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1.
Artigo em Inglês | MEDLINE | ID: mdl-33576791

RESUMO

OBJECTIVES: Although there is a general focus on early diagnosis and treatment of hip osteoarthritis, there are no validated diagnostic criteria for early-stage hip OA. The current study aimed to take the first steps in developing diagnostic criteria for early-stage hip OA, using factors obtained through history taking, physical examination, radiography and blood testing at the first consultation in individuals presenting with hip pain, suspicious for hip OA, in primary care. METHODS: Data of the 543 individuals with 735 symptomatic hips at baseline who had any follow-up data available from the prospective CHECK cohort study were used. A group of 26 clinical experts (GPs, Rheumatologists and Orthopedic surgeons) evaluated standardized clinical assessment forms of all subjects on the presence of clinically relevant hip OA 5 to 10 years after baseline. Using the expert based diagnoses as reference standard, a backward selection method was used to create predictive models based on pre-defined baseline factors from history taking, physical examination, radiography and blood testing. RESULTS: Prevalence of clinically relevant hip OA during follow-up was 22%. Created models contained 4 to 8 baseline factors (mainly WOMAC pain items, painful/restricted movements, and radiographic features) and obtained area under the curve between 0.62 ± 0.002 and 0.71 ± 0.002. CONCLUSION: Based on clinical and radiographic features of hip OA obtained at first consultation at a GP for pain/stiffness of the hip, the prediction of clinically relevant hip OA within 5 to 10 years was 'poor' to 'fair'.

2.
PLoS One ; 15(12): e0241189, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33301475

RESUMO

BACKGROUND: We sought to identify immunoglobin G autoantibodies predictive of early treatment response to methotrexate, the recommended first-line therapy for patients with newly diagnosed rheumatoid arthritis, and to the interleukin-6 receptor inhibitor biologic tocilizumab, initiated as the first disease-modifying anti-rheumatic drug. MATERIALS AND METHODS: In baseline sera of a subset of patients with newly diagnosed rheumatoid arthritis in the U-Act-Early study, selected based on specific responder/non-responder criteria using the Disease Activity Score assessing 28 joints (DAS28) within the first 20 weeks, we measured immunoglobin G antibody reactivity against 463 protein antigens and performed supervised cluster analysis to identify predictive autoantibodies for treatment response. The analysis subset comprised 56 patients in the methotrexate arm (22 responders, 34 non-responders) and 50 patients in the tocilizumab arm (34 responders, 16 non-responders). For comparison, these analyses were also performed in 50 age- and gender-matched healthy controls. RESULTS: Increased reactivity in responders versus non-responders was found in the methotrexate arm against two antigens-DOT1-like histone lysine methyltransferase (p = 0.009) and tropomyosin (p = 0.003)-and in the tocilizumab arm against one antigen-neuro-oncological ventral antigen 2 (p = 0.039). Decreased reactivity was detected against two antigens in the methotrexate arm-G1 to S phase transition 2 (p = 0.023) and the zinc finger protein ZPR1 (p = 0.021). Reactivity against the identified antigens was not statistically significant in either treatment arm for patients with rheumatoid factor-positive versus-negative or anti-cyclic citrullinated test-positive versus test-negative rheumatoid arthritis (p ≥ 0.06). CONCLUSIONS: Comprehensive profiling of baseline sera revealed several novel immunoglobin G autoantibodies associated with early treatment response to methotrexate and to tocilizumab in disease-modifying anti-rheumatic drug-naive patients with rheumatoid arthritis. These findings could eventually yield clinically relevant predictive markers, if corroborated in different patient cohorts, and may facilitate future benefit in personalised healthcare.

3.
Ann Rheum Dis ; 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33355152

RESUMO

BACKGROUND: Non-adherence to treatment could preclude reaching an optimal outcome. Thirty to 80% of patients with rheumatic and musculoskeletal diseases (RMDs) do not adhere to the agreed treatment. OBJECTIVES: The objective was to establish points to consider (PtCs) for the prevention, screening, assessment and management of non-adherence to (non-)pharmacological treatments in people with RMDs. METHODS: An EULAR task force (TF) was established, and the EULAR standardised operating procedures for the development of PtCs were followed. The TF included healthcare providers (HCPs), comprising rheumatologists, nurses, pharmacists, psychologists, physiotherapists, occupational therapists and patient-representatives from 12 European countries. A review of systematic reviews was conducted in advance to support the TF in formulating the PtCs. The level of agreement among the TF was established by anonymous online voting. RESULTS: Four overarching principles and nine PtCs were formulated. The PtCs reflect the phases of action on non-adherence. HCPs should assess and discuss adherence with patients on a regular basis and support patients to treatment adherence. As adherence is an agreed behaviour, the treatment has to be tailored to the patients' needs. The level of agreement ranged from 9.5 to 9.9 out of 10. CONCLUSIONS: These PtCs can help HCPs to support people with RMDs to be more adherent to the agreed treatment plan. The basic scheme being prevent non-adherence by bonding with the patient and building trust, overcoming structural barriers, assessing in a blame-free environment and tailoring the solution to the problem.

4.
RMD Open ; 6(3)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33161377

RESUMO

OBJECTIVE: To analyse how non-adherence to prescribed treatments might be prevented, screened, assessed and managed in people with rheumatic and musculoskeletal diseases (RMDs). METHODS: An overview of systematic reviews (SR) was performed in four bibliographic databases. Research questions focused on: (1) effective interventions or strategies, (2) associated factors, (3) impact of shared decision making and effective communication, (4) practical things to prevent non-adherence, (5) effect of non-adherence on outcome, (6) screening and assessment tools and (7) responsible healthcare providers. The methodological quality of the reviews was assessed using AMSTAR-2. The qualitative synthesis focused on results and on the level of evidence attained from the studies included in the reviews. RESULTS: After reviewing 9908 titles, the overview included 38 SR on medication, 29 on non-pharmacological interventions and 28 on assessment. Content and quality of the included SR was very heterogeneous. The number of factors that may influence adherence exceed 700. Among 53 intervention studies, 54.7% showed a small statistically significant effect on adherence, and all three multicomponent interventions, including different modes of patient education and delivered by a variety of healthcare providers, showed a positive result in adherence to medication. No single assessment provided a comprehensive measure of adherence to either medication or exercise. CONCLUSIONS: The results underscore the complexity of non-adherence, its changing pattern and dependence on multi-level factors, the need to involve all stakeholders in all steps, the absence of a gold standard for screening and the requirement of multi-component interventions to manage it.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33253497

RESUMO

OBJECTIVE: To compare the effect of preventing radiographic progression (in its 3 components) of tocilizumab (TCZ) monotherapy with those of TCZ combined with methotrexate (TCZ+MTX), and to evaluate possible effect modifiers. METHODS: Randomized trials comparing TCZ-monotherapy with TCZ+MTX combination therapy regarding radiographic progression were analyzed on individual patient (n=820) data level for early as well as established RA patients using mixed-effects models. Outcomes were: not having radiographic progression after 2 years (i.e., preventing radiographic progression), respectively in total Sharp van der Heijde (SvdH) score, in erosion score and in joint space narrowing (JSN) score. Effect modification by baseline joint damage, disease duration and DAS28 was studied. RESULTS: Overall, TCZ+MTX was more effective in preventing radiographic progression regarding total SvdH scores compared to TCZ-monotherapy. However, in early RA patients with more joint damage (RR 1.02 vs. 0.91 for the less damage group), or a lower DAS28 (RR 1.04 vs. 0.92) at baseline, this advantage disappeared. In established RA, the advantage of TCZ+MTX over TCZ in preventing radiographic progression disappeared with a longer disease duration at baseline (RR 1.04 vs. 0.83). Results for erosion scores as outcome were in line, but were less clear for JSN. CONCLUSION: Combination therapy with TCZ+MTX is more effective in preventing radiographic progression compared to TCZ-monotherapy, but the effectiveness of TCZ-monotherapy may approximate the effectiveness of TCZ+MTX in early RA patients with more joint damage and/or a lower DAS28 at baseline, and in established RA patients with longer disease duration.

7.
J Clin Med ; 9(10)2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33096821

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the added value of radiographs for diagnosing knee osteoarthritis (KOA) by general practitioners (GPs) and secondary care physicians (SPs). METHODS: Seventeen GPs and nineteen SPs were recruited to evaluate 1185 knees from the CHECK cohort (presenters with knee pain in primary care) for the presence of clinically relevant osteoarthritis (OA) during follow-up. Experts were required to make diagnoses independently, first based on clinical data only and then on clinical plus radiographic data, and to provide certainty scores (ranging from 1 to 100, where 1 was "certainly no OA" and 100 was "certainly OA"). Next, experts held consensus meetings to agree on the final diagnosis. With the final diagnosis as gold standard, diagnostic indicators were calculated (sensitivity, specificity, positive/negative predictive value, accuracy and positive/negative likelihood ratio) for all knees, as well as for clinically "certain" and "uncertain" knees, respectively. Student paired t-tests compared certainty scores. RESULTS: Most diagnoses of GPs (86%) and SPs (82%) were "consistent" after assessment of radiographic data. Diagnostic indicators improved similarly for GPs and SPs after evaluating the radiographic data, but only improved relevantly in clinically "uncertain" knees. Radiographs added some certainty to "consistent" OA knees (GP 69 vs. 72, p < 0.001; SP 70 vs. 77, p < 0.001), but not to the consistent no OA knees (GP 21 vs. 22, p = 0.16; SP 20 vs. 21, p = 0.04). CONCLUSIONS: The added value of radiographs is similar for GP and SP, in terms of diagnostic accuracy and certainty. Radiographs appear to be redundant when clinicians are certain of their clinical diagnosis.

8.
J Rheumatol ; 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739893

RESUMO

OBJECTIVE: Our study aimed to evaluate the cost effectiveness of initiating tocilizumab (TCZ) ± methotrexate (MTX) versus initiating MTX as treat-to-target treatment strategies over 5 years in early disease-modifying antirheumatic drug (DMARD)-naïve rheumatoid arthritis (RA). METHODS: Data on resource use were collected with questionnaires at baseline, 3, 6, 12, and 24 months, and yearly thereafter, and were converted to costs using Dutch reference prices. Quality-adjusted life-years (QALY) were calculated using the EQ5D5L, with utility based on Dutch tariff or estimated by the Health Assessment Questionnaire. To account for missing cost data and QALY data and for sample uncertainty, first bootstraps (10,000 samples) were obtained. Second, single imputation using chained equations nested within these bootstrap samples was performed. An economic evaluation was performed for TCZ + MTX and TCZ, compared to MTX, as initial treatment in a treat-to-target strategy from a healthcare and societal perspective over 5 years. Several sensitivity analyses were performed. RESULTS: Mean differences in QALY were small and not significant (TCZ + MTX vs MTX: 0.06, 95% CI -0.02 to 0.13; TCZ vs. MTX: -0.03, 95% CI -0.05 to 0.11). Limited savings in indirect nonhealthcare costs and productivity loss costs (for TCZ only) were observed, but these did not compensate for the higher medication costs. Sensitivity analyses did not materially change these findings, although lower-priced TCZ, or reserving TCZ as initial therapy for prognostically unfavorable RA patients, improved cost effectiveness considerably but did not individually lead to a strategy being cost effective. CONCLUSION: Based on our analyses, early initiation of TCZ + MTX is not cost effective compared to MTX initiation in a step-up treat-to-target treatment strategy over 5 years in early RA patients.

9.
Ann Rheum Dis ; 79(4): 460-463, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033935

RESUMO

BACKGROUND: In rheumatoid arthritis (RA) trials, inclusion of patients on background treatment with glucocorticoids (GCs) might impact efficacy and safety outcomes. OBJECTIVES: To determine if inclusion of patients on background GC use influenced efficacy and safety outcomes of RA randomised clinical trials on initiation of tocilizumab (TCZ) or adalimumab (ADA) or methotrexate (MTX) monotherapy. METHODS: Data of four double-blind RA randomised controlled trials (AMBITION, ACT-RAY, ADACTA and FUNCTION) with in total four TCZ, one ADA and two MTX monotherapy arms were analysed. Analyses of covariance of changes from baseline to week 24 in efficacy endpoints and radiographic progression up to week 104 were performed, correcting for relevant covariates. Incidence rates of serious adverse events (SAEs) were assessed. RESULTS: No statistically significant differences were found in efficacy parameters between background GC users and non-GC users, except for less radiographic progression associated with GC usage in one MTX arm. SAE rates were not statistically significantly different between GC users and non-GC users in the treatment arms. CONCLUSION: No effect of including patients on background GC treatment on efficacy and safety trial outcomes was found, with the exception of reduced radiological joint damage in one MTX arm.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/uso terapêutico , Adalimumab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/fisiopatologia , Quimioterapia Combinada , Humanos , Infecções/induzido quimicamente , Metotrexato/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
10.
Ann Rheum Dis ; 79(6): 744-759, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32033937

RESUMO

OBJECTIVES: To inform the 2019 update of the European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA). METHODS: A systematic literature research (SLR) to investigate the efficacy of any disease-modifying antirheumatic drug (DMARD) (conventional synthetic (cs)DMARD, biological (b) and biosimilar DMARD, targeted synthetic (ts)DMARD) or glucocorticoid (GC) therapy in patients with RA was done by searching MEDLINE, Embase and the Cochrane Library for articles published between 2016 and 8 March 2019. RESULTS: 234 abstracts were selected for detailed assessment, with 136 finally included. They comprised the efficacy of bDMARDs versus placebo or other bDMARDs, efficacy of Janus kinase (JAK) inhibitors (JAKi) across different patient populations and head-to-head of different bDMARDs versus JAKi or other bDMARDs. Switching of bDMARDs to other bDMARDs or tsDMARDs, strategic trials and tapering studies of bDMARDs, csDMARDs and JAKi were assessed. The drugs evaluated included abatacept, adalimumab, ABT-122, baricitinib, certolizumab pegol, SBI-087, CNTO6785, decernotinib, etanercept, filgotinib, golimumab, GCs, GS-9876, guselkumab, hydroxychloroquine, infliximab, leflunomide, mavrilimumab, methotrexate, olokizumab, otilimab, peficitinib, rituximab, sarilumab, salazopyrine, secukinumab, sirukumab, tacrolimus, tocilizumab, tofacitinib, tregalizumab, upadacitinib, ustekinumab and vobarilizumab. The efficacy of many bDMARDs and tsDMARDs was shown. Switching to another tumour necrosis factor inhibitor (TNFi) or non-TNFi bDMARDs after TNFi treatment failure is efficacious. Tapering of DMARDs is possible in patients achieving long-standing stringent clinical remission; in patients with residual disease activity (including patients in LDA) the risk of flares is increased during the tapering. Biosimilars are non-inferior to their reference products. CONCLUSION: This SLR informed the task force regarding the evidence base of various therapeutic regimen for the development of the update of EULAR's RA management recommendation.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Substituição de Medicamentos , Quimioterapia Combinada , Glucocorticoides/uso terapêutico , Humanos , Inibidores de Janus Quinases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medicamentos Sintéticos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
11.
Ann Rheum Dis ; 79(6): 685-699, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31969328

RESUMO

OBJECTIVES: To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field. METHODS: An international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items. RESULTS: The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high. CONCLUSIONS: These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Sociedades Médicas , Medicamentos Sintéticos/uso terapêutico , Antirreumáticos/economia , Produtos Biológicos/economia , Consenso , Quimioterapia Combinada , Europa (Continente) , Humanos , Inibidores de Janus Quinases/uso terapêutico , Medicamentos Sintéticos/economia , Revisões Sistemáticas como Assunto , Fator de Necrose Tumoral alfa/antagonistas & inibidores
12.
Clin Rheumatol ; 39(3): 627-642, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31127461

RESUMO

Rheumatic and musculoskeletal diseases (RMDs) encompass a spectrum of degenerative, inflammatory conditions predominantly affecting the joints. They are a leading cause of disability worldwide and an enormous socioeconomic burden. However, worldwide deficiencies in adult and paediatric RMD knowledge among medical school graduates and primary care physicians (PCPs) persist. In October 2017, the World Forum on Rheumatic and Musculoskeletal Diseases (WFRMD), an international think tank of RMD and related experts, met to discuss key challenges and opportunities in undergraduate RMD education. Topics included needs analysis, curriculum content, interprofessional education, teaching and learning methods, implementation, assessment and course evaluation and professional formation/career development, which formed a framework for this white paper. We highlight a need for all medical graduates to attain a basic level of RMD knowledge and competency to enable them to confidently diagnose, treat/manage or refer patients. The importance of attracting more medical students to a career in rheumatology, and the indisputable value of integrated, multidisciplinary and multiprofessional care are also discussed. We conclude that RMD teaching for the future will need to address what is being taught, but also where, why and to whom, to ensure that healthcare providers deliver the best patient care possible in their local setting.


Assuntos
Escolha da Profissão , Assistência à Saúde/organização & administração , Educação de Graduação em Medicina/métodos , Reumatologia/educação , Currículo , Humanos , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/epidemiologia , Doenças Musculoesqueléticas/terapia , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/terapia , Reumatologia/métodos
13.
Joint Bone Spine ; 87(1): 13-23, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30981868

RESUMO

OBJECTIVES: To identify, by a systematic literature review, predictors of clinical response to methotrexate treatment in rheumatoid arthritis patients, which would facilitate personalised treatment. METHODS: PubMed and Embase databases were searched for original articles. Additionally, congress abstracts of European League Against Rheumatism and American College of Rheumatology annual meetings of the past 2 years were screened. Articles describing predictors of clinical response to methotrexate after 3 to 6 months were included, since this reflects the time span used to determine treatment effectiveness and decide on treatment changes in treat-to-target recommendations. RESULTS: Thirty articles were included, containing 100 different predictors and 11 predictive models. Nineteen predictors and 2 predictive models were studied in multiple cohorts. Female gender was found to be a predictor of non-response in two studies (odds ratios 0.55 and 0.54), but these findings could not be replicated in two other studies. In two studies, smoking predicted non-response (adjusted odds ratios 0.35 and 0.60), although this was inconsistent over all response criteria assessed. Rheumatoid factor positivity predicted non-response in two studies (adjusted hazard ratio 0.61, adjusted odds ratio 0.4), but this was not found in three other studies. Heterogeneity in studies prohibited further comparison of predictive values between studies. Additionally, a validated epigenetic model was found (area under the curve 0.90 and 0.91). CONCLUSIONS: No predictors were identified reliably predicting clinical response to methotrexate after 3 to 6 months in the individual patient: clinical predictors were weak. However, a promising epigenetic model was found that needs further validation.

14.
Rheumatology (Oxford) ; 59(9): 2325-2333, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31859346

RESUMO

OBJECTIVES: U-Act-Early was a 2-year, randomized placebo controlled, double-blind trial, in which DMARD-naïve early RA patients were treated to the target of sustained remission (SR). Two strategies initiating tocilizumab (TCZ), with and without methotrexate (MTX), were more effective than a strategy initiating MTX. The aim of the current study was to determine longer-term effectiveness in daily clinical practice. METHODS: At the end of U-Act-Early, patients were included in a 3-year post-trial follow-up (PTFU), in which treatment was according to standard care and data were collected every 3 months during the first year and every 6 months thereafter. Primary end point was disease activity score assessing 28 joints (DAS28) over time. Mixed effects models were used to compare effectiveness between initial strategy groups, correcting for relevant confounders. Between the groups as randomized, proportions of patients were tested for DMARD use, SR and radiographic progression of joint damage. RESULTS: Of patients starting U-Act-Early, 226/317 (71%) participated in the PTFU. Over the total 5 years, mean DAS28 was similar between groups (P > 0.20). During U-Act-Early, biologic DMARD use decreased in both TCZ initiation groups and increased in the MTX initiation group, but during follow-up this trend did not continue. SR was achieved at least once in 99% of patients. Of the 226 patients, only 30% had any radiographic progression over 5 years, without significant differences between the groups. CONCLUSION: Although in the short-term the strategies initiating TCZ yielded the most clinical benefit, in the longer-term differences in important clinical outcomes between the strategies disappeared, probably due to continuation of the treat-to-target principle.

15.
Arthritis Care Res (Hoboken) ; 71(12): 1556-1565, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30358135

RESUMO

OBJECTIVE: The implementation of value-based health care in inflammatory arthritis requires a standardized set of modifiable outcomes and risk-adjustment variables that is feasible to implement worldwide. METHODS: The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary working group that consisted of 24 experts from 6 continents, including 6 patient representatives, to develop a standard set of outcomes for inflammatory arthritis. The process followed a structured approach, using a modified Delphi process to reach consensus on the following decision areas: conditions covered by the set, outcome domains, outcome measures, and risk-adjustment variables. Consensus in areas 2 to 4 were supported by systematic literature reviews and consultation of experts. RESULTS: The ICHOM Inflammatory Arthritis Standard Set covers patients with rheumatoid arthritis (RA), axial spondyloarthritis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA). We recommend that outcomes regarding pain, fatigue, activity limitations, overall physical and mental health impact, work/school/housework ability and productivity, disease activity, and serious adverse events be collected at least annually. Validated measures for patient-reported outcomes were endorsed and linked to common reporting metrics. Age, sex at birth, education level, smoking status, comorbidities, time since diagnosis, and rheumatoid factor and anti-citrullinated protein antibody lab testing for RA and JIA should be collected as risk-adjustment variables. CONCLUSION: We present the ICHOM inflammatory arthritis Standard Set of outcomes, which enables health care providers to implement the value-based health care framework and compare outcomes that are important to patients with inflammatory arthritis.


Assuntos
Artrite/terapia , Consenso , Indicadores Básicos de Saúde , Avaliação de Resultados em Cuidados de Saúde/métodos , Medidas de Resultados Relatados pelo Paciente , Artrite/diagnóstico , Humanos , Cooperação Internacional , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença
17.
Clin Exp Rheumatol ; 37(3): 414-421, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30299244

RESUMO

OBJECTIVES: Our aim was to estimate the proportion of knee and hip OA patients showing worsening at 2 years, and to examine the additional predictive value of failure of optimised non-surgical treatment during 3 months for worsening at 2 years. METHODS: Data of patients participating in the longitudinal CONTROL-PRO study (patients fulfilling clinical ACR criteria for knee or hip OA) were used. Measurements of pain, functioning and patient global assessments were performed at baseline, 3 months and 2 years. Worsening at 2 years was defined as fulfilling the recently validated clinical worsening criteria for knee and hip OA, or total joint replacement (TJR). Logistic regression was performed with worsening at 2 years as the dependent variable. RESULTS: The 297 included patients were predominantly women (66%) with a mean age of 55 years. At 2 years, 61% showed worsening (knee 59%; hip 71%) and 24% had undergone a TJR (knee 19%; hip 51%). Clinical worsening at 3 months appeared to be a clear independent predictor for worsening at 2 years (OR 2.8 95% CI 1.5-5.2) with a moderate discriminative ability (AUC 0.68 95% CI 0.57-0.70). Similar results were obtained when only TJR at 2 years was used as the outcome measure (OR 4.1 95% CI 2.0-8.4) with good AUC (0.82 95% CI 0.76-0.87). CONCLUSIONS: Our findings suggest that re-assessment of symptoms after optimised non-surgical treatment could be meaningful in clinical decision making for TJR. Furthermore, this information could be used to identify subgroups of patients potentially eligible for novel and advanced treatment options.


Assuntos
Osteoartrite do Quadril , Osteoartrite do Joelho , Avaliação de Resultados em Cuidados de Saúde , Artroplastia de Quadril , Artroplastia do Joelho , Feminino , Humanos , Articulação do Joelho , Masculino , Pessoa de Meia-Idade , Dor , Medição da Dor , Fatores de Tempo
18.
Arthritis Res Ther ; 20(1): 230, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30322408

RESUMO

BACKGROUND: We previously identified, in newly diagnosed rheumatoid arthritis (RA) patients, networks of co-expressed genes and proteomic biomarkers associated with achieving sustained drug-free remission (sDFR) after treatment with tocilizumab- or methotrexate-based strategies. The aim of this study was to identify, within the same patients, metabolic pathways important for achieving sDFR and to subsequently study the complex interactions between different components of the biological system and how these interactions might affect the therapeutic response in early RA. METHODS: Serum samples were analyzed of 60 patients who participated in the U-Act-Early trial (ClinicalTrials.gov number NCT01034137) and initiated treatment with methotrexate, tocilizumab, or the combination and who were thereafter able to achieve sDFR (n = 37); as controls, patients were selected who never achieved a drug-free status (n = 23). Metabolomic measurements were performed using mass spectrometry on oxidative stress, amine, and oxylipin platforms covering various compounds. Partial least square discriminant analyses (PLSDA) were performed to identify, per strategy arm, relevant metabolites of which the biological pathways were studied. In addition, integrative analyses were performed correlating the previously identified transcripts and proteins with the relevant metabolites. RESULTS: In the tocilizumab plus methotrexate, tocilizumab, and methotrexate strategy, respectively, 19, 13, and 12 relevant metabolites were found, which were subsequently used for pathway analyses. The most significant pathway in the tocilizumab plus methotrexate strategy was "histidine metabolism" (p < 0.001); in the tocilizumab strategy it was "arachidonic acid metabolism" (p = 0.018); and in the methotrexate strategy it was "arginine and proline metabolism" (p = 0.022). These pathways have treatment-specific drug interactions with metabolites affecting either the signaling of interleukin-6, which is inhibited by tocilizumab, or affecting protein synthesis from amino acids, which is inhibited by methotrexate. CONCLUSION: In early RA patients treated-to-target with a tocilizumab- or methotrexate-based strategy, several metabolites were found to be associated with achieving sDFR. In line with our previous observations, by analyzing relevant transcripts and proteins within the same patients, the metabolic profiles were found to be different between the strategy arms. Our metabolic analysis further supports the hypothesis that achieving sDFR is not only dependent on predisposing biomarkers, but also on the specific treatment that has been initiated. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01034137 . Registered on January 2010.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Metabolômica/métodos , Metotrexato/administração & dosagem , Biologia de Sistemas/métodos , Adulto , Idoso , Artrite Reumatoide/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/fisiologia , Pessoa de Meia-Idade , Indução de Remissão/métodos , Resultado do Tratamento
19.
Ann Rheum Dis ; 77(9): 1261-1267, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29760159

RESUMO

OBJECTIVE: To identify and validate clinical baseline predictors associated with inadequate response (IR) to methotrexate (MTX) therapy in newly diagnosed patients with rheumatoid arthritis (RA). METHODS: In U-Act-Early, 108 disease-modifying antirheumatic drug (DMARD)-naive patients with RA were randomised to initiate MTX therapy and treated to target until sustained remission (disease activity score assessing 28 joints (DAS28) <2.6 with four or less swollen joints for ≥24 weeks) was achieved. If no remission, hydroxychloroquine was added to the treatment regimen (ie, 'MTX+') and replaced by tocilizumab if the target still was not reached thereafter. Regression analyses were performed to identify clinical predictors for IR, defined as needing addition of a biological DMARD, to 'MTX+'. Data from the treatment in the Rotterdam Early Arthritis Cohort were used for external validation of the prediction model. RESULTS: Within 1 year, 56/108 (52%) patients in U-Act-Early showed IR to 'MTX+'. DAS28 (adjusted OR (ORadj) 2.1, 95% CI 1.4 to 3.2), current smoking (ORadj 3.02, 95% CI 1.1 to 8.0) and alcohol consumption (ORadj 0.4, 95% CI 0.1 to 0.9) were identified as baseline predictors. The area under the receiver operator characteristic curve (AUROC) of the prediction model was 0.75 (95% CI 0.66 to 0.84); the positive (PPV) and negative predictive value (NPV) were 65% and 80%, respectively. When applying the model to the validation cohort, the AUROC slightly decreased to 0.67 (95% CI 0.55 to 0.79) and the PPV and NPV to 54% and 80%, respectively. CONCLUSION: Higher DAS28, current smoking and no alcohol consumption are predictive factors for IR to step-up 'MTX+' in DMARD-naive patients with new-onset RA. TRIAL REGISTRATION: NCT01034137; Post-results, ISRCTN26791028; Post-results.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento
20.
Clin Exp Rheumatol ; 36(6): 976-983, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29745885

RESUMO

OBJECTIVES: Previously, we identified networks of co-expressed genes related to achieving sustained drug-free remission (sDFR). The aim of the present exploratory analysis was to identify inflammatory proteins associated with achieving sDFR and their enriched biological pathways, and compare these pathways with those found in the previous transcriptomic analyses. METHODS: Serum samples were used from 60 patients who participated in the U-Act-Early trial and were treated-to-target with tocilizumab plus methotrexate, or tocilizumab or methotrexate; 37 achieved sDFR (≥3 months drug-free) and 23 did not (controls). Luminex® multi-analyte profiling (xMAP)® was used to measure 85 proteins. Partial least square discriminant analyses (PLSDA) identified proteins associated with achieving sDFR within each strategy arm, which were thereafter used for pathway analyses. RESULTS: PLSDA identified 9, 14 and 13 relevant proteins in the tocilizumab plus methotrexate, tocilizumab and methotrexate arm, respectively and pathway analyses thereafter identified respectively 49, 88 and 117 significantly enriched gene ontology (GO) terms. When comparing these terms with those previously found in the transcriptomic analyses, corresponding pathways were related in the tocilizumab arm to activity of leukocytes; in the methotrexate arm to response of stimuli and regulation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway. In the tocilizumab plus methotrexate arm, no corresponding enriched pathways were found. CONCLUSIONS: Multiple proteins were associated with achieving sDFR and several biological pathways corresponded, mainly in the methotrexate arm, with our previous transcriptomic findings potentially providing further insights into gene expression and protein translation in newly diagnosed RA patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Proteínas Sanguíneas/metabolismo , Perfilação da Expressão Gênica/métodos , Mediadores da Inflamação/metabolismo , Metotrexato/uso terapêutico , Proteômica/métodos , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/genética , Método Duplo-Cego , Feminino , Redes Reguladoras de Genes , Marcadores Genéticos , Humanos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Países Baixos , Mapas de Interação de Proteínas , Indução de Remissão , Fatores de Tempo , Transcriptoma , Resultado do Tratamento
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