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2.
Artigo em Inglês | MEDLINE | ID: mdl-33770421

RESUMO

OBJECTIVES: To develop and validate a composite RA disease activity index using optical spectral transmission (OST)-scores obtained with the HandScan replacing tender and swollen joint counts. METHODS: RA patients from a single centre routinely undergoing HandScan measurements and at least one concurrent OST-score and DAS28 were included. Data was extracted from medical records. Linear regression analyses with DAS28 as outcome were performed to create a disease activity index (DAS-OST). OST-score, ESR and patient global assessment (PGA-)VAS, gender, age, disease duration and RF-status were evaluated as independent variables. Final models were derived, based on statistical significance of coefficients and model fit. Of the data, 2/3 was used for development and 1/3 for validation; external validation was performed in a cohort from another centre. Agreement between DAS-OST and DAS28 was assessed using the Bland-Altman plot method and intra-class correlation coefficient (ICC). Diagnostic value of DAS-OST was determined for established definitions of remission, and low (L), and high (H) disease activity (DA). RESULTS: Data of 3358 observations from 1505 unique RA patients were extracted. DAS-OST was defined as: -0.44 + OST*0.03 + male*-0.11 + LN(ESR)*0.77 + PGA-VAS*0.03. The ICC between DAS-OST and DAS28 were 0.88 (95%CI 0.87-0.90) and 0.82 (95%CI 0.75-0.86) and measurement errors 0.58 and 0.87 in internal and external validation, respectively. Sensitivity for remission, LDA and HDA were 79%, 91%, 43%, and specificity 92%, 80%, 96% in external validation. CONCLUSION: Using the HandScan, RA disease activity can be accurately estimated if combined with ESR, PGA-VAS and gender into a disease activity index (DAS-OST).

3.
BMJ Open ; 11(3): e044483, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737437

RESUMO

INTRODUCTION: Systemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease associated with high morbidity and mortality, especially in diffuse cutaneous SSc (dcSSc). Currently, there are several treatments available in early dcSSc that aim to change the disease course, including immunosuppressive agents and autologous haematopoietic stem cell transplantation (HSCT). HSCT has been adopted in international guidelines and is offered in current clinical care. However, optimal timing and patient selection for HSCT are still unclear. In particular, it is unclear whether HSCT should be positioned as upfront therapy or rescue treatment for patients refractory to immunosuppressive therapy. We hypothesise that upfront HSCT is superior and results in lower toxicity and lower long-term medical costs. Therefore, we propose this randomised trial aiming to determine the optimal treatment strategy for early dcSSc by comparing two strategies used in standard care: (1) upfront autologous HSCT versus (2) immunosuppressive therapy (intravenous cyclophosphamide pulse therapy followed by mycophenolate mofetil) with rescue HSCT in case of treatment failure. METHODS AND ANALYSIS: The UPSIDE (UPfront autologous hematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) study is a multicentre, randomised, open-label, controlled trial. In total, 120 patients with early dcSSc will be randomised. The primary outcome is event-free survival at 2 years after randomisation. Secondary outcomes include serious adverse events, functional status and health-related quality of life. We will also evaluate changes in nailfold capillaroscopy pattern, pulmonary function, cardiac MR and high-resolution CT of the chest. Follow-up visits will be scheduled 3-monthly for 2 years and annually in the following 3 years. ETHICS AND DISSEMINATION: The study was approved by the Dutch Central Committee on Research Concerning Human Subjects (NL72607.041.20). The results will be disseminated through patient associations and conventional scientific channels. TRIAL REGISTRATION NUMBERS: NCT04464434; NL 8720.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33560301

RESUMO

OBJECTIVES: Treatment non-adherence is more frequent among difficult-to-treat (D2T) than among non-D2T rheumatoid arthritis (RA) patients. Perceptions of non-adherence may differ. We aimed to thematically structure and prioritise barriers (i.e. causes and reasons for non-adherence) and facilitators of optimal adherence from the patients' and rheumatologists' perspectives. METHODS: Patients' perceptions were identified in semi-structured in-depth interviews. Experts selected representative statements regarding 40 barriers and 40 facilitators. Twenty D2T and 20 non-D2T RA patients sorted these statements during two card-sorting tasks: first, by order of content similarity and, second, content applicability. Additionally, 20 rheumatologists sorted the statements by order of content applicability to the general RA population. The similarity sorting was used as input for hierarchical cluster analysis. The applicability sorting was analysed using descriptive statistics, prioritised and compared between D2T RA patients, non-D2T RA patients and rheumatologists. RESULTS: Nine clusters of barriers were identified related to the healthcare system, treatment safety/efficacy, treatment regimen and patient behaviour. D2T RA patients prioritised adverse events and doubts about effectiveness as most important barriers. Doubts about effectiveness were more important to D2T than to non-D2T RA patients (p = 0.02).Seven clusters of facilitators were identified, related to the healthcare system and directly to the patient. All RA patients and rheumatologists prioritised a good relationship with the healthcare professional and treatment information as most helpful facilitators. CONCLUSIONS: D2T RA patients, non-D2T RA patients and rheumatologists prioritised perceptions of non-adherence largely similarly. The structured overviews of barriers and facilitators, provided in this study, may guide improvement of adherence.

5.
J Rheumatol ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526623

RESUMO

OBJECTIVE: Current smoking reduces clinical response to several disease-modifying antirheumatic drugs (DMARDs). It is unknown if this is also the case for prednisone. We aimed to determine whether current smoking affects the clinical response to concomitant prednisone in a methotrexate (MTX)-based treatment strategy. METHODS: In the CAMERA-II trial, early rheumatoid arthritis (RA) patients initiated an MTX-based strategy and were randomized to concomitant prednisone (MTX+pred) or placebo (MTX+plac) for 24 months. Linear mixed modelling was performed with disease activity score assessing 28 joints (DAS28) as dependent variable and strategy group and current smoking status as independent variables, correcting for relevant covariates. The interaction between current smoking and strategy was tested to find out whether the impact of current smoking on clinical response was different between the strategy groups with prednisone or placebo. RESULTS: Current smoking was significantly associated with higher DAS28 over time (mean difference with non-smokers 0.57 (95% confidence interval 0.22 to 0.92), p<0.01). This association was not different between the strategy groups with prednisone or placebo (p=0.73). This negative effect of current smoking on DAS28 was dose dependent. CONCLUSION: Current smoking in early RA patients significantly reduces the clinical effect of an MTX-based strategy, independent of whether concomitant prednisone is used or not. This effect is dose dependent.

6.
RMD Open ; 7(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419871

RESUMO

OBJECTIVES: To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA. METHODS: PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised. RESULTS: Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias. CONCLUSIONS: This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.

7.
ACR Open Rheumatol ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33434395

RESUMO

OBJECTIVE: Electronic health records (EHR) are increasingly being recognized as a major source of data reusable for medical research and quality monitoring, although patient identification and assessment of symptoms (characterization) remain challenging, especially in complex diseases such as systemic lupus erythematosus (SLE). Current coding systems are unable to assess information recorded in the physician's free-text notes. This study shows that text mining can be used as a reliable alternative. METHODS: In a multidisciplinary research team of data scientists and medical experts, a text mining algorithm on 4607 patient records was developed to assess the diagnosis of 14 different immune-mediated inflammatory diseases and the presence of 18 different symptoms in the EHR. The text mining algorithm included key words in the EHR, while mining the context for exclusion phrases. The accuracy of the text mining algorithm was assessed by manually checking the EHR of 100 random patients suspected of having SLE for diagnoses and symptoms and comparing the outcome with the outcome of the text mining algorithm. RESULTS: After evaluation of 100 patient records, the text mining algorithm had a sensitivity of 96.4% and a specificity of 93.3% in assessing the presence of SLE. The algorithm detected potentially life-threatening symptoms (nephritis, pleuritis) with good sensitivity (80%-82%) and high specificity (97%-97%). CONCLUSION: We present a text mining algorithm that can accurately identify and characterize patients with SLE using routinely collected data from the EHR. Our study shows that using text mining, data from the EHR can be reused in research and quality control.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33502493

RESUMO

OBJECTIVES: To determine the impact of difficult-to-treat rheumatoid arthritis (D2T RA) on (costs related to) health care utilisation, other resource use and work productivity. METHODS: Data regarding health care utilisation, other resource use and work productivity of 52 D2T (according to the EULAR definition) and 100 non-D2T RA patients were collected via a questionnaire and an electronic patient record review during a study visit. Annual costs were calculated and compared between groups. Multivariable linear regression analysis was performed to assess whether having D2T RA was associated with higher costs. RESULTS: Mean (95% confidence interval) annual total costs were €37,605 (€27,689-50,378) for D2T and €19,217 (€15,647-22,945) for non-D2T RA patients (p < 0.001). D2T RA patients visited their rheumatologist more frequently, were more often admitted to day care facilities, underwent more laboratory tests and used more drugs (specifically tsDMARDs), compared with non-D2T RA patients (p < 0.01). In D2T RA patients, the main contributors to total costs were informal help of family and friends (28%), drugs (26%) and loss of work productivity (16%).After adjustment for physical functioning (health assessment questionnaire (HAQ)), having D2T RA was no longer statistically significantly associated with higher total costs. HAQ was the only independent determinant of higher costs in multivariable analysis. CONCLUSIONS: The economic burden of D2T RA is significantly higher than that of non-D2T RA, indicated by higher health care utilisation and higher annual total costs. Functional disability is a key determinant of higher costs in RA.

9.
RMD Open ; 7(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33514671

RESUMO

OBJECTIVES: To summarise the evidence on diagnostic issues in difficult-to-treat rheumatoid arthritis (D2T RA) informing the EULAR recommendations for the management of D2T RA. METHODS: A systematic literature review (SLR) was performed regarding the optimal confirmation of a diagnosis of rheumatoid arthritis (RA) and of mimicking diseases and the assessment of inflammatory disease activity. PubMed and Embase databases were searched up to December 2019. Relevant papers were selected and appraised. RESULTS: Eighty-two papers were selected for detailed assessment. The identified evidence had several limitations: (1) no studies were found including D2T RA patients specifically, and only the minority of studies included RA patients in whom there was explicit doubt about the diagnosis of RA or presence of inflammatory activity; (2) mostly only correlations were reported, not directly useful to evaluate the accuracy of detecting inflammatory activity in clinical practice; (3) heterogeneous, and often suboptimal, reference standards were used and (4) (thus) only very few studies had a low risk of bias.To ascertain a diagnosis of RA or relevant mimicking disease, no diagnostic test with sufficient validity and accuracy was identified. To ascertain inflammatory activity in patients with RA in general and in those with obesity and fibromyalgia, ultrasonography (US) was studied most extensively and was found to be the most promising diagnostic test. CONCLUSIONS: This SLR highlights the scarcity of high-quality studies regarding diagnostic issues in D2T RA. No diagnostic tests with sufficient validity and accuracy were found to confirm nor exclude the diagnosis of RA nor its mimicking diseases in D2T RA patients. Despite the lack of high-quality direct evidence, US may have an additional value to assess the presence of inflammatory activity in D2T RA patients, including those with concomitant obesity or fibromyalgia.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33331946

RESUMO

OBJECTIVES: Treatment of difficult-to-treat (D2T) RA patients is generally based on trial-and-error and can be challenging due to a myriad of contributing factors. We aimed to identify risk factors at RA onset, contributing factors and the burden of disease. METHODS: Consecutive RA patients were enrolled and categorised as D2T, according to the EULAR definition, or not (controls). Factors potentially contributing to D2T RA and burden of disease were assessed. Risk factors at RA onset and factors independently associated with D2T RA were identified by logistic regression. D2T RA subgroups were explored by cluster analysis. RESULTS: Fifty-two RA patients were classified as D2T and 100 as non-D2T.Lower socioeconomic status at RA onset was found as an independent risk factor for developing D2T RA (OR 1.97 (95%CI 1.08-3.61)). Several contributing factors were independently associated with D2T RA, occurring more frequently in D2T than non-D2T patients: limited drug options because of adverse events (94% vs 57%) or comorbidities (69% vs 37%), mismatch in patient's and rheumatologist's wish to intensify treatment (37% vs 6%), concomitant fibromyalgia (38% vs 9%) and poorer coping (worse levels). Burden of disease was significantly higher in D2T RA patients. Three subgroups of D2T RA patients were identified: 1) 'non-adherent dissatisfied patients'; 2) patients with 'pain syndromes and obesity'; 3) patients closest to the concept of 'true refractory RA'. CONCLUSIONS: This comprehensive study on D2T RA shows multiple contributing factors, a high burden of disease and the heterogeneity of D2T RA. These findings suggest that these factors should be identified in daily practice in order to tailor therapeutic strategies further to the individual patient.

12.
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.

13.
Ann Rheum Dis ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004335

RESUMO

BACKGROUND: Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic. These patients can be considered to have 'difficult-to-treat RA'. However, uniform terminology and an appropriate definition are lacking. OBJECTIVE: The Task Force in charge of the "Development of EULAR recommendations for the comprehensive management of difficult-to-treat rheumatoid arthritis" aims to create recommendations for this underserved patient group. Herein, we present the definition of difficult-to-treat RA, as the first step. METHODS: The Steering Committee drafted a definition with suggested terminology based on an international survey among rheumatologists. This was discussed and amended by the Task Force, including rheumatologists, nurses, health professionals and patients, at a face-to-face meeting until sufficient agreement was reached (assessed through voting). RESULTS: The following three criteria were agreed by all Task Force members as mandatory elements of the definition of difficult-to-treat RA: (1) Treatment according to European League Against Rheumatism (EULAR) recommendation and failure of ≥2 biological disease-modifying antirheumatic drugs (DMARDs)/targeted synthetic DMARDs (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated); (2) presence of at least one of the following: at least moderate disease activity; signs and/or symptoms suggestive of active disease; inability to taper glucocorticoid treatment; rapid radiographic progression; RA symptoms that are causing a reduction in quality of life; and (3) the management of signs and/or symptoms is perceived as problematic by the rheumatologist and/or the patient. CONCLUSIONS: The proposed EULAR definition for difficult-to-treat RA can be used in clinical practice, clinical trials and can form a basis for future research.

14.
RMD Open ; 6(2): 0, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32868449

RESUMO

INTRODUCTION: The European Reference Network (ERN) ReCONNET is the ERN aimed at improving the management of rare and complex connective tissue and musculoskeletal diseases (rCTDs) across the European Union (EU). In the mission of ERN ReCONNET, clinical practice guidelines (CPGs) play a crucial role, representing a valid tool towards the harmonisation of the management of rCTDs while improving effectiveness and quality of care delivered to patients. METHODS: ERN ReCONNET developed two surveys to map the adherence to rCTDs CPGs among healthcare providers and to assess the knowledge and awareness of CPGs for their diseases among patients, family members and caregivers. RESULTS: The results of the surveys highlighted that healthcare professionals find it useful to apply CPGs in clinical practice (93%), while 62% of them experience difficulties and barriers in the application in their centres. Healthcare professionals also highlighted the need to develop CPGs for all rCTDs and to implement the use of the existing CPGs in clinical practice. On the other hand, patients, families and caregivers are relatively aware of the purpose of CPGs (51%) and 62% of them were aware of the existence of CPGs for their disease. Patient-friendly versions of CPGs and patients' lifestyle guidelines should be systematically developed contributing to the empowerment of patients in the disease management. CONCLUSION: ERN ReCONNET is addressing the main issues identified in the results of the survey, promoting practical actions for the local adaptation of CPGs across Europe, improving their routine clinical use and increasing the awareness on CPGs among rCTDs patients, family members and caregivers.

15.
Lancet Respir Med ; 8(10): 963-974, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32866440

RESUMO

BACKGROUND: A phase 2 trial of tocilizumab showed preliminary evidence of efficacy in systemic sclerosis. We assessed skin fibrosis and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in a phase 3 trial to investigate the safety and efficacy of tocilizumab, an anti-interleukin-6 receptor antibody, in the treatment of systemic sclerosis. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial, participants were recruited from 75 sites in 20 countries across Europe, North America, Latin America, and Japan. Adults with diffuse cutaneous systemic sclerosis for 60 months or less and a modified Rodnan skin score (mRSS) of 10-35 at screening were randomly assigned (1:1) with a voice-web-response system to receive subcutaneous tocilizumab 162 mg or placebo weekly for 48 weeks, stratified by IL-6 levels; participants and investigators were masked to treatment group. The primary endpoint was the difference in change from baseline to week 48 in mRSS. Percentage of predicted forced vital capacity (FVC% predicted) at week 48, time to treatment failure, and patient-reported and physician-reported outcomes were secondary endpoints. This trial is registered with ClinicalTrials.gov (number NCT02453256) and is closed to accrual. FINDINGS: Between Nov 20, 2015, and Feb 14, 2017, 210 individuals were randomly assigned to receive tocilizumab (n=104) or placebo (n=106). In the intention-to-treat population, least squares mean [LSM] change from baseline to week 48 in mRSS was -6·14 for tocilizumab and -4·41 for placebo (adjusted difference -1·73 [95% CI -3·78 to 0·32]; p=0·10). The shift in distribution of change from baseline in FVC% predicted at week 48 favoured tocilizumab (van Elteren nominal p=0·002 vs placebo), with a difference in LSM of 4·2 (95% CI 2·0-6·4; nominal p=0·0002), as did time to treatment failure (hazard ratio 0·63 [95% CI 0·37-1·06]; nominal p=0·08). Change in LSM from baseline to week 48 in Health Assessment Questionnaire-Disability Index and in patient-global and physician-global visual analogue scale assessments did not differ between tocilizumab and placebo. In the safety set, infections were the most common adverse events (54 [52%] of 104 participants in the tocilizumab group, 53 [50%] of 106 in the placebo group). Serious adverse events were reported in 13 participants treated with tocilizumab and 18 with placebo, primarily infections (three events, eight events) and cardiac events (two events, seven events). INTERPRETATION: The primary skin fibrosis endpoint was not met. Findings for the secondary endpoint of FVC% predicted indicate that tocilizumab might preserve lung function in people with early SSc-ILD and elevated acute-phase reactants. Safety was consistent with the known profile of tocilizumab. FUNDING: F Hoffmann-La Roche Ltd.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Adulto , Estudos de Coortes , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Capacidade Vital
16.
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.

17.
Lancet ; 396(10246): 267-276, 2020 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711802

RESUMO

BACKGROUND: Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis. METHODS: The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5-15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints-erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4-6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov, NCT02573012. FINDINGS: Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35-0·73) with tapered prednisone and -0·08 (-0·27 to 0·12) with continued prednisone (difference 0·61 [0·35-0·88]; p<0·0001), favouring continuing prednisone 5 mg per day for 24 weeks. Treatment was regarded as successful (defined as low disease activity at week 24, plus absence of rheumatoid arthritis flare for 24 weeks and no confirmed adrenal insufficiency) in 99 (77%) patients in the continued-prednisone group versus 85 (65%) patients in the tapered-prednisone group (relative risk 0·83; 95% CI 0·71-0·97). Serious adverse events occurred in seven (5%) patients in the tapered-prednisone group and four (3%) patients in the continued-prednisone group; no patients had symptomatic adrenal insufficiency. INTERPRETATION: In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. FUNDING: F Hoffmann-La Roche.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/uso terapêutico , Prednisona/uso terapêutico , Indução de Remissão/métodos , Administração Intravenosa , Administração Oral , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/etnologia , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , França/epidemiologia , Alemanha/epidemiologia , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Injeções Subcutâneas , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Federação Russa/epidemiologia , Sérvia/epidemiologia , Tunísia/epidemiologia
18.
Clin Exp Rheumatol ; 38(4): 763-766, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32452342

RESUMO

OBJECTIVES: Chronic inflammation associated with hyperuricaemia and urate deposition may contribute to an increased risk of developing cardiovascular (CV) events (CVE) in patients with gout. The aim of this study was to explore whether urate deposition on dual-energy CT (DECT) present at the diagnosis of gout is associated with a history of CVE. METHODS: Patients from a study on clinical value of DECT with mono or oligoarthritis who had gout according the 2015 EULAR/ACR classification criteria were included in this cross-sectional study. Urate volume on DECT was calculated. Patients underwent a structured CV consultation, including assessment of CVE-history and of CV risk factors, scored with the Dutch risk prediction SCORE and the Framingham score. The data were analysed using logistic regression analyses. RESULTS: Sixty-eight patients were included. In the multivariable model, -next to significant associations of age (OR per year 1.1, 95% CI 1.04 to 1.02, p=0.02), HDLc per mmol/l (OR 0.04, 95% CI 0.002 to 0.8, p=0.03), and diabetes yes/no (OR 4, 95% CI 0.8 to 20.9, p=0.09)-, urate volumes at ankles/feet on DECT in the third and fourth quartile with first quartile as reference showed a trend of association (OR 4.8, 95% CI 0.6 to 42, p=0.1 and 6.4, 0.7 to 63, 0.1, respectively) with past CVE events (yes/ no). This association could be bidirectional. Almost two-third of newly classified gout patients had a high or very high CV risk. CONCLUSIONS: CVE history probably is associated with urate volumes already present at the time of diagnosis of gout. Our data corroborate the need of assessing and treating CV risk factors when diagnosing gout.


Assuntos
Doenças Cardiovasculares , Gota , Tornozelo , Estudos Transversais , Humanos , Fatores de Risco , Tomografia Computadorizada por Raios X , Ácido Úrico
19.
Ann Rheum Dis ; 79(8): 1084-1089, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32409324

RESUMO

BACKGROUND: Autologous haematopoietic stem cell transplantation (HSCT) improves survival in systemic sclerosis (SSc) with poor prognosis, but is hampered by treatment-related mortality (TRM). OBJECTIVE: To evaluate event-free survival (EFS), TRM, response to treatment, disease progression and patient characteristics associated with events. METHODS: All patients treated with HSCT for SSc in The Netherlands until 2017 (n=92) were included. Data on skin involvement (modified Rodnan skin score (mRSS), pulmonary function (forced vital capacity (FVC) and diffusion capacity of the lungs for carbon monoxide (DLCO)), extent of interstitial lung disease on high-resolution CT using Goh scores and left ventricular ejection fraction (LVEF) were collected at baseline, 1, 2 and 5 years. Occurrence of events, defined as death or major organ failure, were collected until 2019. As control, a comparison between patients treated with cyclophosphamide (CYC) and patients with HSCT who participated in the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial was performed. RESULTS: Median follow-up was 4.6 years. EFS estimates at 5, 10 and 15 years were 78%, 76% and 66%, respectively. Twenty deaths occurred. Mean FVC, DLCO, mRSS and Goh scores all improved significantly. Disease progression occurred in 22 patients. Frequency of TRM decreased over time and occurred more often in males. Events were independently associated with male sex, LVEF <50% and older age. In ASTIS, patients treated with HSCT (n=23) 7 events occurred versus 13 in the CYC group (n=22). CONCLUSION: Our data confirm long-term efficacy of HSCT in improving survival, skin and lung involvement in SSc. Male sex, lower LVEF and older age at baseline were identified as risk factors for events.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Escleroderma Sistêmico/terapia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Intervalo Livre de Progressão , Fatores de Risco , Escleroderma Sistêmico/mortalidade , Transplante Autólogo/efeitos adversos
20.
Rheumatol Adv Pract ; 4(1): rkaa005, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32296743

RESUMO

Machine learning as a field of artificial intelligence is increasingly applied in medicine to assist patients and physicians. Growing datasets provide a sound basis with which to apply machine learning methods that learn from previous experiences. This review explains the basics of machine learning and its subfields of supervised learning, unsupervised learning, reinforcement learning and deep learning. We provide an overview of current machine learning applications in rheumatology, mainly supervised learning methods for e-diagnosis, disease detection and medical image analysis. In the future, machine learning will be likely to assist rheumatologists in predicting the course of the disease and identifying important disease factors. Even more interestingly, machine learning will probably be able to make treatment propositions and estimate their expected benefit (e.g. by reinforcement learning). Thus, in future, shared decision-making will not only include the patient's opinion and the rheumatologist's empirical and evidence-based experience, but it will also be influenced by machine-learned evidence.

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