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1.
Ann Rheum Dis ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568386

RESUMO

BACKGROUND/OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. METHODS: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. RESULTS: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. CONCLUSIONS: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.

2.
PLoS One ; 16(2): e0247256, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33617568

RESUMO

OBJECTIVE: We assessed the association of suPAR (soluble urokinase plasminogen activator receptor) plasma levels with fibrotic and vascular manifestations in patients with systemic sclerosis (SSc). METHODS: suPAR plasma levels were measured in 121 consecutive patients with SSc and correlated to pulmonary and vascular features of SSc, including interstitial lung disease as characterized by percentage of predicted CO diffusing capacity (DLco) and forced vital capacity (FVC), pulmonary fibrosis by computed tomography, and pulmonary arterial hypertension, telangiectasias, and digital ulcers. RESULTS: Overall, 121 SSc patients (84% females; mean age, 57 ± 12 [range: 22-79] years) were enrolled; 35% had diffuse cutaneous SSc. suPAR plasma levels ranged from 1.3-10.2 [median: 2.9 (p25-p75: 2.3-3.9)] ng/mL. Log(suPAR) levels correlated with DLco (r = -0.41, p <0.0001) and FVC (r = -0.26, p = 0.004), also when adjusted for age, sex, and pulmonary hypertension. A suPAR cut-off level of >2.5 ng/mL showed a sensitivity of 91% for identifying patients with either DLco <50% or FVC < 60% of the predicted values. Similarly, 19 (90%) had a suPAR >2.5 ng/mL among those diagnosed with pulmonary fibrosis vs. 59 (60%) among those who did not (p = 0.008). suPAR values were not associated with vascular manifestations. CONCLUSION: suPAR levels strongly correlated with pulmonary involvement in SSc. Future studies should test if suPAR estimation can be used for surveillance of severe pulmonary involvement in SSc.

3.
Clin Exp Rheumatol ; 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33337998

RESUMO

OBJECTIVES: Venous (VTE) and arterial (AT) thrombosis in systemic lupus erythematosus (SLE) are poorly explained and difficult to predict. Leptin and tumour necrosis factor-like weak inducer of apoptosis (TWEAK) have been linked to subclinical atherosclerosis and galectin-3-binding protein (G3BP) to type I interferon activation and a pro-thrombotic environment. Thus, we explore serum G3BP, interferon gamma-induced protein 10 (IP-10), soluble CD163 (sCD163), TWEAK and leptin as predictors of VTE and AT, damage accrual, and all-cause mortality during follow-up in a Swedish SLE cohort. METHODS: Baseline data were available from 162 SLE patients. VTE (deep vein thrombosis and/or pulmonary embolism), AT (myocardial infarction and/or stroke), damage accrual, and survival data were the main study outcomes and available at follow-up (median of five years). Baseline serum G3BP, IP-10, sCD163, TWEAK and leptin were measured and analysed by univariable and multivariable methods for association to the study outcomes. RESULTS: During the follow-up, 10 (6%) VTE and 13 (8%) AT events occurred. The SLICC/ACR Damage Index increased in 78 (48%) patients, and 19 (12%) patients died. In the univariable regression analysis G3BP levels were significantly associated with an increased risk of VTE (hazard ratio (HR) 1.11, 95% confidence interval (CI): 1.01-1.22, p=0.03). This persisted in the adjusted multivariable analyses (HR 1.18, 95% CI: 1.05-1.33, p=0.007). The other biomarkers were not associated with AT/VTE, damage accrual, or all-cause mortality. CONCLUSIONS: Our study identifies serum G3BP as a novel predictor of VTE in SLE. Further studies are needed to understand the role of G3BP in VTE and translate this into clinical practice.

5.
Clin Exp Rheumatol ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33200742

RESUMO

OBJECTIVES: To validate the global antiphospholipid syndrome score (GAPSS) in a cohort of women with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPL). METHODS: This retrospective study included 143 women ever pregnant with SLE who presented in our outpatient clinic were included. Data on cardiovascular risk factors and aPL status were retrospectively collected and their individual GAPSS score was calculated. RESULTS: Significantly higher GAPSS values were found in women with any placental medicated complication (such as foetal death, placental abruption, prematurity, pre-eclampsia or intrauterine growth restriction (IUGR)) (GAPSS 8.2±3.0 vs. 3.5±3.0, p<0.001). Significantly higher GAPSS values were also found in those with recurrent miscarriages (RM) <10 weeks, foetal death, placental abruption, prematurity, pre-eclampsia or IUGR) (GAPSS 8.3±4.5 vs. 3.2±2.6, p<0.001). Patients with 3 or more consecutive early miscarriages (<10 weeks), foetal death, miscarriage <10 weeks' gestation, premature birth (<34 weeks), pre-eclampsia (<34 weeks), stillbirth, and placental infarction had significantly higher GAPSS values compared to those without previous pregnancy complications. The odds ratio of having any pregnancy morbidity when having a GAPSS value ≥8 was 20 compared to those with a GAPSS of ≤1 (p<0.001). CONCLUSIONS: Women with a history of aPL-related pregnancy complications had higher GAPSS values in this retrospective cohort compared to women without pregnancy complications. This study is the first step to assess the clinical utility of the GAPSS score in pregnancy. A prospective validation is needed.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33152181

RESUMO

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in SLE, but its association with hospitalizations has not been described. We estimated the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort. METHODS: Baseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in hospital. Multivariable models were adjusted for relevant baseline characteristics. RESULTS: The 1549 SLE patients eligible for this analysis were mostly female (88.7%) with mean (SD) age 35.7 (13.3) years and median (IQR) disease duration 1.2 (0.9-1.5) years at baseline. Mean (SD) baseline SLICC-FI was 0.17 (0.08). During mean (SD) follow-up of 7.2 (3.7) years, 614 patients (39.6%) experienced 1570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up (Incidence Rate Ratio 1.21; 95%CI 1.13-1.30), adjusting for baseline age, sex, corticosteroid use, immunosuppressive use, ethnicity/location, SLE disease activity index 2000 (SLEDAI-2K), SLICC/ACR damage index (SDI), and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (Relative Rate 1.09; 95%CI 1.02-1.16). CONCLUSION: The SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.

7.
Ann Rheum Dis ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037003

RESUMO

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease with extensive heterogeneity in disease presentation between patients, which is likely due to an underlying molecular diversity. Here, we aimed at elucidating the genetic aetiology of SLE from the immunity pathway level to the single variant level, and stratify patients with SLE into distinguishable molecular subgroups, which could inform treatment choices in SLE. METHODS: We undertook a pathway-centred approach, using sequencing of immunological pathway genes. Altogether 1832 candidate genes were analysed in 958 Swedish patients with SLE and 1026 healthy individuals. Aggregate and single variant association testing was performed, and we generated pathway polygenic risk scores (PRS). RESULTS: We identified two main independent pathways involved in SLE susceptibility: T lymphocyte differentiation and innate immunity, characterised by HLA and interferon, respectively. Pathway PRS defined pathways in individual patients, who on average were positive for seven pathways. We found that SLE organ damage was more pronounced in patients positive for the T or B cell receptor signalling pathways. Further, pathway PRS-based clustering allowed stratification of patients into four groups with different risk score profiles. Studying sets of genes with priors for involvement in SLE, we observed an aggregate common variant contribution to SLE at genes previously reported for monogenic SLE as well as at interferonopathy genes. CONCLUSIONS: Our results show that pathway risk scores have the potential to stratify patients with SLE beyond clinical manifestations into molecular subsets, which may have implications for clinical follow-up and therapy selection.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32813314

RESUMO

OBJECTIVE: To assess cancer risk factors in incident SLE. METHODS: Clinical variables and cancer outcomes were assessed annually among incident SLE patients. Multivariate hazard regression models (over-all risk, and most common cancers) included demographics and time-dependent medications (corticosteroids, antimalarial drugs, immunosuppressants), smoking, and adjusted mean SLE Disease Activity Index-2K. RESULTS: Among 1668 patients (average 9 years follow-up), 65 cancers occurred: 15 breast, 10 non-melanoma skin, seven lung, six hematological, six prostate, five melanoma, three cervical, three renal, two each gastric, head and neck, and thyroid, and one each rectal, sarcoma, thymoma, and uterine cancers. Half of cancers (including all lung cancers) occurred in past/current smokers, versus one-third of patients without cancer. Multivariate analyses indicated over-all cancer risk was related primarily to male sex and older age at SLE diagnosis. In addition, smoking was associated with lung cancer. For breast cancer risk, age was positively and anti-malarial drugs were negatively associated. Anti-malarial drugs and higher disease activity were also negatively associated with non-melanoma skin cancer (NMSC) risk, whereas age and cyclophosphamide were positively associated. Disease activity was associated positively with hematologic and negatively with NMSC risk. CONCLUSIONS: Smoking is a key modifiable risk factor, especially for lung cancer, in SLE. Immunosuppressive medications were not clearly associated with higher risk except for cyclophosphamide and NMSC. Antimalarials were negatively associated with breast cancer and NMSC risk. SLE activity was associated positively with hematologic cancer and negatively with NMSC. Since the absolute number of cancers was small, additional follow-up will help consolidate these findings.

9.
Ann Rheum Dis ; 79(10): 1333-1339, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32816709

RESUMO

OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). CONCLUSIONS: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Índice de Gravidade de Doença , Feminino , Humanos , Masculino , Seleção de Pacientes , Sensibilidade e Especificidade
10.
Arthritis Rheumatol ; 72(10): 1734-1740, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32515554

RESUMO

OBJECTIVE: In previous studies, atherosclerotic vascular events (AVEs) were shown to occur in ~10% of patients with systemic lupus erythematosus (SLE). We undertook this study to investigate the annual occurrence and potential risk factors for AVEs in a multinational, multiethnic inception cohort of patients with SLE. METHODS: A large 33-center cohort of SLE patients was followed up yearly between 1999 and 2017. AVEs were attributed to atherosclerosis based on SLE being inactive at the time of the AVE as well as typical atherosclerotic changes observed on imaging or pathology reports and/or evidence of atherosclerosis elsewhere. Analyses included descriptive statistics, rate of AVEs per 1,000 patient-years, and univariable and multivariable relative risk regression models. RESULTS: Of the 1,848 patients enrolled in the cohort, 1,710 had ≥1 follow-up visit after enrollment, for a total of 13,666 patient-years. Of these 1,710 patients, 3.6% had ≥1 AVEs attributed to atherosclerosis, for an event rate of 4.6 per 1,000 patient-years. In multivariable analyses, lower AVE rates were associated with antimalarial treatment (hazard ratio [HR] 0.54 [95% confidence interval (95% CI) 0.32-0.91]), while higher AVE rates were associated with any prior vascular event (HR 4.00 [95% CI 1.55-10.30]) and a body mass index of >40 kg/m2 (HR 2.74 [95% CI 1.04-7.18]). A prior AVE increased the risk of subsequent AVEs (HR 5.42 [95% CI 3.17-9.27], P < 0.001). CONCLUSION: The prevalence of AVEs and the rate of AVE accrual demonstrated in the present study is much lower than that seen in previously published data. This may be related to better control of both the disease activity and classic risk factors.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32433832

RESUMO

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) 2012 SLE classification criteria and the revised American College of Rheumatology (ACR) 1997 criteria are list-based, counting each SLE manifestation equally. We derived a classification rule based on giving variable weights to the SLICC criteria, and compared its performance to the revised ACR 1997, unweighted SLICC 2012 and the newly reported European League Against Rheumatism (EULAR)/ACR 2019 criteria. METHODS: The physician-rated patient scenarios used to develop the SLICC 2012 classification criteria were re-employed to devise a new weighted classification rule using multiple linear regression. The performance of the rule was evaluated on an independent set of expert-diagnosed patient scenarios and compared to the performance of the previously reported classification rules. RESULTS: Weighted SLICC criteria and the EULAR/ACR 2019 criteria had less sensitivity but better specificity compared to the list-based revised ACR 1997 and SLICC 2012 classification criteria. There were no statistically significant differences between any pair of rules with respect to overall agreement with the physician diagnosis. CONCLUSION: The two new weighted classification rules did not perform better than the existing list-based rules in terms of overall agreement on a dataset originally generated to assess the SLICC criteria. Given the added complexity of summing weights, researchers may prefer the unweighted SLICC criteria. However, the performance of a classification rule will always depend on the populations from which the cases and non-cases are derived, and whether the goal is to prioritize sensitivity or specificity.

13.
Semin Arthritis Rheum ; 50(6): 1507-1512, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32145970

RESUMO

OBJECTIVES: Adult obesity may increase the risks of systemic lupus erythematosus (SLE), and there are genetic links between adult height and SLE. Thus, it is plausible that size earlier in life may be important in the aetiology of SLE as well. We investigated whether birthweight, childhood body mass index (BMI; [kg/m2]), height and growth are associated with risks of adult SLE. METHODS: The study included 346,627 children from the Copenhagen School Health Records Register, born 1930-1996 with measured weights and heights from 7-13 years. Birthweight information was available from 1936. Linkages were made to the Danish National Patient Register for information on registrations of SLE. During follow-up, 435 individuals (366 women) were registered with SLE. Cox proportional hazards regressions were performed to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: No differences by sex were detected in any of the associations. Birthweight was not associated with SLE risks. Childhood BMI and height were positively and linearly associated with SLE risks. For BMI at age 7, the HR was 1.11 (95% CI: 1.01-1.23) per z-score. For height at age 7, the HR was 1.13 (95% CI: 1.02-1.24) per z-score. The estimates were similar in magnitude across all childhood ages for BMI and height. There were limited indications that change in BMI or growth in height during childhood influence the risks of SLE in adulthood. CONCLUSIONS: Childhood body size is associated with risks of adult SLE, which supports the hypothesis that early life factors are important in SLE aetiology.

14.
Ann Rheum Dis ; 79(3): 356-362, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31915121

RESUMO

OBJECTIVES: Using a reversible multistate model, we prospectively examined neuropsychiatric (NP) events for attribution, outcome and association with health-related quality of life (HRQoL), in an international, inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: Annual assessments for 19 NP events attributed to SLE and non-SLE causes, physician determination of outcome and patient HRQoL (short-form (SF)-36 scores) were measured. Time-to-event analysis and multistate modelling examined the onset, recurrence and transition between NP states. RESULTS: NP events occurred in 955/1827 (52.3%) patients and 592/1910 (31.0%) unique events were attributed to SLE. In the first 2 years of follow-up the relative risk (95% CI) for SLE NP events was 6.16 (4.96, 7.66) and non-SLE events was 4.66 (4.01, 5.43) compared with thereafter. Patients without SLE NP events at initial assessment had a 74% probability of being event free at 10 years. For non-SLE NP events the estimate was 48%. The majority of NP events resolved over 10 years but mortality was higher in patients with NP events attributed to SLE (16%) versus patients with no NPSLE events (6%) while the rate was comparable in patients with non-SLE NP events (7%) compared with patients with no non-SLE events (6%). Patients with NP events had lower SF-36 summary scores compared with those without NP events and resolved NP states (p<0.001). CONCLUSIONS: NP events occur most frequently around the diagnosis of SLE. Although the majority of events resolve they are associated with reduced HRQoL and excess mortality. Multistate modelling is well suited for the assessment of NP events in SLE.


Assuntos
Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Adulto , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/mortalidade , Vasculite Associada ao Lúpus do Sistema Nervoso Central/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multinível , Estudos Prospectivos , Qualidade de Vida
15.
Int J Rheum Dis ; 23(4): 488-498, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31994328

RESUMO

OBJECTIVE: To investigate whether magnetic resonance imaging (MRI) pathologies in the wrist/hand of rheumatoid arthritis (RA) patients are associated with patient-reported outcomes (PROs) at clinical remission and relapse. METHODS: Wrist/hand MRIs and wrists/hands/feet radiographs were obtained in 114 established RA patients in clinical remission, before tapering their biologic disease-modifying antirheumatic drugs. MRIs were assessed according to the Outcome Measures in Rheumatology (OMERACT) RA MRI score (RAMRIS) for inflammation (synovitis/tenosynovitis/bone marrow edema) and damage (bone erosion/joint space narrowing) at baseline (ie remission) and in case of a relapse (n = 70). Radiographs were assessed according to the Sharp/van der Heijde (SvH) method at baseline. These scores were assessed for associations with health assessment questionnaires (HAQ), visual analog scales (VAS global/pain), EuroQol-5 dimensions and Short-Form 36 physical and mental component summary (SF-36 PCS/MCS) using Spearman correlations, univariate/multivariable linear regression analyses and generalized estimating equations. Furthermore, MRI pathologies were assessed for association with specific hand-related HAQ items using Jonckheere trend tests. RESULTS: Magnetic resonance imaging-assessed damage was associated with impaired HAQ and SF-36 PCS at remission and relapse (P < .01), independent of clinical and radiographic measures, and was also associated with most of the hand-related HAQ items (P < .03). In multivariate models including MRI, SvH scores were not associated with PROs. MRI-assessed inflammation was not associated with PROs at remission or relapse. CONCLUSION: Magnetic resonance imaging-assessed wrist/hand damage, but not inflammation, in patients with established RA is associated with patient-reported physical impairment at remission and relapse. The amount of damage in the wrist/hand is associated with reduced hand function.

16.
Arthritis Rheumatol ; 72(1): 67-77, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31390162

RESUMO

OBJECTIVE: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. RESULTS: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy. CONCLUSION: PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.


Assuntos
Doenças dos Nervos Cranianos/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Adulto , Fatores Etários , Estudos de Coortes , Doenças dos Nervos Cranianos/etiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Mononeuropatias/etiologia , Mononeuropatias/fisiopatologia , Análise Multivariada , Doenças do Sistema Nervoso Periférico/etiologia , Modelos de Riscos Proporcionais , Índice de Gravidade de Doença , Adulto Jovem
17.
Arthritis Rheumatol ; 72(4): 658-666, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31631584

RESUMO

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC FI values with damage accrual in the SLICC inception cohort. METHODS: The baseline visit was defined as the first visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short Form 36) were assessed. Baseline SLICC FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression was used to estimate the association between baseline SLICC FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics. RESULTS: The 1,549 systemic lupus erythematosus (SLE) patients eligible for this analysis were mostly female (88.7%) with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5 years) at baseline. The mean ± SD baseline SLICC FI was 0.17 ± 0.08. Over a mean ± SD follow-up of 7.2 ± 3.7 years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC FI values (per 0.05 increase) were associated with higher rates of increase in the SDI during follow-up (incidence rate ratio [IRR] 1.19 [95% confidence interval 1.13-1.25]), after adjusting for age, sex, ethnicity/region, education, baseline SLE Disease Activity Index 2000, baseline SDI, and baseline use of glucocorticoids, antimalarials, and immunosuppressive agents. CONCLUSION: Our findings indicate that the SLICC FI predicts damage accrual in incident SLE, which further supports the SLICC FI as a valid health measure in SLE.


Assuntos
Fragilidade/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Qualidade de Vida , Adulto , Progressão da Doença , Feminino , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
18.
J Autoimmun ; 106: 102340, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629628

RESUMO

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.

19.
Arthritis Care Res (Hoboken) ; 72(12): 1800-1808, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31609532

RESUMO

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.

20.
J Rheumatol ; 47(1): 72-81, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30988130

RESUMO

OBJECTIVE: To construct a Frailty Index (FI) as a measure of vulnerability to adverse outcomes among patients with systemic lupus erythematosus (SLE), using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. METHODS: The SLICC inception cohort consists of recently diagnosed patients with SLE followed annually with clinical and laboratory assessments. For this analysis, the baseline visit was defined as the first study visit at which sufficient information was available for construction of an FI. Following a standard procedure, variables from the SLICC database were evaluated as potential health deficits. Selected health deficits were then used to generate a SLICC-FI. The prevalence of frailty in the baseline dataset was evaluated using established cutpoints for FI values. RESULTS: The 1683 patients with SLE (92.1% of the overall cohort) eligible for inclusion in the baseline dataset were mostly female (89%) with mean (SD) age 35.7 (13.4) years and mean (SD) disease duration 18.8 (15.7) months at baseline. Of 222 variables, 48 met criteria for inclusion in the SLICC-FI. Mean (SD) SLICC-FI was 0.17 (0.08) with a range from 0 to 0.51. At baseline, 27.1% (95% CI 25.0-29.2) of patients were classified as frail, based on SLICC-FI values > 0.21. CONCLUSION: The SLICC inception cohort permits feasible construction of an FI for use in patients with SLE. Even in a relatively young cohort of patients with SLE, frailty was common. The SLICC-FI may be a useful tool for identifying patients with SLE who are most vulnerable to adverse outcomes, but validation of this index is required prior to its use.

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