides/uso terapêutico , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
20.
Ned Tijdschr Geneeskd ; 160: A9868, 2015.
Artigo em Holandês | MEDLINE | ID: mdl-27027208

RESUMO

OBJECTIVE: How do healthcare consumers perceive the use of medical data for scientific research, within the framework of protection of their personal data? DESIGN: Survey among 731 members of the Healthcare Consumer Panel of the Netherlands Institute for Health Services Research (NIVEL). METHOD: A written and online questionnaire was used, consisting of general questions and 4 cases per respondent. The questions concerned the degree of trust respondents have in the use of previously registered data for different kinds of healthcare research, and their willingness to make data available under various conditions without being asked for explicit consent. RESULTS: Respondents showed a high degree of trust in scientific researchers and physicians concerning the re-use of medical data for research. A majority agreed that it is not necessary to be explicitly asked for consent for this kind of research, providing they are informed: one-third found their autonomy in being able to decide to be more important than scientific progress; three-quarters found explicit permission unnecessary as long as the data is well-protected and only used for scientific research. CONCLUSION: Data protection in research should be proportional to the risks of misuse and the benefits of the use of the data for research. A large majority of healthcare users trust the researchers, and the existing codes of conduct protect data sufficiently. Therefore, we see no need for stricter requirements for the use of health data, which would unnecessarily limit healthcare research. We do consider greater transparency about the research process to be necessary, in order to maintain a proper balance between personal-data protection and the need to emphasise the necessity for learning in the healthcare system.


Assuntos
Pesquisa sobre Serviços de Saúde/métodos , Consentimento Livre e Esclarecido , Inquéritos e Questionários , Pesquisa sobre Serviços de Saúde/ética , Humanos , Países Baixos , Confiança
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