RESUMO
BACKGROUND: Recently, disease activity states were developed for the Disease Activity index for PSoriatic Arthritis (DAPSA). Here, we assess if different DAPSA disease activity states are associated with different degrees of functional impairment and different extents of joint damage progression in patients with psoriatic arthritis (PsA). METHODS: We used data from two pivotal trials of tumour necrosis factor (TNF) inhibitors in PsA (IMPACT II and GO-REVEAL) and identified patients in DAPSA remission (REM, ≤4), and low, moderate or high disease activity (LDA, ≤14; MDA, ≤28; HDA, >28) at 6â months. Across these groups we compared the functional scores (Health Assessment Questionnaire Disability Index, HAQ and physical component scale of the Short Form-36, PCS), and 1-year structural progression (PsA-modified Sharp/van der Heijde Score). RESULTS: We identified 310 from GO-REVEAL and 130 from IMPACT II, with a mean (SD) baseline DAPSA of 48.8 (26.4) and 44.6 (17.9), respectively. HAQ scores increased across patients groups in the four DAPSA disease activity states, while PCS decreased (p<0.001 for both). The mean progression in the combined cohort was -0.47 for REM, -0.28 for LDA, -0.14 for MDA and 0.51 for HDA (p<0.001). This association was also significant in the individual trial cohorts, and in the subgroups of patients treated with TNF inhibitors or placebo. Higher DAPSA scores were significantly and independently associated with probability of structural progression in multiple analyses. CONCLUSIONS: Disease activity states of the PsA specific DAPSA score are highly valid for future use as endpoints in clinical trials or as targets in clinical practice. TRIAL REGISTRATION NUMBERS: IMPACT 2: NCT02152254; GO-REVEAL: NCT00265096.
Assuntos
Atividades Cotidianas , Artrite Psoriásica/fisiopatologia , Adulto , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/tratamento farmacológico , Ensaios Clínicos como Assunto , Progressão da Doença , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Radiografia , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
Therapy reduction in rheumatoid arthritis (RA) is still a challenge for physicians as well as for patients. Effective therapy with subsequent achievement of low disease activity or even remission is achievable for numerous patients using currently available treatment options. Therapy discontinuation has therefore become a hot topic and the risk of exacerbation of well-controlled RA must be weighed against the medical and economic benefits of reducing or even discontinuing therapy. This article gives a review of data regarding tapering of therapy in RA, focusing on conventional disease-modifying antirheumatic drug (DMARD) monotherapy, reduction of conventional therapy under continuing therapy with biologics and discontinuation of biologics. Important influencing factors for a safe and successful tapering procedure appear to be disease activity, disease duration and the tapering process itself (i.e. gradual dose reduction vs. abrupt discontinuation). Additionally, the so-called nocebo effect should also be taken into consideration for interpretation of drug tapering studies.
Assuntos
Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Medicina Baseada em Evidências , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.
Assuntos
Algoritmos , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Glucocorticoides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Gerenciamento Clínico , Europa (Continente) , Humanos , Reumatologia , Sociedades MédicasRESUMO
BACKGROUND: Sonographic assessment, measuring grey scale (GS) and power Doppler (PD) signals, is a sensitive tool for the evaluation of inflammatory joint activity in patients with rheumatoid arthritis (RA). We evaluated the persistence of PD and GS signals in previously clinically active RA joints that have reached a state of continuous clinical inactivity. METHODS: We performed sonographic imaging of 22 joints of the hands of patients with RA, selected all joints without clinical activity but showing ongoing sonographic signs of inflammation, and evaluated the time from last clinical joint activity. RESULTS: A total of 90 patients with RA with 1980 assessed joints were included in this study. When comparing the mean time from clinical swelling, we found a significantly longer period of clinical inactivity in joints showing low sonographic activity (mean±SD time from swelling of 4.1±3.2 vs 3.1±2.9â years for PD1 vs PD≥2, p=0.031 and 4.5±3.4 vs 3.3±3.2â years for GS1 vs GS≥2, p≤0.0001). CONCLUSIONS: We conclude that subclinical joint activity is long-lasting in RA joints in clinical remission, but attenuates over time. The latter conclusion is based on the observed shorter time duration from last clinical activity for strong compared with weaker sonographic signals.
Assuntos
Artrite Reumatoide/diagnóstico por imagem , Articulações dos Dedos/diagnóstico por imagem , Articulação Metacarpofalângica/diagnóstico por imagem , Sinovite/diagnóstico por imagem , Articulação do Punho/diagnóstico por imagem , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Estudos de Coortes , Feminino , Articulações dos Dedos/irrigação sanguínea , Humanos , Masculino , Articulação Metacarpofalângica/irrigação sanguínea , Pessoa de Meia-Idade , Osteoartrite/complicações , Osteoartrite/diagnóstico por imagem , Indução de Remissão , Índice de Gravidade de Doença , Ultrassonografia Doppler , Articulação do Punho/irrigação sanguíneaRESUMO
OBJECTIVE: To validate ultrasound (US) for measuring metacarpal cartilage thickness (MCT), by comparing it with anatomical measurement using cadaver specimens. To correlate US MCT with radiographic joint space narrowing (JSN) or width (JSW) in patients with rheumatoid arthritis (RA). METHODS: Bilateral metacarpophalangeal (MCP) joints of 35 consecutive outpatients, with recent hand X-rays, were included in the analysis. Metacarpal and phalangeal cartilage of MCP 2-5 was assessed bilaterally by US. JSW and JSN were evaluated on X-rays by the van der Heijde modified Sharp method (vdHS). In addition, cadaver specimens of MCP 2-5 joints (n=19) were evaluated by anatomical measurement and US. RESULTS: The agreement (intraclass correlation coefficient) between sonographic and anatomical MCT on cadaver specimens of MCP joints was 0.61. MCT of individual MCP joints correlated with individual MCP JSN (r=-0.32, p<0.001) and individual MCP JSW (r=0.72, p<0.001). No correlation was found between phalangeal cartilage thickness and JSN in individual MCP joints. The US MCT summary score for MCP joints 2-5 correlated with summary scores for JSW (r=0.78, p<0.001), JSN (r=-0.5, p<0.001), erosion score of the vdHS (r=-0.39, p<0.001) and total vdHS (r=-0.47, p<0.001). CONCLUSIONS: Sonographic cartilage assessment in MCPs is closely related to anatomical cartilage thickness. Both JSW and JSN by radiography represent cartilage thickness in the MCP joints of patients with RA quite well. Thus, US is a valid tool for measuring MCT if radiographs are not available or in case of joint malalignment.
Assuntos
Artrite Reumatoide/diagnóstico por imagem , Cartilagem Articular/diagnóstico por imagem , Articulação Metacarpofalângica/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/patologia , Cartilagem Articular/patologia , Estudos de Casos e Controles , Feminino , Articulação da Mão/diagnóstico por imagem , Articulação da Mão/patologia , Humanos , Masculino , Articulação Metacarpofalângica/patologia , Pessoa de Meia-Idade , Tamanho do Órgão , Radiografia , Reprodutibilidade dos Testes , UltrassonografiaRESUMO
Disease activity assessment is one of the most pivotal aspects in the care of RA patients. Composite measures of disease activity are superior to individual measures, since they capture the multiple facets of the disease. Since swollen joint counts correlate with joint damage progression and tender joint counts with physical function, composite scores that include joint counts are preferable. The simplified and clinical disease activity indices (SDAI, CDAI) are easy to calculate and correlate well with joint damage and physical function. Cutpoints for disease activity states have been established and improvement criteria likewise. The SDAI and CDAI remission criteria (ACR-EULAR index-based remission) are stringent, usually associated with a halt of progression of damage and optimisation of physical function and can still be achieved in 1 of 4 clinic patients and up to one third of patients in trials of early arthritis.
Assuntos
Artrite Reumatoide/diagnóstico , Indicadores Básicos de Saúde , Articulações , Reumatologia/métodos , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/terapia , Avaliação da Deficiência , Progressão da Doença , Nível de Saúde , Humanos , Articulações/patologia , Articulações/fisiopatologia , Valor Preditivo dos Testes , Indução de Remissão , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD). METHODS: The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement. RESULTS: Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extra-articular manifestations of PsA. Five overarching principles and a research agenda were defined. CONCLUSION: These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Antirreumáticos/efeitos adversos , Comorbidade , Europa (Continente) , Medicina Baseada em Evidências/métodos , Glucocorticoides/uso terapêutico , Humanos , Cooperação Internacional , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVE: To develop recommendations to enable successful inclusion of the patient perspective in European League Against Rheumatism (EULAR)-funded scientific research projects. METHODS: The EULAR standardised operational procedures for guideline development were followed. A systematic literature review was presented during a first task force meeting, including 3 rheumatologists, 1 rheumatologist/epidemiologist, 2 allied health professionals, 2 representatives of arthritis research organisations and 7 patient representatives, resulting in 38 statements. A Delphi method was carried out to reduce and refine the statements and agree on a set of eight. Next, a survey among a wider group of experts, professionals and patient representatives (n=42), was completed. Feedback from this wider group was discussed at the second meeting and integrated in the final wording of the recommendations. Subsequently, the level of agreement of the group of experts (n=81) was re-evaluated. RESULTS: The project resulted in a definition of patient research partner and agreement on a set of eight recommendations for their involvement in research projects. These recommendations provide practical guidance for organising patient participation, capturing (1) the role of patient research partners, (2) phase of involvement, (3) the recommended number, (4) recruitment, (5) selection, (6) support, (7) training and (8) acknowledgement. CONCLUSION: Collaboration between patients and professionals in research is relatively new. Trials or effectiveness studies are not yet available. Nevertheless, it is possible to define recommendations for the inclusion of patients in research following a solid expert opinion based consensus process.
Assuntos
Pesquisa Biomédica/organização & administração , Defesa do Paciente , Europa (Continente) , Medicina Baseada em Evidências/métodos , Humanos , Defesa do Paciente/educação , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Relações Profissional-PacienteRESUMO
OBJECTIVE: To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 39,756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. CONCLUSIONS: Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.
Assuntos
Artrite/diagnóstico , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , Diagnóstico Diferencial , Medicina Baseada em Evidências/métodos , Humanos , Cooperação Internacional , Assistência de Longa Duração/métodos , Prognóstico , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: To perform a systematic literature review of effective strategies for the treatment of rheumatoid arthritis (RA). METHODS: As part of a European League Against Rheumatism (EULAR) Task Force investigation, a literature search was carried out from January 1962 until February 2009 in PubMed/Ovid Embase/Cochrane and EULAR/American College of Rheumatism (ACR)) abstracts (2007/2008) for studies with a treatment strategy adjusted to target a predefined outcome. Articles were systematically reviewed and clinical outcome, physical function and structural damage were compared between intensive and less intensive strategies. The results were evaluated by an expert panel to consolidate evidence on treatment strategies in RA. RESULTS: The search identified two different kinds of treatment strategies: strategies in which the reason for treatment adjustment differed between the study arms ('steering strategies', n=13) and strategies in which all trial arms used the same clinical outcome to adjust treatment with different pharmacological treatments ('medication strategies', n=7). Both intensive steering strategies and intensive medication strategies resulted in better outcome than less intensive strategies in patients with early active RA. CONCLUSION: Intensive steering strategies and intensive medication strategies produce a better clinical outcome, improved physical function and less structural damage than conventional steering or treatment. Proof in favour of any steering method is lacking and the best medication sequence is still not known.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/administração & dosagem , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Medicina Baseada em Evidências/métodos , Humanos , Guias de Prática Clínica como Assunto , Resultado do TratamentoRESUMO
OBJECTIVES: To assess the ability of efficacy measures that incorporate onset or sustainability to detect treatment effect or reflect patient satisfaction, using exploratory analyses of data from the ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate Responders) trial. METHODS: 218 abatacept- and 99 placebo-treated patients were evaluated. Reporting methods included time to onset (first American College of Rheumatology [ACR] 50 response/Low Disease Activity State [LDAS; DAS28 < or =3.2]) and sustainability of ACR50/LDAS, both assessed according to discriminatory capacity (number of patients needed to study [NNS]) and patient satisfaction with treatment. RESULTS: Efficacy measures incorporating elements of sustainability or onset decreased discriminatory capacity, while sustainability, but not onset of action, was important in reflecting patient satisfaction. CONCLUSIONS: Optimal assessment methods depend on whether the outcome of interest is ability to detect treatment effects or to reflect patient satisfaction. Sustainability of response (and possibly, at a lower magnitude, fast onset of action) may be important when evaluating patient satisfaction with RA therapies in patients who have previously failed anti-TNF therapy.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Imunoconjugados/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Abatacepte , Bases de Dados Factuais , Humanos , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Índice de Gravidade de Doença , Falha de TratamentoRESUMO
Rheumatoid arthritis (RA) is characterised by both inflammation, as manifested by pain and swelling, and destruction of the joints. Unequivocal evidence indicates that disease activity, and thus the inflammatory response, is linked to joint damage. From this viewpoint we suggest that, vice versa, joint damage might be a cause of the active disease process, thus leading to a vicious cycle of events. The background to this notion stems from the known autoimmune response in RA, the potential of cartilage and bone breakdown products to elicit inflammation and notions that in joints that have undergone surgery with cartilage removal RA does not flare. However, the clinical evidence for this relationship is still to be provided as proof of the concept.
Assuntos
Artrite Reumatoide/fisiopatologia , Inflamação/fisiopatologia , Artrite Reumatoide/imunologia , Doenças Autoimunes/fisiopatologia , Humanos , Doenças do Complexo Imune/fisiopatologia , Inflamação/imunologiaRESUMO
OBJECTIVE: To compare the progression of erosions and joint space narrowing (JSN) in patients with early active rheumatoid arthritis (RA) using data obtained in the "Active-controlled Study of Patients receiving Infliximab for the treatment of Rheumatoid arthritis of Early onset" (ASPIRE) study. METHODS: This was a post hoc analysis of patients in ASPIRE who received placebo plus methotrexate (MTX) or infliximab (3 or 6 mg/kg) plus MTX. Radiographs of the hands (870 patients) and feet (871 patients) were obtained at baseline and week 54 and scored using the van der Heijde/Sharp method. In total, 7160 joints in the placebo plus MTX group and 18,908 joints in the combined infliximab plus MTX group were included in this analysis. RESULTS: At baseline, 83.4% of joints in the placebo plus MTX group had no radiographic damage, 8.5% had only erosions, 4.4% had only JSN and 3.7% had both. The distribution was similar in the infliximab plus MTX group. In the placebo plus MTX group, the majority of joints did not have development or progression of radiographic damage from baseline to week 54; among joints that did have development or progression of damage at week 54, erosions occurred more often than JSN. The same pattern was observed in the infliximab plus MTX group, although the proportions of joints with damage at week 54 were generally larger in the placebo plus MTX group. There was a tendency for joints with existing erosions or JSN to have progression of damage, rather than development of new damage. CONCLUSIONS: Erosions were the predominant type of damage observed in both treatment groups. Erosions and JSN are related but partly independent processes.
Assuntos
Artrite Reumatoide/diagnóstico por imagem , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Progressão da Doença , Quimioterapia Combinada , Seguimentos , Articulações do Pé/diagnóstico por imagem , Articulações do Pé/patologia , Articulação da Mão/diagnóstico por imagem , Articulação da Mão/patologia , Humanos , Infliximab , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Radiografia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto JovemRESUMO
OBJECTIVES: To evaluate different methods of reporting response to treatment or disease status for their ability to discriminate between active therapy and placebo, or to reflect structural progression or patient satisfaction with treatment using an exploratory analysis of the Abatacept in Inadequate Responders to Methotrexate (AIM) trial. METHODS: 424 active (abatacept approximately 10 mg/kg) and 214 placebo-treated patients with rheumatoid arthritis (RA) were evaluated. METHOD: of reporting included: (1) response (American College of Rheumatology (ACR) criteria) versus state (disease activity score in 28 joints (DAS28) criteria); (2) stringency (ACR20 vs 50 vs 70; moderate disease activity state (MDAS; DAS28 <5.1) vs low disease activity state (LDAS; DAS28
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Imunoconjugados/uso terapêutico , Abatacepte , Doença Crônica , Análise Discriminante , Progressão da Doença , Método Duplo-Cego , Humanos , Metotrexato/uso terapêutico , Satisfação do Paciente , Resultado do TratamentoRESUMO
OBJECTIVE: To validate and compare the definition of the Disease Activity Score 28 based on C-reactive protein (DAS28 (CRP)) to the definition based on erythrocyte sedimentation rate (ESR). METHODS: Data were analysed from two randomised, double-blind, placebo-controlled trials of abatacept of 6-month and 12-month duration in patients with rheumatoid arthritis. European League Against Rheumatism (EULAR) response criteria and the proportion of patients in remission (DAS28 <2.6) based on the two DAS28 definitions were examined. Trends in radiographic progression (erosion score, joint space narrowing score and total score) and physical function (Health Assessment Questionnaire Disability Index (HAQ-DI)) across the EULAR responder states (none, moderate and good) were analysed. RESULTS: There was general agreement in determining the EULAR responder state using both DAS28 definitions (kappa = 0.80, 95% CI 0.76 to 0.83). Overall, there was 82.4% agreement on the EULAR response criteria; when disagreements occurred, the DAS28 (CRP) yielded a better EULAR response more often then DAS28 (ESR) (12.6% vs 4.9%, respectively). There was also agreement in determining remission: kappa = 0.69 (95% CI 0.60 to 0.78). Radiographic progression decreased in patients treated with abatacept across EULAR states (from none to moderate to good) based on both definitions. For patients treated with placebo, the trend was not as pronounced, with radiographic scores higher for moderate vs non-responders. For physical function, similar trends were observed across the EULAR states for both DAS28 definitions. CONCLUSIONS: The DAS28 (CRP) has been validated against radiographic progression and physical function. While the DAS28 (CRP) yielded a better EULAR response more often than the DAS28 (ESR), the validation profile was similar to the DAS28 (ESR), indicating that both measures are useful for assessing disease activity in patients with rheumatoid arthritis.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Imunoconjugados/uso terapêutico , Abatacepte , Doença Aguda , Adulto , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico por imagem , Artrografia , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: To examine the association of radiographic progression and disease activity states in patients with rheumatoid arthritis (RA) treated with methotrexate with or without infliximab. METHODS: Patients (n = 1049) with active RA for 3 years or less and no previous methotrexate treatment were randomly assigned (4 : 5 : 5) to receive methotrexate plus placebo or methotrexate plus infliximab 3 or 6 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter to week 46. Disease activity was classified by the simplified disease activity index as remission (< or =3.3), low (>3.3 to < or =11), moderate (>11 to < or =26), high (>26). Radiographic progression was measured as a change from baseline to week 54 in total Sharp score. RESULTS: At weeks 14 and 54, more patients receiving methotrexate plus infliximab than methotrexate plus placebo were in remission (10.7% versus 2.8% week 14; 21.3% versus 12.3% week 54; p<0.001 for both). Methotrexate plus placebo halted radiographic progression only if patients achieved remission within 3 months, whereas methotrexate plus infliximab also halted or minimised progression in patients with low or moderate activity, respectively. Patients with persistently high disease activity levels had much less progression of joint damage if treated with methotrexate plus infliximab versus methotrexate monotherapy. Even with infliximab plus methotrexate there was a direct relationship between disease activity and radiographic changes, although the slope was deflected when compared with methotrexate monotherapy. CONCLUSION: With methotrexate, joint damage progresses even at low and moderate disease activity levels, whereas methotrexate plus infliximab inhibits radiographic progression across all disease activity states.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Metotrexato/administração & dosagem , Adulto , Análise de Variância , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Artrografia , Progressão da Doença , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Infliximab , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Rheumatoid arthritis is a chronic disabling disease that results in considerable loss of physical function in patients over time. The ultimate goal of therapy is remission, a clinical state with a highly variable definition in the literature. For the purpose of achieving the best patient outcome, it is important to maintain the lowest possible disease activity. Therefore, stringent remission criteria should be chosen, which will lead to the best possible prevention of structural and functional decline. Standardised intensive therapeutic strategies and algorithms should form the basis for the administration of anti-rheumatic medication.
Assuntos
Artrite Reumatoide/diagnóstico , Artrite Reumatoide/terapia , Indicadores Básicos de Saúde , Avaliação de Resultados em Cuidados de Saúde/métodos , Reumatologia/métodos , Alemanha , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Physical function in rheumatoid arthritis (RA) has reversible and irreversible components, and is typically assessed by the Health Assessment Questionnaire Disability Index (HAQ). Since irreversible components are expected to increase with longer duration of RA and reduce the ability for improvement in physical function, we analysed responsiveness of HAQ scores in patient populations with differing RA durations in randomised controlled trials (RCTs). METHODS: Data from all RCTs published between 1980 and 2005 that reported changes from baseline in HAQ at 6 and/or 12 months were analysed. Treatments were grouped as "biologics", or "traditional" disease modifying antirheumatic drugs (DMARDs), and "placebo". We computed effect sizes of HAQ in each trial, and contrasted the association between these effects and duration of RA among treatment groups using regression models. RESULTS: We identified 42 RCTs with complete data for the statistical models. The models indicate that discrimination of functional improvement between active drug groups and placebo is reduced in patients with a longer duration of RA (p = 0.02 for the change in discrimination over time). The placebo-adjusted HAQ responses decreased on average by 0.37 per year of RA duration. CONCLUSION: Responsiveness in HAQ scores is inversely associated with mean disease duration in RA. This impacts assessment of physical function, a key outcome measure in RCTs and practice, and impacts the ability to discriminate active treatment from placebo.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Interpretação Estatística de Dados , Feminino , Seguimentos , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Established thresholds for low levels of disease activity need to be examined from a patients' perspective. OBJECTIVE: To identify new cut-off points for patients' perception of satisfactory condition (patient acceptable symptom state (PASS)) in composite indices and patient-reported outcomes, and to examine the agreement between the new PASS cut-off points for composite indices and existing thresholds for remission, low and moderate disease activity. METHODS: Patients with rheumatoid arthritis from a treatment register (n = 1496, 72.1% women, mean (SD) age 53.9 (13.5) years, disease duration 7.6 (9.1) years, 28-joint Disease Activity Score (DAS28) 4.98 (1.36)) responded during follow-up (12, 24 and 52 weeks) to a global dichotomised question on satisfactory condition (PASS). New PASS cut-off points were identified with the 75th centile estimation and receiver operating characteristic analyses for a variety of outcome measures, and cut-off points for composite indices were examined for agreement with the low disease activity threshold (1.625) of the Patient Activity Scale (PAS) and thresholds for remission, low and moderate disease activity in DAS28, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI). RESULTS: New PASS cut-off points for DAS28, SDAI and CDAI were in the moderate range of disease activity, and the cut-off point was 3.56 for PAS. Agreement between thresholds for disease activity levels and the PASS cut-off points was best for low disease activity (accuracy 64.5-74.6), and better for moderate disease activity (accuracy 61.3-67.2) than for remission (accuracy 30.7-45.8). CONCLUSION: The current PASS concept seems to be in the range of moderate disease activity.
Assuntos
Artrite Reumatoide/reabilitação , Atitude Frente a Saúde , Índice de Gravidade de Doença , Adulto , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To use an evidence-based and consensus-based approach to elaborate recommendations on how to report disease activity in clinical trials of patients with rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: After an initial expert meeting, during which relevant research questions were identified, a systematic literature search was performed using Medline, Embase and the Cochrane Library as sources. To ensure literature retrieved was comprehensive, we emphasised search algorithms that were sensitive rather than specific. The results of the literature search were discussed by the expert panel, modified and expanded, and were used as the basis for the elaboration of the recommendation in the consensus process. Finally, an independent ACR panel approved these items with some minor modifications. RESULTS: The following pieces of evidence were obtained from the literature search: (1) timing and the sustaining of a response is relevant to achieve better outcomes; (2) composite disease activity indices have been used to define low disease activity and remission and these definitions have been validated as has the American Rheumatism Association (ARA) remission criteria. The "patient-reported symptom state" (PASS) is not yet well validated; (3) evidence was obtained to identify those measures, scales and patient-reported instruments, for which there is a documented association with relevant outcomes; (4) baseline disease activity is associated with disease activity levels at the end of follow-up; and (5) there was not sufficient evidence relating the added benefit of MRI or ultrasound over clinical assessments. Most data stemmed from observational studies rather than clinical trials and literature review was supplemented by input from experts. The results served as the basis for the elaboration of the seven recommendations by the experts. CONCLUSIONS: The approach based on scientific evidence from the literature as well as on expert input provided sufficient information to derive recommendations on reporting disease activity in RA clinical trials. The methodology, results and conclusions of this project were endorsed by EULAR and the ACR.