| 1. |
- Askling, Johan, et al.
(författare)
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Is Rheumatoid Arthritis a Mortal Disease?
- 2017
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Ingår i: Arthritis & Rheumatology. - : Wiley-Blackwell. - 2326-5191 .- 2326-5205. ; 69:8, s. 1509-1511
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Brink, Mikael, et al.
(författare)
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Anti-citrullinated protein antibody specificities and pulmonary fibrosis in relation to genetic loci in early rheumatoid arthritis
- 2022
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 61:12, s. 4985-4990
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Pulmonary manifestations in RA are common comorbidities, but the underlying mechanisms are largely unknown. The added value of a multiplex of ACPA and genetic risk markers was evaluated for the development of pulmonary fibrosis (PF) in an inception cohort. Methods A total of 1184 patients with early RA were consecutively included and followed prospectively from the index date until death or 31 December 2016. The presence of 21 ACPA fine specificities was analysed using a custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden). Three SNPs, previously found related to PF were evaluated, rs2609255 (FAM13A), rs111521887 (TOLLIP) and rs35705950 (MUC5B). ACPA and genetic data were available for 841 RA patients, of whom 50 developed radiologically defined PF. Results In unadjusted analyses, 11 ACPA specificities were associated with PF development. In multiple variable analyses, six ACPA specificities were associated with increased risk of PF: vimentin (Vim)60-75, fibrinogen (Fib)beta 62-78 (72), Fib alpha 621-635, Bla26, collagen (C)II359-369 and F4-CIT-R (P < 0.01 to P < 0.05). The number of ACPA specificities was also related to PF development (P < 0.05 crude and adjusted models). In multiple variable models respectively adjusted for each of the SNPs, the number of ACPA specificities (P < 0.05 in all models), anti-Vim60-75 (P < 0.05, in all models), anti-Fib beta 62-78 (72) (P < 0.001 to P < 0.05), anti-CII359-369 (P < 0.05 in all models) and anti-F4-CIT-R AQ4 (P < 0.01 to P < 0.05), anti-Fib alpha 621-635 (P < 0.05 in one) and anti-Bla26 (P < 0.05 in two) were significantly associated with PF development. Conclusion The development of PF in an inception cohort of RA patients was associated with both presence of certain ACPA and the number of ACPA specificities and risk genes.
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| 3. |
- Delcoigne, Bénédicte, et al.
(författare)
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How does current disease activity in rheumatoid arthritis affect the short-term risk of acute coronary syndrome? : A clinical register based study from Sweden and Norway
- 2023
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Ingår i: European journal of internal medicine. - 0953-6205 .- 1879-0828. ; 115, s. 55-61
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To estimate short-term risks of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) as a function of current RA disease activity including remission.Methods: Data from clinical visits of RA patients in Sweden (SE) and Norway (NO) between January 1st 2012 until December 31st 2020 were used. At each visit, patient's disease activity was assessed including remission status (measured with several metrics). Through linkage to national health and death registers, patients were followed up for incident ACS up to six months from each visit. We compared the short-term risk of ACS in patients not in remission vs. in remission using Cox regression analyses with robust standard errors, adjusted for country and covariates (e.g., age, sex, prednisolone use, comorbidities). We also explored disease activity categories as exposure.Results: We included 212,493 visits (10,444 from Norway and 202,049 from Sweden) among 41,250 patients (72% women, mean age at visit 62 years). During the 6-month follow-ups, we observed 524 incident ACS events. Compared to patients in remission, patients currently not in remission had an increased rate of ACS: adjusted hazard ratio (95% confidence interval) 1.52 (1.24–1.85) with DAS28 metric. The crude absolute six-month risks were 0.2% for patients in remission vs. 0.4% for patients with DAS28 high disease activity. The use of alternative RA disease activity and remission metrics provided similar results.Conclusion: Failure to reach remission is associated with elevated short-term risks of ACS, underscoring the need for CV risk factor optimization in these patients.
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| 4. |
- Delcoigne, B., et al.
(författare)
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SHORT- AND LONGER-TERM RISKS FOR ACUTE CORONARY SYNDROME IN PATIENTS WITH RHEUMATOID ARTHRITIS STARTING TREATMENT WITH DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS : A COLLABORATIVE OBSERVATIONAL HEAD-TO-HEAD STUDY ACROSS FIVE NORDIC RHEUMATOLOGY REGISTERS
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80, s. 63-64
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid Arthritis (RA) is associated with increased cardiovascular co-morbidity including acute coronary syndrome (ACS), partly due to effects of systemic inflammation. Disease-modifying anti-rheumatic drugs (DMARDs) may reduce RA disease activity, but act through several pathways and may themselves have an impact on cardiovascular risks. Whether the risks of ACS associated with biologic (b) and targeted synthetic (ts) DMARDs differ is still unknown.Objectives:To assess and compare incidences of ACS during treatment of RA with etanercept (ETA), adalimumab (ADA), infliximab (INF), certolizumab pegol (CTZ), golimumab (GOL), rituximab (RIT), abatacept (ABA), tocilizumab (TCZ), baricitinib (BAR) or tofacitinib (TOF).Methods:We defined and pooled treatment cohorts of patients starting any of the above treatments between 2008 and 2017 from clinical rheumatology registers in Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE). One patient could contribute several treatment episodes. Age, sex, co-medication (methotrexate, prednisolone), number of previous b/tsDMARDs, CRP, comorbidities (cardiovascular (including ACS (defined as ICD-10: I20.0, I21.0-4, I21.9) and cerebrovascular disease, thromboembolic events, diabetes, hospitalized infection, cancer, kidney failure, COPD) and associated drugs were extracted and used as adjustment in Cox regression analyses comparing the incidence of ACS between treatments. We used several follow-up lengths (1, 2, and up to 5 years) and two different risk windows (ACS on drug [ending follow-up on treatment discontinuation] and ACS ever since treatment start [disregarding any treatment discontinuation]). We also stratified by age and number of previous b/tsDMARDs.Results:We included 40850 treatment courses in 24083 patients (DK 7271, FI 3732, NO 1540, and SE 11540; around 75% women). ETA was the most common treatment (27%) whereas BAR and TOF comprised <1%, and the other DMARDs 6-14% each. The proportions with a history of ACS at treatment start ranged from 1.2% (NO) to 1.8% (DK).We found 780 incident ACS events during 141 326 person-years (pyrs) in the 5-year follow-up time and “ACS ever since treatment start” risk window, resulting in a crude incidence rate of 5.5 events per 1000 pyrs. No event was recorded for BAR nor TOF, which also had the shortest follow-up. Adjusted hazard ratios (HR) increased slightly with longer follow-up times, but the two risk windows provided similar HRs. For the 5-year follow-up, RIT was associated with an increased risk of ACS compared to ETA (Table), while no association was observed for shorter follow-up times. Stratifying on age did not modify the associations. Separate analyses by number of previous b/tsDMARDs suggested that ABA (HR=1.8, 95% CI 1.0-3.3), INF (HR=2.2, 95% CI 1.0-4.6) and RIT (HR=1.9, 95% CI 1.1-3.4) were associated with increased risks of ACS compared to ETA in the subgroup of patients with two or more previous bDMARDs (Figure), whereas no differences were found among patients starting either drug as 1st/2nd bDMARD.Table 1.Comparisons of risks for ACS during a 5-year follow-up since start of bDMARD treatment.DrugN eventspyrsCrude incidence rate/ 1000 pyrsHR (95% CI)1ETA175359174.9ref.ADA115240934.81.0 (0.8-1.3)CTZ54141583.80.9 (0.6-1.2)GOL4090064.41.1 (0.8-1.5)INF106178036.01.2 (0.9-1.5)ABA70107956.51.1 (0.8-1.4)RIT158166229.51.3 (1.0-1.6)TCZ62128664.80.9 (0.5-1.2)BAR036TOF030Pyrs: person-years; HR: hazards ratio1 adjustment: see text.Conclusion:In this cohort including ≥ 24,000 patients followed for up to 5 years, the ACS incidence rate was 5.5/1000 pyrs, with RIT showing an increased risk compared to ETA. In clinical practice, the choice of bDMARD does not seem to influence ACS risk in the short term. In the longer term, differences in ACS risk between bDMARDs may reflect channeling to these, or truly differential effects in subpopulations of patients.Acknowledgements:Partly funded by Nordforsk and ForeumDisclosure of Interests:Bénédicte Delcoigne: None declared, Lotta Ljung: None declared, Sella Aa. Provan Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Boehringer- Ingelheim, Bente Glintborg Grant/research support from: Pfizer, BMS, AbbVie, Kathrine Lederballe Gron Grant/research support from: BMS, Merete L. 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, Niels Steen Krogh: None declared, Nina Trokovic: None declared, Heikki Relas Speakers bureau: Abbvie, Celgene, Pfizer, Grant/research support from: Abbvie, Celgene, Pfizer, Carl Turesson Speakers bureau: Abbvie, Bristol-Myers Squibb, Medac, Pfizer, Roche, Consultant of: Roche, Brigitte Michelsen Consultant of: Novartis (paid to employer), Grant/research support from: Novartis (paid to employer), Johan Askling Consultant of: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB. These entities have entered into agreements with Karolinska Institutet with JA as principal investigator, mainly in the context of safety monitoring of biologics via the ARTIS national safety monitoring system.
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| 5. |
- Delcoigne, Benedicte, et al.
(författare)
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Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs : Results from four Nordic countries
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 81:6, s. 789-797
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare the 1-year, 2-year and 5-year incidences of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) starting any of the biologic disease-modifying antirheumatic drugs (bDMARDs) currently available in clinical practice and to anchor these results with a general population comparator.Methods: Observational cohort study, with patients from Denmark, Finland, Norway and Sweden starting a bDMARD during 2008-2017. Time to first ACS was identified through register linkages. We calculated the 1-year, 2-year and 5-year incidence rates (IR) (on drug and ever since treatment start) and used Cox regression (HRs) to compare ACS incidences across treatments taking ACS risk factors into account. Analyses were further performed separately in subgroups defined by age, number of previous bDMARDs and history of cardiovascular disease. We also compared ACS incidences to an individually matched general population cohort.Results: 24 083 patients (75% women, mean age 56 years) contributing 40 850 treatment courses were included. During the maximum (5 years) follow-up (141 257 person-years (pyrs)), 780 ACS events occurred (crude IR 5.5 per 1000 pyrs). Overall, the incidence of ACS in RA was 80% higher than that in the general population. For all bDMARDs and follow-up definitions, HRs were close to 1 (etanercept as reference) with the exception of the 5-year risk window, where signals for abatacept, infliximab and rituximab were noted.Conclusion: The rate of ACS among patients with RA initiating bDMARDs remains elevated compared with the general population. As used in routine care, the short-term, intermediate-term and longer-term risks of ACS vary little across individual bDMARDs.
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| 6. |
- Delcoigne, Benedicte, et al.
(författare)
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The influence of patient demographics on disease activity measurments in theumatoid arthritis
- 2019
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 78, s. 1423-1424
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Several indexes have been constructed for the measurement of disease activity in rheumatoid arthritis (RA) patients, including the Disease Activity Score 28-joint count, which either includes the Erythrocyte Sedimentation Rate (DAS28ESR) or the C-reactive protein concentration (DAS28CRP), and the Clinical Disease Activity Index (CDAI). The categorization of the results of these three indexes into levels of disease activity (Remission, Low, Moderate and High) is used to assess patient outcomes, and to guide medical decisions regarding treatment. However, the different indexes can lead to somewhat different classification, and hence influence treatment decisions.1 Objectives: To investigate how DAS28ESR, DAS28CRP and CDAI indexes are associated to age and sex in RA patients. To investigate the agreement between indexes and between categories of disease activity levels.Methods: We identified a cohort of RA patients, registered in the Swedish Rheumatology Quality Register between January 1st2014 and December 31st2017. The indexes were obtained from the first visit at the time point of RA diagnosis, and at the visit registered at the start of a first ever biological treatment prescription. Linear models were used to investigate the correlation between the indexes, age and sex. The agreement between the indexes was explored with Bland-Altman plots. The agreement between disease activity levels was evaluated through kappa statistics.Results: Data were analyzed for 3855 RA patients (2576 women, mean age ±SD=60±15) at their first diagnosis visit and for 3062 RA patients (2313 women, mean age ±SD=57±14) at the start of their first biologic. Similar results for all subsequently described analyses were obtained at both time points. The correlation coefficient and 95% confidence interval (95%CI) between the indexes and age were 0.093 (0.063-0.124) for DAS28ESR and 0.055 (0.025-0.085) for DAS28CRP at the first visit, while CDAI was not correlated to age. There was no difference between men and women for CDAI and DAS28CRP, while DAS28ESR presented a mean difference of 0.1 unit between men and women. The agreement between categories of disease activity was moderate: at the RA diagnosis visit, the kappa statistics and 95% CI were: 0.63 (0.61-0.65) between DAS28ESR and DAS28CRP, 0.59 (0.57-0.61) between DAS28ESR and CDAI, and 0.55 (0.53-0.57) between DAS28CRP and CDAI. About 25% of the patients were classified differently. The Bland-Altman plot revealed that the difference between DAS28ESR and DAS28CRP depended on sex and slightly increased with age.Conclusion: Factors related to patient demographics might influence the results of disease activity indexes. This has a potential to affect clinical decisions, as the definition into disease activity categories can differ depending on the score used. This suggests the need to consider sex and age when defining such categories and interpreting results from these indexes.
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| 7. |
- Di Giuseppe, Daniela, et al.
(författare)
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Meat Consumption and Risk of Rheumatoid Arthritis in Women : A Population-Based Cohort Study
- 2018
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Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 70:S9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Purpose: Mixed results have been reported for the association between meat consumption and the risk of developing rheumatoid arthritis (RA). The aim of this study was to evaluate the association between red meat, particularly processed meat, and the risk of RA using data from a population-based cohort of women.Methods: We prospectively followed 35,600 women aged 48-83 years from the Swedish Mammography Cohort (SMC), between 2003 and 2014. Meat consumption was assessed with a 96-item self-administered questionnaire in 1997. A corresponding questionnaire data from 1987 was available, enabling identification of long-term meat consumption. The relative risk (RR) of RA associated with meat consumption and its 95% confidence interval (CI) were estimated using Cox proportional hazard regression models. Multivariable models were adjusted for age, body mass index, educational level, physical activity, use of dietary supplements, energy intake, and smoking.Results: During the 12 years of follow-up (381 456 person years), 368 new cases of rheumatoid arthritis were identified. Meat consumption was not associated with the development of RA in age-adjusted (RR=0.96 (95% CI: 0.69-1.32)) or multivariable adjusted (RR=1.08 (95%CI: 0.77-1.53)) models (Table 1). No association was observed either for consumption of type-specific meat, such as red meat (RR=1.08 (95% CI: 0.77-1.50)), processed meat (RR=0.84 (95% CI: 0.59-1.22)), or poultry (RR=0.88 (95% CI: 0.60-1.31)). , Women with a consistent long-term consumption of meat of >7 servings/week over a period of 10 years had no increased risk of RA, HR 1.19 (95% CI: 0.78-1.80), compared to women with a consistent consumption of <=4 servings/week.Conclusion: In this large population-based cohort study, meat consumption, in total, by sub-types, or over time, was not associated with the risk of RA development in women.
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| 8. |
- Forsblad-D’Elia, Helena, et al.
(författare)
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Biomechanical properties of common carotid arteries assessed by circumferential 2D strain and β stiffness index in patients with ankylosing spondylitis
- 2021
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 48:3, s. 352-360
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Ankylosing spondylitis (AS) is associated with an elevated risk of cardiovascular disease (CVD) related to atherosclerosis, preceded by arterial stiffness. We aimed to examine common carotid artery (CCA) biomechanical properties using ultrasound to calculate β stiffness index (indicating arterial stiffness) and, a more recently developed technique, 2-dimensional (2D) speckle tracking strain (indicating arterial motion and deformation, strain) to (1) compare with age- and sex-matched controls, and (2) analyze relationships between strain and stiffness with disease characteristics and traditional risk factors for CVD in patients with AS. Methods. In this cross-sectional study, a cohort of 149 patients with AS, mean age 55.3 ± 11.2 years, 102 (68.5%) men, and 146 (98%) HLA-B27–positive, were examined. Bilateral CCA were examined for circumferential 2D strain and β stiffness index. A subgroup of 46 patients was compared with 46 age- and sex-matched controls, both groups without hypertensive disease, diabetes, myocardial infarction, or stroke. Results. Mean bilateral circumferential 2D strain was lower in AS patients compared with controls (7.9 ± 2.6% vs 10.3 ± 1.9%, P < 0.001), whereas mean bilateral β stiffness index was higher (13.1 ± 1.7 mmHg/mm vs 12.3 ± 1.3 mmHg/mm, P = 0.02). In multivariable linear regression analyses, strain was associated with age, erythrocyte sedimentation rate, history of anterior uveitis, and treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARD) and/or biological DMARD (R2 0.33), while stiffness was associated with age (R2 0.19). Conclusion. Both CCA circumferential 2D strain and β stiffness index differed between patients with AS and controls. Strain was associated with AS-related factors and age, whereas only age was associated with stiffness, suggesting that the obtained results reflect different pathogenic vascular processes.
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| 9. |
- Forsblad-d'Elia, Helena, et al.
(författare)
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Biomechanical properties of common carotid arteries assessed by circumferential two-dimensional strain and β stiffness index in patients with ankylosing spondylitis
- 2021
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:3, s. 352-360
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Ankylosing spondylitis (AS) is associated with an elevated risk of cardiovascular disease (CVD) related to atherosclerosis, preceded by arterial stiffness. We aimed to examine common carotid artery (CCA) biomechanical properties using ultrasound to calculate β stiffness index (indicating arterial stiffness) and, a more recently developed technique, two-dimensional (2D) speckle tracking strain (indicating arterial motion and deformation, strain) to 1) compare with age- and sex-matched controls and to 2) analyze relationships between strain and stiffness with disease characteristics and traditional risk factors for CVD in AS patients.METHODS: In this cross-sectional study, a cohort of 149 patients with AS, mean age 55.3±11.2 years, 102(68.5%) men, 146 (98%) HLA-B27 positive, were examined. Bilateral CCAs were examined for circumferential 2D strain and β stiffness index. A subgroup of 46 patients were compared with 46 age- and sex-matched controls, both groups without hypertensive disease, diabetes, myocardial infarction or stroke.RESULTS: Mean bilateral circumferential 2D strain was lower in AS patients compared with controls, 7.9±2.6% vs 10.3±1.9%, p<0.001 whereas mean bilateral β stiffness index was higher, 13.1±1.6mmHg/mm vs 12.3±1.3mmHg/mm, p=0.018. In multivariable linear regression analyses strain was associated with age, erythrocyte sedimentation rate, history of anterior uveitis and treatment with csDMARD and/or bDMARD (R2 0.33), while stiffness was associated with age (R2 0.19).CONCLUSION: Both CCA circumferential 2D strain and β stiffness index differed between AS patients and controls. Strain was associated with AS-related factors and age while stiffness with age, suggesting that the obtained results reflect different pathogenic vascular processes.
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| 10. |
- Gros Calvo, Meritxell, et al.
(författare)
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Pharmaceuticals in source separated sanitation systems : Fecal sludge and blackwater treatment
- 2019
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Ingår i: Science of the Total Environment. - : Elsevier B.V.. - 0048-9697 .- 1879-1026.
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated, for the first time, the occurrence and fate of 29 multiple-class pharmaceuticals (PhACs) in two source separated sanitation systems based on: (i) batch experiments for the anaerobic digestion (AD) of fecal sludge under mesophilic (37 °C) and thermophilic (52 °C) conditions, and (ii) a full-scale blackwater treatment plant using wet composting and sanitation with urea addition. Results revealed high concentrations of PhACs in raw fecal sludge and blackwater samples, with concentrations up to hundreds of μg L−1 and μg kg−1 dry weight (dw) in liquid and solid fractions, respectively. For mesophilic and thermophilic treatments in the batch experiments, average PhACs removal rates of 31% and 45%, respectively, were observed. The average removal efficiency was slightly better for the full-scale blackwater treatment, with 49% average removal, and few compounds, such as atenolol, valsartan and hydrochlorothiazide, showed almost complete degradation. In the AD treatments, no significant differences were observed between mesophilic and thermophilic conditions. For the full-scale blackwater treatment, the aerobic wet composting step proved to be the most efficient in PhACs reduction, while urea addition had an almost negligible effect for most PhACs, except for citalopram, venlafaxine, oxazepam, valsartan and atorvastatin, for which minor reductions (on average 25%) were observed. Even though both treatment systems reduced initial PhACs loads considerably, significant PhAC concentrations remained in the treated effluents, indicating that fecal sludge and blackwater fertilizations could be a relevant vector for dissemination of PhACs into agricultural fields and thus the environment.
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