| 1. |
- Bowes, John, et al.
(författare)
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PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis : evidence for a further PsA-specific risk locus
- 2015
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 74:10, s. 1882-1885
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis; it has a higher estimated genetic component than psoriasis alone, however most genetic susceptibility loci identified for PsA to date are also shared with psoriasis. Here we attempt to validate novel single nucleotide polymorphisms selected from our recent PsA Immunochip study and determine specificity to PsA. Methods A total of 15 single nucleotide polymorphisms were selected (P-Immunochip <1x10(-4)) for validation genotyping in 1177 cases and 2155 controls using TaqMan. Meta-analysis of Immunochip and validation data sets consisted of 3139 PsA cases and 11 078 controls. Novel PsA susceptibility loci were compared with data from two large psoriasis studies (WTCCC2 and Immunochip) to determine PsA specificity. Results We found genome-wide significant association to rs2476601, mapping to PTPN22 (p=1.49x10(-9), OR=1.32), but no evidence for association in the psoriasis cohort (p=0.34) and the effect estimates were significantly different between PsA and psoriasis (p=3.2x10(-4)). Additionally, we found genome-wide significant association to the previously reported psoriasis risk loci; NOS2 (rs4795067, p=5.27x10(-9)). Conclusions For the first time, we report genome-wide significant association of PTPN22 (rs2476601) to PsA susceptibility, but no evidence for association to psoriasis.
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| 2. |
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| 3. |
- Alenius, Gerd-Marie, 1957-
(författare)
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A Clinical and Genetic Study of Psoriatic Arthritis
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. PsA has a heterogeneous pattern, expressed by different manifestations such as mild mono-oligoarthritis or very severe, erosive and destructive polyarthritis. Measurable inflammatory activity is not always prominent. The aetiology is unknown but genetic factors are believed to be of importance. The pattern of inheritance is proposed to be polygenic. The aim of this study was to estimate the prevalence of joint and axial manifestations, characterise the disease in relation to inflammatory and genetic markers, and to identify disease susceptibility gene(s) for PsA in patients from northern Sweden. All patients from the city of Umeå (n=276), selected from a community and hospital based psoriasis register (n=1737) at the Dept of Dermatology, were invited to a prevalence study. Two hundred-two patients were examined and 97 (48%) had inflammatory manifestations such as peripheral arthritis, axial disease, undifferentiated spondylarthropathy (uSpA) and enthesopathies. Of the 67 patients (33 %) with peripheral arthritis and/or axial disease, 30 were not previously diagnosed. The association of clinical manifestations and potential markers of aggressive joint disease with HLA associations were analysed in 88 patients with PsA. We were not able to confirm findings of other groups reporting strong association with several HLA-antigens. The prevalence of HLA-B17, B37 and B62 was increased compared with controls, but the strongest predictive factors among our patients for an aggressive disease, in a multiple logistic analysis, were polyarthritic disease and distal interphalangeal engagement. In order to investigate for disease susceptibility genes, five genetic loci were analysed with microsatellites and single nucleotide polymorphisms in an association study of 120 patients with PsA. There was a significant association with the TNFB locus on chromosome 6p but not with any other loci examined; 1q21 (PSORS4), 3q21 (PSORS5), 8q24 and CTLA4. When stratifying for the TNFB alleles the association was confined to allele 123. In a subgroup of patients who were HLA-typed (n=83), we were not able to verify linkage disequilibrium with the TNFB allele 123 and the HLA antigens; B17, B27, B37, B62 or Cw*0602. The presence of renal abnormalities was evaluated as a manifestation of systemic inflammation in 73 patients with PsA. Renal abnormalities defined as decreased creatinine-clearance (≤ mean - 2SD) and/or urinary albumin >25 mg/24 h was found in 23% of the patients. The predictive factors for renal abnormalities was inflammatory activity (ESR > 25 mm/h and/or CRP >15 mg/L) indicating a systemic effect in some of the patients. In conclusion, we found high prevalence of inflammatory manifestations in patients with psoriasis. There was no strong association between PsA and HLA antigens and predictive factors for aggressive disease were polyarthritic disease and DIP joint engagement. The TNFB locus was associated with PsA and there were no linkage disequilibrium with the HLA antigens B17, B27, B62 or Cw*0602. There were evidence for systemic effects as renal abnormalities in patients with PsA and measurable inflammatory activity.
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| 4. |
- Alenius, Gerd-Marie, et al.
(författare)
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Analysis of 6 genetic loci for disease susceptibility in psoriatic arthritis.
- 2004
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Ingår i: The Journal of rheumatology. - 0315-162X .- 1499-2752. ; 31:11, s. 2230-5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze the association of several autoimmune disease susceptibility loci in a population of patients with psoriasis and defined joint disease from northern Sweden. METHOD: One hundred twenty patients with psoriasis and defined joint disease were examined clinically, radiologically, and with laboratory-based analyses. Disease classification was based on peripheral and/or axial engagement. The tumor necrosis factor (TNF) locus, 1q21 (PSORS4), 3q21 (PSORS5), 8q24, 16q21, and the CTLA4 gene were analyzed using a total of 38 microsatellite markers and 2 single nucleotide polymorphisms (SNP). Ninety-four controls with the same ethnic background as the patients were randomly selected from the same region of Sweden. RESULTS: An association was found with one of the markers in the TNFB locus within the HLA region (p = 0.012, pc = 0.024). Three markers at the PSORS4 locus on chromosome 1q21 and 2 markers at the 8q24 locus showed nominal p values of < 0.05. After applying the Bonferroni correction for multiple analyses these markers did not reach significance. No other marker showed significant association. In a subgroup of the patients, possible linkage disequilibrium between the TNFB123 and HLA-B antigens, B17, B27, B37, B44, and B62 was analyzed. A significant linkage (p = 0.0001) was found. CONCLUSION: We identified an association between psoriatic arthritis and one of the microsatellite markers within the TNFB locus at the HLA region on chromosome 6. Linkage disequilibrium between TNFB123 and certain HLA-B antigens was found.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Alenius, Gerd-Marie, et al.
(författare)
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Disease manifestations and HLA antigens in psoriatic arthritis in northern Sweden
- 2002
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Ingår i: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 21:5, s. 357-362
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to identify potential markers of aggressive joint manifestations and HLA associations in patients with psoriatic arthritis (PsA) in northern Sweden. Patients with PsA were examined clinically, with laboratory tests and radiologically. The classification of the disease was based on peripheral and/or axial engagement. HLA B17, B37 and B62 were significantly increased in PsA patients. Univariate analyses suggest that the HLA antigens B37, B62 and some clinical variables were associated with disease course. However, in multivariate analyses distal interphalangeal joint affliction and polyarticular manifestations were the only variables remaining significantly associated with irreversible joint destruction or deformity. There were no significant effects of HLA antigens. In this cross-sectional study, clinical manifestations were more reliable predictors of aggressive joint damage than were specific HLA antigens. However, HLA antigens seemed to modify the expression of the joint disease rather than being involved in joint disease susceptibility.
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| 9. |
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| 10. |
- Alenius, Gerd-Marie, et al.
(författare)
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Interleukin-6 and soluble interleukin-2 receptor alpha-markers of inflammation in patients with psoriatic arthritis?
- 2009
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 27:1, s. 120-123
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate a possible systemic effect of joint inflammation in contrast to skin disease only, by measuring IL-6 and IL-2sRalpha. METHODS: Two hundred and nineteen patients (111 male / 108 female, age 50.4+/-14.5 yrs (mean+/-SD)) with psoriasis were clinically and laboratory examined. 134 patients had inflammatory joint manifestations defined as peripheral arthritis and/or axial disease, of whom 37 had measurable inflammation, defined as ESR >25 mm/h and/or CRP >15 mg/L. RESULTS: Interleukin-6 was significantly higher in patients with joint disease and measurable inflammation ((median, Q1-Q3) 4.07, 0.92-14.60), and in patients without measured inflammation (1.22, 0.70-3.46), compared to patients with skin disease only (0.70, 0.70-1.73, p<0.001 and p=0.002 respectively). The difference between the two groups of patients with inflammatory joint manifestations was significant (p=0.001). The levels of IL-6 correlated with the actual number of joints affected with arthritis (p<0.001; rs=0.248), ESR (p<0.001; rs=0.459), CRP (p<0.001; rs=0.314) and IL-2sRalpha (p=0.002; rs=0.210). The levels of IL-2sRalpha. did not differ between the 3 groups. CONCLUSION: In this study, IL-6 was significantly higher in patients with psoriasis and inflammatory joint disease with or without routine measurable inflammatory activity compared with patients having psoriasis of the skin. We found that patients with psoriasis and joint inflammation may have systemic effects that could be captured by serum measurements of IL-6. Soluble IL-2Ralpha was not a marker of inflammation in this study.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Apel, Maria, et al.
(författare)
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Variants in RUNX3 Contribute to Susceptibility to Psoriatic Arthritis, Exhibiting Further Common Ground With Ankylosing Spondylitis
- 2013
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 65:5, s. 1224-1231
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Tidskriftsartikel (refereegranskat)abstract
- Objective Psoriatic arthritis (PsA) is a common inflammatory joint disease distinct from other chronic arthritides and frequently accompanied by psoriasis vulgaris. In a first genome-wide association study (GWAS), we were able to identify several genetic risk factors. However, even combined with previously identified factors, the genetic contribution to disease was not fully explained. Therefore, we undertook this study to investigate further 17 loci from our GWAS that did not reach genome-wide significance levels of association in the initial analysis. Methods Twenty-one of 22 single-nucleotide polymorphisms were successfully genotyped in independent cohorts of 1,398 PsA patients and 6,389 controls and in a group of 964 German patients with psoriasis vulgaris. Results Association with a RUNX3 variant, rs4649038, was replicated in independent patients and controls and resulted in a combined P value of 1.40 x 108 by Cochran-Mantel-Haenszel test and an odds ratio (OR) of 1.24 (95% confidence interval [95% CI] 1.151.33). Further analyses based on linkage disequilibrium (LD) at RUNX3 refined the most significant association to an LD block located in the first intron of one isoform. Weaker evidence for association was detected in German patients with psoriasis vulgaris (P = 5.89 x 102; OR 1.13 [95% CI 1.001.28]), indicating a role in the skin manifestations of psoriasis. Conclusion Our analyses identified variants in RUNX3 as susceptibility factors for PsA. RUNX3 has already been implicated in susceptibility to ankylosing spondylitis, another spondyloarthritis, although its risk allele is independent from the one for PsA. RUNX-3 is involved in CD8+ T lymphocyte differentiation and is therefore a good candidate for involvement in PsA and psoriasis vulgaris as T cellmediated diseases.
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| 15. |
- Boman, Antonia, 1991-
(författare)
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Early rheumatoid arthritis : biomarkers and hormonal factors in relation to disease progression
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, affecting approximately 0.5 to 1% of the adult population. Although the aetiology is not fully known, a complex interaction between genetic, environmental and stochastic factors is thought to trigger the pathogenic mechanisms. A distinguishing feature of RA is the presence of disease associated autoantibodies, mainly rheumatoid factor (RF) and anti-cyclic citrullinated antibodies (ACPA), which are important in both diagnostic and prognostic purpose. The disease is systemic but primarily affects the joints, and can cause irreversible destructions of cartilage and bone, eventually leading to functional disabilities. Moreover, extra-articular features (i.e., symptoms outside the joints) can occur and the patients have an increased risk for comorbidities, predominantly cardiovascular disease. Since the disease is heterogenous, varying from mild to more severe forms, the prognosis can be difficult to predict. Improvements in early diagnosis and identification of patients at risk of a more severe disease course can lead to better outcomes for the patients. The overall aim of this thesis was to evaluate prognostic biomarkers, and to evaluate hormonal and reproductive factors in relation to cardiovascular events (CVE) in patients with newly diagnosed RA (symptoms <12 months).Methods: The patients were included in a prospective inception cohort from the years of 1996 to 2017 and followed-up regularly at the early RA clinics in the northern region of Sweden. Clinical and laboratory parameters, and treatment were regularly recorded in the Swedish Rheumatology Quality Register (SRQ). Enzyme-linked immunosorbent assays (ELISA) and a multiplex assay were used to analyse bone remodelling factors and ACPA reactivities, respectively. Questionnaires regarding hormonal and reproductive factors were sent out to female patients ≤80 years. Information of CVE was extracted from the Swedish National Health Register and Cause of Death Register. Potential markers for disease progression i.e., bone remodelling factors and autoantibodies were analysed in relation to disease progression. Hormonal and reproductive factors were analysed in relation to CVE. Results: In paper I we found associations between receptor activator of nuclear factor kappa-B (RANKL), a central molecule of bone metabolism, and radiological findings at baseline, 24 months, and radiological progression analysed in 407 RA patients. The combination of RANKL and anti-CCP positivity indicated a more severe disease course in terms of joint destruction. Sclerostin was not associated with radiological outcome. Polymorphisms of the genes for sclerostin (SOST) and RANKL (TNFSF11) did not show significant associations with radiological outcome or with the concentrations, respectively. In paper II, we found that even though antibody status is considered in clinical practice and modern treatment reduces disease activity, the radiographic joint damage remained increased among anti-CCP positive patients. In paper III, 22 different ACPA reactivities were analysed in relation to disease courses of RA. The presence of a higher number of different ACPA reactivities, and different ACPA subtypes could provide prognostic information of disease activity and radiological destruction. In paper IV, we found that hormonal and reproductive factors were associated with CVE in female patients. A higher number of childbirths increased the risk for CVE, whilst oral contraceptives decreased the risk. The majority of patients with later CVE had their RA disease onset after menopause and had a longer duration from menopause until RA onset.Conclusion: RANKL can function as a prognostic marker for the disease course of RA. Even though anti-CCP antibodies are taken into account in clinical practice and treatment reduce disease activity, the joint damage can progress, supporting the direct bone degrading effects by ACPA. The number of, and different subtypes of ACPA, can predict different disease progression. These markers can be valuable to identify patients at need for more aggressive treatment and careful radiographic monitoring, even if disease activity is under control. Finally, hormonal factors such as childbirths, oral contraceptives and the timing of RA onset in relation to hormonal status can add value for the evaluation of CVE risk in female RA patients.
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| 16. |
- Boman, Antonia, et al.
(författare)
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Hormonal and reproductive factors in relation to cardiovascular events in women with early rheumatoid arthritis
- 2023
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Hormonal and reproductive factors affect the risk for cardiovascular events (CVE) in the general population. Although the risk of CVE is increased in rheumatoid arthritis (RA), the knowledge about the impact of hormonal factors for CVE in RA is sparse. Female postmenopausal patients ≤80 years with early RA were consecutively included in this observational study (n = 803) between 1 January 1996 until 31 December 2017. Questionnaires regarding hormonal factors were distributed from the index date. Data regarding CVE were obtained from the Swedish National Health Register and Cause of Death Register. Associations between CVE and hormonal factors were analyzed using Cox proportional hazard regression. Of the postmenopausal women, 64 women had a CVE after RA onset. The time period from menopause to RA onset was significantly longer for CVE cases with higher proportion of postmenopausal women. In Cox proportional hazard regression models, years from last childbirth and multiparity were associated with higher CVE risk. Adjustments for traditional risk factors did not affect the results except for hypertension. RA onset after menopause and a longer duration from menopause until onset increased the CVE risk. Multiparity was associated with higher CVE risk whilst oral contraceptives decreased the risk. These results can contribute to identification of high-risk patients for CVE beyond traditional risk factors.
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| 17. |
- Bower, H., et al.
(författare)
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Effects of the COVID-19 pandemic on patients with inflammatory joint diseases in Sweden: from infection severity to impact on care provision
- 2021
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Ingår i: Rmd Open. - : BMJ. - 2056-5933. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To compare risks for COVID-19-related outcomes in inflammatory joint diseases (IJDs) and across disease-modifying antirheumatic drugs (DMARDs) during the first two waves of the pandemic and to assess effects of the pandemic on rheumatology care provision. Methods Through nationwide multiregister linkages and cohort study design, we defined IJD and DMARD use annually in 2015-2020. We assessed absolute and relative risks of hospitalisation or death listing COVID-19. We also assessed the incidence of IJD and among individuals with IJD, rheumatologist visits, DMARD use and incidence of selected comorbidities. Results Based on 115 317 patients with IJD in 2020, crude risks of hospitalisation and death listing COVID-19 (0.94% and 0.33% across both waves, respectively) were similar during both waves (adjusted HR versus the general population 1.33, 95% CI 1.23 to 1.43, for hospitalisation listing COVID-19; 1.23, 95% CI 1.08 to 1.40 for death listing COVID-19). Overall, biological disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) did not increase risks of COVID-19 related hospitalisation (with the exception of a potential signal for JAK inhibitors) or death. During the pandemic, decreases were observed for IJD incidence (-7%), visits to rheumatology units (-16%), DMARD dispensations (+6.5% for bDMARD/tsDMARDs and -8.5% for conventional synthetic DMARDs compared with previous years) and for new comorbid conditions, but several of these changes were part of underlying secular trends. Conclusions Patients with IJD are at increased risk of serious COVID-19 outcomes, which may partially be explained by medical conditions other than IJD per se. The SARS-CoV-2 pandemic has exerted measurable effects on aspects of rheumatology care provision demonstrated, the future impact of which will need to be assessed.
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| 18. |
- Bower, Hannah, et al.
(författare)
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Impact of the COVID-19 pandemic on morbidity and mortality in patients with inflammatory joint diseases and in the general population : a nationwide Swedish cohort study
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80:8, s. 1086-1093
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To estimate absolute and relative risks for all-cause mortality and for severe COVID-19 in inflammatory joint diseases (IJDs) and with antirheumatic therapies.Methods: Through Swedish nationwide multiregister linkages, we selected all adult patients with rheumatoid arthritis (RA, n=53 455 in March 2020), other IJDs (here: spondyloarthropathies, psoriatic arthritis and juvenile idiopathic arthritis, n=57 112), their antirheumatic drug use, and individually matched population referents. We compared annual all-cause mortality March-September 2015 through 2020 within and across cohorts, and assessed absolute and relative risks for hospitalisation, admission to intensive care and death due to COVID-19 March-September 2020, using Cox regression.Results: During March-September 2020, the absolute all-cause mortality in RA and in other IJDs was higher than 2015-2019, but relative risks versus the general population (around 2 and 1.5) remained similar during 2020 compared with 2015-2019. Among patients with IJD, the risks of hospitalisation (0.5% vs 0.3% in their population referents), admission to intensive care (0.04% vs 0.03%) and death (0.10% vs 0.07%) due to COVID-19 were low. Antirheumatic drugs were not associated with increased risk of serious COVID-19 outcomes, although for certain drugs, precision was limited.Conclusions: Risks of severe COVID-19-related outcomes were increased among patients with IJDs, but risk increases were also seen for non-COVID-19 morbidity. Overall absolute and excess risks are low and the level of risk increases are largely proportionate to those in the general population, and explained by comorbidities. With possible exceptions, antirheumatic drugs do not have a major impact on these risks.
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| 19. |
- Exarchou, S., et al.
(författare)
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MORTALITY IN PATIENTS WITH PSORIATIC ARTHRITIS IN SWEDEN
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80, s. 130-131
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In contrast to the increased mortality reported in other inflammatory diseases such as rheumatoid arthritis and psoriasis, prior mortality studies in psoriatic arthritis (PsA) have shown inconsistent results.Objectives:To compare all-cause mortality between PsA patients in Sweden and matched general population controls, and to describe cause of death distributions in the two groups.Methods:All individuals in Sweden with ≥1 main diagnosis of PsA (ICD-10: L40.5/M07.0-M07.3) from outpatient visits to rheumatology or internal medicine clinics at age ≥18 years (y) 2001-2017 were identified from the Swedish National Patient Register. Each case was matched to 5 general population controls based on sex, county and age in the year of the first registered arthritis diagnosis for the case. Cases and controls were followed from 1 Jan, 2007, or from first PsA diagnosis thereafter for index cases, until first occurrence of death (data from the Swedish Cause of Death Register), emigration or 31 Dec, 2018. Mortality was assessed overall, as well as stratified by sex (45% males) and disease duration (PsA diagnosis prior to 2007 [38% of cases] vs. 2007-2017), using matched Cox proportional hazard regression, or – in case the Cox assumption regarding proportionality did not hold – matched Breslow test. To account for potential PsA misclassification (in a previous validation study, 86% of 400 cases fulfilled PsA classification criteria), a sensitivity analysis was performed by randomly replacing 20% of cases with one of their own controls. Moreover, incidence rate ratios (IRR) of death were calculated overall and stratified by sex, disease duration and age. Finally, causes of death (from the Cause of Death Register) were described for PsA cases and controls.Results:Over the 12y follow-up, 3 121 deaths occurred among 33 036 PsA cases (268 402 person-years at risk) and 12 884 deaths among 161 144 controls (1 302 250 person-years), resulting in an increased mortality among the PsA cases (HR 1.11 [95%CI 1.07-1.16], p<0.001, Figure and Table; sensitivity analysis HR 1.09 [1.05-1.14]). The increased mortality was seen mainly among female PsA cases and among cases with longer disease duration (Figure; Table). IRR:s of death were significantly increased for all ages except <40y, with the numerically highest point-estimates for ages 40-49y and 50-59y (Table). Cause of death frequencies among the PsA cases/controls: cardiovascular disease 29/27%; diabetes mellitus 2.1/2.5%; chronic kidney disease 0.4/0.3%; infection 5.7/4.5%; chronic pulmonary disease 5.1/4.1%; malignancy 29/34%; suicide 2.3/2.0%; other 27/26%.Table 1.Mortality rates and incidence rate ratiosPsA casesPopulation controlsNumber of deathsPerson-yearsat riskMortality rate*Number of deathsPerson-yearsat riskMortality rate*Incidence rate ratio (95%CI)Overall3 121268 40211.612 8841 302 2509.91.18 (1.13-1.22)Males1 459120 51712.16 468580 28511.11.09 (1.03-1.15)Females1 662147 88611.26 416721 9668.91.27 (1.20-1.34)Longer disease duration1 943139 37913.97 459670 17411.11.25 (1.19-1.32)Shorter disease duration1 178129 0239.15 425632 0778.61.06 (1.00-1.13)Age intervals (years)<401833 5680.598163 2780.60.89 (0.54-1.48)40-499050 5521.8322246 9551.31.37 (1.08-1.73)50-5928065 8204.31 131321 7303.51.21 (1.06-1.38)60-6972370 22410.33 132341 5879.21.12 (1.04-1.22)70-7996037 23225.84 160178 90923.31.11 (1.03-1.19)≥801 05011 00795.44 04149 79181.21.18 (1.10-1.26)* Per 1000 person-years.Conclusion:In this nationwide 12y assessment, the mortality risk among PsA patients in Sweden was increased by around 10% as compared to the general population, mainly driven by increased risks among females and patients with longer disease duration. Cause of death distributions were numerically similar between PsA cases and controls.References:Disclosure of Interests:Sofia Exarchou Consultant of: AbbVie, Novartis, Daniela Di Giuseppe: None declared, Gerd-Marie Alenius: None declared, Eva Klingberg Speakers bureau: Eli Lilly, Consultant of: Novartis, Grant/research support from: Roche, Valgerdur Sigurdardottir Consultant of: Novartis, Sanofi, Sara Wedrén: None declared, Ulf Lindström: None declared, Carl Turesson Speakers bureau: AbbVie, BMS, Pfizer, Roche, Consultant of: Roche, Grant/research support from: BMS, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Johan Askling Grant/research support from: For ARTIS: AbbVie, BMS, Eli Lilly, Merck, Pfizer, Roche, Samsung Bioepis, Sanofi, UCB. This study was supported by AbbVie, Amgen, Eli Lilly, Novartis and Pfizer. The sponsors were allowed to comment on the study protocol and were provided with a report of the results, but had no influence on the study design or decision to submit the abstract., Johan K Wallman Consultant of: Celgene, Eli Lilly, Novartis
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| 20. |
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| 21. |
- Geijer, Mats, 1957, et al.
(författare)
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Health-related quality of life in early psoriatic arthritis compared with early rheumatoid arthritis and a general population
- 2021
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Ingår i: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 51:1, s. 246-252
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Both psoriatic arthritis (PsA) and rheumatoid arthritis (RA) have a significant impact on quality of life, but few reports have compared the two diseases. The current study assessed health-related quality of life (HRQoL) in PsA at diagnosis and after five years compared with early rheumatoid arthritis (RA) and a matched general population. Methods: Patients with early PsA and early RA included in two Swedish registries with HRQoL data measured by the Medical Outcomes Study Short Form 36 (SF-36) at baseline and at five years follow-up were included. Differences in SF-36 scores compared with the general population were calculated for each patient. Physical function, disease activity, the delay before diagnosis, pain, and general wellbeing were used as explanatory variables. Statistical tests included t-tests and univariate and multivariate linear regression. Results: PsA (n = 166) and RA (n = 133) patients of both sexes had significantly reduced HRQoL at disease onset. After five years, PsA patients still had impairments in several domains of SF-36, whereas RA patients had an almost normalized HRQoL. The time from symptom onset to diagnosis, disease activity, and disability independently contributed to the reduced improvement in PsA. Conclusion: Both early PsA and RA are characterized by severely reduced HRQoL. Despite more severe disease at inclusion, normalization of HRQoL is seen in patients with RA but not PsA. This may be due to delay in the diagnosis of PsA or more powerful interventions in RA. Earlier detection, lifestyle intervention, and more aggressive management strategies may be needed for PsA. (C) 2020 Elsevier Inc. All rights reserved.
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| 22. |
- Geijer, Mats, et al.
(författare)
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The Swedish Early Psoriatic Arthritis Registry 5-year Followup : Substantial Radiographic Progression Mainly in Men with High Disease Activity and Development of Dactylitis
- 2015
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 42:11, s. 2110-2117
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To describe early radiographic findings in patients from the Swedish psoriatic arthritis (SwePsA) registry, progression of destruction, correlations with clinical disease variables, and predictors of destruction. Methods. Hand and foot radiographs were available for 72 of 197 SwePsA patients followed for 5 years. Clinical data were collected according to the SwePsA protocol. Results. Disease characteristics and clinical improvement were similar in men and women. Radiographic abnormalities were more pronounced in men. Total Wassenberg radiographic score at baseline was 0 in 45% of men and 51% of women. One man and one woman had a score >10. At 5 years, total score was 0 in 14% of men and 40% of women (p = 0.018); 17% of men and 7% of women had scores >10. Mean total scores for men and women had increased. Baseline erythrocyte sedimentation rate was associated with baseline total radiographic score. In men, swollen joint count was positively, and in women tender joint count negatively, correlated to total radiographic score. After 5 years, only male scores, mainly hand scores, significantly correlated with 28-joint Disease Activity Score and Disease Activity Index for Psoriatic Arthritis scores, swollen joint count, and dactylitis. Achieving remission or minimal disease activity after 5 years protected against structural damage, mainly in men. Conclusion. Radiographic progression in early PsA was generally slow but substantial. Male sex appears to be a risk factor for early radiographic damage while the presence of baseline radiographic damage and dactylitis developing during followup seem to predict further destruction. Hand and foot radiograph scoring cannot be substituted with clinical signs.
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| 23. |
- Gylfe, Åsa, et al.
(författare)
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Mosquitoborne Sindbis Virus Infection and Long-Term Illness
- 2018
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 24:6, s. 1141-1142
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Tidskriftsartikel (refereegranskat)abstract
- An unexpected human outbreak of the mosquitoborne Sindbis virus occurred in a previously nonendemic area of Sweden. At follow-up, 6-8 months after infection, 39% of patients had chronic arthralgia that affected their daily activities. Vectorborne infections may disseminate rapidly into new areas and cause acute and chronic disease.
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| 24. |
- Hansson, Claes, et al.
(författare)
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S-Calprotectin (S100A8/S100A9) : A Potential Marker of Inflammation in Patients with Psoriatic Arthritis
- 2014
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Ingår i: Clinical & Developmental Immunology. - : Hindawi Limited. - 1740-2522 .- 1740-2530. ; , s. 696415-
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To analyse levels of S100A8/S100A9 (calprotectin) and selected cytokines, in blood, in patients with psoriatic arthritis (PsA). Methods. Sixty-five patients with PsA were examined for clinical manifestations and laboratory measurements of S-calprotectin, ESR, hs-CRP, and selected cytokines. Thirty-two patients had mono-/oligoarthritis and 33 had polyarthritis. S-calprotectin, hs-CRP, and cytokines were measured using ELISA, immunoturbidimetry, and multiplex technology (Bio-Plex). Patients with PsA were compared with 31 healthy controls. Results. S-calprotectin and hs-CRP levels were significantly higher in patients with PsA compared with controls (P < 0.001 and P < 0.001, resp.). Patients suffering a polyarthritic disease pattern presented with significantly higher levels of S-calprotectin compared with controls and patients with mono-/oligoarthritis (P < 0.001 and P = 0.017, resp.). The levels of S-calprotectin correlated with hs-CRP (P < 0.001; r(s) = 0.441), swollen joint count (P = 0.002, r(s) = 0.397), and CXCL10 (P = 0.046, r(s) = 0.678) but not with any of the other cytokines evaluated. In multiple logistic regression analysis, S-calprotectin was the only variable significantly associated with psoriatic arthritis (P = 0.002, OR = 1.006, 95% CI = 1.002-1.010). Conclusion. S-calprotectin and hs-CRP levels were significantly higher in patients with PsA. A polyarthritic disease pattern showed higher levels of S-calprotectin thanmono-/oligoarthritis. S-calprotectin is considered a potential marker of disease activity in patients with PsA.
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| 25. |
- Helliwell, Philip S., et al.
(författare)
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Treatment of psoriatic arthritis and rheumatoid arthritis with disease modifying drugs : comparison of drugs and adverse reactions
- 2008
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 35:3, s. 472-476
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory diseases of the musculoskeletal system. Although it seems likely that these conditions have a different pathogenesis, the drugs used to treat them are the same. Our study used a cross-sectional clinical database to compare drug use and side-effect profile in these 2 diseases. METHODS: The CASPAR study collected data on 588 patients with PsA and 536 controls, 70% of whom had RA. Data on disease modifying drug treatments used over the whole illness were recorded, together with their outcomes, including adverse events, for RA and PsA. RESULTS: For both diseases methotrexate (MTX) was the most frequently used disease modifying drug (39% of patients with PsA, 30% with RA), with over 70% of patients in both diseases still taking the drug. Other drugs were used with the following frequencies in PsA and RA, respectively: sulfasalazine 22%/13%, gold salts 7%/11%, antimalarial drugs 5%/14%, corticosteroids 10%/17%, and anti-tumor necrosis factor (TNF) drugs 6%/5%. Compared to RA, cyclosporine and anti-TNF agents were less likely to be ineffective in PsA. Compared to RA, subjects with PsA were less likely to be taking MTX and more likely to be taking anti-TNF agents. Hepatotoxicity with MTX was more common in PsA and pulmonary toxicity with MTX was found more often in RA. CONCLUSION: These data provide insight into prescribing patterns of disease modifying drugs in RA and PsA in a large international cohort, together with the differential adverse events of these drugs between these diseases.
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| 26. |
- Hofstedt, Oscar E., et al.
(författare)
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Comparison of agreement between internet-based registration of patient-reported outcomes and clinic-based paper forms within the Swedish Rheumatology Quality Register
- 2019
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Ingår i: Scandinavian Journal of Rheumatology. - : TAYLOR & FRANCIS LTD. - 0300-9742 .- 1502-7732. ; 48:4, s. 326-330
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Swedish Rheumatology Quality Register has implemented an internet-based method (PER) for registering patient-recorded outcome measures. The aim of this study was to compare the agreement between visual analogue scales (VASs) reported via PER and clinic-based reporting using paper forms.Methods: In a cross-sectional study (70 patients), the results of 79 registrations of VASs for global health, pain, and fatigue from PER were compared with corresponding clinic-based paper registrations. For patients with polyarthritis, 28-joint count Disease Activity Scores (DAS28) were computed. Patients with axial disease also completed Bath Ankylosing Spondylitis Disease Activity Index and Functional Index (BASDAI and BASFI) questionnaires. Mean differences and intraclass correlation coefficients (ICCs) were calculated. Agreement was visualized using Bland-Altman plots.Results: No statistically significant differences in VASs were found comparing PER and paper forms for VAS Global, VAS Pain, and VAS Fatigue (p=0.295, 0.463, and 0.288, respectively). ICCs for VAS Global, Pain, and Fatigue ranged from 0.889 to 0.952, indicating excellent agreement. Bland-Altman plots for VAS did not show any proportional bias. The mean difference for DAS28 calculated by VASs from paper vs PER was -0.02 (n=65, p =0.660), and the mean difference for BASDAI was 0.04 (n=11, p =0.742). ICCs for DAS28 and BASDAI were 0.962 and 0.985, respectively. Of the participating patients, 60% preferred PER.Conclusion: Internet-based reporting for patient-reported outcomes in a clinical setting resulted in similar data for VASs and corresponding disease activity scores to clinic-based reporting on paper forms.
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| 27. |
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| 28. |
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| 29. |
- Hüffmeier, Ulrike, et al.
(författare)
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Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 996-999
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Tidskriftsartikel (refereegranskat)abstract
- Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10⁻¹⁷). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10⁻³). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10⁻²⁰, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.
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| 30. |
- Isaksson, J., et al.
(författare)
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Screening and simple counselling affect traditional cardiovascular risk factors in patients with early rheumatoid arthritis
- 2014
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa Healthcare. - 0300-9742 .- 1502-7732. ; 43:Suppl. 127 Meeting Abstract PP234, s. 76-76
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD) and increased mortality in CVD. The cause of this increase has not been completely established, but chronic inflammation is thought to play a role. Traditional cardiovascular risk factors also appear to be important and may be potentiated by this inflammation. The Swedish Society for Rheumatology (SRF) has developed a set of guidelines for screening and primary prevention of CVD in patients with RA. The aim of this study was to evaluate these guidelines in a clinical setting.Method: Forty-seven patients newly diagnosed with RA during 2012 at the Department of Rheumatology, University Hospital of Umeå were recruited. Three months after initial diagnosis of RA, patients were examined physically and blood samples were collected with regard to traditional cardiovascular risk factors according to the guidelines from the SRF. Tests of cardiorespiratory fitness were also performed. Additionally, patients received simple counselling regarding matters of diet, tobacco use and exercise from a nurse and a physiotherapist, respectively. The counselling session, based upon national guidelines from the National Food Agency and the Public Health Agency, was performed once per patient and lasted for approximately 45 minutes. A follow-up was performed 9 months after the first examination. This intervention was integrated into the clinic’s pre-existing early RA follow-up programme. The results were adjusted for disease activity and disability.Results: Among the 47 included patients, 45 reached the 9-month follow-up. Two were excluded because of delayed follow-up. Mean diastolic blood pressure decreased significantly from 80 to 77 mmHg (p < 0.05). Mean S-cholesterol decreased significantly from 5.5 to 5.2 mmol/L (p < 0.05). Mean ApoA1/ApoB decreased significantly from 0.73 to 0.65 (p < 0.05). In all the remaining variables (waist circumference, BMI, systolic blood pressure, LDL, HDL, triglycerides, FP-glucose), a clear decreasing trend could be observed (p > 0.05). Aerobic capacity according to Åstrand remained unchanged (p > 0.05).Conclusions: Several traditional risk factors for CVD were improved at the 9-month follow-up. This suggests that this model of screening according to the SRF guidelines and simple counselling according to national guidelines might be useful in primary prevention of CVD in patients with RA.
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| 31. |
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| 32. |
- Juneblad, Kristina, et al.
(författare)
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Association between inflammasome-related polymorphisms and psoriatic arthritis
- 2021
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Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis. - 0300-9742 .- 1502-7732. ; 50:3, s. 206-212
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease associated with psoriasis. Underlying genetic factors are considered important for disease expression and prognosis of PsA. Interleukin-1β-regulating protein complexes called inflammasomes are associated with several inflammatory diseases, e.g. rheumatoid arthritis and psoriasis. The aim was to determine whether inflammasome-related genetic variation is associated with PsA susceptibility or different disease phenotypes.Method: DNA from 724 patients with PsA and 587 population-based controls from northern Sweden was analysed for single-nucleotide polymorphisms in NLRP3-Q750K (rs35829419), NLRP3 (rs10733113), CARD8-C10X (rs2043211), NLRP1 (rs8079034), and NLRP1 (rs878329).Results: Significant associations were found with the genotype AA (vs AT+TT) of rs2043211 for PsA patients compared with controls [odds ratio (OR), 95% confidence interval (CI) 1.32 (1.05–1.65), p = 0.016]; and between the C-allele of rs878329 and axial involvement of PsA [OR (95% CI) 1.37 (1.02–1.84), p = 0.035], the T-allele of rs8079034 with prescription of conventional synthetic disease-modifying anti-rheumatic drugs [OR (95% CI) 1.76 (1.23–2.53), p = 0.0020], the G-allele of rs10733113 and patients with a skin disease with early onset [OR (95% CI) 1.58 (1.13–2.21), p = 0.007], and the C-allele of rs35829419 and a destructive/deforming disease [OR (95% CI) 1.63 (1.04–2.55), p = 0.030].Conclusions: This study is the first to show an association with a genetic polymorphism in an inflammasome-related gene, CARD8-C10X (rs2043211), in patients with PsA. Associations between different phenotypes of PsA and different polymorphisms of the inflammasome genes were also found. Our results indicate the involvement of inflammasome genes in the pathogenesis and disease expression of PsA.
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| 33. |
- Juneblad, Kristina, et al.
(författare)
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Association between the PTPN22 +1858 C/T polymorphism and psoriatic arthritis
- 2011
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Ingår i: Arthritis Research & Therapy. - : BioMed Central. - 1478-6362. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The purpose of the present study was to investigate the frequency of the PTPN22 +1858 C/T single nucleotide polymorphism (SNP) (rs 2476601), previously shown to be associated with several autoimmune diseases, in patients with psoriatic arthritis (PsA) in comparison with population based controls.METHODS: A total of 291 patients (145 male/146 female, mean age (± S.D.) 52.2 (± 13.1) years) with PsA were examined clinically, by standard laboratory tests and their DNA was genotyped for the SNP rs2476601 (PTPN22 +1858 C/T). Allelic frequencies were determined and compared with 725 controls.RESULTS: Carriage of the risk allele, PTPN22+1858T, showed a significant association with patients with PsA compared with controls (χ2 = 6.56, P = 0.010, odds ratio (OR) 1.49; 95% confidence interval (CI) 1.10 to 2.02). A significantly higher proportion of carriers of the risk allele (T) had significantly more deformed joints (n ± SEM) (5.9 ± 1.2 vs 2.8 ± 0.5; P = 0.005).CONCLUSIONS: In this study the +1858T allele of the PTPN22 gene, known to be associated with several autoimmune diseases, was associated with PsA. The finding of significantly more joints with deformities among carriers of the T variant could indicate a more aggressive phenotype of disease.
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| 34. |
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| 35. |
- Juneblad, Kristina, et al.
(författare)
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Disease activity and increased risk of cardiovascular death among patients with psoriatic arthritis
- 2016
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 43:12, s. 2155-2161
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Recent studies indicate increased cardiovascular (CV) morbidity and mortality in patients with psoriatic arthritis (PsA), but results are inconsistent. This prompted our investigation of the mortality rate, cause of death, and incidence of acute CV events in patients from northern Sweden with PsA.Methods: Patients with established PsA (464) were included. To calculate standardized mortality ratio (SMR) and standardized incidence ratio (SIR) for CV events, data were extracted from the National Causes of Death Register and the National Inpatient Care Register in Sweden, and compared with the general population. The study period was 1995-2011. To study the effect of inflammatory activity, a composite disease activity index (DAI) was used.Results: The SMR (95% CI) for overall mortality and diseases of the circulatory system (International Classification of Diseases, 10th edition; I00-I99) was 1.22 (0.89-1.63) and 1.64 (1.02-2.52), respectively. In regression analysis, DAI was significantly associated with death (OR 1.99, 95% CI 1.41-2.80) when adjusted for age and sex (p < 0.001), and remained significant after stratifying patients into the 2 major causes of death: diseases of the circulatory system and malignant neoplasms. Peripheral and axial disease was associated with death (OR 4.02, 95% CI 1.84-8.84, p < 0.001) compared with peripheral disease only. The SIR (95% CI) for a CV event (myocardial infarction or stroke) was 0.597 (0.40-0.86); this association was only significant in men.Conclusion: Patients with PsA had a small but significant increase in SMR for death due to diseases of the circulatory system compared with the general population. Among patients, death was associated with DAI, as well as axial involvement in combination with peripheral disease, indicating more aggressive disease phenotypes.
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| 36. |
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| 37. |
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| 38. |
- Juneblad, Kristina, 1965-
(författare)
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Psoriatic arthritis: a complex disease : analyses on genetic and serological biomarkers and of comorbidity
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psoriatic Arthritis (PsA) is a heterogonous inflammatory arthritis associated with psoriasis. The disease leads to inflammation of peripheral joints, axial skeleton and/or enthesites, and can result in severe destruction of affected joints. In contrast to rheumatoid arthritis (RA), most individuals with PsA are seronegative for rheumatoid factor (RF) and/or anti-citrullinated protein/peptide antibodies (ACPA) and the distal interphalangeal (DIP) joints are often involved. Dactylitis, a diffuse swelling of an entire digit (finger or toe), is also common. Traditional markers of systemic inflammation, such as erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) are elevated in only 50% of the individuals with PsA.Underlying genetic factors are considered important for the aetiology, disease expression and prognosis of PsA. To date no specific biomarker for PsA disease or disease activity/severity is available and there is a need for diagnostic and prognostic tools to meet the challenge of early diagnosis and assessment of disease severity.An increased risk of co-morbidity, particularly cardiovascular disease (CVD), has been demonstrated in patients suffering from different rheumatic diseases, e.g. systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Corresponding data for patients with PsA are more limited, but evidence exists for an increased risk of mortality and cardiovascular morbidity. However, published results are conflicting and heterogeneity among studies makes interpretation of data difficult.The aim of this study was to investigate genetic and serological biomarkers, and also mortality and cardiovascular comorbidity, in different phenotypes of PsA and in comparison with healthy controls. Patients with PsA were included between 1995 and 2015, the majority from the county of Västerbotten, except for two cohorts from Örnsköldsvik (n=55) and Östersund (n=98).The genetic polymorphism PTPN22+1858C/T, previously found to be associated with several autoimmune diseases, was also found associated with PsA, the results were later confirmed in a genome wide association study (GWAS). Additionally, among PsA patients, the minor allele, T, was associated with the number of deformed joints and dactylitis (Paper I). Genetic polymorphisms in genes related to the inflammasome were also investigated, both in comparison with healthy controls and in relation to different phenotypes of PsA (Paper II). An association was identified between patients with PsA and the polymorphism CARD8-C10X in comparison with controls. In addition, associations between various inflammasome polymorphisms and different clinical phenotypes of PsA were detected.To investigate the relation of serological biomarkers and PsA, individuals with blood samples collected in conjunction with clinical investigation were selected (Paper III). Associations with different biomarkers and different clinical phenotypes of PsA were identified In addition, associations were found with different biomarkers and patients with moderate/high disease activity at clinical investigation, confirming the inflammatory nature of the disease.Mortality and incidence of acute cardiovascular disease were investigated with standardized mortality rateratio (SMR) and standardized incidence ratio (SIR) compared with the general population of Västerbotten (Paper IV). An increased SMR for diseases of the circulatory system in PsA compared with controls was found. Among PsA patients, death was associated with a composite disease activity index (DAI) and with a disease phenotype including both axial- and peripheral joint involvement. In conclusion, associations were found with different clinical phenotypes of PsA, both with genetic polymorphisms and serological biomarkers that confirm the inflammatory nature of the disease and illustrate the disease heterogeneity. As in many other inflammatory diseases, an increased cardiovascular mortality was found that highlights the importance of considering cardiovascular risk factors in patients with PsA.
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| 39. |
- Karlsson Sundbaum, Johanna, 1969-
(författare)
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Studies of drug safety in the treatment of rheumatoid arthritis
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mainly smaller joints. Patients are at risk for complications as joint destruction, but starting treatment soon after onset of disease, has reduced the risk for complications. Methotrexate (MTX) is the anchor drug in the treatment of RA and has proven effects on both inflammatory symptoms and joint destruction. apy. Identifying patients at risk for MTX-induced hepatotoxicity before treatment could be a way to minimize the risk for Adverese effects.Following the introduction of pre-treatment screening, the risk of tuberculosis (TB) among patients with RA starting biologic treatment has decreased. By contrast, the risk remains several-fold increased in RA patients non-exposed to biological treatment. Knowledge about risk factors for TB and TB characteristics in this group of patients, and thus optimal clinical risk stratification and preven-tion, is still limited.In Paper I, only a small number of ALT tests (7%) performed during MTX therapy in RA patients, capture an elevation of ALT > upper limit of normal (ULN). ALT >1.5 × ULN was observed in 44 (21%) patients and the strongest predictor was a pre-treatment elevation of ALT. Recurrent elevations occurred in 70% of patients who continued treatment, and the proportion was similar in those with and without interventions. The results support a more individualized approach to monitoring and handling of ALT elevations during MTX therapy. In Paper II MTHFR A1298C (rs1801131) was nominally associated with ALT >1.5 x ULN within 6 months after the start of MTX (OR=1.7 [95% CI 1.04-2.9], p=0.03). In a multi-ple regression analysis for ALT >1.5 X ULN within 6 months of treatment start, including known risk factors for ALT elevation and MTHFR A1298C, the C-statistic was 0.734. A mod-el containing clinical risk factors and MTHFR A1298C might be used for prediction of ALT elevation in MTX treated patients. In Paper III a Genome-Wide Association Study (GWAS) and analysis of candidate Single Nucleotide Polymorphisms (SNPs) were performed. Four SNPs in and upstream of the ribonucleoprotein, PTB Binding 2 gene on chromosome 1 were associated with max ALT within 6 months on a genome wide level (p<5x10-8). Our results indicate that the RAVER2 and/or JAK1 genes might play a role in MTX- induced hepatotoxici-ty, but further studies are necessary for confirmation of the results. In Paper IV, we performed a population based case-control study. Several RA-associated risk factors (treatment with leflunomide, azathioprine or prednisolone and concomitant obstructive lung disease) may contribute to the increased TB risk in biologics-naïve RA patients. We could not confirm previous findings of an association with the use of moderate to high doses of prednisolone (≥15 mg). TB risk seems difficult to predict with precision in the individual biologics-naïve patient based on RA-associated risk factors. This suggests TB screening should be considered in biologics-naïve patients.In conclusion, results from these studies suggest that several factors could increase the risk of AEs in RA patients. The risk might be reduced by utilizing prediction models that include knowledge about the medical history of the individual patient and genetic data in combination with screening for TB.
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| 40. |
- Lindquist, Susanne, et al.
(författare)
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A novel target for treatment of inflammatory joint diseases
- 2019
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 78, s. 1525-1526
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The bile salt-stimulated lipase (BSSL) is a hitherto unrecognized player in inflammation. Animals devoid of BSSL (knockout mice) are protected from developing collagen induced arthritis (CIA) and collagen antibody induced arthritis (CAIA), and antibodies directed towards BSSL has been proven to prevent or mitigate arthritis in mouse and rat arthritis models1. In humans, BSSL is present in blood2 and accumulate at sites of inflammation. Patients with acute pancreatitis have significantly increased plasma BSSL levels compared to healthy controls. Whether BSSL in blood originates from pancreas, inflammatory cells, or both remains to be elucidated.Objectives: To determine BSSL concentration in blood samples from patients with inflammatory joint disorders and to evaluate possible relationships between circulating BSSL levels and disease-activity variables.Methods: BSSL concentrations in plasma or serum were determined in patients with rheumatoid arthritis (RA), psoriasis arthritis (PsA), and juvenile idiopathic arthritis (JIA) by a sandwich enzyme-linked immunosorbent assay (ELISA). Correlations between BSSL concentrations and disease activity score, erythrocyte sedimentation rate (ESR), blood levels of C-reactive protein (CRP), S100A8/9, leukocyte- and neutrophil counts, proinflammatory cytokines and chemokines were analyzed using Spearman rank-order correlation.Results: Significant correlations between BSSL concentration in plasma and disease activity score (DAS28, rS=0.31, p=0.007), ESR (rS=0.58, p<0.000), CRP (rS=0.42, p=0.012), leukocytes (rS=0.66, p<0.000), and neutrophils (rS=0.71, p<0.000) were found in RA. The BSSL plasma concentration decreased with duration of treatment with the TNFα inhibitor infliximab, in parallel with decreasing DAS28 score.BSSL concentration was significantly higher in sera from PsA patients with both oligo- and polyarthritis compared with healthy controls. Moreover, BSSL concentration in serum correlated significantly with S100A8/A9 and CRP concentrations (rS=0.54, p<0.001 and rS=0.49, p<0.001, respectively). No correlation between levels of BSSL and cytokines or chemokines were found in RA or PsA plasma or serum, respectively.In JIA, levels of BSSL in serum correlated significantly with JIA disease activity score (JADAS27) (rS=0.26, p=0.007), ESR (rS=0.47, p<0.000), and leukocytes (rS=0.32, p<0.000).Conclusion: BSSL concentration in serum and plasma correlated with disease activity in patients with inflammatory joint disorders, i.e. RA, PsA and JIA. These data in humans support the relevance of our previous studies in rodents and therefore also our hypothesis 1 that BSSL is a novel target for treatment of inflammatory diseases.
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| 41. |
- Lindquist, Susanne, et al.
(författare)
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Effects of bile salt-stimulated lipase on blood cells and associations with disease activity in human inflammatory joint disorders
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:8
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Tidskriftsartikel (refereegranskat)abstract
- The bile salt-stimulated lipase (BSSL) was originally recognized as a lipolytic enzyme expressed by the exocrine pancreas and in some species, notably humans, the lactating mammary gland, being secreted into the duodenum and with the mother’s milk, respectively. However, BSSL is also present in the blood and has been assigned additional functions, even beyond the gastrointestinal tract. Conventional BSSL knockout mice are protected from developing disease in animal models of arthritis, and antibodies directed towards BSSL prevent or mitigate disease in similar models. The aim of this study was to investigate the role of BSSL as a newly discovered player in inflammation and specifically in inflammatory joint disorders. As part of mechanism of action, we here show that BSSL is secreted by neutrophils, interacts with monocytes and stimulates their migration in vitro. An anti-BSSL antibody that blocks the human BSSL-monocyte interaction was shown to simultaneously prevent the signaling pathway by which BSSL induce cell migration. Moreover, in this cohort study we show that BSSL levels are significantly higher in blood samples from patients with rheumatoid arthritis and psoriatic arthritis compared to healthy controls. The BSSL levels in patients’ blood also correlated with disease activity scores and established inflammatory markers. Hence, although the mode of action is not yet fully clarified, we conclude that BSSL could be considered a proinflammatory component in the innate immune system and thus a possible novel target for treatment of chronic inflammation.
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| 42. |
- Lindqvist, U., 1948-, et al.
(författare)
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DAPSA, DAS28 and MDA predict long-term treatment regime in psoriatic arthritis : The Swedish Early Psoriatic Arthritis Cohort
- 2017
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Ingår i: Clinical and Experimental Rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 35:6, s. 936-942
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe treatment patterns in the Swedish early psoriatic arthritis cohort (SwePsA) of the mono-/oligo-arthritic (M/O) and polyarthritis (P) and identify early predictive factors for treatment with disease-modifying anti-rheumatic (DMARD), non-steroidal anti-inflammatory drugs (NSAID), and tumour necrosis factor inhibition (TNFi) after 5 years.Methods: Data for 198 M/O and P PsA were obtained within the programme for SwePsA. Multinomial and binary logistic regression analyses were used to assess the association between early predictive factors and treatment after 5 years adjusted for age at inclusion. The analysis of DMARD/NSAID was adjusted for medication at inclusion.Results: After inclusion visit, DMARD was prescribed in 30% of M/O and 56% of P PsA; mainly methotrexate. TNFi was not prescribed at inclusion, but 23 patients were treated at 5-year follow-up. The adjusted OR (95% CI) for treatment with both DMARD and NSAID after 5 years was 3.65 (1.34 - 9.89) (p=0.010) for Disease Activity Score 28 (DAS28) >3.2 and 2.90 (1.20-6.99) (p=0.038) for Disease Activity Index in Psoriatic Arthritis (DAPSA) >14 at inclusion. TNFi treatment was, after adjusting for age, associated with high erythrocyte sedimentation rate (p=0.0043), high C-reactive protein (p=0.013), DAPSA (p<0.001), not reaching minimal disease activity (p=0.001) high health assessment questionnaire (p=0.001), patient's overall assessment on the visual analogue scale (VAS) (p=0.009), high pain VAS (p=0.007), and high number of tender and swollen joints (p=0.031) at inclusion.Conclusion: Disease activity in early M/O and P PsA is to be considered in deciding the level of health care assessment and future pharmacological treatment. DAS28 >3.2 and DAPSA>14 early in the disease predict subsequent treatment with DMARD. For prediction of biological treatment, not reaching MDA at onset of disease, would be the composite index of choice.
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| 43. |
- Lindqvist, Ulla, 1948-, et al.
(författare)
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Psoriasisartrit
- 2011. - 2. uppl
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Ingår i: Reumatologi. - Stockholm : Studentlitteratur. - 9789144055329 ; , s. 111-118
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 44. |
- Lindqvist, Ulla R., et al.
(författare)
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The Swedish early psoriatic arthritis register--2-year followup : a comparison with early rheumatoid arthritis
- 2008
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 35:4, s. 668-673
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Patients with symptoms and signs compatible with psoriatic arthritis (PsA), with or without psoriasis, have been documented in the Swedish Early Psoriatic Arthritis (SwePsA) register. Our aim was to find markers for disease progression and to evaluate treatments for PsA using these data. METHODS: Patients referred to rheumatology outpatient clinics within 2 years of onset were assessed on inclusion and at followup 2 years later. Data collection was performed according to the program for SwePsA, and classification was as described by Moll and Wright and the ClASsification Criteria for Psoriatic ARthritis (CASPAR). Remission was recorded if the patient had no tender or swollen joints and if erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were within the reference range. Patients with early rheumatoid arthritis (RA) recruited from the Swedish Early Rheumatoid Arthritis Register (Ramona) provided comparison data. RESULTS: One hundred thirty-five patients with PsA according to CASPAR were assessed; 44% were classified as having mono/oligoarthritis and 47% as polyarthritis. Two patients (1%) were in remission initially, and 23 (17%) at followup. Patients with polyarticular disease had the highest inflammatory activity, measured by swollen and tender joint counts, ESR, Health Assessment Questionnaire, and self-assessment by visual analog scale of pain and global disease activity. Dactylitis was associated with radiological findings. Compared with RA patients, they had significantly lower CRP, ESR, and number of swollen joints (p = 0.0003, p = 0.0026, p = 0.0380, respectively) at inclusion, but equal numbers of tender joints and self-assessment of pain and disease activity. CONCLUSION: About half the patients had polyarthritis and the other half had mono/oligoarthritis at followup after 2 years. Patients with polyarthritis had the highest inflammatory activity. Apart from ESR, CRP, and swollen joint count, there were no significant differences in activity between RA and polyarticular PsA.
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- Lindström, Ulf, et al.
(författare)
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Methotrexate treatment in early psoriatic arthritis in comparison to rheumatoid arthritis: an observational nationwide study
- 2023
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Ingår i: Rmd Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionWe aimed to compare the proportions of patients with newly diagnosed psoriatic arthritis (PsA) and rheumatoid arthritis (RA) remaining on methotrexate (regardless of other disease-modifying antirheumatic drug (DMARD)-changes), and proportions not having started another DMARD (regardless of methotrexate discontinuation), within 2 years of starting methotrexate, as well as methotrexate effectiveness. MethodsPatients with DMARD-naive, newly diagnosed PsA, starting methotrexate 2011-2019, were identified from high-quality national Swedish registers and matched 1:1 to comparable patients with RA. Proportions remaining on methotrexate and not starting another DMARD were calculated. For patients with disease activity data at baseline and 6 months, response to methotrexate monotherapy was compared through logistic regression, applying non-responder imputation. ResultsIn total, 3642/3642 patients with PsA/RA were included. Baseline patient-reported pain and global health were similar, whereas patients with RA had higher 28-joint scores and evaluator-assessed disease activity. Two years after methotrexate start, 71% of PsA vs 76% of patients with RA remained on methotrexate, 66% vs 60% had not started any other DMARD, and 77% vs 74% had not started specifically a biological or targeted synthetic DMARD. At 6 months, the proportions of patients with PsA versus RA achieving pain-scores <= 15 mm were 26% vs 36%; global health <= 20 mm: 32% vs 42%; evaluator-assessed 'remission': 20% vs 27%, with corresponding adjusted ORs (PsA vs RA) of 0.63 (95% CI 0.47 to 0.85); 0.57 (95% CI 0.42 to 0.76) and 0.54 (95% CI 0.39 to 0.75). DiscussionIn Swedish clinical practice, methotrexate use is similar in PsA and RA, both regarding initiation of other DMARDs and methotrexate retention. On a group level, disease activity improved during methotrexate monotherapy in both diseases, although more so in RA.
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| 48. |
- Madsen, Rasmus Kirkegaard, 1979-, et al.
(författare)
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Diagnostic properties of metabolic perturbations in rheumatoid arthritis
- 2011
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 13:1, s. R19-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of the study was to assess the feasibility of diagnosing early rheumatoid arthritis (RA) by measuring selected metabolic biomarkers. METHODS: We compared the metabolic profile of patients with RA with those of healthy controls and patients with psoriatic arthritis (PsoA). The metabolites were measured using two different chromatography-mass spectrometry platforms, thereby giving a broad overview of serum metabolites. The metabolic profiles of patient and control groups were compared using multivariate statistical analysis. The findings were validated in a follow-up study of RA patients and healthy volunteers. RESULTS: RA patients were diagnosed with a sensitivity of 93 % and a specificity of 70 % in a validation study using detection of 52 metabolites. Patients with RA or PsoA could be distinguished with a sensitivity of 90 % and a specificity of 94 %. Glyceric acid, D-ribofuranoise and hypoxanthine were increased in RA patients, whereas histidine, threonic acid, methionine, cholesterol, asparagine and threonine were all decreased when compared with healthy controls. CONCLUSIONS: Metabolite profiling (metabolomics) is a potentially useful technique for diagnosing RA. The predictive value was irrespective of the presence of antibodies against cyclic citrullinated peptides (ACPA).
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| 49. |
- Testor, Pierre, et al.
(författare)
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OceanGliders: A component of the integrated GOOS
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
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Forskningsöversikt (refereegranskat)abstract
- The OceanGliders program started in 2016 to support active coordination and enhancement of global glider activity. OceanGliders contributes to the international efforts of the Global Ocean Observation System (GOOS) for Climate, Ocean Health and Operational Services. It brings together marine scientists and engineers operating gliders around the world: (1) to observe the long-term physical, biogeochemical, and biological ocean processes and phenomena that are relevant for societal applications; and, (2) to contribute to the GOOS through real-time and delayed mode data dissemination. The OceanGliders program is distributed across national and regional observing systems and significantly contributes to integrated, multi-scale and multi-platform sampling strategies. OceanGliders shares best practices, requirements, and scientific knowledge needed for glider operations, data collection and analysis. It also monitors global glider activity and supports the dissemination of glider data through regional and global databases, in real-time and delayed modes, facilitating data access to the wider community. OceanGliders currently supports national, regional and global initiatives to maintian and expand the capabilities and application of gliders to meet key global challenges such as improved measurement of ocean boundary currents, water transformation and storm forecast.
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- Theander, Elke, et al.
(författare)
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Early psoriatic arthritis : short symptom duration, male gender and preserved physical functioning at presentation predict favourable outcome at 5-year follow-up. Results from the Swedish Early Psoriatic Arthritis Register (SwePsA)
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 73:2, s. 407-413
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe Swedish Early Psoriatic Arthritis Register describes the course of early psoriatic arthritis (PsA) in a real life clinical setting in Sweden. The aim of this study was to obtain information on predictors of clinical outcomes over a 5-year period with special focus on effects of gender, joint patterns, diagnostic delay and initial disease activity.MethodsIn six centres, patients with signs suggestive of PsA were included in the Swedish Early Psoriatic Arthritis Register within 2 years of symptom onset. CASPAR (classification for psoriatic arthritis) criteria were fulfilled by 197 patients who had passed the 5-year follow-up. Disease activity was measured by the Disease Activity Score including 28 joints (DAS28) and the Disease Activity Index for Psoriatic Arthritis (DAPSA). Remission and minimal disease activity (MDA) were used as outcome measures.ResultsMean age at inclusion was 46 years, younger in male than female patients (43 vs 48 years). Mean DAS28 was 3.7 and 3.0 at inclusion and 2.8 and 2.1 at follow-up for women and men, respectively-significantly higher in women at both visits. Likewise, DAPSA scores were significantly higher in women. The degree of improvement (change in DAS28 and DAPSA) was similar. Men achieved MDA or remission (50% vs 33%, 25% vs 13%, respectively) more often, and women had significantly more polyarthritis at inclusion (49% vs 27%) and after 5 years (25% vs 15%). Axial or mono/oligoarticular disease was predominant in men. Independent predictors of MDA at the 5-year follow-up were: shorter symptom duration; greater general wellbeing (global visual analogue scale); and low Health Assessment Questionnaire at inclusion.ConclusionsIn early PsA, short delay between onset of symptoms and diagnosis, preserved function, and male gender are the most important predictors of favourable clinical outcome at the 5-year follow-up. Early recognition of PsA and active treatment may be important, particularly in women with polyarticular disease.
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