| 1. |
- Askling, J., et al.
(författare)
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How comparable are rates of malignancies in patients with rheumatoid arthritis across the world? A comparison of cancer rates, and means to optimise their comparability, in five RA registries
- 2016
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 75:10, s. 1789-1796
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Tidskriftsartikel (refereegranskat)abstract
- Background The overall incidence of cancer in patients with rheumatoid arthritis (RA) is modestly elevated. The extent to which cancer rates in RA vary across clinical cohorts and patient subsets, as defined by disease activity or treatment is less known but critical for understanding the safety of existing and new antirheumatic therapies. We investigated comparability of, and means to harmonise, malignancy rates in five RA registries from four continents. Methods Participating RA registries were Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (several countries) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data, and sensitivity analyses of sub-cohorts defined by disease activity, treatment change, prior comorbidities and restricted by calendar time or follow-up, respectively. Malignancy rates with 95% CIs were estimated, and standardised for age and sex, based on the distributions from a typical RA clinical trial programme population (fostamatinib). Results There was a high consistency in rates for overall malignancy excluding non-melanoma skin cancer (NMSC), for malignant lymphomas, but not for all skin cancers, across registries, in particular following age/sex standardisation. Standardised rates of overall malignancy excluding NMSC varied from 0.56 to 0.87 per 100 person-years. Within each registry, rates were generally consistent across sensitivity analyses, which differed little from the main analysis. Conclusion In real-world RA populations, rates of both overall malignancy and of lymphomas are consistent.
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| 2. |
- Che, WI, et al.
(författare)
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Familial aggregation and heritability: a nationwide family-based study of idiopathic inflammatory myopathies
- 2021
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 80:11, s. 1461-1466
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Tidskriftsartikel (refereegranskat)abstract
- The magnitude of the genetic contribution to idiopathic inflammatory myopathies (IIMs) is unknown. In this project, we aimed to investigate the familial aggregation and heritability of IIM.MethodsThis is a family-based study using nationwide healthcare register data in Sweden. We matched each patient with IIM to individuals without IIM, identified their first-degree relatives and determined the IIM status among all first-degree relatives. We estimated the adjusted ORs (aORs) of familial aggregation of IIM using conditional logistic regression. In addition, we used tetrachoric correlation to estimate the heritability of IIM.ResultsWe included 7615 first-degree relatives of 1620 patients with IIM diagnosed between 1997 and 2016 and 37 309 first-degree relatives of 7797 individuals without IIM. Compared with individuals without IIM, patients with IIM were more likely to have ≥1 first-degree relative affected by IIM (aOR=4.32, 95% CI 2.00 to 9.34). Furthermore, the aOR of familial aggregation of IIM in full siblings was 2.53 (95% CI 1.62 to 3.96). The heritability of IIM was 22% (95% CI 12% to 31%) among any first-degree relatives and 24% (95% CI 12% to 37%) among full siblings.ConclusionsIIM has a familial component with a risk of aggregation among first-degree relatives and a heritability of about 20%. This information is of importance for future aetiological studies and in clinical counselling.
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| 3. |
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| 4. |
- Dobloug, GC, et al.
(författare)
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Mortality in idiopathic inflammatory myopathy: results from a Swedish nationwide population-based cohort study
- 2018
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 77:1, s. 40-47
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Tidskriftsartikel (refereegranskat)abstract
- Patients with idiopathic inflammatory myopathies (IIMs) suffer an increased burden of comorbidities, but data on mortality in recently diagnosed IIM are conflicting. Also, little is known when, if ever, in relation to IIM diagnosis, mortality is increased.A population-based IIM cohort of patients diagnosed between 2002 and 2011 and general population comparators were identified using healthcare registers. They were linked to the cause of death register for follow-up.Results224 (31%) of the 716 patients with IIM and 870 (12%) of the 7100 general population died during follow-up. This corresponded to a mortality rate of 60/1000 person-years in IIM and 20/1000 person-years in the general population. The cumulative mortality at 1 year after diagnosis was 9% in IIM and 1% in the general population, and increased in both IIM and the general population with time. The overall hazard ratio (HR) 95%CI of death comparing IIM with the general population was 3.7 (3.2 to 4.4). When we stratified on time since diagnosis, we noted an increase in mortality already within the first year of diagnosis compared with the general population, HR 9.6 (95% CI 6.9 to 13.5). This HR then plateaued around 2 after >10 years with the disease, although the estimates were not statistically significant. Malignancies, diseases of the circulatory and respiratory system were common causes of death.ConclusionMortality is increased in patients with contemporary IIM. The increased mortality was noted within a year of diagnosis, which calls for extra vigilance during the first year of IIM diagnosis.
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| 5. |
- Espinosa-Ortega, F, et al.
(författare)
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AUTOANTIBODIES CAN PARTLY PREDICT SEVERITY OF DAMAGE BUT NOT EXTENT IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOSITIS
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 398-399
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Patients with idiopathic inflammatory myopathies (IIM) might suffer from irreversible damage once inflammation has decreased. Autoantibodies are found in up to 80% of patients with IIM and are coupled with specific clinical features. Whether autoantibodies can be used as biomarkers to predict patterns of damage in IIM remains unknown.Objectives:To investigate the association between autoantibodies and organ damage in patients with IIM using longitudinal national register data.Methods:Data were retrieved from the electronic Swedish Rheumatology Quality Register (SRQ). Patients (n=302) with a clinical diagnosis of IIM (2017 EULAR/ACR criteria) were included. Autoantibody status was tested by either line blot or RNA- and protein immunoprecipitation; HMGCR and FHL-1 autoantibodies were tested by ELISA. Patients were grouped into six categories of autoantibodies (Table 1). TheMyositis Damage Index(MDI) score was applied to measure organ damage using both components (extentandseverity) as a continuous variable and were analyzed using generalized estimating equations (GEE). A categorical variable for each time point of MDI assessment since diagnosis was created to adjust for time (Table 2). A base model which included autoantibody group and time was fit. Other potential predictors included age at diagnosis, sex, disease duration from diagnosis to inclusion to SRQ, arthritis, Raynaud, mechanics’ hands and heart involvement at registry; core set measures at each MDI time point allowing multiple longitudinal observations were also tested.Table 1.Clinical diagnosis and autoantibody groups.DiagnosisN (%)Polymyositis119 (38)Dermatomyositis (DM)99 (33)Inclusion body myositis35 (12)Amyopathic DM9 (3)Juvenile DM8 (3)Low probability myositis32 (11)Autoantibody286 (%)Antisynthetase (AS)74 (26)Necrotizing myopathy NM)20 (7)DM- specific44 (15)FHL-118 (6)Associated antibodies AA)50 (18)Negative to any80 (28)AS: Jo1, PL7, PL12, EJ, OJ;NM: SRP, HMGCR;DM-specific: TIF1γ, Mi2, MDA5, SAE;AA: Ro52, PmScl, U1RNP, KU.Table 2.Predictors of damage severity and extent.EstimateP valueSeverityTime#0.20NSAutoantibody group1Negativereference--Antisynthetase-0.6NSIMNM1.6NSDM- specific-2.6**FHL-10.4NSAssociated0.7NSMMT score1-0.1***ExtentTime#0.33NSCK, mkat/L2-0.006*#Time from diagnosis to MDI. *<0.05**<0.01***<0.0011. Adjusted for gender + disease duration + time.2. Adjusted for disease duration + time.Results:Mean age at diagnosis was 54 years (SD 16), 205 were female (68%), median disease duration was 4 months (IQR 1-39). Clinical diagnosis and the autoantibody groups are shown in Table 1. The median time from diagnosis to the first MDI assessment was 2.2 years (IQR 1.2 – 5.5), 227 patients had a second MDI assessment at median 4.5 years (3.3-8.6 years) and 114 patients had a third assessment at 7.8 (5.8-9.9) years.Severity of damage:Only the DM-specific autoantibodies (P = 0.01) and manual muscle test score (MMT) (P = 0.007) were independent negative predictors; disease duration was a positive predictor (P = 0.01).Extent of damage: Autoantibodies were not significant predictors; creatine kinase (CK) levels were negative predictors (P = 0.01) (Table 2).Conclusion:Presence of DM-specific autoantibodies, a high MMT score over time and short disease duration seem to predict less damage severity whereas high CK levels seem to predict of less extent of damage. These findings indicate that some myositis specific autoantibodies may serve as predictors of damage along with other clinical measures.References:[1]Sultan SM, et al. Interrater reliability and aspects of validity of the myositis damage index. Annals of the Rheumatic Diseases. 2011;70:1272-6.Disclosure of Interests:Fabricio Espinosa-Ortega: None declared, Marie Holmqvist: None declared, Maryam Dastmalchi: None declared, Andrew Mammen: None declared, Ingrid E. Lundberg Grant/research support from: Bristol Meyer Squibb, Corbus Pharmaceuticals, Inc and Astra Zeneca, Helene Alexanderson: None declared
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| 6. |
- Hart, JE, et al.
(författare)
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Ambient air pollution exposures and risk of rheumatoid arthritis: results from the Swedish EIRA case-control study
- 2013
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 72:6, s. 888-894
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Tidskriftsartikel (refereegranskat)abstract
- Environmental factors may play a role in the development of rheumatoid arthritis (RA). We examined whether long-term exposures to air pollution were associated with the risk of RA in the Swedish Epidemiological Investigation of Rheumatoid Arthritis Study.MethodsWe studied 1497 incident RA cases and 2536 controls. Local levels of particulate matter (PM10) and gaseous pollutants (sulphur dioxide (SO2) and nitrogen dioxide (NO2)) from traffic and home heating were predicted for all residential addresses. We examined the association of an IQR increase (2 µg/m3for PM10, 8 µg/m3for SO2and 9 µg/m3for NO2) in each pollutant at different time points before symptom onset and average exposure with the risk of all RA and the risk of the rheumatoid factor and anti-citrullinated protein antibody (ACPA) RA phenotypes.ResultsThere was no evidence of an increased risk of RA with PM10. Total RA risks were modestly elevated for the gaseous pollutants, but were not statistically significant after adjustment for smoking and education (OR 1.18, 95% CI 0.97 to 1.43 and OR 1.09, 95% CI 0.99 to 1.19 for SO2and NO2in the 10th year before onset). Stronger elevated risks were observed for individuals with less than a university education and with the ACPA-negative RA phenotype.ConclusionsNo consistent overall associations between air pollution in the Stockholm area and the risk of RA were observed. However, there was a suggestion of increased risks of RA incidence with increases in NO2from local traffic and SO2from home heating sources with stronger associations for the ACPA-negative phenotype.
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| 9. |
- Leclair, V, et al.
(författare)
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HLA-DRB1 ASSOCIATIONS WITH AUTOANTIBODY-DEFINED SUBGROUPS IN IDIOPATHIC INFLAMMATORY MYOPATHIES (IIM)
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 104-105
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- There is a gap between how IIM patients are classified in practice and current validated classification criteria1. Also, different associations with genetic variations in HLA can inform about different T-cell mechanisms involved in disease pathogenesis.ObjectivesWe aimed to systematically study associations between HLA-DRB1 alleles, clinical manifestations, and autoantibody-defined IIM subgroups.MethodsWe included 1348 IIM patients from five European countries. An unsupervised cluster analysis was performed using 14 autoantibodies: anti-Jo1, -PL7, -PL12, -EJ, -OJ, -SRP, -U1RNP, -Ro52, -Mi2, -TIF1γ, -MDA5, -PMScl, -SAE1, and -NXP2 to identify patients’ subgroups. Logistic regressions were used to estimate the associations between HLA-DRB1 alleles, clinical manifestations and the identified subgroups.ResultsEight subgroups were defined by the autoantibody status (Table 1). Three of the subgroups (1, 2 and 6) have overlapping autoantibodies, while four are almost monospecific (3,4,5 and 7), and one (8) has patients negative for tested autoantibodies. Figure 1 represents the significant associations between HLA-DRB1 alleles and the eight subgroups. Heliotrope rash and Gottron’s sign were significantly more frequent in subgroups 3 (OR:2.2 95%CI:[1.1-4.8], OR:2.6 95%CI:[1.3-5.9], respectively), 4 (OR:12 95%CI:[3.6-75], OR:7.8 95%CI:[2.8-33], respectively) and 7 (OR:22 95%CI:[4.5-385], OR:10 95%CI:[3.1-65], respectively), and Raynaud’s phenomenon was significantly more frequent in subgroup 6 (OR:3.3 95%CI:[1.2-11]).Table 1.Autoantibody-defined subgroups using an unsupervised cluster analysis.Subgroups/ MedoidsVariables1 Ro522 U1RNP3 PMScl4 Mi25 Jo16 Jo1/Ro527 TIF18 None*Alln (%)137 (10)183 (14)107 (8)65 (5)119 (9)140 (10)78 (6)519 (39)1348 (100)Female (%)93 (68)116 (63)79 (74)45 (69)76 (64)96 (69)64 (82)313 (60)882 (65)Age at diagnosis, median (IQR)56 (16)51.5 (23)51 (25)57 (22.5)47.5 (23.25)52 (19.5)53.5 (21.75)58 (22)55 (23)AutoantibodiesAnti-Jo106 (3)01 (2)119 (100)140 (100)00266 (20)Anti-PL77 (5)13 (7)00000020 (1.5)Anti-PL125 (4)3 (2)1 (1)01 (1)00010 (0.7)Anti-EJ2 (2)00000002 (0.1)Anti-OJ07 (4)0000007 (0.5)Anti-TIF110 (7)2 (1)2 (2)00078 (100)092 (7)Anti-Mi21 (1)1 (1)1 (1)65 (100)02 (1)0070 (5)Anti-SAE18 (6)23 (13)00000031 (2)Anti-NXP21 (1)23 (13)1 (1)0000025 (2)Anti-MDA59 (7)10 (6)1 (1)1 (2)01 (1)0022 (2)Anti-SRP8 (6)32 (18)00000040 (3)Anti-Ro52137 (100)16 (9)000140 (100)00293 (22)Anti-PMScl11 (8)1 (1)107 (100)00000119 (9)Anti-U1RNP079 (43)0003 (2)0082 (6)*IIM patients negative for the tested autoantibodies.Figure 1.Forest plot of significant associations of HLA. *DRB1 alleles with autoantibody-defined subgroups. Scandinavia includes patients from Denmark, Norway, and Sweden.ConclusionOur study reveals that certain subgroups of IIM patients are characterized by overlap of myositis -specific and -associated autoantibodies, which in turn are associated with different HLA-DRB1 alleles including potential novel associations. These results point to different disease mechanisms in the subgroups, as well as suggest that IIM classification could be improved by integrating broader serological and genetic data.References[1]Parker MJS, Oldroyd A, Roberts ME, et al. The performance of the European League Against Rheumatism/American College of Rheumatology idiopathic inflammatory myopathies classification criteria in an expert-defined 10 year incident cohort. Rheumatology (Oxford). 2019;58(3):468-475.AcknowledgementsWe thank all the patients who participated in the study.Disclosure of InterestsValerie Leclair: None declared, Angeles Shunashy Galindo-Feria: None declared, Simon Rothwell: None declared, Olga Kryštůfková: None declared, Heřman Mann: None declared, Louise Pyndt Diederichsen: None declared, helena andersson: None declared, Martin Klein: None declared, Sarah Tansley: None declared, Neil McHugh: None declared, Janine Lamb: None declared, Jiří Vencovský Speakers bureau: Abbvie, Biogen, Boehringer, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Werfen, Consultant of: Abbvie, Argenx, Boehringer, Eli Lilly, Gilead, Octapharma, Pfizer, UCB, Grant/research support from: Abbvie, Hector Chinoy: None declared, Marie Holmqvist: None declared, Leonid Padyukov: None declared, Ingrid E. Lundberg Shareholder of: Roche and Novartis, Consultant of: Corbus Pharmaceuticals Inc, Astra Zeneca, Bristol Myer´s Squibb, Corbus Pharmaceutical, EMD Serono Research & Development Institute, Argenx, Octapharma, Kezaar, Orphazyme, and Janssen, Grant/research support from: Astra Zeneca, Lina M. Diaz-Gallo: None declared
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