| 1. |
- Huang, X. F., et al.
(författare)
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Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci
- 2020
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 61:6
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B 27 , implying a shared etiology. This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS. METHODS. We undertook the GWAS analyses in 2752 patients with AS with AAU (cases) and 3836 patients with AS without AAU (controls). There were 7,436,415 single-nucleotide polymorphisms (SNPs) available alter SNP microarray genotyping, imputation, and quality-control filtering. RESULTS. We identified one locus associated with AAU at genomewide significance: rs9378248 (P = 2.69 x 10(-8), odds ratio [OR] = 0.78), lying close to HLA-B. Suggestive association was observed at 11 additional loci, including previously reported AS loci ERAP1 (rs27529, P = 2.19 x 10(-7), OR = 1.22) and NOS2 (rs2274894, P = 8.22 x 10(-7), OR = 0.83). Multiple novel suggestive associations were also identified, including MERTK (rsl0171979, P = 2.56 x 10(-6), OR = 1.20), KIFAP3 (rs508063, P = 5.64 x 10(-7), OR = 1.20), CLCN7 (rs67412457, P = 1.33 x 10(-6), OR = 1.25), ACAA2 (rs9947182, P = 9.70 x 10(-7), OR = 1.37), and 5 intergenic loci. The SNP-based heritability is approximately 0.5 for AS alone, and is much higher (approximately 0.7) for AS with AAU. Consistent with the high heritability, a genomewide polygenic risk score shows strong power in identifying individuals at high risk of either AS with AAU or AS alone. CONCLUSIONS. We report here the first GWAS for AAU and identify new susceptibility loci. Our findings confirm the strong overlap in etiopathogenesis of AAU with AS, and also provide new insights into the genetic basis of AAU.
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| 2. |
- Bengtsson, K., et al.
(författare)
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Higher risk of incident fracture in patients with ankylosing spondylitis compared to the general population
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79, s. 745-746
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Ankylosing spondylitis (AS) is characterized by pathologic new bone formation and bone loss. Vertebral fracture (VF) is a known complication of AS, whereas the risk of other major osteoporotic fractures (MOFs) is less studied.Objectives: To estimate incidence rates (IRs) of incident fractures (any, VF and other MOF (humerus, forearm and hip)) in patients with AS compared to controls from general population.Methods: This is a nationwide, register-based and observational cohort study including patients diagnosed with AS (n=11611, 65% men, mean age 48 years) identified in the National patient register (NPR) 2001 through 2015, and age- and sex-matched controls (n=58050) from the Swedish Population Register. The study period started 1 January 2007 or 3 months after the first AS diagnosis, whichever came later, and ended at the first occurrence of each fracture outcome (identified in the NPR), death, emigration or 31 December 2016. Patients and controls with any prior fracture in NPR within a 6-year period before start of the study period were not included. Any fracture (except skull and phalangeal fractures), VF and other MOF were identified in NPR according to pre-specified ICD codes. Each fracture outcome was analysed separately. Poisson regression was used to calculate IRs and incidence rate ratios (IRRs), overall and stratified by sex. Kaplan-Meier curves were plotted.Results: In total 807 (7.0%) of patients with AS and 3201 (5.5%) of matched controls had a history of prior fracture within a 6-year period, and were excluded from further analyses. We noted higher IRs for any fracture, VF and other MOF in AS vs controls, see Figure for Kaplan-Meier curves and Table for IRs and IRRs. In sex-stratified analyses, men with AS (vs. male controls) had a higher relative risk for all fracture outcomes, whereas among women with AS (vs. female controls), a higher relative risk was demonstrated for any fracture and VF. 5-year cumulative incidence for any fracture, VF and other MOF was 6.2%, 1.6% and 1.7%, respectively in AS and 4.3%, 0.3% and 1.2%, respectively in controls.
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| 3. |
- Dehlin, Mats, 1968, et al.
(författare)
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Consequences of Gout and Hyperuricemia : Gikt och hyperurikemi starkt associerade med folksjukdomar
- 2020
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Ingår i: Läkartidningen. - 1652-7518. ; 117
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Tidskriftsartikel (refereegranskat)abstract
- Hyperuricemia (HU) and gout are strongly associated with CVD, associations that are most likely due to shared etiologies rather than causality. HU is for example causally related to the metabolic syndrome and in particular to obesity. Gout and HU can both be caused by and lead to decreased kidney function. On the other hand, there are observational data suggesting that HU may protect against neurodegenerative diseases such as Alzheimer and Parkinson's disease. Ongoing RCTs with urate and urate lowering therapy (ULT) will help to resolve some of these controversies. Nevertheless, gout is a "curable disease" by ULT, a treatment which in adequate doses may also have positive effect on several associated co-morbidities.
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| 4. |
- Drivelegka, Panagiota, et al.
(författare)
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Association between serum level of urate and subclinical atherosclerosis: results from the SCAPIS Pilot
- 2020
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background Hyperuricemia is closely associated with cardiovascular disease (CVD). However, it has not been definitively established whether this association is independent of traditional cardiovascular risk factors (CVRFs) and whether it is gender-dependent. The aim of this study was to investigate in a population-based cohort (age range, 50-64 years) stratified by sex the association between the serum urate (SU) concentration and subclinical atherosclerosis, as reflected in the coronary artery calcification (CAC) score, common carotid intima-media thickness (CIMT), and carotid plaque score. Methods The study involved participants in the Swedish CArdioPulmonary bioImage Study (SCAPIS) Pilot cohort (N = 1040; 48.8% males). This pilot cohort is part of the large population-based SCAPIS with 30,000 participants in the age range of 50-64 years, aimed at improving risk prediction for CVD. Subjects with a self-reported previous history of CVD (N = 68) or gout (N = 3) were excluded. The CAC score was assessed with the Agatston method using computed tomography. CIMT and carotid plaques were quantified by ultrasound. The associations between the SU quartiles and different levels of CAC, CIMT, and carotid plaques were assessed by multivariable logistic regression. Results Age, BMI, education level, smoking, physical activity, hs-CRP, hypertension, and dyslipidemia showed no differences between males and females, while CAC (score > 0) and diabetes were both twice as common in men than in women (58% vs 26% and 8% vs 4%, respectively). Higher SU quartiles were in both sexes associated with BMI, hs-CRP, and the prevalence of hypertension, and in women, they were also associated with the prevalence of dyslipidemia. The three upper quartiles of SU (>308 mu mol/L) were linked to higher CAC scores in men, when adjusting for CVRFs, but not in women. CIMT and carotid plaques showed no correlation to SU in either sex. Conclusions Higher levels of SU are associated with the presence of CAC in men but not in women, whereas SU is not associated with CIMT or carotid plaques in either men or women. This implies that the biological effects of SU differ in men and women or that SU has varying effects on different vascular beds or during the different stages of the atherosclerotic process.
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| 5. |
- Hofstedt, O, et al.
(författare)
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Authors' reply
- 2020
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Ingår i: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 49:2, s. 171-172
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Lindström, U., et al.
(författare)
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Comparison of anterior uveitis occurrence during treatment with secukinumab, adalimumab, infliximab and etanercept in spondyloarthritis
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79, s. 9-10
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Randomized controlled trials indicate that compared to tumor necrosis factor inhibitors (TNFi), secukinumab (SEC) has similar efficacy regarding axial inflammation in spondyloarthritis (SpA), better efficacy regarding cutaneous psoriasis, but is inferior in inflammatory bowel disease (IBD). However, the efficacy of SEC compared to TNFi in anterior uveitis (AU) has not been extensively studied.Objectives:To compare the occurrence of AU in patients with SpA treated with SEC, adalimumab (ADA), infliximab (IFX) or etanercept (ETN), in clinical practice.Methods:Patients with ankylosing spondylitis or undifferentiated SpA starting either SEC, ADA, IFX or ETN, in 2015 through 2017, were identified in the Swedish Rheumatology Quality register, and were linked to the national patient register for identification of AU. AU-flares were defined as the number of visits with an AU diagnosis, separated by a ≥60 days penalty interval, within ophthalmology outpatient care, during the respective bDMARD treatment.Follow-up started at the bDMARD initiation, and ended at the first of Dec 31st2017, death, emigration or discontinuation date of the bDMARD.To assess and accommodate treatment channeling, crude incidence rates for AU-flares were determined (A) for all bDMARD treatment starts, (B) excluding patients with an AU diagnosis during the year prior to the bDMARD start, and (C) in addition, excluding all first line bDMARD treatment starts.Hazard ratios (HR) for time until a first on-treatment AU diagnosis were estimated using Cox regression (ADA=reference), adjusted for sex, age, and any history of AU, and estimating robust confidence intervals to account for the individuals contributing multiple lines of treatment.Results:In total, 2,684 patients (52% women) contributed 3,255 treatment initiations. SEC was less frequently used as first line bDMARD and there was channeling of patients with previous AU, towards treatment with ADA, and away from ETN (Table 1). Further, AU occurred almost exclusively in patients with a pre-treatment history of AU (data not shown).Table 1.AnalysisTreat-ment starts, NPrevious AU1Age at treat-ment start, mean (sd)N Previous bDMARD, medianHR (95% CI) for first AU-diagnosisAU flares, NFollow-up2, yearsA. All treatment starts, N=3255SEC33321%48 (13)22.0 (1.2-3.3)52241ADA87234%44 (12)1Ref175973IFX71421%43 (14)00.9 (0.6-1.4)68677ETN133617%44 (14)00.9 (0.7-1.3)1021290B. Excluding patients with prior AU within 1 year before treatment start, N=2907SEC30413%47 (13)23.1 (1.4-7.3)10212ADA71119%44 (13)1Ref18792IFX63311%43 (14)01.0 (0.4-2.3)8599ETN125912%44 (14)01.8 (1.0-3.4)431204C. Excluding patients with prior AU within 1 year before treatment start and first line bDMARD, N=1288SEC28414%48 (13)22.5 (1.0-6.2)10198ADA37418%45 (13)1Ref11384IFX18512%45 (14)21.3 (0.4-4.0)4166ETN44517%47 (14)11.9 (0.9-4.0)234391) Anterior uveitis between 2001 and treatment start; 2) Total follow-up time for analyses of incidence rate.The incidence rates of AU-flares were higher for SEC and ETN compared to ADA and IFX, in the analyses (B, C) accommodating for channeling, figure 1.Compared to ADA, the adjusted HRs of a first on-treatment AU-diagnosis were also higher for SEC and ETA, Table 1.Conclusion:In clinical practice, SEC and ETN are associated with a higher incidence of AU than ADA and INF, suggesting a poorer protective effect of SEC and ETN against AU. These preliminary results should be interpreted in light of pronounced treatment channeling, which was only partly accommodated for.Disclosure of Interests:Ulf Lindström: None declared, Karin Bengtsson: None declared, Tor Olofsson: None declared, Daniela Di Giuseppe: None declared, Bente Glintborg Grant/research support from: Grants from Pfizer, Biogen and Abbvie, Helena Forsblad-d’Elia Grant/research support from: Unrestricted grant from Novartis., Consultant of: Advisory Board Fees from Sandoz, Novartis, and Abbvie, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis and Pfizer, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma
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| 7. |
- Sigurdardottir, Valgerdur, et al.
(författare)
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Gout - a common and well known disease : Gikt – en känd och vanlig sjukdom.
- 2020
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Ingår i: Läkartidningen. - 1652-7518. ; 117:35-36
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Forskningsöversikt (refereegranskat)abstract
- Hyperuricemia is defined by a blood urate level > 405 µmol/L, the cut-off value at which urate forms crystals in vivo. In 15-20% these individuals develop gout, clinically characterized by attacks of acute arthritis, initially and most commonly affecting MTP 1 or other joints, tendons and soft tissues of the foot. These attacks usually subside within 1 to 2 weeks. Over time attacks occur more frequently and can transform into chronic arthritis characterized by tophi. The gold standard for diagnosis relies on identification of urate crystals by polarization microscopy in aspirated joint fluid. This procedure is rarely performed in primary care where the majority of patients are seen, and gout is usually diagnosed by clinical criteria. New imaging technologies (ultrasound, dual-energy CT) can be helpful when aspiration is not available and when the diagnosis is unclear. Gout has a prevalence of 1.7% and incidence rate of approximately 200 per 100000 person-years in Sweden, figures that increase over time.
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