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- Elhai, M, et al.
(författare)
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Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
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Tidskriftsartikel (refereegranskat)abstract
- To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
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- Distler, J. H. W., et al.
(författare)
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Is there a role for TNF-alpha antagonists in the treatment of SSc? EUSTAR expert consensus development using the Delphi technique
- 2011
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Ingår i: Clinical and Experimental Rheumatology. - 1593-098X. ; 29:2, s. 40-45
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To obtain experiences and expert opinion on treatment of SSc patients with TNF-alpha antagonists. Methods: An investigation was carried out among the EUSTAR centres into their expertise on use of TNF-alpha antagonists. Assessment forms on the frequency of TNF-alpha inhibitor use were distributed to EULAR Scleroderma Trials and Research Group (EUSTAR) centres. Afterwards, a three round Delphi exercise was performed to obtain expert consensus on the use of TNF-alpha inhibitors in SSc. Results: Seventy-nine centres returned information on use of TNF-alpha antagonists in SSc patients. A total of 65 patients were treated with TNF-alpha inhibitors in 14 different centres. Forty-eight of the 65 patients treated with TNF-alpha inhibitors improved. Improvement was mainly seen in patients with arthritis, whereas the effects on fibrosis varied. In the first round of the subsequent Delphi approach, 71 out of 79 experts stated that they would use TNF-alpha antagonists in SSc. Arthritis was suggested as an indication for TNF alpha antagonists by 75% of the experts. However; after the third stage of the Delphi exercise, the acceptance for the off-label use of TNF-alpha antagonists decreased and 59% recommended that TNF-alpha antagonists should not be used or only used in clinical trials in SSc patients, while 38% of the experts suggested the use of TNF-alpha antagonists for arthritis associated with SSc. Conclusions: Most of the experts do not recommend the routine use of TNF-alpha antagonists in systemic sclerosis. Arthritis might be a potential indication in SSc, although controlled clinical trials with TNF-alpha antagonists are needed before general recommendations can be given.
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- Alchi, B, et al.
(författare)
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Autologous haematopoietic stem cell transplantation for systemic lupus erythematosus: data from the European Group for Blood and Marrow Transplantation registry
- 2013
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Ingår i: Lupus. - : SAGE Publications. - 1477-0962 .- 0961-2033. ; 22:3, s. 245-253
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Tidskriftsartikel (refereegranskat)abstract
- Patients with systemic lupus erythematosus (SLE) refractory to conventional immunosuppression suffer substantial morbidity and mortality due to active disease and treatment toxicity. Immunoablation followed by autologous stem cell transplantation (ASCT) is a novel therapeutic strategy that potentially offers new hope to these patients. Methods This retrospective survey reviews the efficacy and safety of ASCT in 28 SLE patients from eight centres reported to the European Group for Blood and Marrow Transplantation (EBMT) registry between 2001 and 2008. Results Median disease duration before ASCT was 52 (nine to 396) months, 25/28 SLE patients (89%) were female, age 29 (16–48) years. At the time of ASCT, eight (one to 11) American College of Rheumatology (ACR) diagnostic criteria for SLE were present and 17 (60%) patients had nephritis. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte-colony stimulating factor in 93% of patients, and ex vivo CD34 stem cell selection was performed in 36%. Conditioning regimens were employed with either low ( n = 10) or intermediate (18) intensities. With a median follow-up of 38 (one to 110) months after ASCT, the five-year overall survival was 81 ± 8%, disease-free survival was 29 ± 9%, relapse incidence (RI) was 56 ± 11% and non-relapse mortality was 15 ± 7%. Graft manipulation by CD34+ selection was associated with a lower RI ( p = 0.001) on univariate analysis. There were five deaths within two years after ASCT: three caused by infection, one by secondary autoimmune disease and one by progressive SLE. Conclusions Our data further support the concept of immunoablation and ASCT to re-induce long-term clinical and serologic remissions in refractory SLE patients even in the absence of maintenance therapy. This study also suggests a beneficial effect of ex vivo graft manipulation on prevention of relapses post-transplantation in SLE.
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| 7. |
- Fransen, J., et al.
(författare)
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Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:10, s. 1788-1792
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Tidskriftsartikel (refereegranskat)abstract
- Objective Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accurate in other patients, especially from other centres or countries. A study was undertaken to validate the prognostic model to predict 5-year survival in SSc in other centres throughout Europe. Methods A European multicentre cohort of patients with SSc diagnosed before 2002 was established. Patients with SSc according to the preliminary American College of Rheumatology classification criteria were eligible for the study when they were followed for at least 5 years or shorter if they died. The primary outcome was 5-year survival after diagnosis of SSc. The predefined prognostic model uses the following baseline variables: age, gender, presence of urine protein, erythrocyte sedimentation rate (ESR) and carbon monoxide diffusing capacity (DLCO). Results Data were available for 1049 patients, 119 (11%) of whom died within 5 years after diagnosis. Of the patients, 85% were female, the mean (SD) age at diagnosis was 50 (14) years and 30% were classified as having diffuse cutaneous SSc. The prognostic model with age (OR 1.03), male gender (OR 1.93), urine protein (OR 2.29), elevated ESR (1.89) and low DLCO (OR 1.94) had an area under the receiver operating characteristic curve of 0.78. Death occurred in 12 (2.2%) of 509 patients with no risk factors, 45 (13%) of 349 patients with one risk factor, 55 (33%) of 168 patients with two risk factors and 7 (30%) of 23 patients with three risk factors. Conclusion A simple prognostic model using three disease factors to predict 5-year survival at diagnosis in SSc showed reasonable performance upon validation in a European multicentre study.
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| 9. |
- Herrick, A. L., et al.
(författare)
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Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study
- 2018
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:4, s. 563-570
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). Methods The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). Results 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. Conclusions Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. Trial registration number NCT02339441. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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- Farge, G., et al.
(författare)
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Protein sliding and DNA denaturation are essential for DNA organization by human mitochondrial transcription factor A
- 2012
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondria organize their genome in protein-DNA complexes called nucleoids. The mitochondrial transcription factor A (TFAM), a protein that regulates mitochondrial transcription, is abundant in these nucleoids. TFAM is believed to be essential for mitochondrial DNA compaction, yet the exact mechanism has not been resolved. Here we use a combination of single-molecule manipulation and fluorescence microscopy to show the nonspecific DNA-binding dynamics and compaction by TFAM. We observe that single TFAM proteins diffuse extensively over DNA (sliding) and, by collisions, form patches on DNA in a cooperative manner. Moreover, we demonstrate that TFAM induces compaction by changing the flexibility of the DNA, which can be explained by local denaturation of the DNA (melting). Both sliding of TFAM and DNA melting are also necessary characteristics for effective, specific transcription regulation by TFAM. This apparent connection between transcription and DNA organization clarifies how TFAM can accomplish two complementary roles in the mitochondrial nucleoid at the same time.
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| 16. |
- Greco, R, et al.
(författare)
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Hematopoietic stem cell transplantation for autoimmune diseases in the time of COVID-19: EBMT guidelines and recommendations
- 2021
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Ingår i: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 56:7, s. 1493-1508
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), represents one of the biggest challenges of 21st century, threatening public health around the globe. Increasing age and presence of co-morbidities are reported risk factors for severe disease and mortality, along with autoimmune diseases (ADs) and immunosuppressive treatments such as haematopoietic stem cell transplantation (HSCT), which are also associated with adverse outcomes. We review the impact of the pandemic on specific groups of patients with neurological, rheumatological, and gastroenterological indications, along with the challenges delivering HSCT in adult and pediatric populations. Moving forward, we developed consensus-based guidelines and recommendations for best practice and quality of patient care in order to support clinicians, scientists, and their multidisciplinary teams, as well as patients and their carers. These guidelines aim to support national and international organizations related to autoimmune diseases and local clinical teams delivering HSCT. Areas of unmet need and future research questions are also highlighted. The waves of the COVID-19 pandemic are predicted to be followed by an “endemic” phase and therefore an ongoing risk within a “new normality”. These recommendations reflect currently available evidence, coupled with expert opinion, and will be revised according to necessary modifications in practice.
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| 17. |
- Snarski, E, et al.
(författare)
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Onset and outcome of pregnancy after autologous haematopoietic SCT (AHSCT) for autoimmune diseases : a retrospective study of the EBMT autoimmune diseases working party (ADWP)
- 2015
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 50:2, s. 216-220
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Tidskriftsartikel (refereegranskat)abstract
- Autologous haematopoietic SCT (AHSCT) is increasingly used to control severe and refractory autoimmune diseases (AD). Many patients are women of reproductive age with a potential desire for children. We present a multicentre retrospective analysis of pregnancy and childbirth in patients who underwent AHSCT for AD. The databases of the European Blood and Marrow Transplantation and University of Sao Paulo, Ribeirão Preto, Brazil were searched for female patients aged 18-50 years who had received AHSCT for AD between 1994-2011. In 324 adult female patients, 22 pregnancies were reported in 15 patients between 1997-2011. Indications for AHSCT included multiple sclerosis (n=7), systemic sclerosis (n=5), rheumatoid arthritis (n=1), juvenile idiopathic arthritis (n=1) and Takayasu disease (n=1). Of the 22 reported pregnancies, 20 followed natural conception. 15 pregnancies (68%) resulted in healthy life births, whereas 7 (32%) failed. Exacerbations of AD occurred in two patients during second pregnancies. No maternal mortality was associated with pregnancy or postpartum. There were no reports of congenital, developmental or any other disease in the children. This retrospective analysis confirms the possibility of pregnancy and childbirth following AHSCT for severe AD. The outcome of pregnancy is generally good and most led to the birth of a healthy child.
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