Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 135
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-33560332

RESUMO

OBJECTIVES: To identify predictors of complete renal response (CRR) and renal flares in SLE patients with active proliferative lupus nephritis (LN). METHODS: Retrospective cohort study over 36 months including patients with biopsy-proven proliferative LN (class III/IV), from two European tertiary centers. CRR and renal flare were defined as proteinuria <0.5g/day with normal renal function and proteinuria >1g/day after CRR attainment, respectively. Demographic, clinical and analytic parameters were evaluated as early predictors of renal outcome, using survival analysis. Candidate variables were tested as predictors for CRR at time 0, 3 and 6 months after starting induction treatment. Potential predictors for renal flare were evaluated at time of reaching CRR. Variables with p < 0.10 on univariate analysis with Log-Rank tests were further tested with multivariate Cox proportional hazards regression models. RESULTS: We included 104 patients (81.7% female, age at baseline 32.0±13.3 years). Over follow-up, 91.7% reached CRR, within a median time of 6.0 months. Proteinuria <2g/day at baseline (HR = 1.80, CI 95% 1.16-2.79, p < 0.01) and 3 months (HR = 2.32, 95%CI 1.24-4.32, p < 0.01) after starting induction therapy were independent predictors of CRR. Renal flares occurred in 18.4% of patients reaching CRR, after a mean time of 16.5±8.6 months. Age up to 25 years at time of LN diagnosis (HR = 5.41, 95%CI 1.72-16.97, p < 0.01) and positive anti-RNP (HR = 3.52, 95%CI 1.21-10.20, p = 0.02) were independent predictors of renal flares. CONCLUSION: In patients with SLE and proliferative LN, factors assessed at baseline and 3 months from starting induction treatment can predict CRR and renal flares once CRR is achieved.

2.
BMJ Case Rep ; 14(1)2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452071

RESUMO

We present a 51-year-old Caucasian woman, with a medical history of systemic lupus erythematosus (SLE) who had dyspnoea at exertion. The SLE was clinically quiescent but serologically active. Echocardiography showed preserved left ventricular (LV) systolic function, pseudonormal mitral inflow pattern (diastolic dysfunction grade III), absence of wall motion abnormalities and elevated E/e' at exercise. An exercise right heart catheterisation was performed, confirming the diagnosis of heart failure with preserved ejection fraction (HFpEF). In the absence of other possible causes, we assumed that HFpEF was mediated by systemic inflammation secondary to SLE. Based on the Paulus' paradigm, that systemic inflammation may lead to diastolic dysfunction, we decided to add belimumab (a biological agent against soluble B-lymphocyte stimulator protein). After 16 weeks of treatment, patient reported an improved condition. Also, cardiopulmonary exercise test and echocardiography results improved, confirming resolution of the underlying LV diastolic dysfunction. This case supports the idea that targeting inflammation has therapeutic potential in a subset of HFpEF-patients.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33447846

RESUMO

OBJECTIVE: RA is associated with higher risk of cardiovascular (CV) disease. Ongoing systemic inflammation is presumed to accelerate atherosclerosis by increasing inflammation in the arterial wall. However, evidence supporting this hypothesis is limited. We aimed to investigate arterial wall inflammation in RA vs OA, and its association with markers of inflammation and CV risk factors. METHODS: 18-fluorodeoxyglucose PET combined with CT (18F-FDG-PET/CT) was performed in RA (n = 61) and OA (n = 28) to investigate inflammatory activity in the wall of large arteries. Secondary analyses were performed in patients with early untreated RA (n = 30), and established RA, active under DMARD treatment (n = 31) vs OA. RESULTS: Patients with RA had significantly higher 18F-FDG uptake in the wall of the carotid arteries (beta 0.27, 95%CI 0.11-0.44, P <0.01) and the aorta (beta 0.47, 95%CI 0.17-0.76, P <0.01) when compared with OA, which persisted after adjustment for traditional CV risk factors. Patients with early RA had the highest 18F-FDG uptake, followed by patients with established RA and OA respectively. Higher ESR and DAS of 28 joints values were associated with higher 18F-FDG uptake in all arterial segments. CONCLUSION: Patients with RA have increased 18F-FDG uptake in the arterial wall compared with patients with OA, as a possible marker of early atherosclerosis. Furthermore, a higher level of clinical disease activity and circulating inflammatory markers was associated with higher arterial 18F-FDG uptake, which may support a role of arterial wall inflammation in the pathogenesis of vascular complications in patients with RA.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33241288

RESUMO

OBJECTIVES: Pre-pregnancy counselling in women with systemic lupus erythematosus (SLE) is important in order to improve knowledge on the risks of pregnancy and to optimize pregnancy outcomes. Knowledge on the preferences of women with SLE regarding pre-pregnancy counselling have not yet been studied. In a closely monitored cohort of women with SLE we enquired about the present status of their wish to have children, and wish for and experiences with pre-pregnancy counselling. METHODS: A questionnaire developed by physicians in collaboration with two women with SLE was sent to all (n = 177) women participating in the Amsterdam SLE cohort. The questionnaire comprised 32 items, of which 15 focused on the above-mentioned three themes. RESULTS: A total of 124 women (70%) returned the questionnaire. The median disease duration was 13 years (interquartile range 9-19). Childlessness occurred in 51 women and 31% declared this was due to SLE [conscious decision (21%), stringent medical advice (6%), infertility due to medication (4%)]. Half of the women preferred the first pre-pregnancy counselling immediately after the SLE diagnosis (53%), together with their partner (69%). Information given by healthcare providers (81%) was preferred over information provided via brochures (35%) or the internet (26%). Pre-pregnancy face-to-face counselling from a rheumatologist and/or gynaecologist separately was preferred in 54%. CONCLUSION: One-third of women attributed their childlessness to SLE-related reasons. Pre-pregnancy counselling was preferred shortly after the onset of the disease in a non-multidisciplinary setting. The results of this study underline the importance of timely pre-conceptional counselling by healthcare providers on fertility, risks and pregnancy outcomes in women with SLE.

5.
Ann Rheum Dis ; 79(6): 713-723, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32220834

RESUMO

OBJECTIVE: To update the 2012 EULAR/ERA-EDTA recommendations for the management of lupus nephritis (LN). METHODS: Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements. RESULTS: The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria <0.5-0.7 g/24 hours with (near-)normal glomerular filtration rate) by 12 months, but this can be extended in patients with baseline nephrotic-range proteinuria. Hydroxychloroquine is recommended with regular ophthalmological monitoring. In active proliferative LN, initial (induction) treatment with mycophenolate mofetil (MMF 2-3 g/day or mycophenolic acid (MPA) at equivalent dose) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), both combined with glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3-0.5 mg/kg/day) is recommended. MMF/CNI (especially tacrolimus) combination and high-dose CY are alternatives, for patients with nephrotic-range proteinuria and adverse prognostic factors. Subsequent long-term maintenance treatment with MMF or azathioprine should follow, with no or low-dose (<7.5 mg/day) glucocorticoids. The choice of agent depends on the initial regimen and plans for pregnancy. In non-responding disease, switch of induction regimens or rituximab are recommended. In pure membranous LN with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite renin-angiotensin-aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease. CONCLUSIONS: We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.


Assuntos
Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Sociedades Médicas , Antirreumáticos/uso terapêutico , Azatioprina/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Quimioterapia Combinada , Europa (Continente) , Taxa de Filtração Glomerular , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Nefrite Lúpica/complicações , Nefrite Lúpica/patologia , Nefrite Lúpica/fisiopatologia , Ácido Micofenólico/uso terapêutico , Proteinúria/etiologia , Proteinúria/terapia
6.
Joint Bone Spine ; 87(3): 221-224, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31958575

RESUMO

OBJECTIVES: Patients with ANCA-associated vasculitis are at increased risk of cardiovascular events. The aim of the present study was to assess predictors of cardiovascular events in patients with granulomatosis with polyangiitis or eosinophilic granulomatosis with polyangiitis. METHODS: This retrospective cohort study included patients from the Canadian Vasculitis Research Network cohort in Toronto. Characteristics at diagnosis were collected. During follow-up, non-fatal cardiovascular events were determined from the Vasculitis Damage Index; mortality and causes of death were recorded. Cox regression models were developed to determine predictors of cardiovascular events, defined as stroke or myocardial infarction. RESULTS: A total of 336 patients were included (231 [69%] granulomatosis with polyangiitis; 105 [31%] eosinophilic granulomatosis with polyangiitis). The mean age at diagnosis was 44 (±18) years and 44% were male. The incidence rate for the combined outcome of all fatal and non-fatal events was 7.2 events per 1000 patient-years. In a multivariate model, family history of cardiovascular events and a higher Birmingham Vasculitis Activity Score at diagnosis were predictive of cardiovascular events (hazard ratio and 95% confidence interval 3.46 [1.06-11.28] and 1.09 [1.02-1.16] respectively). In a subgroup analysis there was no association between cardiovascular or disease-specific characteristics and cardiovascular events in eosinophilic granulomatosis with polyangiitis. CONCLUSIONS: In this cohort of patients with granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis, both traditional and disease-related risk factors were predictive of cardiovascular events. Further prospective studies should elucidate the impact of these and other modifiable risk factors on cardiovascular risk in ANCA-associated vasculitis.

8.
Sci Rep ; 10(1): 1047, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974480

RESUMO

Non-invasive imaging of arthritis activity in rheumatoid arthritis (RA) patients using macrophage PET holds promise for early diagnosis and therapeutic response monitoring. Previously obtained results with macrophage tracer (R)-[11C]PK11195 were encouraging, but the imaging signal could be further improved by reduction of background uptake. Recently, the novel macrophage tracer [18F]fluoro-PEG-folate was developed. This tracer showed excellent targeting of the folate receptor ß on activated macrophages in synovial tissue in a preclinical arthritic rat model. We performed three substudies to investigate the biodistribution, potential for imaging arthritis and kinetic properties of [18F]fluoro-PEG-folate in RA patients. Firstly, biodistribution demonstrated fast clearance of [18F]fluoro-PEG-folate from heart and blood vessels and no dose limiting uptake in organs. Secondly, [18F]fluoro-PEG-folate showed uptake in arthritic joints with significantly lower background and hence significantly higher target-to-background ratios as compared to reference macrophage tracer (R)-[11C]PK11195. Lastly, dynamic scanning demonstrated fast tracer uptake in affected joints, reaching a plateau after 1 minute, co-existing with a rapid blood clearance. In conclusion, this first in man study demonstrates the potential of [18F]fluoro-PEG-folate to image arthritis activity in RA with favourable imaging characteristics of rapid clearance and low background uptake, that allow for detection of inflammatory activity in the whole body.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Receptor 2 de Folato/metabolismo , Ácido Fólico/análogos & derivados , Macrófagos/fisiologia , Polietilenoglicóis/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Diagnóstico Precoce , Feminino , Radioisótopos de Flúor/farmacocinética , Ácido Fólico/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Molecular/métodos , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/metabolismo
9.
Int J Cardiovasc Imaging ; 36(3): 545-551, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31898005

RESUMO

Vascular wall 18F-FDG uptake is often used as a surrogate marker of atherosclerotic plaque inflammation. A potential caveat is that vascular wall 18F-FDG uptake is higher simply because more atherosclerosis is present. To determine if the degree of inflammation is high or low relative to the extent of atherosclerosis, vascular wall 18F-FDG uptake may require statistical adjustment for a non-inflammatory marker reflecting the extent of atherosclerosis, e.g. calcification. Adjustments is probably needed if (1) vascular wall 18F-FDG uptake correlates sufficiently strongly with arterial calcification and (2) adjustment for extent of calcification affects determinants of vascular 18F-FDG uptake. This study addresses these questions. 18F-FDG PET/low-dose-CT scans of 99 patients were used. Cardiovascular risk factors were assessed and PET/CT scans were analysed for standardized 18F-FDG uptake values and calcification. ANOVA was used to establish the association between vascular 18F-FDG uptake and calcification. Multiple linear regression (with and without calcification as independent variable) was used to show whether determinants of vascular 18F-FDG uptake were affected by the degree of calcification. 18F-FDG uptake was related to increased calcification in the aortic arch, descending and abdominal aorta. However, 18F-FDG uptake showed considerable overlap between categories of calcification. Age and body mass index were main determinants of vascular 18F-FDG uptake. In multiple regression analyses, most standardized beta coefficients of these determinants were not affected by adjustment for the degree of calcification. Although vascular 18F-FDG uptake is related to total atherosclerotic burden, as reflected by vascular calcification, the association is weak and unlikely to affect the identification of determinants of atherosclerotic inflammation implicating no need for adjustment in future studies.


Assuntos
Artérias/diagnóstico por imagem , Aterosclerose/diagnóstico por imagem , Fluordesoxiglucose F18/administração & dosagem , Inflamação/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/administração & dosagem , Calcificação Vascular/diagnóstico por imagem , Idoso , Artérias/metabolismo , Artérias/patologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Valor Preditivo dos Testes , Estudos Prospectivos , Compostos Radiofarmacêuticos/metabolismo , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia , Imagem Corporal Total
10.
Rheumatology (Oxford) ; 59(6): 1226-1232, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31539063

RESUMO

OBJECTIVES: To gain insight into SSc patients' perspective on quality of care and to survey their preferred quality indicators. METHODS: An online questionnaire about healthcare setting, perceived quality of care (CQ index) and quality indicators, was sent to 2093 patients from 13 Dutch hospitals. RESULTS: Six hundred and fifty patients (mean age 59 years, 75% women, 32% limited cutaneous SSc, 20% diffuse cutaneous SSc) completed the questionnaire. Mean time to diagnosis was 4.3 years (s.d. 6.9) and was longer in women compared with men (4.8 (s.d. 7.3) vs 2.5 (s.d. 5.0) years). Treatment took place in a SSc expert centre for 58%, regional centre for 29% or in both for 39% of patients. Thirteen percent of patients was not aware of whether their hospital was specialized in SSc. The perceived quality of care was rated with a mean score of 3.2 (s.d. 0.5) (range 1.0-4.0). There were no relevant differences between expert and regional centres. The three prioritized process indicators were: good patient-physician interaction (80%), structural multidisciplinary collaboration (46%) and receiving treatment according to SSc guidelines (44%). Absence of disease progression (66%), organ involvement (33%) and digital ulcers (27%) were the three highest rated outcome indicators. CONCLUSION: The perceived quality of care evaluated in our study was fair to good. No differences between expert and regional centres were observed. Our prioritized process and outcome indicators can be added to indicators suggested by SSc experts in earlier studies and can be used to evaluate the quality of care in SSc.


Assuntos
Satisfação do Paciente , Relações Médico-Paciente , Qualidade da Assistência à Saúde , Escleroderma Sistêmico/terapia , Adulto , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Indicadores de Qualidade em Assistência à Saúde , Escleroderma Sistêmico/diagnóstico , Inquéritos e Questionários , Resultado do Tratamento
11.
J Rheumatol ; 47(3): 316-324, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31092721

RESUMO

OBJECTIVE: Cardiovascular (CV) disease (CVD) risk is increased in rheumatoid arthritis (RA). However, longterm followup studies investigating this risk are scarce. METHODS: The CARRÉ (CARdiovascular research and RhEumatoid arthritis) study is a prospective cohort study investigating CVD and its risk factors in 353 patients with longstanding RA. CV endpoints were assessed at baseline and 3, 10, and 15 years after the start of the study and are compared to a reference cohort (n = 2540), including a large number of patients with type 2 diabetes (DM). RESULTS: Ninety-five patients with RA developed a CV event over 2973 person-years, resulting in an incidence rate of 3.20 per 100 person-years. Two hundred fifty-seven CV events were reported in the reference cohort during 18,874 person-years, resulting in an incidence rate of 1.36 per 100 person-years. Age- and sex-adjusted HR for CV events were increased for RA (HR 2.07, 95% CI 1.57-2.72, p < 0.01) and DM (HR 1.51, 95% CI 1.02-2.22, p = 0.04) compared to the nondiabetic participants. HR was still increased in RA (HR 1.82, 95% CI 1.32-2.50, p < 0.01) after additional adjustment for CV risk factors. Patients with both RA and DM or insulin resistance had the highest HR for developing CVD (2.21, 95% CI 1.01-4.80, p = 0.046 and 2.67, 95% CI 1.30-5.46, p < 0.01, respectively). CONCLUSION: The incidence rate of CV events in established RA was more than double that of the general population. Patients with RA have an even higher risk of CVD than patients with DM. This risk remained after adjustment for traditional CV risk factors, suggesting that systemic inflammation is an independent contributor to CV risk.

12.
Rheumatology (Oxford) ; 59(6): 1407-1415, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31642912

RESUMO

OBJECTIVES: The reversibility of interstitial lung disease (ILD) in SSc is difficult to assess by current diagnostic modalities and there is clinical need for imaging techniques that allow for treatment stratification and monitoring. 18F-Fluorodeoxyglucose (FDG) PET/CT scanning may be of interest for this purpose by detection of metabolic activity in lung tissue. This study aimed to investigate the potential role of 18F-FDG PET/CT scanning for the quantitative assessment of SSc-related active ILD. METHODS: 18F-FDG PET/CT scans and high resolution CT scans of eight SSc patients, including five with ILD, were analysed. For comparison, reference groups were included: eight SLE patients and four primary Sjögren's syndrome (pSS) patients, all without ILD. A total of 22 regions of interest were drawn in each patient at apical, medial and dorsobasal lung levels. 18F-FDG uptake was measured as mean standardized uptake value (SUVmean) in each region of interest. Subsequently, basal/apical (B/A) and medial/apical (M/A) ratios were calculated at patient level (B/A-p and M/A-p) and at tissue level (B/A-t and M/A-t). RESULTS: SUVmean values in dorsobasal ROIs and B/A-p ratios were increased in SSc with ILD compared with SSc without ILD (P = 0.04 and P = 0.07, respectively), SLE (P = 0.003 and P = 0.002, respectively) and pSS (P = 0.03 and P = 0.02, respectively). Increased uptake in the dorsobasal lungs and increased B/A-t ratios corresponded to both ground glass and reticulation on high resolution CT. CONCLUSION: Semi-quantitative assessment of 18F-FDG PET/CT is able to distinguish ILD from non-affected lung tissue in SSc, suggesting that it may be used as a new biomarker for SSc-ILD disease activity.


Assuntos
Fluordesoxiglucose F18 , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Compostos Radiofarmacêuticos , Escleroderma Sistêmico/diagnóstico por imagem , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/métodos , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Síndrome de Sjogren/diagnóstico por imagem
13.
Rheumatology (Oxford) ; 59(8): 2052-2061, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31808528

RESUMO

OBJECTIVES: To examine the treatment decision-making process of patients with dcSSc in the context of haematopoietic stem cell transplantation (HSCT). METHODS: A qualitative semi-structured interview study was done in patients before or after HSCT, or patients who chose another treatment than HSCT. Thematic analysis was used. Shared decision-making (SDM) was assessed with the 9-item Shared Decision Making Questionnaire (SDM-Q-9). RESULTS: Twenty-five patients [16 male/nine female, median age 47 (range 27-68) years] were interviewed: five pre-HSCT, 16 post-HSCT and four following other treatment. Whereas the SDM-Q-9 showed the decision-making process was perceived as shared [median score 81/100 (range 49-100)], we learned from the interviews that the decision was predominantly made by the rheumatologist, and patients were often steered towards a treatment option. Strong guidance of the rheumatologist was appreciated because of a lack of accessible, reliable and SSc-specific information, due to the approach of the decision-making process of the rheumatologist, the large consequence of the decision and the trust in their doctor. Expectations of outcomes and risks also differed between patients. Furthermore, more than half of patients felt they had no choice but to go for HSCT, due to rapid deterioration of health and the perception of HSCT as 'the holy grail'. CONCLUSION: This is the first study that provides insight into the decision-making process in dcSSc. This process is negatively impacted by a lack of disease-specific education about treatment options. Additionally, we recommend exploring patients' preferences and understanding of the illness to optimally guide decision-making and to provide tailor-made information.

15.
Rheumatology (Oxford) ; 58(4): 628-635, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30517706

RESUMO

OBJECTIVE: To investigate the relationship between remission and health-related quality of life (HRQoL) in patients with SLE in a longitudinal observational cohort. METHODS: HRQoL was measured at cohort visits using the physical and mental component score (PCS and MCS, respectively) of the Short Form 36 questionnaire. Definitions of Remission in SLE remission categories (no remission/remission on therapy/remission off therapy) were applied. Determinants of PCS and MCS were identified with simple linear regression analyses. Association between remission and HRQoL was assessed using generalized estimating equation models. RESULTS: Data from 154 patients with 2 years of follow-up were analysed. At baseline 60/154 (39.0%) patients were in either form of remission. Patients in remission had higher Short Form 36 scores in all subdomains compared with patients not in remission. PCS was positively associated with remission and employment, and negatively associated with SLICC damage index, ESR, medication, patient global assessment and BMI. MCS was positively associated with Caucasian ethnicity and negatively associated with patient global assessment. In generalized estimating equation analysis, a gradual and significant increase of PCS was observed from patients not in remission (mean PCS 36.0) to remission on therapy (41.8) to remission off therapy (44.8). No significant difference in MCS was found between remission states. CONCLUSION: we show a strong and persistent association between remission and PCS, but not MCS. These results support the relevance (construct validity) of the Definition of Remission in SLE remission definitions and the further development of a treat-to-target approach in SLE.


Assuntos
Lúpus Eritematoso Sistêmico/psicologia , Qualidade de Vida , Índice de Gravidade de Doença , Adulto , Feminino , Nível de Saúde , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/terapia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Inquéritos e Questionários
16.
RMD Open ; 4(Suppl 1): e000782, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30402270

RESUMO

Systemic sclerosis (SSc) is an orphan disease characterised by autoimmunity, fibrosis of the skin and internal organs, and vasculopathy. SSc may be associated with high morbidity and mortality. In this narrative review we summarise the results of a systematic literature research, which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases project, aimed at evaluating existing clinical practice guidelines or recommendations. Only in the domains 'Vascular & Ulcers' (ie, non-pharmacological approach to digital ulcer), 'PAH' (ie, screening and treatment), 'Treatment' and 'Juveniles' (ie, evaluation of juveniles with Raynaud's phenomenon) evidence-based and consensus-based guidelines could be included. Hence there is a preponderance of unmet needs in SSc referring to the diagnosis and (non-)pharmacological treatment of several SSc-specific complications. Patients with SSc experience significant uncertainty concerning SSc-related taxonomy, management (both pharmacological and non-pharmacological) and education. Day-to-day impact of the disease (loss of self-esteem, fatigue, sexual dysfunction, and occupational, nutritional and relational problems) is underestimated and needs evaluation.

17.
BMJ Open ; 8(8): e020479, 2018 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127049

RESUMO

INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disease characterised by inflammation, fibrosis and vasculopathy. Digital ulcers (DUs) are a frequent manifestation of vasculopathy in patients with SSc. Despite recent advances in pharmacological treatments, DU still have major health and economic implications. As there is currently no proven therapeutic strategy to promote DU healing, new treatments are urgently needed. Mesenchymal stem or stromal cells (MSCs) may provide a novel therapy for DU in SSc, because of their immunomodulatory and vasculoregenerative properties. Allogeneic MSC therapy involves functionally competent MSCs from healthy donors and may be used as 'off-the-shelf' available treatment. This study will evaluate whether allogeneic MSC therapy is a safe and potentially efficacious treatment for DU of SSc. METHODS AND ANALYSIS: The MANUS (Mesenchymal stromal cells for Angiogenesis and Neovascularization in digital Ulcers of Systemic Sclerosis) Trial is a double-blind randomised placebo-controlled trial. 20 patients with SSc with refractory DU will be randomised to receive eight intramuscular injections with either placebo or 50*106 MSCs. The primary outcome is the toxicity of the treatment at 12 weeks after administration. Secondary outcomes include (serious) adverse events, number and time to healing of DU, pain, reported hand function, quality of life and SSc disease activity. We will also evaluate changes in nailfold capillaroscopy pattern, as well as biochemical parameters and biomarkers in peripheral blood and skin biopsies. Follow-up visits will be scheduled at 48 hours and 2, 4, 8, 12, 24 and 52 weeks post-treatment. If the results confirm safety, feasibility and potential efficacy, a large multicentre randomised controlled trial with longer follow-up will be initiated focusing on efficacy. ETHICS AND DISSEMINATION: The study has been approved by the Dutch Central Committee on Research Concerning Human Subjects (protocol no: NL51705.000.15). The results will be disseminated through patient associations and conventional scientific channels. TRIAL REGISTRATION NUMBER: NCT03211793; Pre-results.


Assuntos
Transplante de Células-Tronco Mesenquimais , Escleroderma Sistêmico/complicações , Úlcera Cutânea/cirurgia , Adulto , Aloenxertos , Protocolos Clínicos , Método Duplo-Cego , Humanos , Injeções Intramusculares , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Úlcera Cutânea/etiologia
19.
Rheumatology (Oxford) ; 57(4): 631-638, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29329443

RESUMO

Objectives: Excessive bone formation is an important hallmark of AS. Recently it has been demonstrated that axial bony lesions in AS patients can be visualized using 18F-fluoride PET-CT. The aim of this study was to assess whether 18F-fluoride uptake in clinically active AS patients is related to focal bone formation in spine biopsies and is sensitive to change during anti-TNF treatment. Methods: Twelve anti-TNF-naïve AS patients [female 7/12; age 39 years (SD 11); BASDAI 5.5 ± 1.1] were included. 18 F-fluoride PET-CT scans were performed at baseline and in two patients, biopsies were obtained from PET-positive and PET-negative spine lesions. The remaining 10 patients underwent a second 18F-fluoride PET-CT scan after 12 weeks of anti-TNF treatment. PET scans were scored visually by two blinded expert readers. In addition, 18F-fluoride uptake was quantified using the standardized uptake value corrected for individual integrated whole blood activity concentration (SUVAUC). Clinical response to anti-TNF was defined according to a ⩾ 20% improvement in Assessment of SpondyloArthritis international Society criteria at 24 weeks. Results: At baseline, all patients showed at least one axial PET-positive lesion. Histological analysis of PET-positive lesions in the spine confirmed local osteoid formation. PET-positive lesions were found in the costovertebral joints (43%), facet joints (23%), bridging syndesmophytes (20%) and non-bridging vertebral lesions (14%) and in SI joints (75%). After 12 weeks of anti-TNF treatment, 18F-fluoride uptake in clinical responders decreased significantly in the costovertebral (mean SUVAUC -1.0; P < 0.001) and SI joints (mean SUVAUC -1.2; P = 0.03) in contrast to non-responders. Conclusions: 18F-fluoride PET-CT identified bone formation, confirmed by histology, in the spine and SI joints of AS patients and demonstrated alterations in bone formation during anti-TNF treatment.


Assuntos
Antirreumáticos/uso terapêutico , Fluordesoxiglucose F18/farmacologia , Osteogênese/fisiologia , Coluna Vertebral/diagnóstico por imagem , Espondilite Anquilosante/diagnóstico por imagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Adulto , Idoso , Biópsia , Feminino , Seguimentos , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacologia , Espondilite Anquilosante/tratamento farmacológico , Adulto Jovem
20.
Joint Bone Spine ; 85(2): 219-226, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28363827

RESUMO

OBJECTIVES: To validate the IFN response gene (IRG) set for the prediction of non-response to rituximab in rheumatoid arthritis (RA) and assess the predictive performance upon combination of this gene set with clinical parameters. METHODS: In two independent cohorts of 93 (cohort I) and 133 (cohort II) rituximab-starting RA patients, baseline peripheral blood expression of eight IRGs was determined, and averaged into an IFN score. Predictive performance of IFN score and clinical parameters was assessed by logistic regression. A multivariate prediction model was developed using a forward stepwise selection procedure. Patients with a decrease in disease activity score (ΔDAS28)≥1.8 after 6 months of therapy were considered responders. RESULTS: The mean IFN score was higher in non-responders compared to responders in both cohorts, but this difference was most pronounced in patients who did not use prednisone, as described before. Univariate analysis in cohort I showed that baseline DAS28, IFN score, DMARD use and negativity for IgM-RF and/or ACPA were associated with rituximab non-response. The multivariate model consisted of DAS28, IFN score and DMARD use, which showed an area under the curve (AUC) of 0.82. In cohort II, this model revealed a comparable AUC in PREDN-negative patients (0.78), but AUC in PREDN-positive patients was significantly lower (0.63), which seemed due to effect modification of the IFN score by prednisone. CONCLUSIONS: Combination of predictive parameters provided a promising model for the prediction of non-response to rituximab, with possibilities for optimization via definition of the exact interfering effect of prednisone on IFN score. TRIAL REGISTRATION (COHORT II, SMART TRIAL): NCT01126541, registered 18 May 2010.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Interferon-alfa/genética , Rituximab/uso terapêutico , Fatores Etários , Idoso , Artrite Reumatoide/genética , Estudos de Coortes , Feminino , França , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Análise Multivariada , Valor Preditivo dos Testes , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA