| 1. |
- Almeida-Brasil, Celline C., et al.
(författare)
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Flares after hydroxychloroquine reduction or discontinuation : results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 81:3, s. 370-378
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate systemic lupus erythematosus (SLE) flares following hydroxychloroquine (HCQ) reduction or discontinuation versus HCQ maintenance. METHODS: We analysed prospective data from the Systemic Lupus International Collaborating Clinics (SLICC) cohort, enrolled from 33 sites within 15 months of SLE diagnosis and followed annually (1999-2019). We evaluated person-time contributed while on the initial HCQ dose ('maintenance'), comparing this with person-time contributed after a first dose reduction, and after a first HCQ discontinuation. We estimated time to first flare, defined as either subsequent need for therapy augmentation, increase of ≥4 points in the SLE Disease Activity Index-2000, or hospitalisation for SLE. We estimated adjusted HRs (aHRs) with 95% CIs associated with reducing/discontinuing HCQ (vs maintenance). We also conducted separate multivariable hazard regressions in each HCQ subcohort to identify factors associated with flare. RESULTS: We studied 1460 (90% female) patients initiating HCQ. aHRs for first SLE flare were 1.20 (95% CI 1.04 to 1.38) and 1.56 (95% CI 1.31 to 1.86) for the HCQ reduction and discontinuation groups, respectively, versus HCQ maintenance. Patients with low educational level were at particular risk of flaring after HCQ discontinuation (aHR 1.43, 95% CI 1.09 to 1.87). Prednisone use at time-zero was associated with over 1.5-fold increase in flare risk in all HCQ subcohorts. CONCLUSIONS: SLE flare risk was higher after HCQ taper/discontinuation versus HCQ maintenance. Decisions to maintain, reduce or stop HCQ may affect specific subgroups differently, including those on prednisone and/or with low education. Further study of special groups (eg, seniors) may be helpful.
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| 2. |
- Almeida-Brasil, Celline C., et al.
(författare)
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Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine
- 2022
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Ingår i: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Methods Data were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity. Results We studied 1460 patients (89% female, 52% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95% CI 1.01 to 1.09). Conclusions This is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis.
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| 3. |
- Barber, Megan R.W., et al.
(författare)
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Economic Evaluation of Damage Accrual in an International Systemic Lupus Erythematosus Inception Cohort Using a Multistate Model Approach
- 2020
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-464X .- 2151-4658. ; 72:12, s. 1800-1808
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Tidskriftsartikel (refereegranskat)abstract
- Objective: There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with damage states across the disease course using multistate modeling. Methods: Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten-year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multistate model. Results: A total of 1,687 patients participated; 88.7% were female, 49.0% were white, mean ± SD age at diagnosis was 34.6 ± 13.3 years, and mean time to follow-up was 8.9 years (range 0.6–18.5 years). Mean annual costs were higher for those with higher SDI scores as follows: $22,006 (Canadian) (95% confidence interval [95% CI] $16,662, $27,350) for SDI scores ≥5 versus $1,833 (95% CI $1,134, $2,532) for SDI scores of 0. Similarly, 10-year cumulative costs were higher for those with higher SDI scores at the beginning of the 10-year interval as follows: $189,073 (Canadian) (95% CI $142,318, $235,827) for SDI scores ≥5 versus $21,713 (95% CI $13,639, $29,788) for SDI scores of 0. Conclusion: Patients with the highest SDI scores incur 10-year cumulative costs that are ~9-fold higher than those with the lowest SDI scores. By estimating the damage trajectory and incorporating annual costs, data on damage can be used to estimate future costs, which is critical knowledge for evaluating the cost-effectiveness of novel therapies.
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| 4. |
- Barber, Megan R.W., et al.
(författare)
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Remission and low disease activity are associated with lower healthcare costs : results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - 0003-4967.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study aims to determine the independent impact of definitions of remission/low disease activity (LDA) on direct/indirect costs (DCs, ICs) in a multicentre inception cohort. Methods: Patients from 31 centres in 10 countries were enrolled within 15 months of diagnosis and assessed annually. Five mutually exclusive disease activity states (DAS) were defined as (1) remission off-treatment: clinical (c) SLEDAI-2K=0, without prednisone/immunosuppressants; (2) remission on-treatment: cSLEDAI-2K=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; (3) LDA-Toronto Cohort (TC): cSLEDAI-2K≤2, without prednisone/immunosuppressants; (4) modified lupus LDA state (mLLDAS): SLEDAI-2K≤4, no activity in major organs/systems, no new activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants and (5) active: all remaining assessments. At each assessment, patients were stratified into the most stringent DAS fulfilled and the proportion of time in a DAS since cohort entry was determined. Annual DCs/ICs (2021 Canadian dollars) were based on healthcare use and lost workforce/non-workforce productivity over the preceding year. The association between the proportion of time in a DAS and annual DC/IC was examined through multivariable random-effects linear regressions. Results: 1692 patients were followed a mean of 9.7 years; 49.0% of assessments were active. Remission/LDA (per 25% increase in time in a remission/LDA state vs active) were associated with lower annual DC/IC: remission off-treatment (DC -$C1372; IC -$C2507), remission on-treatment (DC -$C973; IC -$C2604,) LDA-TC (DC -$C1158) and mLLDAS (DC -$C1040). There were no cost differences between remission/LDA states. Conclusions: Our data suggest that systemic lupus erythematosus patients who achieve remission, both off and on-therapy, and reductions in disease activity incur lower costs than those experiencing persistent disease activity.
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| 5. |
- Bernatsky, Sasha, et al.
(författare)
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Cancer risk in systemic lupus: An updated international multi-centre cohort study
- 2013
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 42, s. 130-135
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To update estimates of cancer risk in SLE relative to the general population. Methods: A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Results: Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin's lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61-0.88), endometrial (SIR 0.44, 95% CI 0.23-0.77), and possibly ovarian cancers (0.64, 95% Cl 0.34-1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23). Conclusion: These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing. (C) 2013 Elsevier Ltd. All rights reserved.
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| 6. |
- Chew, Christine, et al.
(författare)
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Lower vitamin D is associated with metabolic syndrome and insulin resistance in systemic lupus : Data from an international inception cohort
- 2021
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Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 60:10, s. 4737-4747
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Vitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in SLE. We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance. Methods: The Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE (<15 months) from 33 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected. Vitamin D level was defined according to tertiles based on distribution across this cohort, which were set at T1 (10-36 nmol/l), T2 (37-60 nmol/l) and T3 (61-174 nmol/l). MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Insulin resistance was determined using the HOMA-IR model. Linear and logistic regressions were used to assess the association of variables with vitamin D levels. Results: Of the 1847 patients, 1163 (63%) had vitamin D measured and 398 (34.2%) subjects were in the lowest 25(OH)D tertile. MetS was present in 286 of 860 (33%) patients whose status could be determined. Patients with lower 25(OH)D were more likely to have MetS and higher HOMA-IR. The MetS components, hypertension, hypertriglyceridemia and decreased high-density lipoprotein (HDL) were all significantly associated with lower 25(OH)D. Increased average glucocorticoid exposure was associated with higher insulin resistance. Conclusions: MetS and insulin resistance are associated with lower vitamin D in patients with SLE. Further studies could determine whether vitamin D repletion confers better control of these cardiovascular risk factors and improve long-term outcomes in SLE.
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| 7. |
- Clarke, Ann E., et al.
(författare)
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Assessing the Costs of Neuropsychiatric Disease in the Systemic Lupus International Collaborating Clinics Cohort Using Multistate Modeling
- 2023
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-464X .- 2151-4658. ; 75:9, s. 1859-1870
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To estimate direct and indirect costs associated with neuropsychiatric (NP) events in the Systemic Lupus International Collaborating Clinics inception cohort. Methods: NP events were documented annually using American College of Rheumatology definitions for NP events and attributed to systemic lupus erythematosus (SLE) or non-SLE causes. Patients were stratified into 1 of 3 NP states (no, resolved, or new/ongoing NP event). Change in NP status was characterized by interstate transition rates using multistate modeling. Annual direct costs and indirect costs were based on health care use and impaired productivity over the preceding year. Annual costs associated with NP states and NP events were calculated by averaging all observations in each state and adjusted through random-effects regressions. Five- and 10-year costs for NP states were predicted by multiplying adjusted annual costs per state by expected state duration, forecasted using multistate modeling. Results: A total of 1,697 patients (49% White race/ethnicity) were followed for a mean of 9.6 years. NP events (n = 1,971) occurred in 956 patients, 32% attributed to SLE. For SLE and non-SLE NP events, predicted annual, 5-, and 10-year direct costs and indirect costs were higher in new/ongoing versus no events. Direct costs were 1.5-fold higher and indirect costs 1.3-fold higher in new/ongoing versus no events. Indirect costs exceeded direct costs 3.0 to 5.2 fold. Among frequent SLE NP events, new/ongoing seizure disorder and cerebrovascular disease accounted for the largest increases in annual direct costs. For non-SLE NP events, new/ongoing polyneuropathy accounted for the largest increase in annual direct costs, and new/ongoing headache and mood disorder for the largest increases in indirect costs. Conclusion: Patients with new/ongoing SLE or non-SLE NP events incurred higher direct and indirect costs.
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| 8. |
- 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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| 9. |
- Ferreira, Isabel, et al.
(författare)
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Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus; a multi-center retrospective case-control study
- 2017
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: In patients with systemic lupus erythematosus (SLE) there is no serological test that will reliably distinguish neuropsychiatric (NP) events due to active SLE from those due to other causes. Previously we showed that serum levels of nitrated nucleosomes (NN) were elevated in a small number of patients with NPSLE. Here we measured serum NN in samples from a larger population of patients with SLE and NP events to see whether elevated serum NN could be a marker for NPSLE. Methods: We obtained serum samples from patients in the Systemic Lupus International Collaborative Clinics (SLICC) inception cohort. This included 216 patients with NP events and two matched controls with SLE but no NP events for each of these patients. For the NP patients we tested samples taken before, during and after the NP event. Results: Twenty-six patients had events attributed to SLE according to the most stringent SLICC attribution rule. In these patients there was no association between onset of event and elevated serum NN. In 190 patients in whom events were not attributed to SLE by the SLICC rules, median serum NN was elevated at the onset of event (P = 0.006). The predominant clinical features in this group of 190 patients were headache, mood disorders and anxiety. Conclusions: Serum NN levels rise at the time of an NP event in a proportion of patients with SLE. Further studies are needed to determine the value of serum NN as a biomarker for NPSLE.
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| 10. |
- Hanly, John G., et al.
(författare)
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A Longitudinal Analysis of Outcomes of Lupus Nephritis in an International Inception Cohort Using a Multistate Model Approach
- 2016
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 68:8, s. 1932-1944
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study bidirectional change and predictors of change in estimated glomerular filtration rate (GFR) and proteinuria in lupus nephritis (LN) using a multistate modeling approach. Methods: Patients in the Systemic Lupus International Collaborating Clinics inception cohort were classified annually into estimated GFR state 1 (>60 ml/minute), state 2 (30–60 ml/minute), or state 3 (3.0 gm/day), or end-stage renal disease (ESRD) or death. Using multistate modeling, relative transition rates between states indicated improvement and deterioration. Results: Of 1,826 lupus patients, 700 (38.3%) developed LN. During a mean ± SD follow-up of 5.2 ± 3.5 years, the likelihood of improvement in estimated GFR and estimated proteinuria was greater than the likelihood of deterioration. After 5 years, 62% of patients initially in estimated GFR state 3 and 11% of patients initially in estimated proteinuria state 3 transitioned to ESRD. The probability of remaining in the initial states 1, 2, and 3 was 85%, 11%, and 3%, respectively, for estimated GFR and 62%, 29%, and 4%, respectively, for estimated proteinuria. Male sex predicted improvement in estimated GFR states; older age, race/ethnicity, higher estimated proteinuria state, and higher renal biopsy chronicity scores predicted deterioration. For estimated proteinuria, race/ethnicity, earlier calendar years, damage scores without renal variables, and higher renal biopsy chronicity scores predicted deterioration; male sex, presence of lupus anticoagulant, class V nephritis, and mycophenolic acid use predicted less improvement. Conclusion: In LN, the expected improvement or deterioration in renal outcomes can be estimated by multistate modeling and is preceded by identifiable risk factors. New therapeutic interventions for LN should meet or exceed these expectations.
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