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1.
J Clin Virol ; 165: 105518, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37354690

RESUMO

BACKGROUND: Commercially available ELISA-based antibody tests are used to approximate vaccination success against SARS-CoV-2 in at-risk patients, but it is unclear whether they correlate with neutralization of the Omicron variant. METHODS: 269 serum samples of a cohort of 44 non-immunosuppressed participants and 65 MTX-treated rheumatic patients taken before and after COVID-19 booster vaccinations were measured using COVID-19 antibody testing systems with wild-type and Omicron BA.1 antigens developed by three different manufacturers (surrogate virus neutralization test cPass, and binding antibody tests QuantiVac and SeraSpot), as well as with a pseudovirus neutralization test (pVNT). The pVNT was considered the gold standard for determining the presence and level of anti-SARS-CoV-2 antibodies. RESULTS: All three wild-type ELISAs showed excellent test performance compared with wild-type neutralization in pVNT. However, out of 56 samples without Omicron BA.1 neutralization in pVNT, 71.4% showed positive results in at least one and 28.6% in all three wild-type ELISAs at the manufacturer-defined cut-offs. Omicron ELISAs showed either decreased specificity (57.1% and 55.4% for binding ELISAs) or sensitivity (51.2% in cPass) compared to Omicron neutralization in pVNT. The proportion of any false positive results among all samples decreased from 26.5% before to 3.2% after booster vaccination, however binding antibody test specificities remained below 70%. CONCLUSIONS: We found a poorer test performance of new Omicron antibody test systems compared to wild-type tests in detecting neutralizing antibodies against the corresponding SARS-CoV-2 variants. Decisions for booster vaccination or passive immunization of at-risk patients should not be based solely on antibody test results.


Assuntos
COVID-19 , Vírus de RNA , Humanos , Testes de Neutralização , Teste para COVID-19 , COVID-19/diagnóstico , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais
2.
Arthritis Res Ther ; 24(1): 183, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35932087

RESUMO

BACKGROUND: There is no international consensus on an optimal ultrasound score for monitoring of rheumatoid arthritis (RA) on patient-level yet. Our aim was to reassess the US7 score for the identification of the most frequently pathologic and responsive joint/tendon regions, to optimize it and contribute to an international consensus. Furthermore, we aimed to evaluate the impact of disease duration on the performance of the score. METHODS: RA patients were assessed at baseline and after 3 and 6 months of starting/changing DMARD therapy by the US7 score in greyscale (GS) and power Doppler (PD). The frequency of pathologic joint/tendon regions and their responsiveness to therapy were analyzed by Friedman test and Cochrane-Q test respectively, including the comparison of palmar vs. dorsal regions (chi-square test). The responsiveness of different reduced scores and the amount of information retained from the original US7 score were assessed by standardized response means (SRM)/linear regression. Analyses were also performed separately for early and established RA. RESULTS: A total of 435 patients (N = 138 early RA) were included (56.5 (SD 13.1) years old, 8.2 (9.1) years disease duration, 80% female). The dorsal wrist, palmar MCP2, extensor digitorum communis (EDC) and carpi ulnaris (ECU) tendons were most frequently affected by GS/PD synovitis/tenosynovitis (wrist: 45%/43%; MCP2: 35%/28%; EDC: 30%/11% and ECU: 25%/11%) and significantly changed within 6 months of therapy (all p ≤0.003 by GS/PD). The dorsal vs. palmar side of the wrist by GS/PD (p < 0.001) and the palmar side of the finger joints by PD (p < 0.001) were more frequently pathologic. The reduced US7 score (GS/PD: palmar MCP2, dorsal wrist, EDC and ECU, only PD: dorsal MCP2) showed therapy response (SRM 0.433) after 6 months and retained 76% of the full US7 score's information. No major differences between the groups of early and established RA could be detected. CONCLUSIONS: The wrist, MCP2, EDC, and ECU tendons were most frequently pathologic and responsive to therapy in both early and established RA and should therefore be included in a comprehensive score for monitoring RA patients on patient-level.


Assuntos
Artrite Reumatoide , Sinovite , Adolescente , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Sinovite/patologia , Tendões/diagnóstico por imagem , Ultrassonografia , Punho , Articulação do Punho/diagnóstico por imagem , Articulação do Punho/patologia
3.
Arthritis Res Ther ; 24(1): 117, 2022 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-35596202

RESUMO

BACKGROUND: Fluorescence optical imaging (FOI) enables visualisation of inflammation in both hands in rheumatoid arthritis (RA). OBJECTIVE: To investigate the usefulness of FOI in treatment monitoring under anti-TNFα therapy with certolizumab pegol (CZP) in patients with RA in comparison to clinical and laboratory outcome parameters. METHODS: CZP-naïve patients with RA were eligible for this open-label study with an observational period of 52 weeks. Disease activity was monitored by the clinical score DAS28, tender/swollen joint count (TJC-28/SJC-28) and laboratory outcomes for systemic inflammation (CRP and ESR). FOI results were analysed in three different phases (P1-3) and PrimaVistaMode (PVM) by the FOI activity score (FOIAS). RESULTS: Twenty-eight RA patients (median age 52.5 years, 26 females, thirteen with a history of other biologic therapy) were included. DAS28 (CRP) decreased from moderate disease activity at baseline (median 4.6, IQR 1.8) to low disease activity at week (w)52 (median 2.7, IQR 2.1; p < 0.001). Statistically significant decreases could also be demonstrated for SJC-28 and TJC-28. CRP/ESR were reduced numerically from baseline to w52. FOIAS in P1 (early phase) showed a continuous decrease of enhancement during the course of treatment period: from baseline (median 1.5, IQR 9.3) over w6 (median 1.0, IQR 3.0; p = 0.069), w12 (median 0.5, IQR 3.0; p = 0.171), w24 (n = 27, median 0.0, IQR 3.0; p = 0.004), until w52 (n = 18, median 0.0, IQR 2.8; p = 0.091), which could not be presented for FOIAS in P2, P3 and PVM. CONCLUSION: FOI in P1 appears to be a valuable tool for fast and easy monitoring of treatment response to certolizumab in a clinical setting.


Assuntos
Antirreumáticos , Artrite Reumatoide , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Certolizumab Pegol/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Verde de Indocianina/uso terapêutico , Inflamação/tratamento farmacológico , Pessoa de Meia-Idade , Imagem Óptica , Resultado do Tratamento
5.
Scand J Rheumatol ; 50(4): 299-306, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33622159

RESUMO

Objective: Pregnancy may influence the course of inflammatory rheumatic diseases and, conversely, rheumatic and musculoskeletal diseases (RMDs) can affect the outcome of pregnancy. This study aimed to retrospectively analyse the outcome of pregnancy and disease in women with RMDs.Method: Subjects were patients with high-risk pregnancy and connective tissue diseases (CTDs) or inflammatory joint diseases (IJDs) managed at a specialized rheumatology outpatient clinic from 2007 to 2014. Data from conception to 6 months postpartum were collected from medical records and a questionnaire, and analysed regarding clinical symptoms, medications, pregnancy complications, birth outcomes, and infant development. Generalized estimating equations were used to compare the groups (CTD vs IJD).Results: The eligible 66 pregnancies in 57 RMD patients were divided into two groups by RMD type: CTD (n = 48) or IJD (n = 18). The live birth rate was 97% overall. Pregnancy complications (excluding two twin pregnancies) were incurred in 39.1%: miscarriage (n = 2), premature delivery (n = 12), small-for-gestational-age infants (n = 5), and/or pregnancy-related diseases (n = 14). Three children born to women with CTDs had affected development (autism spectrum disorder, congenital heart disease, bronchopulmonary dysplasia). CTD infants had a significantly lower mean gestational age (in weeks) (p = 0.042), weight (p = 0.009), and length (p = 0.016) at birth than IJD infants.Conclusion: Although the live birth rate was high, complications occurred in 39.1% of pregnancies in this cohort. Therefore, interdisciplinary management of pregnant women with RMDs at specialized clinics is strongly recommended.


Assuntos
Doenças do Tecido Conjuntivo/complicações , Complicações na Gravidez , Nascimento Prematuro/etiologia , Doenças Reumáticas/complicações , Adolescente , Adulto , Feminino , Humanos , Recém-Nascido , Nascido Vivo , Masculino , Gravidez , Resultado da Gravidez , Adulto Jovem
6.
Arthritis Res Ther ; 22(1): 192, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811543

RESUMO

OBJECTIVES: To investigate the frequency of subclinical skin inflammation in both hands by fluorescence optical imaging (FOI) in patients with psoriasis/psoriatic arthritis (Pso/PsA) vs. rheumatoid arthritis (RA) and healthy individuals, and to correlate these findings with cardiovascular (CV) risk factors. PATIENTS AND METHODS: The FOI scans were analyzed retrospectively to detect clinically invisible skin enhancement (0-3 scale) in both hands without relationship to underlying joints or blood vessels. We further characterized the FOI patterns and sorted the scans into groups based on the assumed diagnosis (Pso/PsA, RA, and healthy controls), which was compared with the physician's diagnosis. Furthermore, the associations between CV risk factors and imaging findings were investigated by regression analyses. RESULTS: We included FOI scans of patients with Pso/PsA (n = 80), RA (n = 78), and healthy controls (n = 25). Subclinical skin enhancement on the back of their hands was more common in Pso/PsA (72.5%) than in RA patients (20.5%) and healthy individuals (28.0%) (p < 0.001). Based on the FOI pattern, the majority of patients with Pso/PsA (72.5%), RA (76.9%), and healthy controls (68.0%) were classified correctly using the physician-based diagnosis as reference (overall agreement of 74%, kappa = 0.57). No CV risk factors except body weight (kg) were associated with subclinical skin enhancement (OR 1.04, 95% CI 1.02-1.06; p < 0.001). CONCLUSION: Subclinical subdermal skin inflammation was common in Pso/PsA patients using FOI. Based on the FOI pattern, most patients with Pso/PsA and were classified with the correct diagnosis. We demonstrated an important influence of the body weight on our FOI results. FOI may be a helpful novel tool to study microcirculation in rheumatic diseases with skin involvement.


Assuntos
Artrite Psoriásica , Artrite Reumatoide , Psoríase , Artrite Psoriásica/complicações , Artrite Psoriásica/diagnóstico por imagem , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Humanos , Imagem Óptica , Psoríase/complicações , Psoríase/diagnóstico por imagem , Estudos Retrospectivos
7.
Arthritis Res Ther ; 22(1): 144, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539806

RESUMO

BACKGROUND: Digital ulcers (DU) present a challenging complication in systemic sclerosis (SSc). The aim of this study was to combine clinical characteristics and imaging methods to a composite score for the prediction of DU in SSc patients. METHODS: Seventy-nine SSc patients received clinical examination, their patient history was taken and nailfold capillaroscopy (NC), colour Doppler ultrasonography (CDUS) and fluorescence optical imaging (FOI) of the hands were performed at baseline. Newly developed DU over a period of approximately 12 months were registered. We used criteria with area under the curve (AUC) of at least 0.6 in regard to the development of these new DU to create the score (CIP-DUS, clinical features, imaging, patient history-digital ulcer score). RESULTS: Twenty-nine percent of all SSc patients developed new DU during follow-up (48.1% diffuse, 18.4% limited SSc). Based on the cross-validated (cv) AUC, a weight (cvAUC > 0.6 and ≤ 0.65: 1; cvAUC > 0.65 and ≤ 0.7: 2; cvAUC > 0.7: 3) was assigned to each selected parameter. The performance of the final CIP-DUS was assessed with and without the CDUS/FOI component. For the scleroderma patterns in NC, three points were appointed to late, two to active and one point to early capillaroscopy pattern according to Cutolo et al. The CIP-DUS including the CDUS and FOI parameters resulted in a good diagnostic performance (AUC after cross-validation: 0.83, 95%CI 0.74 to 0.92) and was well calibrated (chi-square = 12.3, p = 0.58). The cut-off associated with the maximum of sensitivity and specificity was estimated at ≥ 10 points resulting in a sensitivity of 100% and specificity of 74% for new DU during follow-up. Excluding CDUS and FOI parameters leads to a non-statistically significant lower performance (AUC after cross-validation: 0.81, 95%CI 0.72 to 0.91). However, including CDUS and FOI resulted in a better classification of patients in respect to the outcome new DU in follow-up due to significantly better reclassification performance (NRI = 62.1, p = 0.001) and discrimination improvement (IDI = 9.7, p = 0.01). CONCLUSION: A new score was introduced with the aim to predict digital ulcers. If applied correctly and with the new imaging techniques proposed, all patients at risk of digital ulcers throughout 12 months could be identified.


Assuntos
Escleroderma Sistêmico , Úlcera Cutânea , Dedos/diagnóstico por imagem , Mãos , Humanos , Angioscopia Microscópica , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico por imagem , Úlcera Cutânea/diagnóstico por imagem , Úlcera Cutânea/etiologia , Úlcera
9.
Z Rheumatol ; 78(5): 404-412, 2019 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-31001653

RESUMO

The prognosis of rheumatoid arthritis (RA) has been significantly improved in recent decades. This is mainly due to earlier detection, better diagnostics and new treatment options, such as the optimized use of classical disease-modifying antirheumatic drugs (DMARD) and biologicals. Other factors involved were earlier intervention, improved availability of information and analyses and certainly also standardization of care (e.g. guidelines). An additional important component is close monitoring of disease activity in order to be able to adapt the treatment in a timely manner and thus prevent damage. The demand for tight control is the subject of this article.


Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Diagnóstico Precoce , Humanos , Prognóstico
10.
Arthritis Res Ther ; 21(1): 96, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30987674

RESUMO

OBJECTIVE: Systemic sclerosis (SSc) can lead to ischemic complications such as digital ulcers (DUs). The aim of the study was to find predictors of DUs by clinical and new imaging methods. PATIENTS AND METHODS: All 79 SSc patients included in the study received a clinical, colour Doppler ultrasound (CDUS), fluorescence optical imaging (FOI) and capillaroscopy examination at baseline, and their capacity to predict new DU development was analysed in 76 patients at 12 months follow-up. RESULTS: Twenty-two of 76 patients (28.9%) developed new ulcers during follow-up (diffuse SSc 48.1%; limited SSc 18.4%). Receiver operating characteristic (ROC) curve analysis revealed an area under the curve of 0.7576 for DU development, with a specificity of 87% and a sensitivity of 54.6% (p = 0.0003, OR = 8.1 [95%CI 2.5-25.6]) at a cut-off of ≥ 21 points (ACR/EULAR classification criteria for SSc). Capillaroscopy and CDUS had high sensitivity (100% and 95.5%) but low specificity (28.9% and 22.2%) for ulcer occurrence when used alone, but better specificity (46.3%) when combined (OR = 18.1 [95%CI 2.3-144.4]; p = 0.0004). Using FOI, fingers with pathologic staining had a higher risk for new ulcer development in the same finger (p = 0.0153). General future DU (i.e. DU also in other fingers) was associated with a missing FOI signal in the right digit III at baseline (p = 0.048). CONCLUSION: New imaging modalities can predict digital ulcer development in SSc patients with high sensitivity for capillaroscopy and CDUS and enhanced specificity when combined. A missing signal of FOI in the right digit III at baseline was associated with general future DU.


Assuntos
Dedos/diagnóstico por imagem , Angioscopia Microscópica/métodos , Imagem Óptica/métodos , Escleroderma Sistêmico/diagnóstico por imagem , Úlcera Cutânea/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escleroderma Sistêmico/epidemiologia , Úlcera Cutânea/epidemiologia
11.
Z Rheumatol ; 78(9): 820-831, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-30511171

RESUMO

BACKGROUND: Many studies and registry data confirm that depression, often associated with anxiety disorders is very often found in patients with rheumatoid arthritis (RA). To what extent these psychiatric disorders are already relevant at a very early stage of the disease, has currently not been adequately investigated. METHODS: In this study 176 patients with early joint symptoms (<1 year) were surveyed in an early arthritis consultation (EAC). The hospital anxiety and depression scale (HADS) was completed by the patients to examine the prevalence of depressive and anxiety symptoms. The results were compared to normative data of the general German population and between the diagnosis groups. RESULTS: With 47.7% the prevalence of global distress for EA patients was almost twice as high compared to the corresponding group from the general population. This was also confirmed for depressive and anxiety symptoms. The EA patients without confirmed evidence of musculoskeletal inflammatory rheumatic disease (RD) showed nearly the same point prevalence as patients with confirmed RD. In multiple logistic regression the health assessment questionnaire (HAQ) was positively associated with global distress (odds ratio, OR 3.63) while the visual analogue scale (VAS) for global disease activity was positively associated with symptoms of depression (OR 1.03). Female EA patients (OR 5.45) appear to have a higher probability for experiencing corresponding symptoms, whereas patients over 60 years old appear to have less anxiety than younger patients (OR 0.11). CONCLUSION: The high prevalence of symptoms of depression and anxiety in EA patients compared to the general population is a challenge for rheumatologists, orthopedists and general practitioners, particularly with respect to the differentiation of possible psychosomatic components in noninflammatory joint complaints. The results suggest that screening for psychiatric problems in patients with rheumatism should be evaluated as soon as possible as these can have a great impact on the perception of pain and physical functional status from the very beginning.


Assuntos
Ansiedade , Artrite Reumatoide , Depressão , Fatores Etários , Ansiedade/epidemiologia , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/psicologia , Depressão/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores Sexuais , Inquéritos e Questionários
12.
Z Rheumatol ; 77(7): 587-592, 2018 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-29947948

RESUMO

When it comes to legal aspects and doctors have to go to court, most likely they will serve as an expert or regular witness or as a defendant in a civil litigation in case of recourse claims and only rarely as defendants in a criminal case. With the exception of expert testimonies by seasoned physicians, this is not usually an easy situation. This article addresses important aspects of the preparation for a trial and its procedures. If appropriately prepared, and if necessary represented by a good attorney, these sometimes emotionally stressful situations can be mastered quite well.


Assuntos
Prova Pericial , Médicos
13.
Z Rheumatol ; 77(Suppl 1): 16-23, 2018 May.
Artigo em Alemão | MEDLINE | ID: mdl-29691690

RESUMO

Rheumatic diseases are among the most common chronic inflammatory disorders. Besides severe pain and progressive destruction of the joints, rheumatoid arthritis (RA), spondyloarthritides (SpA) and psoriatic arthritis (PsA) impair working ability, reduce quality of life and if treated insufficiently may enhance mortality. With the introduction of biologics to treat these diseases, the demand for biomarkers of early diagnosis and therapeutic stratification has been growing continuously. The main goal of the consortium ArthroMark is to identify new biomarkers and to apply modern imaging technologies for diagnosis, follow-up assessment and stratification of patients with RA, SpA and PsA. With the development of new biomarkers for these diseases, the ArthroMark project contributes to research in chronic diseases of the musculoskeletal system. The cooperation between different national centers will utilize site-specific resources, such as biobanks and clinical studies for sharing and gainful networking of individual core areas in biomarker analysis. Joint data management and harmonization of data assessment as well as best practice characterization of patients with new imaging technologies will optimize quality of marker validation.


Assuntos
Artrite Psoriásica/diagnóstico , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , Diagnóstico Precoce , Espondilartrite/diagnóstico , Artrite Psoriásica/sangue , Artrite Psoriásica/classificação , Artrite Psoriásica/genética , Artrite Reumatoide/sangue , Artrite Reumatoide/classificação , Artrite Reumatoide/genética , Autoanticorpos/sangue , Diagnóstico por Imagem , Avaliação da Deficiência , Genótipo , Humanos , Comunicação Interdisciplinar , Colaboração Intersetorial , Qualidade de Vida , Espondilartrite/sangue , Espondilartrite/classificação , Espondilartrite/genética
15.
Z Rheumatol ; 77(1): 28-39, 2018 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-28589389

RESUMO

BACKGROUND: The German Registry of Autoimmune Diseases 2 (GRAID2) is a retrospective, non-interventional, multicenter registry study collecting data from patients with inflammatory, mainly rheumatic diseases refractory to standard of care therapy and treated with an off-label biologic therapy. The retrospective documentation comprised case history, diagnosis, course of disease (including safety and global efficacy). The objective was to evaluate the global clinical outcome and safety of off-label biologic therapy in clinical practice. RESULTS: Data from 311 patients with an overall observation period of 338.5 patient-years were collected. The mean patients age was 47.8 years with 56.9% females. The most frequently documented diagnoses comprised rejection prophylaxis/therapy after renal transplantation (NTX, 18.3%), ANCA-vasculitides (17.4%), systemic lupus erythematosus (SLE, 10.3%), autoinflammatory fever syndromes (8.4%), autoimmune myositis (7.4%) and pemphigus (5.8%). Documented biologic therapies included rituximab (RTX, 70.1%), tocilizumab (TCZ, 9.3%), infliximab (IFX, 7.1%), anakinra (ANK, 5.5%), adalimumab (ADA, 3.5%), etanercept (ETA, 2.3%) and certolizumab (CTZ, 0.6%). After initiation of off-label biologic treatment, tolerability was assessed by the physicians as "very good"/"good" in 95.5%. Altogether, 275 adverse events were documented and of these, 104 were classified as serious adverse events and occurred in 62 patients. In 19 of these patients severe infections (30.6%) were documented, resulting in a rate of 5.6 severe infections per 100 patient years. A total of six deaths were documented, while five of these cases were rated as not related to the biologics treatment. Notably, the use of RTX in patients with small vessel vasculitides and of TCZ in patients with large vessel vasculitides prior to their approval support their relevance in clinical management of patients with severe diseases. CONCLUSION: The results of this registry together with data of GRAID1 provide evidence that use of off-label biologic therapies in patients with inflammatory rheumatic diseases refractory to conventional treatment did not result in any new safety signal already known for these compounds or subsequently shown by clinical trials in certain entities.


Assuntos
Doenças Autoimunes , Terapia Biológica , Uso Off-Label , Doenças Autoimunes/tratamento farmacológico , Feminino , Humanos , Masculino , Sistema de Registros , Estudos Retrospectivos , Padrão de Cuidado
16.
Ann Rheum Dis ; 76(1): 96-104, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27165179

RESUMO

OBJECTIVES: To assess the efficacy and safety of certolizumab pegol (CZP)+dose-optimised methotrexate (MTX) versus placebo (PBO)+dose-optimised MTX in inducing and sustaining clinical remission in DMARD-naïve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks. METHODS: DMARD-naïve patients with ≤1 year of active RA were randomised (3:1) in a double-blind manner to CZP (400 mg Weeks 0, 2, 4, then 200 mg Q2W to Week 52)+MTX or PBO+MTX (the mean optimised-MTX dose=21 and 22 mg/week, respectively). Sustained remission (sREM) and sustained low disease activity (sLDA; DAS28(ESR)<2.6 and DAS28(ESR)≤3.2, respectively, at both Weeks 40 and 52) were the primary and secondary endpoints. RESULTS: Patients were randomised to CZP+MTX (n=660) and PBO+MTX (n=219). At Week 52, significantly more patients assigned to CZP+MTX compared with PBO+MTX achieved sREM (28.9% vs 15.0%, p<0.001) and sLDA (43.8% vs 28.6%, p<0.001). Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX (van der Heijde modified total Sharp score (mTSS) mean absolute change from baseline (CFB): 0.2 vs 1.8, p<0.001, rate of mTSS non-progressors: 70.3% vs 49.7%, p<0.001; least squares (LS) mean CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI): -1.00 vs -0.82, p<0.001). Incidence of adverse events (AEs) and serious AEs was similar between treatment groups. Infection was the most frequent AE, with higher incidence for CZP+MTX (71.8/100 patient-years (PY)) versus PBO+MTX (52.7/100 PY); the rate of serious infection was similar between CZP+MTX (3.3/100 PY) and PBO+MTX (3.7/100 PY). CONCLUSIONS: CZP+dose-optimised MTX treatment of DMARD-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX. TRIAL REGISTRATION NUMBER: NCT01519791.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Certolizumab Pegol/uso terapêutico , Metotrexato/uso terapêutico , Adulto , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico por imagem , Certolizumab Pegol/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Infecções/induzido quimicamente , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prognóstico , Radiografia , Indução de Remissão
17.
Immunol Res ; 64(5-6): 1195-1206, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27629117

RESUMO

The initial inflammatory phase of fracture healing is of great importance for the clinical outcome. We aimed to develop a detailed time-dependent analysis of the initial fracture hematoma. We analyzed the composition of immune cell subpopulations by flow cytometry and the concentration of cytokines and chemokines by bioplex in 42 samples from human fractures of long bones <72 h post-trauma. The early human fracture hematoma is characterized by maturation of granulocytes and migration of monocytes/macrophages and hematopoietic stem cells. Both T helper cells and cytotoxic T cells proliferate within the fracture hematoma and/or migrate to the fracture site. Humoral immunity characteristics comprise high concentration of pro-inflammatory cytokines such as IL-6, IL-8, IFNγ and TNFα, but also elevated concentration of anti-inflammatory cytokines, e.g., IL-1 receptor antagonist and IL-10. Furthermore, we found that cells of the fracture hematoma represent a source for key chemokines. Even under the bioenergetically restricted conditions that exist in the initial fracture hematoma, immune cells are not only present, but also survive, mature, function and migrate. They secrete a cytokine/chemokine cocktail that contributes to the onset of regeneration. We hypothesize that this specific microenvironment of the initial fracture hematoma is among the crucial factors that determine fracture healing.


Assuntos
Osso e Ossos/imunologia , Fraturas Ósseas/imunologia , Hematoma/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Movimento Celular , Proliferação de Células , Separação Celular , Células Cultivadas , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Granulócitos , Humanos , Macrófagos , Masculino , Pessoa de Meia-Idade
20.
Ann Rheum Dis ; 75(3): 566-70, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26311723

RESUMO

BACKGROUND: In rheumatoid arthritis (RA), hand synovitis appears especially in wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. In hand osteoarthritis (OA), potential inflammatory changes are mainly present in PIP and distal interphalangeal (DIP) joints. Joint inflammation can be visualised by fluorescence optical imaging (FOI) and musculoskeletal ultrasound (US). OBJECTIVE: Comparison of the amount and distribution of inflammatory signs in wrist and finger joints of the clinically dominant hand in patients with OA and RA by FOI and gray-scale (GSUS) and power Doppler US (PDUS). METHODS: FOI and GSUS/PDUS were performed in 1.170 joints (wrists, MCP, PIP, DIP) in 90 patients (67 RA, 23 OA). Joint inflammation was graded by a semiquantitative score (0-3) for each imaging method. RESULTS: GSUS/PDUS showed wrist and MCP joints mostly affected in RA. DIP joints were graded higher in OA. In FOI, RA and OA featured inflammatory changes in the respective joint groups depending on the phase of fluorescence dye flooding. CONCLUSIONS: US and FOI detected inflammation in both RA and OA highlighting the inflammatory component in the course of OA. The different inflammatory patterns and various shapes of fluorescence enhancement in FOI may offer opportunities to distinguish and determine the inflammatory status in both diseases.


Assuntos
Artrite Reumatoide/diagnóstico , Articulação da Mão/patologia , Inflamação/diagnóstico , Osteoartrite/diagnóstico , Sinovite/diagnóstico , Adulto , Idoso , Artrite Reumatoide/imunologia , Feminino , Articulações dos Dedos/diagnóstico por imagem , Articulações dos Dedos/imunologia , Articulações dos Dedos/patologia , Articulação da Mão/diagnóstico por imagem , Articulação da Mão/imunologia , Humanos , Inflamação/imunologia , Masculino , Articulação Metacarpofalângica/diagnóstico por imagem , Articulação Metacarpofalângica/imunologia , Articulação Metacarpofalângica/patologia , Pessoa de Meia-Idade , Imagem Óptica , Osteoartrite/imunologia , Projetos Piloto , Índice de Gravidade de Doença , Sinovite/imunologia , Ultrassonografia , Articulação do Punho/diagnóstico por imagem , Articulação do Punho/imunologia , Articulação do Punho/patologia
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