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| 8. |
- 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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- Hoshino, Ayuko, et al.
(författare)
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Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers
- 2020
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Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 182:4, s. 1044-
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Tidskriftsartikel (refereegranskat)abstract
- There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n =151) and plasma-derived (n =120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.
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| 13. |
- Hetland, M. L., et al.
(författare)
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Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial
- 2020
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 371
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI <= 2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.
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- Ji, Xuemei, et al.
(författare)
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Protein-altering germline mutations implicate novel genes related to lung cancer development
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.
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| 18. |
- Budeus, B., et al.
(författare)
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Human cord blood b cells differ from the adult counterpart by conserved ig repertoires and accelerated response dynamics
- 2021
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 206:12, s. 2839-2851
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Tidskriftsartikel (refereegranskat)abstract
- Neonatal and infant immune responses are characterized by a limited capability to generate protective Ab titers and memory B cells as seen in adults. Multiple studies support an immature or even impaired character of umbilical cord blood (UCB) B cells themselves. In this study, we provide a comprehensive molecular and functional comparison of B cell subsets from UCB and adult peripheral blood. Most UCB B cells have a mature, naive B cell phenotype as seen in adults. The UCB Ig repertoire is highly variable but interindividually conserved, as BCR clonotypes are frequently shared between neonates. Furthermore, UCB B cells show a distinct transcriptional program that confers accelerated responsiveness to stimulation and facilitated IgA class switching. Stimulation drives extensive differentiation into Ab-secreting cells, presumably limiting memory B cell formation. Humanized mice suggest that the distinctness of UCB versus adult B cells is already reflected by the developmental program of hematopoietic precursors, arguing for a layered B-1/B-2 lineage system as in mice, albeit our findings suggest only partial comparability to murine B-1 cells. Our study shows that UCB B cells are not immature or impaired but differ from their adult mature counterpart in a conserved BCR repertoire, efficient IgA class switching, and accelerated, likely transient response dynamics. © 2021 by TheAmericanAssociation of Immunologists, Inc.
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- Lend, K., et al.
(författare)
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Sex differences in remission rates over 24 weeks among three different biological treatments compared to conventional therapy in patients with early rheumatoid arthritis (NORD-STAR): a post-hoc analysis of a randomised controlled trial
- 2023
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Ingår i: The Lancet Rheumatology. - 2665-9913. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Rheumatoid arthritis is a chronic inflammatory disease with a well-recognised female preponderance. In this post-hoc analysis of the NORD-STAR trial, we aimed to examine sex differences in remission rates with three different biological treatments combined with methotrexate versus active conventional treatment over 24 weeks, in patients with early rheumatoid arthritis. Methods: NORD-STAR was a multicentre, investigator-initiated, assessor-blinded, phase 4, randomised, controlled trial of early rheumatoid arthritis, done in Denmark, Finland, Iceland, Norway, Sweden, and the Netherlands. Newly diagnosed patients, naive to disease-modifying antirheumatic drugs, aged 18 years or older with early rheumatoid arthritis and with a symptom duration less than 24 months were randomly assigned (1:1:1:1) to receive active conventional treatment, certolizumab-pegol, abatacept, or tocilizumab. Sex was reported in case report forms by study physicians or by study nurses. Data on gender were not collected. Remission outcomes were analysed with logistic generalised estimating equations (GEE), using a logit link and exchangeable correlation matrix. The model included treatment, time, sex, and the relevant interactions. For this post-hoc analysis, the co-primary outcomes were differences in Clinical Disease Activity Index (CDAI) remission (CDAI score ≤2·8) between sexes over time and at week 24, assessed with interaction terms (men vs women within each treatment comparison) and using active conventional treatment as the reference. We present adjusted average marginal differences in remission rates (risk differences) with 95% CIs. Findings: Between Dec 14, 2012, and Dec 11, 2018, 812 patients were enrolled and randomly assigned; 217 received active conventional treatment, 203 received certolizumab-pegol, 204 received abatacept, and 188 received tocilizumab. All 812 patients were included in this analysis; 561 (69%) were women and 251 (31%) were men. Observed CDAI remission rates at 24 weeks were numerically higher among men than among women despite comparable disease activity at baseline (55% vs 50% with active conventional treatment, 57% vs 52% with certolizumab-pegol, 65% vs 51% with abatacept, and 61% vs 40% with tocilizumab). In the adjusted analysis, with active conventional treatment as the reference, the only significant difference between men and women was in the tocilizumab group (pinteraction=0·015); men in the tocilizumab group had a higher probability of CDAI remission, on average over time, than did men in the active conventional treatment group (0·12; 95% CI 0·00 to 0·23), whereas women in the tocilizumab group had a lower probability of remission than did women in the active conventional treatment group (–0·05, 95% CI –0·13 to 0·02). Interpretation: Numerically higher remission rates were observed in men than in women in all four treatment groups at week 24, suggesting that this generalised sex difference is not related to the treatment. The difference between men and women was significantly greater with tocilizumab, an interleukin (IL)-6 inhibitor, than with active conventional treatment, suggesting a possible additional sex-based effect specific for IL-6 blockade. Funding: None. © 2022 Elsevier Ltd
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| 21. |
- Stockfelt, Marit, et al.
(författare)
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Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis-a spin-off study of the NORD-STAR randomized clinical trial
- 2021
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFN alpha have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. Methods Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFN alpha protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. Results IFN alpha protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFN alpha protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFN alpha protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. Conclusion IFN alpha protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFN alpha positivity did not predict remission in any of the treatment arms, suggesting that the IFN alpha system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, .
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| 22. |
- Dijkshoorn, B, et al.
(författare)
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PROFOUND ANTICOAGULANT EFFECTS OF INITIAL ANTIRHEUMATIC TREATMENTS IN EARLY RHEUMATOID ARTHRITIS PATIENTS: A NORD-STAR SPIN-OFF STUDY
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 40-41
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Patients with rheumatoid arthritis (RA) are at an increased risk of venous thromboembolism. Thus far, there have not been any comparative studies investigating the effects of initial antirheumatic treatments in (very) early RA patients.ObjectivesTo assess the effects of different initial treatments on hemostatic parameters in patients with early RA.MethodsNORD-STAR is an international, multicentre, open-label, assessor-blinded, phase 4 study where patients with newly diagnosed RA started methotrexate (MTX) and were randomised 1:1:1:1 to a) conventional treatment (either prednisolone tapered to 5mg/day, or sulfasalazine combined with hydroxychloroquine and intra-articular corticosteroids), b) certolizumab pegol, c) abatacept, d) tocilizumab1. This study is a spin-off from the main NORD-STAR study extensively investigating hemostatic system in 24 per protocol consecutive Dutch participants at baseline, 12 weeks and 24 weeks after the start of the treatment. Statistical analysis was done using paired samples t-test in SPSS version 28.ResultsThe mean age of investigated patients was 51.8 (± 12.7) years and 58.3% were female. At baseline patients had an average DAS28 score of 4.6 (± 0.9) and had elevated levels of investigated coagulation biomarkers: Factor 1 + 2, fibrinogen, D-dimer and parameters of the two global hemostatic assays, i.e. endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). These biomarkers decreased significantly at 12 and 24 weeks in patients in all groups (Table 1). Overall fibrinolytic potential (OFP) was decreased and clot lysis time (CLT) was prolonged at baseline, demonstrating impaired fibrinolytic activity in early RA. The reduction of coagulation parameters was significantly higher in biological treatment arms in comparison to the standard MTX treatment arm. In addition, tocilizumab was more effective compared to certolizumab and abatacept, (Figure 1), which was expected considering the direct inhibitory effect of this drug on the IL-6 synthesis and consequently the coagulation activation as well. After 24 weeks of treatment with methotrexate and tocilizumab, the average fibrinogen of patients was reduced by 63% vs 31% and 36% in the certolizumab and abatacept groups, respectively. The changes in DAS-28 and the changes in fibrinogen had a correlation of 0.385 which did not reach statistical significance.Table 1.Measurements are marked with * if p<0.05, ** if p<0.01 and *** if p<0.001BaselineW12W24Factor 1 + 2 (pmol/L)270.25 (149.4)190.36 (108.6)**179.52 (85.3)***Fibrinogen (g/L)4.64 (1.5)3.61 (1.6)**2.63 (1.2)***D-dimer (mg/L)2.17 (3.0)0.33 (0.23)**0.29 (0.2)**OHP (Abs-sum)157.38 (64.9)120.62 (68.7)*100.49 (53.8)***OCP (Abs-sum)369.52 (58.8)305.04 (101.7)*275.91 (83.1)***OFP (%)57.97 (13.1)63.20 (12.7)*65.25 (11.4)***Lag time (s)304.5 (71.1)306.8 (71.8)312.7 (65.4)Slope0.07 (0.02)0.066 (0.03)0.094 (0.12)Max Abs1.17 (0.3)1.00 (0.4)*0.91 (0.3)**CLT (s)1405 (356)1317 (377)1231 (320)**ETP (nM*min)1480 (471)1395 (395)*1337 (429)*Peak (nM)231 (78)223 (68)223 (74)Lagtime (min)4.06 (2.1)3.28 (1.2)**2.87 (1.0)***ttPeak (min)7.40 (2.2)6.61 (1.5)*6.13 (1.4)**Figure 1.ConclusionOur results indicate an enhanced coagulation and fibrinolytic impairment in newly diagnosed RA patients. Effective antirheumatic treatments reduce this hemostatic imbalance, with significantly more pronounced effects of biologic drugs compared to conventional (MTX+glucocorticoids) treatment.References[1]Hetland M et al. BMJ. 2020Disclosure of InterestsBas Dijkshoorn: None declared, Aleksandra Antovic: None declared, Daisy Vedder: None declared, Anna Rudin: None declared, Dan Nordström Speakers bureau: Novartis, UCB, Consultant of: Abbvie, BMS, Lilly, Novartis, Pfizer, Roche, UCB, Björn Gudbjornsson Speakers bureau: Amgen and Novartis - not related to this work, Consultant of: Novartis - not related to this work, Kristina Lend: None declared, Till Uhlig Speakers bureau: Grünenthal, Novartis, Consultant of: Grünenthal, Novartis, Grant/research support from: NORDFORSK, Espen A Haavardsholm Consultant of: Pfizer, AbbVie, Celgene, Novartis, Janssen, Gilead, Eli-Lilly, UCB, Grant/research support from: NORDFORSK, Norwegian Regional Health Authorities, South-Eastern Norway Regional Health Authority, Gerdur Gröndal: None declared, Merete Lund Hetland Consultant of: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Grant/research support from: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Marte Heiberg: None declared, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Orion, Pfizer, Roche and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, Amgen, BMS, Merck, Celgene and Novartis, Kim Hørslev-Petersen: None declared, Jon Lampa Speakers bureau: Pfizer, Janssen, Novartis, Ronald van Vollenhoven Speakers bureau: Abbvie, Galapagos, GSK, Janssen, Pfizer, R-Pharma, UCB, Consultant of: Abbvie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pifzer, UCB, Grant/research support from: BMS, GSK, UCB, Michael Nurmohamed Speakers bureau: Abbvie, Janssen, Celgene, Consultant of: Abbvie, Grant/research support from: Abbvie, Amgen, Pfizer, Galapagos, BMS.
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| 25. |
- Glinatsi, D., et al.
(författare)
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Head-to-head comparison of aggressive conventional therapy and three biological treatments and comparison of two de-escalation strategies in patients who respond to treatment: Study protocol for a multicenter, randomized, open-label, blinded-assessor, phase 4 study
- 2017
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: New targeted therapies and improved treatment strategies have dramatically improved the outcomes of patients with rheumatoid arthritis (RA). However, it is unknown whether different early aggressive interventions can induce stable remission or a low-active disease state that can be maintained with conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy, and whether they differ in efficacy and safety. The Nordic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) study will assess and compare (1) the proportion of patients who achieve remission in a head-to-head comparison between csDMARD plus glucocorticoid therapy and three different biological DMARD (bDMARD) therapies with different modes of action and (2) two de-escalation strategies in patients who respond to first-line therapy. Methods/design: In a pragmatic, 80-160-week, multicenter, randomized, open-label, assessor-blinded, phase 4 study, 800 patients with early RA (symptom duration less than 24 months) are randomized 1:1:1:1 to one of four different treatment arms: (1) aggressive csDMARD therapy with methotrexate + sulphasalazine + hydroxychloroquine + i.a. glucocorticoids (arm 1A) or methotrexate + prednisolone p.o. (arm 1B), (2) methotrexate + certolizumab-pegol, (3) methotrexate + abatacept, or (4) methotrexate + tocilizumab. The primary clinical endpoint is the proportion of patients reaching Clinical Disease Activity Index (CDAI) remission at week 24. Patients in stable remission over 24 consecutive weeks enter part 2 of the study earliest after 48 weeks. Patients not achieving sustained CDAI remission over 24 consecutive weeks, exit the study after 80 weeks. In part 2, patients are re-randomized to two different de-escalation strategies, either immediate or delayed (after 24 weeks) tapering, followed by cessation of study medication. All patients remain on stable doses of methotrexate. The primary clinical endpoint in part 2 is the proportion of patients in remission (CDAI ≤2.8) 24 weeks after initiating treatment de-escalation. Radiographic assessment will be performed regularly throughout the trial, and blood and urine samples will be stored in a biobank for later biomarker analyses. Discussion: NORD-STAR is the first investigator-initiated, randomized, early RA trial to compare (1) csDMARD and three different bDMARD therapies head to head and (2) two different de-escalation strategies. The trial has the potential to identify which treatment strategy to apply in early RA to achieve the best possible outcomes for both patients and society. Trial registration:NCT01491815and NCT02466581. Registered on 8 December 2011 and May 2015, respectively. EudraCT: 2011-004720-35 © 2017 The Author(s).
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| 27. |
- Stevens, D, et al.
(författare)
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PLASMA CALPROTECTIN WAS ASSESSED IN MULTIPLE BIOLOGICAL TREATMENT STRATEGIES FOR EARLY RHEUMATOID ARTHRITIS
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 515-515
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Plasma calprotectin is a sensitive inflammatory marker in patients with rheumatoid arthritis (RA) and reflects activation of granulocytes and macrophages. Plasma calprotectin has not previously been studied in a head-to-head trial of multiple biological mechanisms of action versus active conventional therapy (ACT) with methotrexate and prednisolone.ObjectivesTo assess the effect of treatment on plasma calprotectin levels in patients with early RA by determining the 24-week change in the four arms of the NORD-STAR Study, a large multicenter randomized head-to-head clinical trial of ACT versus tumor necrosis factor inhibition, T-cell co-stimulation inhibition, and interleukin-6 inhibition (1).MethodsCalprotectin was analyzed in plasma samples at baseline, week 4 and week 24 from 400 treatment naïve patients with early RA in the NORD-STAR Study. Samples were analyzed using a calprotectin ELISA alkaline phosphatase (ALP) kit from CalproLab (Oslo, Norway) in a Dynex DS2 processing system (normal levels <910 µg/L). Patients were assessed by clinical (CRP, 28 SJC/TJC, physician global) and patients’ reported assessments. Crude and adjusted linear regression analyses were performed in R 4.0.3 with calprotectin levels at week 24 as the outcome. The four arms were represented by three dummy variables. The adjustment variables were age, sex, anti-CCP status and country. Both analyses were adjusted for baseline calprotectin levels.ResultsAt baseline, the mean time since diagnosis was 15.7 days (SD) (22.9), mean age 53.7 (15.0) years, ACPA positive 81%, and female 66%. Mean calprotectin levels were 1931 (1495) µg/L at baseline, 866 (951) µg/L at week 4, and 629 (661) µg/L at week 24. At baseline, normal calprotectin levels (<910 µg/L) were observed in 27% of all patients (ACT 22%, certolizumab-pegol and methotrexate 30%, abatacept and methotrexate 25%, tocilizumab and methotrexate 31%). At week 24, normal calprotectin levels were observed in 82% of all patients (ACT 68%, certolizumab-pegol and methotrexate 91%, abatacept and methotrexate 80%, tocilizumab and methotrexate 90%).Observed calprotectin levels at week 24 were significantly lower in patients treated with certolizumab-pegol and methotrexate -336µg/L (97) (p< 0.006) or tocilizumab and methotrexate -284 (99) (p < 0.004), versus ACT when adjusted for age, sex, anti-CCP status, baseline calprotectin level, and country; however, a significant difference was not observed in patients treated with abatacept and methotrexate -110 (96) (p = 0.25). The Figure 1 shows the average percentage change in calprotectin levels from baseline to week 24 for all treatment groups.Figure 1.Average percentage change in calprotectin levels from baseline to week 24. ACT: active conventional therapy, CZP+MTX: certolizumab-pegol and methotrexate, ABA+MTX: abatacept and methotrexate, TCZ+MTX: tocilizumab and methotrexate.ConclusionCalprotectin, a sensitive biomarker of inflammation, normalized in the majority of patients. The decline differed between treatment groups and was largest in patients treated with a TNF inhibitor and methotrexate, suggesting that calprotectin reflects the activity of specific inflammatory pathways rather than overall inflammation. The findings of this study should be further explored.References[1]Hetland ML, et. al., Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial. BMJ. 2020 Dec 2;371:m4328. doi: 10.1136/bmj.m4328. PMID: 33268527; PMCID: PMC7708829.AcknowledgementsI would like to acknowledge the NORD-STAR Study group.Disclosure of InterestsDavid Stevens: None declared, Marte Heiberg: None declared, Amirhossein Kazemi: None declared, Ronald van Vollenhoven: None declared, Jon Lampa: None declared, Anna Rudin: None declared, Kristina Lend: None declared, Merete Lund Hetland: None declared, Mikkel Østergaard: None declared, Michael Nurmohamed: None declared, Kim Hørslev-Petersen: None declared, Dan Nordström Consultant of: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Björn Gudbjornsson: None declared, Till Uhlig: None declared, Espen A Haavardsholm: None declared, Hilde Berner Hammer Speakers bureau: AbbVie, Novartis, and Lilly.
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| 30. |
- Zhang, Yuan, et al.
(författare)
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Adiponectin Associates with Rheumatoid Arthritis Risk in Overweight and Obesity Independently of Other Adipokines
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 10:13
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Tidskriftsartikel (refereegranskat)abstract
- We recently reported that increased serum adiponectin was associated with rheumatoid arthritis (RA) risk in subjects with obesity. We hereby aim to determine if other adipokines associate with RA risk and if the association between adiponectin and RA is independent of other adipokines. Two nested-case control studies were performed in two different cohorts: 82 participants of the Swedish Obese Subjects (SOS) study who developed RA during follow-up matched with 410 controls, and 88 matched pairs from the Medical Biobank of Northern Sweden. Baseline levels of circulating adipokines were measured using ELISA. In a multivariable analysis in the SOS cohort, higher adiponectin was associated with an increased risk of RA independently of other adipokines (OR for RA risk: 1.06, 95% CI: 1.01-1.12, p = 0.02). No association between leptin, resistin, and visfatin levels and the risk of RA was detected. In the cohort from the Medical Biobank of Northern Sweden, higher adiponectin was associated with an increased risk of RA only in participants with overweight/obesity (OR: 1.17, 95% CI: 1.01-1.36, p = 0.03), independently of other adipokines. Our results show that in individuals with overweight/obesity, higher circulating levels of adiponectin, but not leptin, resistin, or visfatin, were associated with an increased RA risk.
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| 31. |
- Zhang, Y, et al.
(författare)
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Elevated adiponectin predicts the development of rheumatoid arthritis in subjects with obesity
- 2020
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 49:6, s. 452-460
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the current study is to determine whether baseline serum adiponectin levels predict the development of rheumatoid arthritis (RA). Method: The current report includes 3693 individuals from the Swedish Obese Subjects (SOS) study. The original SOS study is a longitudinal non-randomized controlled study aiming to assess the effect of bariatric surgery on obesity-related mortality and morbidity. Participants included in the present report had adiponectin measurement available at baseline and no prevalent RA. The diagnosis of RA was retrieved through the Swedish National Patient Register. Results: During a follow-up for up to 29years, 82 study participants developed RA. Elevated baseline adiponectin levels were associated with a higher risk of developing RA independently of other factors, including C-reactive protein (CRP) and smoking [hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.12–2.60 for an increase in adiponectin of 10 mg/L, p =0.01]. After stratifying the population according to adiponectin and CRP median at baseline, study participants with both adiponectin and CRP above the median had a higher risk of developing RA compared to subjects with adiponectin and CRP below the median (HR 2.80, 95% CI 1.25–6.31, p =0.01). Conclusions: In this cohort of subjects with obesity followed up for up to 29years, high serum adiponectin levels at baseline were associated with an increased risk for RA. Moreover, subjects with both high adiponectin and CRP levels at baseline were at particular risk of developing RA. ClinicalTrials.gov Identifier: NCT01479452. © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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| 32. |
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| 33. |
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| 34. |
- Aldridge, Jonathan, et al.
(författare)
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Sex-based differences in association between circulating T cell subsets and disease activity in untreated early rheumatoid arthritis patients
- 2018
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is not known if sex-based disparities in immunological factors contribute to the disease process in rheumatoid arthritis (RA). Hence, we examined whether circulating T cell subset proportions and their association with disease activity differed in male and female patients with untreated early rheumatoid arthritis (ueRA). Methods: Proportions of T cell subsets were analyzed in peripheral blood from 72 ueRA DMARD-and corticosteroid-naive patients (50 females and 22 males) and in 31 healthy age-and sex-matched controls. Broad analysis of helper and regulatory CD4(+) T cell subsets was done using flow cytometry. Disease activity in patients was assessed using DAS28, CDAI, swollen joint counts, tender joint counts, CRP, and ESR. Results: Multivariate factor analyses showed that male and female ueRA patients display distinct profiles of association between disease activity and circulating T cell subset proportions. In male, but not female, ueRA patients Th2 cells showed a positive association with disease activity and correlated significantly with DAS28-ESR, CDAI, and swollen and tender joint counts. Likewise, proportions of non-regulatory CTLA-4(+) T cells associated positively with disease activity in male patients only, and correlated with DAS28-ESR. In contrast, there was a negative relation between Th1Th17 subset proportions and disease activity in males only. The proportions of Th17 cells correlated positively with DAS28-ESR in males only, while proportions of Th1 cells showed no relation to disease activity in either sex. There were no significant differences in proportions of T cell subsets between the sexes in patients with ueRA. Conclusions: Our findings show sex-based differences in the association between T cell subsets and disease activity in ueRA patients, and that Th2 helper T cells may have a role in regulating disease activity in male patients.
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| 35. |
- Andersson, Maria L.E., et al.
(författare)
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Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis
- 2023
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:7, s. 1110-1119
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Tidskriftsartikel (refereegranskat)abstract
- Objective. This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints.Methods. We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead-based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n = 2,110), Swedish age- and sex-matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE).Results. Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98-100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19-26%) of early RA patients seronegative for anti-cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE.Conclusion. A multiplex immunoassay with peptides from disease-related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA.
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| 36. |
- Axelsson, H, et al.
(författare)
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Differential Optical Absorption Spectroscopy (DOAS) Measurements of Ozone in the 280--290 nm Wavelength Region
- 1990
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Ingår i: Applied Spectroscopy. - : SAGE Publications. - 1943-3530 .- 0003-7028. ; 44:10, s. 1654-1658
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Tidskriftsartikel (refereegranskat)abstract
- The differential absorption structure of the ozone spectrum between 250 and 330 nm has been investigated in order to determine the optimal wavelength region to be utilized for active differential optical absorption spectroscopy (DOAS) measurements. Considering aspects of atmospheric attenuation and interference from other species as well as the magnitude of the differential absorption cross section, an interval around 283 nm was found to be a good candidate for this application. This result was also verified during 12 months of continuous ozone monitoring in an urban environment.
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| 37. |
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| 38. |
- Drevinge, Christina, 1983, et al.
(författare)
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Intermediate monocytes correlate with CXCR3(+) Th17 cells but not with bone characteristics in untreated early rheumatoid arthritis
- 2021
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Rheumatoid arthritis (RA) is associated with development of generalized osteoporosis. Bone-degrading osteoclasts are derived from circulating precursor cells of monocytic lineage, and the intermediate monocyte population is important as osteoclast precursors in inflammatory conditions. T cells of various subsets are critical in the pathogenesis of both RA and associated osteoporosis, but so far, no studies have examined associations between circulating intermediate monocytes, T cell subsets and bone characteristics in patients with RA. The aim of this study was to investigate the frequency of intermediate monocytes in patients with untreated early rheumatoid arthritis (ueRA) compared to healthy controls (HC), and to explore the correlation between intermediate monocytes and a comprehensive panel of T helper cell subsets, bone density and bone microarchitecture in ueRA patients. Methods 78 patients with ueRA fulfilling the ACR/EULAR 2010 criteria were included and compared to 29 age- and sex-matched HC. Peripheral blood samples were obtained before start of treatment and proportions of monocyte subsets and CD4(+) helper and regulatory T cell subsets were analyzed by flow cytometry. Bone densitometry was performed on 46 of the ueRA patients at inclusion using DXA and HR-pQCT. Results Flow cytometric analyses showed that the majority of ueRA patients had frequencies of intermediate monocytes comparable to HC. The intermediate monocyte population correlated positively with CXCR3(+) Th17 cells in ueRA patients but not in HC. However, neither the proportions of intermediate monocytes nor CXCR3(+) Th17 cells were associated with bone density or bone microarchitecture measurements. Conclusions Our findings suggest that in early RA, the intermediate monocytes do not correlate with bone characteristics, despite positive correlation with circulating CXCR3(+) Th17 cells. Future longitudinal studies in patients with longer disease duration are required to fully explore the potential of intermediate monocytes to drive bone loss in RA.
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| 39. |
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| 40. |
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| 41. |
- Herrick, Ariane L, et al.
(författare)
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Treatment outcome in early diffuse cutaneous systemic sclerosis : The European Scleroderma Observational Study (ESOS)
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:7, s. 1207-1218
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.
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| 42. |
- Holdfeldt, André, et al.
(författare)
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Reactivation of Gαi-coupled formyl peptide receptors is inhibited by Gαq-selective inhibitors when induced by signals generated by the platelet-activating factor receptor.
- 2017
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Ingår i: Journal of Leukocyte Biology. - 0741-5400. ; 102:3, s. 871-880
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Tidskriftsartikel (refereegranskat)abstract
- Formyl peptide receptor (FPR)-desensitized neutrophils display increased production/release of superoxide (O2(-)) when activated by platelet-activating factor (PAF), a priming of the response achieved through a unique receptor crosstalk mechanism. The aim of this study was to determine the effect of an inhibitor selective for small, heterotrimeric G proteins belonging to the Gαq subclass on that receptor crosstalk. We show that signals generated by FPRs and the PAF receptor (PAFR) induce activation of the neutrophil O2(-), producing NADPH-oxidase, and that response was sensitive to Gαq inhibition in cells activated by PAF, but no inhibition was obtained in cells activated by FPR agonists. Signaling in naive neutrophils is terminated fairly rapidly, and the receptors become homologously desensitized. The downstream sensitivity to Gαq inhibition in desensitized cells displaying increased production/release of O2(-) through the PAFR receptor crosstalk mechanism also comprised the reactivation of the FPRs, and the activation signals were redirected from the PAFR to the desensitized/reactivated FPRs. The Gαq-dependent activation signals generated by the PAFRs activate the Gαi-coupled FPRs, a receptor crosstalk that represents a novel pathway by which G protein-coupled receptors can be regulated and signaling can be turned on and off.
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| 43. |
- Kundakci, Burak, et al.
(författare)
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International, multidisciplinary Delphi consensus recommendations on non-pharmacological interventions for fibromyalgia
- 2022
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Ingår i: Seminars in Arthritis & Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 57
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To develop evidence-based expert recommendations for non-pharmacological treatments for pain, fatigue, sleep problems, and depression in fibromyalgia.Methods: An international, multidisciplinary Delphi exercise was conducted. Authors of EULAR and the Canadian Fibromyalgia Guidelines Group, members of the American Pain Society and clinicians with expertise in fibromyalgia were invited. Participants were asked to select non-pharmacological interventions that could be offered for specific fibromyalgia symptoms and to classify them as either core or adjunctive treatments. An evidence summary was provided to aid the decision making. Items receiving >70% votes were accepted, those receiving <30% votes were rejected and those obtaining 30-70% votes were recirculated for up to two additional rounds.Results: Seventeen experts participated (Europe (n = 10), North America (n = 6), and Israel (n = 1)) in the Delphi exercise and completed all three rounds. Aerobic exercise, education, sleep hygiene and cognitive behavioural therapy were recommended as core treatments for all symptoms. Mind-body exercises were recommended as core interventions for pain, fatigue and sleep problems. Mindfulness was voted core treatment for depression, and adjunctive treatment for other symptoms. Other interventions, namely music, relaxation, hot bath, and local heat were voted as adjunctive treatments, varying between symptoms.Conclusions: This study provided evidence-based expert consensus recommendations on non-pharmacological treatments for fibromyalgia that may be used to individualise treatments in clinical practice targeting the diverse symptoms associated with fibromyalgia.
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| 44. |
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| 45. |
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| 46. |
- Lonnblom, E, et al.
(författare)
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AUTOANTIBODIES TO JOINT PROTEINS AS NOVEL BIOMARKERS FOR THE DIAGNOSIS OF UNTREATED EARLY RHEUMATOID ARTHRITIS
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 546-546
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Autoantibodies to citrullinated protein (ACPA; measured as anti-CCP; aCCP) and rheumatoid factor (RF) appear years before clinical onset of RA and are essential tools in today’s classification criteria for RA. In animal models, antibodies to joint specific proteins (JP) can induce arthritis, and they are also present at onset of RA [1]. As there is a need for increased precision for early diagnosis of RA as well as identification of different subtypes of the disease, we aim to assess whether autoantibodies to native or modified JP can be used for early and precise diagnosis of RA.ObjectivesTo study whether antibodies to JP, alone or in combination with ACPA/RF, could increase the diagnostic sensitivity and specificity in untreated early (ue)RA patients.MethodsAntibodies to JP were analysed in serum from patients in three independent ueRA cohorts as well as from population controls without rheumatic diseases (WINGA, Gothenburg and MFM-ÅUS, Malmö n=1062). ERAp (n=66), the smallest and most recent cohort was chosen for screening, and BARFOT and TIRA-2 (n=1939) for validation. We have developed a bead-based multianalyte flow immunoassay [2] and screened approx. 350 peptides derived from JPs of interest. We included monoclonal antibodies as assay calibrators and determined limit of detection (LoD). To assess positivity for autoantibodies to JP of interest above LoD, we used 5MAD (median absolute deviation) of the control populations as the cut-off.ResultsIn the ERAp cohort, 5 autoantibodies discriminated RA patients from controls with 81% sensitivity and 100% specificity (Table 1). The same autoantibodies had 68% sensitivity and 98% specificity in the combined BARFOT and TIRA-2 cohorts. Together with RF and aCCP, only 2 of the 5 autoantibodies added statistically significant diagnostic value, increasing the sensitivity from 48% to 61% with 99% specificity. In aCCP- and RF-negative ueRA patients (n=536), the novel biomarkers identified 22.5% of the patients with 99% specificity compared to controls.Table 1.Diagnostic capacity of the joint-specific antibodiesTest panelPerformanceGroup of patientsaCCP+RF+JP+SensitivitySpecificityAUC(ROC)ERApAll patients (n=66)--X81%100%89%RF and aCCP-neg patients (n=7)1------BARFOT and TIRA-2, combined dataAll patients (N=1939)--X68%98%86%All patients (N=1939)X--58%99%78%All patients (N=1939)2XX-48%100%84%All patients (N=1939)2, 3XXX61%99%86%RF and/or aCCP-pos patients (N=1403)--X84%99%93%RF and aCCP-neg patients (N=536)--X22%99%67%RA, literature valuesAnti-CCP testXN/AN/A53–71%95–96%N/A1Not analysed due to lack of power2This patient population is both aCCP+ and RF+3Only 2 of the 5 autoantibodies added statistically significant to the diagnostic valueAUC, Area under the curve; ROC, receiver operating characteristic curve; N/A, not applicable. Controls without rheumatic diseases: N=935 for BARFOT / TIRA-2 and N=27 for ERAp.ConclusionAutoantibodies to JP discriminate ueRA patients better then aCCP and RF alone and add an increased diagnostic value in particular for seronegative patients.References[1]Holmdahl, R., V. Malmstrom, and H. Burkhardt, Autoimmune priming, tissue attack and chronic inflammation - the three stages of rheumatoid arthritis. Eur J Immunol, 2014. 44(6): p. 1593-9.[2]Viljanen, J., et al., Synthesis of an Array of Triple-Helical Peptides from Type II Collagen for Multiplex Analysis of Autoantibodies in Rheumatoid Arthritis. ACS Chem Biol, 2020. 15(9): p. 2605-2615. Correction: ACS Chem Biol, 2020. 15(11): p. 3072AcknowledgementsBARFOT study group.Disclosure of InterestsErik Lönnblom: None declared, Monica Leu Agelii: None declared, Outi Sareila Employee of: Part time employee in Vacara AB, Ingiäld Hafström: None declared, Maria Andersson: None declared, Lei Cheng: None declared, Göran Bergström: None declared, Anna-Karin H Ekwall: None declared, Anna Rudin: None declared, Alf Kastbom: None declared, Christopher Sjowall: None declared, Bingze Xu: None declared, Lennart T.H. Jacobsson: None declared, Johan Viljanen: None declared, Jan Kihlberg: None declared, Inger Gjertsson: None declared, Rikard Holmdahl Shareholder of: Rikard Holmdahl the founder of Vacara AB.
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| 47. |
- Maglio, Cristina, 1983, et al.
(författare)
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Bariatric Surgery and the Incidence of Psoriasis and Psoriatic Arthritis in the Swedish Obese Subjects Study.
- 2017
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Ingår i: Obesity. - : Wiley. - 1930-739X .- 1930-7381. ; 25:12, s. 2068-2073
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess the effect of bariatric surgery (vertical gastroplasty, gastric banding, or gastric bypass) compared with usual care on the incidence of psoriasis and psoriatic arthritis (PsA) in the Swedish Obese Subjects study.This report includes 1,991 subjects who underwent bariatric surgery and 2,018 controls with obesity from the SOS study; none of them had psoriasis or PsA at baseline. Information about psoriasis and PsA diagnosis was retrieved through the Swedish National Patient Register and questionnaires.During follow-up for up to 26 years, bariatric surgery was associated with a lower incidence of psoriasis compared with usual care (number of events=174; hazard ratio 0.65; 95% CI: 0.47-0.89; P=0.008). Both smoking and a longer duration of obesity were independently associated with a higher risk for psoriasis. No significant difference was detected among the three surgical procedures in terms of lowering the risk of developing psoriasis. The association between bariatric surgery and psoriasis incidence was not influenced by baseline confounders. No significant difference in the risk of developing PsA (number of events=46) was detected when comparing the surgery and the control groups.This study shows that bariatric surgery is associated with a lower risk of developing psoriasis compared with usual care.
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| 48. |
- Maglio, Cristina, et al.
(författare)
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Bariatric surgery and the incidence of rheumatoid arthritis - a Swedish Obese Subjects study.
- 2020
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 59:2, s. 303-309
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine the effect of bariatric surgery on the incidence of RA in participants of the Swedish Obese Subjects (SOS) study.The SOS is a longitudinal study aiming to assess the effect of bariatric surgery on mortality and obesity-related diseases. This report includes 2002 subjects with obesity who underwent bariatric surgery and 2034 matched controls; none of them had RA at baseline. Cases of incident RA were identified through the Swedish National Patient Register by searching for International Classification of Diseases codes. Both intention-to-treat analyses and per-protocol analyses are reported. In the per-protocol analysis, participants from the control group who underwent bariatric surgery later on during follow-up were censored at the time of surgery.During follow-up, 92 study participants developed RA. The median follow-up was 21 years (range 0-29). Bariatric surgery was neither associated with the incidence of RA in the intention-to-treat analysis [hazard ratio (HR) 0.92 (95% CI 0.59, 1.46), P = 0.74], nor in the per-protocol analysis [HR 0.86 (95% CI 0.54, 1.38), P = 0.53]. Weight change at the 2 year follow-up, expressed as the change in BMI compared with baseline, did not associate with the development of RA. Higher serum CRP levels and smoking associated with the future development of RA independent of other factors.We did not detect any association between bariatric surgery and the incidence of RA in subjects affected by obesity followed up for up to 29 years.(http://clinicaltrials.gov): NCT01479452.
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| 49. |
- Maglio, Cristina, 1983, et al.
(författare)
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Effects of bariatric surgery on gout incidence in the Swedish Obese Subjects study: a non-randomised, prospective, controlled intervention trial.
- 2017
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:4, s. 688-693
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Tidskriftsartikel (refereegranskat)abstract
- To assess the long-term effect of bariatric surgery on the incidence of gout and hyperuricaemia in participants of the Swedish Obese Subjects (SOS) study.This report includes 1982 subjects who underwent bariatric surgery and 1999 obese controls from the SOS study, a prospective intervention trial designed to assess the effect of bariatric surgery compared with conventional treatment. None of the subjects had gout at baseline. An endpoint on gout incidence was created based on information on gout diagnosis and use of gout medications through national registers and questionnaires. Median follow-up for the incidence of gout was about 19years for both groups. Moreover, the incidence of hyperuricaemia over up to 20years was examined in a subgroup of participants having baseline uric acid levels <6.8mg/dL.Bariatric surgery was associated with a reduced incidence of gout compared with usual care (adjusted HR 0.60, 95% CI 0.48 to 0.75, p<0.001). The difference in absolute risk between groups was 3 percentage points at 15years, and the number of subjects needed to be treated by bariatric surgery to prevent one incident gout event was 32 (95% CI 22 to 59). The effect of bariatric surgery on gout incidence was not influenced by baseline risk factors, including body mass index. During follow-up, the surgery group had a lower incidence of hyperuricaemia (adjusted HR 0.47, 95% CI 0.39 to 0.58, p<0.001). The difference in absolute risk between groups was 12 percentage points at 15years, and the number of participants needed to be treated by bariatric surgery to prevent hyperuricaemia was 8 (95% CI 6 to 13).Bariatric surgery prevents gout and hyperuricaemia in obese subjects.NCT01479452; Results.
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| 50. |
- Pandya, Jayesh M., et al.
(författare)
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Blood chemokine profile in untreated early rheumatoid arthritis: CXCL10 as a disease activity marker
- 2017
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 The Author(s).Background: We have recently analyzed the profile of T-cell subtypes based on chemokine receptor expression in blood from untreated early rheumatoid arthritis (ueRA) patients compared to healthy controls (HC). Here, we compared the levels of the respective chemokines in blood plasma of ueRA patients with those of HC. We also studied the association of chemokine levels with the proportions of circulating T-cell subsets and the clinical disease activity. Methods: Peripheral blood was obtained from 43 patients with ueRA satisfying the ACR 2010 criteria and who had not received any disease-modifying anti-rheumatic drugs (DMARD) or prednisolone, and from 14 sex- and age-matched HC. Proportions of T helper cells in blood, including Th0, Th1, Th2, Th17, Th1Th17, TFh, and regulatory T cells, were defined by flow cytometry. Fifteen chemokines, including several CXCL and CCL chemokines related to the T-cell subtypes as well as to other major immune cells, were measured in blood plasma using flow cytometry bead-based immunoassay or ELISA. Clinical disease activity in patients was evaluated by assessing the following parameters: Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), swollen joint counts (SJC), tender joint counts (TJC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The data were analyzed using multivariate factor analyses followed by univariate analyses. Results: Multivariate discriminant analysis showed that patients with ueRA were separated from HC based on the blood plasma chemokine profile. The best discriminators were CXCL9, CXCL10, CXCL13, CCL4, and CCL22, which were significantly higher in ueRA compared to HC in univariate analyses. Among the chemokines analyzed, only CXCL10 correlated with multiple disease activity measures, including DAS28-CRP, DAS28-ESR, CDAI, SJC in 66 joints, CRP, and ESR. Conclusions: High circulating levels of CXCL10 in the plasma of ueRA patients and the association with the clinical disease activity suggests that CXCL10 may serve as a disease activity marker in early rheumatoid arthritis.
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