RESUMEN
OBJECTIVE: In this study we aimed to evaluate the effect of lowering the cut point of the 2010 criteria to identify more patients with RA among early inflammatory arthritis patients. METHODS: We included early arthritis patients from the Rotterdam Early Arthritis Cohort with at least one joint with clinical synovitis and symptoms for <1 year, with no other explanation for their symptoms. The demographic and clinical characteristics of each patient were recorded at baseline. Patients were classified as case or non-case at the 1-year follow-up by the definition used in the development of the 2010 criteria (MTX initiation). To assess the diagnostic performance of the 2010 criteria, the sensitivity and specificity at each cut point were determined. RESULTS: We included 557 patients in our analysis. At the 1-year follow-up, 253 patients (45%) were classified as case (MTX use). In the group of patients who scored 0-5 points (n = 328), 98 patients (30%) were classified as case (MTX use). The sensitivity and specificity of the 2010 criteria using the cut point of 6 were 61% and 76%, respectively. With the cut point of 5, the sensitivity would increase to 76% and the specificity would decrease to 68%. CONCLUSION: By lowering the cut point of the 2010 criteria from 6 to 5 points, we were able to identify 15% more RA patients at the cost of 8% more false-positive patients.
Asunto(s)
Artritis Reumatoide/diagnóstico , Índice de Severidad de la Enfermedad , Adulto , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Estudios de Cohortes , Diagnóstico Precoz , Reacciones Falso Positivas , Femenino , Estudios de Seguimiento , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To investigate the prevalence of underdiagnosis and undertreatment of traditional cardiovascular risk factors in RA patients. METHODS: RA patients ⩽70 years of age without cardiovascular disease (CVD) or diabetes mellitus were included. Systolic blood pressure and a fasting lipid profile were measured. The 10-year CVD risk was estimated using the Dutch Cardiovascular Risk Management (CVRM) guideline and EULAR modifications of the Systemic Coronary Risk Evaluation tables. RESULTS: A total of 327 patients were included (female gender: 68%). The mean age was 53 (11) years [mean (s.d.)]. The median disease duration was 7 years (inter quartile range: 2-14 years). According to the CVRM guideline, 52% of the patients had a CVD risk ⩾20% and according to the EULAR guidelines, 18% of the patients had a CVD risk ≥ 20%. Low-density lipoprotein cholesterol (LDL-C) >2.5 mmol/l was found in >80% of the patients with a CVD risk ⩾10% as estimated by both the CVRM and EULAR guidelines, and 32-42% of the patients with a CVD risk ⩾10% had a systolic blood pressure >140 mmHg, depending on the risk model used. Statins were used in 6% and antihypertensives in 23-25%, and 50-86% of these patients did not reach the recommended treatment targets. CONCLUSION: Regardless of the adapted risk assessment model used, untreated hypertension and hypercholesterolaemia were frequently found in RA patients with increased CVD risk. Treatment of these cardiovascular risk factors deserves more attention in RA. TRIAL REGISTRATION: The Dutch Trial Register, www.trialregister.nl, NTR3873.
Asunto(s)
Artritis Reumatoide/complicaciones , Hipercolesterolemia/epidemiología , Hipertensión/epidemiología , Adulto , Antihipertensivos/uso terapéutico , Artritis Reumatoide/sangre , Artritis Reumatoide/fisiopatología , Presión Sanguínea , Proteína C-Reactiva/análisis , LDL-Colesterol/sangre , Estudios Transversales , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/tratamiento farmacológico , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
OBJECTIVE: To evaluate direct and indirect costs per quality adjusted life year (QALY) for different initial treatment strategies in very early RA. METHODS: The 1-year data of the treatment in the Rotterdam Early Arthritis Cohort trial were used. Patients with a high probability (>70%) according to their likelihood of progressing to persistent arthritis, based on the prediction model of Visser, were randomized into one of following initial treatment strategies: (A) initial triple DMARD therapy (iTDT) with glucocorticoids (GCs) intramuscular (n = 91); (B) iTDT with an oral GC tapering scheme (n = 93); and (C) initial MTX monotherapy (iMM) with GCs similar to B (n = 97). Data on QALYs, measured with the Dutch EuroQol, and direct and indirect cost were used. Direct costs are costs of treatment and medical consumption, whereas indirect costs are costs due to loss of productivity. RESULTS: Average QALYs (sd) for A, B and C were, respectively, 0.75 (0.12), 0.75 (0.10) and 0.73 (0.13) for Dutch EuroQol. Highest total costs per QALY (sd) were, respectively, 12748 (18767), 10 380 (15 608) and 17 408 (21 828) for strategy A, B and C (P = 0.012, B vs C). Direct as well as indirect costs were higher with iMM (strategy C) compared with iTDT (strategy B). Higher direct costs were due to â¼40% more biologic usage over time. Higher indirect costs, on the other hand, were caused by more long-term sickness and reduction in contract hours. iTDT was >95% cost-effective across all willingness-to-pay thresholds compared with iMM. CONCLUSION: iTDT was more cost-effective and had better worker productivity compared with iMM.
Asunto(s)
Antirreumáticos/economía , Artritis Reumatoide/economía , Metotrexato/economía , Administración Oral , Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Análisis Costo-Beneficio , Esquema de Medicación , Costos de los Medicamentos , Quimioterapia Combinada/economía , Femenino , Gastos en Salud , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de Vida , Método Simple Ciego , Resultado del TratamientoAsunto(s)
Arteritis de Células Gigantes , Pneumocystis carinii , Neumonía por Pneumocystis , Arteritis de Células Gigantes/complicaciones , Arteritis de Células Gigantes/tratamiento farmacológico , Humanos , Neumonía por Pneumocystis/tratamiento farmacológico , Neumonía por Pneumocystis/etiología , Neumonía por Pneumocystis/prevención & control , EsteroidesRESUMEN
OBJECTIVE: To evaluate the therapeutic and economic consequences of various disease activity indices (DAIs) in RA according to 1987 and 2010 criteria. METHODS: Data on disease activity states from all sustained visits were assessed from all patients who participate in the treatment in the Rotterdam Early Arthritis Cohort (tREACH) study, a stratified randomized trial to evaluate different treatment strategies in patients with a symptom duration of <1 year. Frequencies of treatment adaptations, based upon exclusive thresholds of various DAIs, were visualized in reclassification tables. The Stuart-Maxwell test was applied to analyse any significant differences between treatment decisions according to the different DAIs. Simulated annual median medication costs were estimated using the tREACH medication protocol with standard national costs. RESULTS: DAIs perform similar in RA according to 1987 and 2010 criteria. A total of 1104 DASs per DAI were available from 296 patients. DAIs differ significantly, compared with DASs, in classifying a patient's disease state. Consequently, treatment intensifications occur more frequently with SDAI, CDAI and DAS-28 usage, compared with DAS. Tapering treatment occurs less frequently with SDAI and CDAI and more frequently with DAS-28 usage. Simulated annual median medication costs are significantly higher if DAS-28, SDAI and CDAI are used compared with DAS usage. CONCLUSION: Usage of various DAIs in a single patient leads to inconsistent disease state categorizations. Consequently, these inconsistencies significantly influence therapeutic decisions and accompanying costs. As DAI usage is imperative to uphold current European League Against Rheumatology (EULAR) treatment recommendations, physicians should consider these therapeutic and economic consequences before choosing a particular DAI.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/clasificación , Artritis Reumatoide/tratamiento farmacológico , Toma de Decisiones , Guías de Práctica Clínica como Asunto , Artritis Reumatoide/diagnóstico , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Método Simple Ciego , Resultado del TratamientoRESUMEN
INTRODUCTION: An ACR/EULAR task force released new criteria to classify rheumatoid arthritis at an early stage. This study evaluates the diagnostic performance of these criteria and algorithms by van der Helm and Visser in REACH. METHODS: Patients with symptoms ≤12 months from REACH were used. Algorithms were tested on discrimination, calibration and diagnostic accuracy of proposed cut-points. Two patient sets were defined to test robustness; undifferentiated arthritis (UA) (n=231) and all patients including those without synovitis (n=513). The outcomes evaluated were methotrexate use and persistent disease at 12 months. RESULTS: In UA patients all algorithms had good areas under the curve 0.79, 95% CI 0.73 to 0.83 for the ACR/EULAR criteria, 0.80, 95% CI 0.74 to 0.87 for van der Helm and 0.83, 95% CI 0.77 to 0.88 for Visser. All calibrated well. Sensitivity and specificity were 0.74 and 0.66 for the ACR/EULAR criteria, 0.1 and 1.0 for van der Helm and 0.59 and 0.93 for Visser. Similar results were found in all patients indicating robustness. CONCLUSION: The ACR/EULAR 2010 criteria showed good diagnostic properties in an early arthritis cohort reflecting daily practice, as did the van der Helm and Visser algorithms. All were robust. To promote uniformity and comparability the ACR/EULAR 2010 criteria should be used in future diagnostic studies.
Asunto(s)
Algoritmos , Artritis Reumatoide/diagnóstico , Adulto , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Diagnóstico Precoz , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana EdadRESUMEN
BACKGROUND: Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis. METHODS: A multicenter stratified randomized single-blind controlled trial is currently being performed in patients 18 years or older with recent-onset arthritis. Eight hundred ten patients are being stratified according to the likelihood of their developing persistent arthritis. In patients with a high probability of persistent arthritis, we will study combination Disease Modifying Antirheumatic Drug therapy compared to monotherapy methotrexate. In patients with an intermediate probability of persistent arthritis, we will study Disease Modifying Antirheumatic Drug of various intensities. In patients with a low probability, we will study non-steroidal anti-inflammatory drugs, hydroxychloroquine and a single dose of corticosteroids. If disease activity is not sufficiently reduced, treatment will be adjusted according to a step-up protocol. If remission is achieved for at least six months, medication will be tapered off. Patients will be followed up every three months over two years. DISCUSSION: This is the first rheumatological study to base treatment in early arthritis on a prediction rule. Treatment will be stratified according to the probability of persistent arthritis, and different combinations of treatment per stratum will be evaluated. Treatment will be started early, and patients will not need to meet the ACR-criteria for rheumatoid arthritis. TRIAL REGISTRATION: This trial has been registered in Current Controlled Trials with the ISRCTN26791028.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Protocolos Clínicos/normas , Ensayos Clínicos como Asunto/métodos , Proyectos de Investigación/normas , Antirreumáticos/normas , Combinación de Medicamentos , Costos de los Medicamentos , Diagnóstico Precoz , Humanos , Estudios Longitudinales , Evaluación de Resultado en la Atención de Salud/métodos , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Medición de Riesgo/métodos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: In patients with early rheumatoid arthritis, initial combination therapies provide earlier clinical improvement and less progression of joint damage after 1 year compared with initial monotherapies (as demonstrated in the BeSt study). OBJECTIVE: To evaluate whether the initial clinical and radiographic efficacy of combination therapies could be maintained during the second year of follow-up in patients with early rheumatoid arthritis. DESIGN: Randomized, controlled clinical trial with blinded assessors. SETTING: 18 peripheral and 2 university medical centers in the Netherlands. PATIENTS: 508 patients with early active rheumatoid arthritis. INTERVENTION: Sequential monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with tapered high-dose prednisone (group 3), or initial combination therapy with infliximab (group 4). Trimonthly treatment adjustments were made to achieve low disease activity. MEASUREMENTS: Primary end points were functional ability (Health Assessment Questionnaire) and Sharp-van der Heijde score for radiographic joint damage. RESULTS: Groups 3 and 4 had more rapid clinical improvement during the first year; all groups improved further to a mean functional ability score of 0.6 (overall, P = 0.257) and 42% were in remission (overall, P = 0.690) during the second year. Progression of joint damage remained better suppressed in groups 3 and 4 (median scores of 2.0, 2.0, 1.0, and 1.0 in groups 1, 2, 3, and 4, respectively [P = 0.004]). After 2 years, 33%, 31%, 36%, and 53% of patients in groups 1 through 4, respectively, were receiving single-drug therapy for initial treatment. There were no significant differences in toxicity. LIMITATIONS: Patients and physicians were aware of the allocated group, and the assessors were blinded. CONCLUSIONS: Currently available antirheumatic drugs can be highly effective in patients with early rheumatoid arthritis in a setting of tight disease control. Initial combination therapies seem to provide earlier clinical improvement and less progression of joint damage, but all treatment strategies eventually showed similar clinical improvements. In addition, combination therapy can be withdrawn successfully and less treatment adjustments are needed than with initial monotherapies.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Antiinflamatorios/efectos adversos , Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/efectos adversos , Artritis Reumatoide/diagnóstico por imagen , Esquema de Medicación , Quimioterapia Combinada , Humanos , Infliximab , Prednisona/efectos adversos , Prednisona/uso terapéutico , Radiografía , Método Simple Ciego , Resultado del TratamientoRESUMEN
OBJECTIVES: Rheumatoid arthritis (RA) has been identified as an independent cardiovascular risk factor. The importance of risk factors such as hypertension and hyperlipidemia in the generation of atherosclerosis in RA patients is unclear. This study analyzed clinical parameters associated with carotid intima media thickness (cIMT) in patients with RA. METHODS: Subjects with RA and healthy controls without RA, both without known cardiovascular disease, were included. Participants underwent a standard physical examination and laboratory measurements including a lipid profile. cIMT was measured semi-automatically by ultrasound. RESULTS: In total 243 RA patients and 117 controls were included. The median RA disease duration was 7 years (IQR 2-14 years). The median DAS28 was 2.4 (IQR 1.6-3.2) and 114 (50.4%) of the RA patients were in remission. The presence of RA and cIMT were not associated (univariate analysis). Multivariable regression analysis showed that cIMT in RA patients was associated with age (B = 0.006, P<0.001) and systolic blood pressure (B = 0.003, P = 0.003). In controls, cIMT was associated with age (B = 0.006, P<0.001) and smoking (B = 0.097, P = 0.001). CONCLUSION: cIMT values were similar between RA patients and controls. Hypertension was strongly associated with cIMT in RA patients. After adjustment, no association between cIMT and specific RA disease characteristics was found in this well treated RA cohort.
Asunto(s)
Artritis Reumatoide/diagnóstico por imagen , Enfermedades Cardiovasculares/etiología , Grosor Intima-Media Carotídeo , Adulto , Artritis Reumatoide/sangre , Artritis Reumatoide/complicaciones , Enfermedades Cardiovasculares/diagnóstico por imagen , Estudios Transversales , Femenino , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Genetic and disease-related factors give rise to a wide spectrum of glucocorticoid (GC) sensitivity in rheumatoid arthritis (RA). In clinical practice, GC treatment is not adapted to these differences in GC sensitivity. In vitro assessment of GC sensitivity before the start of therapy could allow more individualized GC therapy. The aim of the study was to investigate the association between in vitro and in vivo GC sensitivity in RA. METHODS: Thirty-eight early and 37 established RA patients were prospectively studied. In vitro GC sensitivity was assessed with dexamethasone-induced effects on interleukin-2 (IL-2) and glucocorticoid-induced leucine zipper (GILZ) messenger RNA expression in peripheral blood mononuclear cells (PBMCs). A whole-cell dexamethasone-binding assay was used to measure number and affinity (1/KD) of glucocorticoid receptors (GRs). RESULTS: GR number was positively correlated with improvement in DAS. IL-2-EC50 and GILZ-EC50 values both had weak near-significant correlations with clinical improvement in DAS in intramuscularly treated patients only. HAQ responders had lower GILZ-EC50 values and higher GR number and KD. CONCLUSIONS: Baseline cellular in vitro glucocorticoid sensitivity is modestly associated with in vivo improvement in DAS and HAQ-DI score after GC bridging therapy in RA. Further studies are needed to evaluate whether in vitro GC sensitivity may support the development of tailor-made GC therapy in RA.
Asunto(s)
Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Metilprednisolona/administración & dosificación , Prednisona/administración & dosificación , Administración Oral , Adulto , Anciano , Estudios de Cohortes , Femenino , Glucocorticoides/administración & dosificación , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate societal costs and quality-adjusted life years (QALYs) of treatment strategies for patients with recent-onset active rheumatoid arthritis (RA). METHODS: Patients (n = 508) were randomly allocated to 1 of 4 treatment strategy groups: sequential monotherapy, step-up combination therapy, initial combination therapy with prednisone, or initial combination therapy with infliximab. For 2 years, patients reported cost and utility measures. RESULTS: Average QALYs (ideally 2.00) for groups 1-4 were 1.29, 1.31, 1.32, and 1.41, respectively, for the British EuroQol (P Asunto(s)
Antirreumáticos/administración & dosificación
, Antirreumáticos/economía
, Artritis Reumatoide/tratamiento farmacológico
, Artritis Reumatoide/economía
, Costos de la Atención en Salud
, Adulto
, Anciano
, Anticuerpos Monoclonales/administración & dosificación
, Análisis Costo-Beneficio
, Esquema de Medicación
, Quimioterapia Combinada
, Femenino
, Humanos
, Infliximab
, Masculino
, Persona de Mediana Edad
, Prednisona/administración & dosificación
, Años de Vida Ajustados por Calidad de Vida
RESUMEN
OBJECTIVES: To determine the efficacy of subsequent disease modifying antirheumatic drug (DMARD) therapies after initial methotrexate (MTX) failure in patients with recent onset rheumatoid arthritis (RA), treated according to the DAS for 2 years. METHODS: In groups 1 and 2 of the BeSt study, 244 RA patients were initially treated with MTX 15-25 mg/week. Patients who discontinued MTX because of insufficient clinical response (disease activity score, DAS >2.4) or toxicity were classified as "MTX failures." In group 1, these patients switched to sulfasalazine (SSA), then leflunomide and finally to MTX + infliximab (IFX). In group 2, "MTX failures" added SSA to MTX, then hydroxychloroquine (HCQ), then prednisone, and eventually switched to MTX + IFX. "MTX successes" were patients who achieved a DAS =2.4 after 2 years while still on MTX monotherapy. Total Sharp/van der Heijde score (TSS) progression from 0-2 years was assessed in "MTX failures" versus "MTX successes." RESULTS: After 2 years, 162/244 patients (66%) had discontinued MTX because of insufficient response or toxicity. Of these, 78% also failed on SSA (adding or switching), 87% subsequently failed on leflunomide (in group 1), and 64% on MTX + SSA + HCQ (in group 2). 34 of 48 patients (71%) in groups 1 and 2 were successfully treated with MTX + IFX. After 2 years, regardless of the "success" on subsequent DMARDs, " MTX failures" had a median TSS progression of 3 units (mean 9) versus 1 unit (mean 3) in "MTX successes" (p = 0.007). CONCLUSION: After failure on initial MTX, treatment with subsequent conventional DMARDs is unlikely to result in a DAS =2.4 and allows progression of joint damage.
Asunto(s)
Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Metotrexato/administración & dosificación , Antiinflamatorios/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Artritis Reumatoide/diagnóstico por imagen , Artrografía , Protocolos Clínicos , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Infliximab , Isoxazoles/administración & dosificación , Estimación de Kaplan-Meier , Leflunamida , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Sulfasalazina/administración & dosificación , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine associations of methotrexate (MTX) efficacy and toxicity with single-nucleotide polymorphisms (SNPs) in genes coding for folate pathway enzymes in patients with early rheumatoid arthritis (RA). METHODS: Patients (n=205) with active RA received MTX at an initial dosage of 7.5 mg/week, which was increased to 15 mg/week and combined with folic acid (1 mg/day) after 4 weeks. If the Disease Activity Score in 44 joints (DAS44) was >2.4 at 3 months, MTX was increased to 25 mg/week. MTX efficacy was evaluated at 3 and 6 months and compared for genotypes in 3 analyses: patients with and without good response (DAS44