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| 2. |
- Enocsson, Helena, et al.
(författare)
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Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus
- 2020
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 106
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE. Methods: Included were 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who met the 1997 American College of Rheumatology classification criteria with 5-years of follow-up data available. Baseline sera from patients and age- and sex-matched controls were assayed for suPAR. Organ damage was assessed annually using the SLICC/ACR damage index (SDI). Results: The levels of suPAR were higher in patients who accrued damage, particularly those with SDI≥2 at 5 years (N = 32, 46.8% increase, p = 0.004), as compared to patients without damage. Logistic regression analysis revealed a significant impact of suPAR on SDI outcome (SDI≥2; OR = 1.14; 95% CI 1.03–1.26), also after adjustment for confounding factors. In an optimized logistic regression to predict damage, suPAR persisted as a predictor, together with baseline disease activity (SLEDAI-2K), age, and non-Caucasian ethnicity (model AUC = 0.77). Dissecting SDI into organ systems revealed higher suPAR levels in patients who developed musculoskeletal damage (SDI≥1; p = 0.007). Conclusion: Prognostic biomarkers identify patients who are at risk of acquiring early damage and therefore need careful observation and targeted treatment strategies. Overall, suPAR constitutes an interesting biomarker for patient stratification and for identifying SLE patients who are at risk of acquiring organ damage during the first 5 years of disease.
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| 3. |
- Walhelm, T., et al.
(författare)
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FACTORS ASSOCIATED WITH SURVIVAL AND DISCONTINUATION OF ANTIMALARIAL AGENTS IN SYSTEMIC LUPUS ERYTHEMATOSUS : RESULTS FROM A SWEDISH LONGITUDINAL REGISTRY
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 902-903
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Hydroxychloroquine (HCQ) and chloroquine, referred to as antimalarial agents (AMA), are cornerstone drugs in systemic lupus erythematosus (SLE), which inhibit type I interferon release via toll-like receptor binding and increasing the pH in plasmacytoid dendritic cell lysosomes [1]. AMA use has established benefits in SLE, such as improved prognosis and decelerated accrual of organ damage. Use of HCQ is safe for most patients and serious side-effects are uncommon, even during pregnancy. Medical therapy to prevent repeated disease flares is of essential weight in the treatment of SLE. However, it is well-known that non-adherence to prescription of AMA is a considerable problem [2].Objectives: The aim of this cross-sectional study was to investigate the frequency of AMA prescription, and evaluate factors associated with ongoing use and discontinuation of AMA in a Swedish SLE population.Methods: We retrieved data from the Clinical Lupus Register in North-Eastern Gothia (Swedish acronym: KLURING), a longitudinal research and quality registry, including all prevalent and incident cases of SLE in the Östergötland County from 2008 onwards. All included subjects fulfilled the validated 1982 American College of Rheumatology (ACR) and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria and had been diagnosed from 1963 onwards. Factors associated with ongoing use and discontinuation of AMA were investigated using logistic regression analysis, Mann-Whitney U test and chi-square test.Results: A total of 328 subjects were included in the analysis. The mean age at diagnosis was 40.0 years (range: 3–85; standard deviation [SD]: 17.7) and 85.7% were females. The mean SLICC/ACR damage index (SDI) score at last visit was 2.0 (range: 0—11; SD: 2.5). In total, 92.4% had used AMA at some point during their disease course (“ever” users; Table 1). Data from the last available visit indicated that 73.2% were currently prescribed AMA, exclusively HCQ, yielding a daily mean HCQ dose of 228.0 mg (range: 100—400; SD: 71.0). Among individuals who had discontinued AMA, 25.9% had developed a contraindication, mostly on ophthalmological basis (33.3%). Less common reasons were cardiac conditions (19.0%) and renal failure (9.5%). Subjective side-effects were also common; the most frequently reported were gastrointestinal symptoms (n=20/37). Most common patient-related factor associated with discontinuation was intentional non-adherence (e.g., low motivation; 8/11). Patients who had discontinued AMA showed a higher SDI score at the last visit (mean: 2.9; SD: 2.8; mean follow-up: 20.0 years) compared with patients on AMA (mean: 1.4; SD: 1.8; p=0.001; mean follow-up: 15.3 years). Those who fulfilled the immunological disorder ACR criterion (ACR-10) were more likely to continue on AMA (p=0.003). No significant differences were found regarding gender or smoking status. Conclusion: The vast majority of patients in KLURING had been exposed to AMA, and approximately 25% discontinued AMA therapy during follow-up. The main reason for discontinuation were therapy-related factors, such as contraindications and experience of side-effects. Above 50% of the reported side-effects that led to discontinuation were gastrointestinal symptoms. The group of discontinued AMA users accrued more damage over time.References:[1]Crow MK, Rönnblom L. Type I interferons in host defence and inflammatory diseases. Lupus Sci Med 2019;6:e000336[2]Costedoat-Chalumeau N, Houssiau F, Izmirly P, et al. A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self-Administered Questionnaires. Clin Pharmacol Ther 2018;103:1074-1082
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| 4. |
- Wirestam, Lina, 1986-, et al.
(författare)
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Osteopontin and disease activity in patients with recent-onset systemic Lupus Erythematosus : Results from the SLICC Inception Cohort
- 2019
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 46:5, s. 492-500
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Tidskriftsartikel (refereegranskat)abstract
- Objective. In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes. Methods. We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively. Results. Compared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01). Conclusion. The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.
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