Effect of Disease Activity on Organ Damage Progression in Systemic Lupus Erythematosus: University of Toronto Lupus Clinic Cohort.

OBJECTIVE: To examine the role of disease activity on organ damage over 5 years in patients with active systemic lupus erythematosus (SLE) despite standard of care. METHODS: This analysis of the University of Toronto Lupus Clinic cohort assessed organ damage [measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)] in patients with active SLE [SLE Disease Activity Index 2000 (SLEDAI-2K) ≥ 6], using Cox proportional time-independent hazard models. Subgroup analyses were conducted in patients with SLEDAI-2K 6 or 7, 8 or 9, and ≥ 10 at baseline, and in the overall study population by steroid dose at study entry (< 7.5 vs ≥ 7.5 mg/day). RESULTS: Among the overall study population (n = 649), SDI progression was observed in 209 (32.2%) patients over the 5-year follow-up period. Mean SDI change in patients with a score > 0 was generally consistent across all SLEDAI-2K subgroups. Multivariable analyses identified age at study start (HR 1.03, P < 0.0001), steroid dose (HR 2.03, P < 0.0001), immunosuppressants (HR 1.44, P = 0.021), and SLEDAI-2K (subgroup analyses HR 1.64-2.03, P = 0.0017 to < 0.0001) as the greatest risk factors for SDI progression, while a study start date after the year 2000 had a protective effect on SDI progression compared with a start date prior to the year 2000 (HR 0.65, P = 0.0004). CONCLUSION: Patients within the higher SLEDAI-2K subgroups at study entry or receiving high doses of steroids were more likely to have organ damage progression.

Efficacy of "High in" Nutrient Specific Front of Package Labels-A Retail Experiment with Canadians of Varying Health Literacy Levels.

BACKGROUND: In 2018, Health Canada, the Federal department responsible for public health, put forward a regulatory proposal to introduce regulations requiring a "High in" front-of-package label (FOPL) on foods that exceed predetermined thresholds for sodium, sugars, or saturated fat. This study evaluated the efficacy of the proposed FOPL as a quick and easy tool for making food choices that support reduction in the intakes of these nutrients. METHODS: Consumers (n = 625) of varying health literacy levels (HL) were assigned to control (current labeling with no FOPL) or one of four FOPL designs. They completed six shopping tasks, designed to control for internal motivations. Efficacy was measured with correct product selection and response time (seconds) to make food choices using repeated measures statistical modeling, adjusting for HL, task type, and task order. Eye-tracking and structured interviews were used to gather additional insights about participants' choices. RESULTS: Overall, FOPL was significantly more effective than current labeling at helping consumers of varying HL levels to identify foods high in nutrients of concern and make healthier food choices. All FOPL were equally effective. CONCLUSIONS: "High in" FOPL can be effective at helping Canadians of varying HL levels make more informed food choices in relation to sugars, sodium, and saturated fat.

Early Experience Analyzing Dietary Intake Data from the Canadian Community Health Survey-Nutrition Using the National Cancer Institute (NCI) Method.

BACKGROUND: One of the underpinning elements to support evidence-based decision-making in food and nutrition is the usual dietary intake of a population. It represents the long-run average consumption of a particular dietary component (i.e., food or nutrient). Variations in individual eating habits are observed from day-to-day and between individuals. The National Cancer Institute (NCI) method uses statistical modeling to account for these variations in estimation of usual intakes. This method was originally developed for nutrition survey data in the United States. The main objective of this study was to apply the NCI method in the analysis of Canadian nutrition surveys. METHODS: Data from two surveys, the 2004 and 2015 Canadian Community Health Survey-Nutrition were used to estimate usual dietary intake distributions from food sources using the NCI method. The effect of different statistical considerations such as choice of the model, covariates, stratification compared to pooling, and exclusion of outliers were assessed, along with the computational time to convergence. RESULTS: A flowchart to aid in model selection was developed. Different covariates (e.g., age/sex groups, cycle, weekday/weekend of the recall) were used to adjust the estimates of usual intakes. Moreover, larger differences in the ratio of within to between variation for a stratified analysis or a pooled analysis resulted in noticeable differences, particularly in the tails of the distribution of usual intake estimates. Outliers were subsequently removed when the ratio was larger than 10. For an individual age/sex group, the NCI method took 1 h-5 h to obtain results depending on the dietary component. CONCLUSION: Early experience in using the NCI method with Canadian nutrition surveys data led to the development of a flowchart to facilitate the choice of the NCI model to use. The ability of the NCI method to include covariates permits comparisons between both 2004 and 2015. This study shows that the improper application of pooling and stratification as well as the outlier detection can lead to biased results. This early experience can provide guidance to other researchers and ensures consistency in the analysis of usual dietary intake in the Canadian context.

Modified Framingham Risk Factor Score for Systemic Lupus Erythematosus.

OBJECTIVE: The traditional Framingham Risk Factor Score (FRS) underestimates the risk for coronary artery disease (CAD) in patients with systemic lupus erythematosus (SLE). We aimed to determine whether an adjustment to the FRS would more accurately reflect the higher prevalence of CAD among patients with SLE. METHODS: Patients with SLE without a previous history of CAD or diabetes followed regularly at the University of Toronto Lupus Clinic were included. A modified FRS (mFRS) was calculated by multiplying the items by 1.5, 2, 3, or 4. In the first part of the study, using one-third of all eligible patients, we evaluated the sensitivity and specificity of the FRS and the different multipliers for the mFRS. In the second part of the study, using the remaining 2/3 of the eligible patients, we compared the predictive ability of the FRS to the mFRS. In the third part of the study, we assessed the prediction for CAD in a time-dependent analysis of the FRS and mFRS. RESULTS: There were 905 women (89.3%) with a total of 95 CAD events included. In part 1, we determined that a multiplier of 2 provided the best combination of sensitivity and specificity. In part 2, 2.4% of the patients were classified as moderate/high risk based on the classic FRS and 17.3% using the 2FRS (the FRS with a multiplier of 2). In part 3, a time-dependent covariate analysis for the prediction of the first CAD event revealed an HR of 3.22 (p = 0.07) for the classic FRS and 4.37 (p < 0.0001) for the 2FRS. CONCLUSION: An mFRS in which each item is multiplied by 2 more accurately predicts CAD in patients with SLE.

Lack of Interferon and Proinflammatory Cyto/chemokines in Serologically Active Clinically Quiescent Systemic Lupus Erythematosus.

OBJECTIVE: Serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE) remain clinically quiescent for prolonged periods despite anti-dsDNA antibodies and/or low complements, indicating the presence of immune complexes. The immune mechanisms leading to this quiescence are unknown. However, in addition to activating complement, immune complex uptake by various cells leads to the production of interferon (IFN)-α and other proinflammatory factors that are also involved in tissue damage. Here we investigate whether production of these factors is reduced in SACQ patients. METHODS: The levels of 5 IFN-induced genes and 19 cyto/chemokines were measured in SACQ patients and were compared with those in serologically and clinically active (SACA) and serologically and clinically quiescent (SQCQ) patients. SACQ and SQCQ were defined as ≥ 2 years without clinical activity, with/without persistent serologic activity, respectively, and off corticosteroids/immunosuppressives. SACA was defined as disease activity compelling immunosuppression. Levels of OAS1, IFIT1, MX1, LY6E, and ISG15 were measured by quantitative real-time polymerase chain reaction (PCR) and a composite score (IFN-5) derived from this. Plasma cyto/chemokines were measured by Luminex assay. Nonparametric univariate and logistic regression analyses were conducted. RESULTS: There were no differences in gene expression or cyto/chemokine levels between SACQ and SQCQ patients. The SACQ IFN-5 score was significantly lower than that of SACA (p = 0.003) and was driven by SACQ status, not by autoantibody profile or disease duration. Levels of granulocyte-macrophage colony-stimulating factor, interleukin (IL) 6, IL-10, IFN-γ-inducible protein 10, monocyte chemoattractant protein 1, and tumor necrosis factor-α were significantly lower in SACQ than SACA. CONCLUSION: The levels of proinflammatory factors in SACQ mirror those of SQCQ patients, indicating reduced production of these factors despite the presence of immune complexes.

SLEDAI-2K Does Not Conceal Worsening in a Particular System When There Is Overall Improvement.

OBJECTIVE: To determine whether the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) is valid in identifying patients who had a clinically important overall improvement with no worsening in other descriptors/systems. METHODS: Consecutive patients with systemic lupus erythematosus with active disease who attended the Lupus Clinic between 2000 and 2012 were studied. Based on the change in the total SLEDAI-2K scores on last visit, patients were grouped as improved, flared/worsened, and unchanged. Patients showing improvement were evaluated for the presence of new active descriptors at last visit compared with baseline visit. RESULTS: Of the 158 patients studied, 109 patients had improved, 38 remained unchanged, and 11 flared/worsened at last visit. In the improved group, 11 patients had a new laboratory descriptor that was not present at baseline visit. In those 11 patients, this new laboratory descriptor was not clinically significant and did not require a change in disease management. CONCLUSION: The SLEDAI-2K identifies improvement in disease activity overall without concealing clinically important worsening.

Anti-dsDNA and Antichromatin Antibody Isotypes in Serologically Active Clinically Quiescent Systemic Lupus Erythematosus.

OBJECTIVE: Serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE) are clinically quiescent despite serologic activity. Since studies suggest that antichromatin antibodies are more sensitive than anti-dsDNA antibodies in detecting active SLE, and that immunoglobulin (Ig) G, in particular complement-fixing subclasses, may be more pathogenic than IgM, we investigated the levels of anti-dsDNA and antichromatin isotypes in SACQ patients as compared to non-SACQ patients with SLE. METHODS: Levels of IgM, IgA, IgG, and IgG1-4 antichromatin and anti-dsDNA were measured by ELISA. SACQ was defined as ≥ 2 years with the SLE Disease Activity Index 2000 (SLEDAI-2K) at 2 or 4 from serologic activity, during which patients could be taking antimalarials, but not corticosteroids or immunosuppressives. Unselected non-SACQ patients with SLE were used as comparators. SACQ patient serum samples were further stratified based on subsequent development of flare, defined as clinical SLEDAI-2K ≥ 1 and/or treatment initiation. Nonparametric statistics were used, and generalized estimating equations were applied to account for multiple samples in the same patient. RESULTS: SACQ patients' complement-fixing antichromatin and anti-dsDNA IgG subclasses were significantly higher than those of non-SACQ patients. When the sample drawn latest in a SACQ period was analyzed, there was no difference between antichromatin or anti-dsDNA isotype or IgG subclass levels between patients who flared and those who remained SACQ, nor were consistent trends seen when samples were examined during SACQ and flare in the same patient. CONCLUSION: The SACQ phenotype does not arise from a lack of pathogenic anti-dsDNA and/or antichromatin autoantibodies. Neither increases in antichromatin nor anti-dsDNA isotype or IgG subclass levels were predictive of or coincident with flare in SACQ patients.

Isolated hematuria and sterile pyuria may indicate systemic lupus erythematosus activity.

OBJECTIVE: To identify patients presenting with isolated hematuria and/or pyuria in the absence of other systemic lupus erythematosus (SLE) disease activity, describe their demographics, and determine whether they present with evidence of SLE flare in a period adjacent to the presentation. METHODS: We studied patients followed at the University of Toronto Lupus Clinic between 1970 and 2012. An episode of isolated hematuria (> 5 red blood cells per high power field) and/or pyuria (> 5 white blood cells per high power field) was defined as 2 consecutive visits with these findings in the absence of other concurrent SLE manifestations such as proteinuria, casts, or azotemia. We then excluded patients whose findings might be explained by urinary tract infections, menstruation, urolithiasis, and/or anticoagulation. Only patients presenting with no other SLE disease activity were included. RESULTS: Isolated hematuria and/or pyuria were identified in 49 patients, of whom 17 were excluded according to the criteria above, leaving 32. Twenty-four patients had another renal manifestation 1 year before and/or after the occurrence; 27 had a non-renal manifestation 1 year before and/or after the occurrence; 3 patients had a biopsy in the same time frame, all with evidence of active lupus nephritis. Therefore the majority of patients with an occurrence of isolated hematuria and/or pyuria had evidence of renal or other non-renal SLE disease activity at a time adjacent to this presentation. CONCLUSION: Although not proven, our results suggest that these manifestations were associated with SLE activity, either before or after the episode, and therefore may represent a phase of active disease.

Prolonged clinical remission in patients with systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is typically a relapsing/remitting disease. However, some patients experience prolonged remission. These patients may provide further insights into SLE pathophysiology. In this study we characterize their clinical course. METHODS: Prolonged remission was defined as Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) = 0, = 2, or = 4 (based on serology) for ≥ 5 consecutive years, with visits ≤ 18 months apart. The patients could be taking antimalarials, but not corticosteroids or immunosuppressives. Flare was defined as clinical activity on SLEDAI-2K, or by corticosteroid/immunosuppressive initiation. Each patient's preremission course was classified as monophasic, relapsing/remitting, or chronic active. These patients were compared to matched SLE controls and patients achieving remission on medications. RESULTS: A total of 38/1613 (2.4%) patients achieved prolonged remission while taking no medications. The mean duration was 11.5 ± 6.4 years. Twenty-seven patients (71.0%) had relapsing/remitting disease, 11 (28.9%) had monophasic illness, and none had chronic active disease prior to remission. They differed from matched controls in ethnicity, disease activity at first visit, and cumulative organ damage. There were 34/1613 patients (2.1%) who achieved prolonged remission while taking steroids and/or immunosuppressives, with mean duration 8.5 ± 2.9 years. Twelve patients (35.3%) experienced disease flare. They were younger at diagnosis, with more disease activity prior to remission than patients taking no medications. CONCLUSION: Prolonged remission is an infrequent outcome among patients and is preceded by an atypically monophasic clinical course in a significant minority. Those taking medications represent a heterogeneous group: those who will tolerate eventual taper, and those whose disease activity was merely suppressed by ongoing immunosuppression. Prolonged remission may reflect unique pathophysiologic mechanisms, and warrants further investigation.

Switching treatment between mycophenolate mofetil and azathioprine in lupus patients: indications and outcomes.

OBJECTIVE: To determine the reasons for changing treatment from mycophenolate mofetil (MMF) to azathioprine (AZA) or vice versa in lupus patients and to evaluate the effect of the change. METHODS: Lupus patients were identified from the University of Toronto Lupus Clinic database. Global disease activity in the 6 months prior to the change in therapy and 6 months after the change was calculated. The reasons for changing therapy were identified. RESULTS: One hundred eight switches occurred among 92 lupus patients: 89 switches from AZA to MMF and 19 from MMF to AZA. There was significant improvement in disease activity in the 6 months after drug switching compared to the 6 months prior to the switch when the reason was a drug failure. There was no statistically significant deterioration in disease activity in the 6 months after drug switching when the reason for the switch was a side effect, pregnancy, renal transplant, or financial. In the 19 patients who switched because of side effects, 15 (79%) had resolution of the side effects. CONCLUSION: Switching from AZA to MMF is most often due to AZA failure, whereas switching from MMF to AZA is mostly due to side effects and pregnancy. When the reason for the switch was drug failure, improvement in disease activity occurred and there was a reduction of steroid dose after 6 months. When the reason for switching was something other than drug failure, there was no deterioration in global disease activity. Switching for side effects usually resulted in elimination of the side effect.

American College of Rheumatology criteria at inception, and accrual over 5 years in the SLICC inception cohort.

OBJECTIVE: To determine the frequency of each American College of Rheumatology (ACR) criterion met at time of enrollment, and the increase in each of the criteria over 5 years. METHODS: In 2000 the Systemic Lupus International Collaborating Clinics (SLICC) recruited an international inception cohort of patients with systemic lupus erythematosus (SLE; ≥ 4 ACR criteria) who were followed at yearly intervals according to a standard protocol. Descriptive statistics were used to assess the total and cumulative number of ACR criteria met at each visit. Regression models were done to compare the increase of individual and cumulative criteria as a function of race/ethnicity group, and sex. RESULTS: In all, 768 patients have been followed for a minimum of 5 years. Overall, 59.1% of the patients had an increase in the number of ACR criteria they met over the 5-year period. The mean number of ACR criteria met at enrollment was 5.04 ± 1.13 and at year 5 was 6.03 ± 1.42. At enrollment, nonwhite patients had a higher number of ACR criteria (5.19 ± 1.23) than white patients. The total number of criteria increased in both white and nonwhite ethnicities, but increased more among whites. Males had a slightly lower number of criteria at enrollment compared to females and males accrued fewer criteria at 5 years. CONCLUSION: In this international inception cohort of SLE patients with at least 4 ACR criteria at entry, there was an accumulation of ACR criteria over the following 5 years. The distribution of criteria both at inception and over 5 years is affected by sex and ethnicity.

Time to recovery from proteinuria in patients with lupus nephritis receiving standard treatment.

OBJECTIVE: The recovery time from abnormal levels of proteinuria with standard treatment in longitudinal studies of patients with systemic lupus erythematosus has not been well described. We aimed (1) to determine the recovery time from proteinuria in patients with lupus nephritis (LN) receiving standard treatment, and (2) to determine whether the initial level of proteinuria predicts time to improvement. METHODS: We studied all patients with LN recorded in the database from 1970 until 2011. Proteinuria was defined as ≥0.5 g/24 h. Patients were grouped as follows: group 1 having 0.5-0.9 g/day, group 2 having 1-1.9 g/day, and group 3 having ≥2 g/day. Recovery from proteinuria was defined as proteinuria<0.5 g/24 h. Time to recovery from proteinuria was studied with the Kaplan-Meier curves. Factors associated with proteinuria recovery were evaluated using proportional hazard models. RESULTS: Among the 212 patients studied, 52% recovered from proteinuria within 2 years and an additional 22% recovered within 5 years, for a total of 74%. The level of proteinuria at baseline visit predicted the time to improvement. Patients with a higher level of proteinuria at baseline needed a longer time to normalize their proteinuria. Male sex, hypocomplementemia, high level of proteinuria at diagnosis of LN, and disease duration>5 years at onset of LN each independently predicted late recovery of proteinuria and had an effect on the percentage of patients who recovered. CONCLUSION: The tempo of recovery from proteinuria in LN is slow and the level of proteinuria at baseline visit predicts the time to complete recovery.

Assessment of coronary risk based on cumulative exposure to lipids in systemic lupus erythematosus.

OBJECTIVE: To quantify the independent role of each of low-density lipoprotein cholesterol (LDL-C), total cholesterol:high-density lipoprotein cholesterol ratio (TC:HDL-C), triglyceride (TG) level, and HDL-C as a marker of coronary risk in systemic lupus erythematosus (SLE). METHODS: Patients with lipid measurements taken before a coronary event (or last clinic visit) were included. Mean and time-adjusted mean (TAM) levels were calculated for each lipid variable in each patient. Time-dependent proportional hazards regression models were used to quantify the risk of coronary event [myocardial infarction (MI) or angina], after adjustment for age. RESULTS: Among 384 patients, over a mean (SD) followup of 3.81 (2.58) years, there were 21 "first" coronary events (6 MI, 15 angina). Mean and TAM LDL-C (HR 1.83, 95% CI 1.19-2.81, p = 0.006), TC:HDL ratio (HR 1.43, 95% CI 1.02-2.00, p = 0.04), and TG (HR 2.11, 95% CI 1.32-3.39, p = 0.0019) were predictive of coronary event at subsequent visits. In contingency table analysis, TAM LDL-C cutpoint of 2.0 mmol/l had a sensitivity and negative predictive value for coronary event of 85.7% (95% CI 63.7-97.0) and 93.9% (95% CI 83.1-98.7), respectively. However, at this cutpoint the specificity was only 12.7% (95% CI 9.4-16.5). CONCLUSION: This study links LDL-C, TC:HDL-C ratio, and TG to coronary risk in patients with SLE and quantifies the magnitude of this risk. SLE-specific risk assessment levels for lipids may be selected to optimize positive or negative predictive values.

Recommendations for frequency of visits to monitor systemic lupus erythematosus in asymptomatic patients: data from an observational cohort study.

OBJECTIVE: The aim of our study was to determine the optimal frequency of followup visits in patients with systemic lupus erythematosus (SLE). METHODS: Patients followed in the lupus clinic over a 2-year period who had at least 3 visits and at least 18 months of followup were included. At each visit patients undergo a complete history, physical examination, and laboratory evaluation. The following variables that would not have been recognized by the patient were identified: proteinuria, hematuria, pyuria, casts, low hemoglobin, leukopenia, thrombocytopenia, elevated serum creatinine, positive anti-DNA antibodies, and low complement. When one of these variables was detected, it was determined whether it was new, and whether other features of activity were present. Thus isolated new variables of interest were identified. Descriptive statistics were used. RESULTS: A total of 515 patients (89% female, 61% white) met the inclusion criteria, with an average of 6.1 ± 1.5 for a total of 3126 visits. The average length of time between visits was 3.8 ± 1.0 months. In the 515 patients, the variables of interest were the sole manifestation of SLE in 126 (24.5%) patients (in a total of 175 visits). The commonest manifestations were renal, low complement, and DNA antibodies followed by thrombocytopenia, low hemoglobin, and elevated creatinine. CONCLUSION: One in 4 patients with SLE seen over a 2-year period will have a solitary silent variable of interest that could be detected only by routine laboratory followup. Patients with mild or inactive disease should be followed with clinical and laboratory measures at 3-4 month intervals.

Comparison of three anti-dsDNA assays: performance and correlation with systemic lupus erythematosus disease activity.

OBJECTIVE: To investigate the BioPlex 2200 multiplex immunoassay and Farrzyme ELISA assays as alternatives to the established Farr radioimmunoassay for the correlation of anti-dsDNA antibodies in the assessment of disease activity in systemic lupus erythematosus (SLE). DESIGN AND METHODS: Standard protocols were used to verify analytical performance claims. Anti-dsDNA antibody levels in SLE patient specimens (N=105) were measured and assessed for clinical performance using manufacturer cut-off limits along with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score. RESULTS: Assay precision, measurable range and normal reference interval met the manufacturers' stated claims. Agreement between Farr and BioPlex assays was moderate (positive agreement=62%; negative agreement=85%; kappa=0.48), as was agreement between Farr and Farrzyme assays (positive agreement=56%; negative agreement=91%; kappa=0.51). Mean SLEDAI-2K scores differed significantly between the anti-dsDNA positive and negative groups for BioPlex (p=0.0006), but not Farr (p=0.11) or Farrzyme (p=0.34). ROC curve analysis showed a similar area under the curve (AUC) for all three assays (0.76, 0.74, and 0.73 for Farr, BioPlex, and Farrzyme, respectively) in the discrimination of clinically active disease. Furthermore, increased anti-dsDNA levels from BioPlex showed significant correlation with active renal disease. However, results suggested a lower cut-off for the Farrzyme assay for assessment of global disease activity. CONCLUSIONS: BioPlex and Farrzyme assays had similar overall agreement with the Farr assay, with BioPlex best reflecting disease activity in SLE patients.

Systemic lupus erythematosus disease activity Index 2000 Responder Index 50: sensitivity to response at 6 and 12 months.

OBJECTIVE: The SLEDAI 2000 (SLEDAI-2K) Responder Index 50 (SRI-50) is a novel index that measures ≥ 50% in each of the 24 descriptors of SLEDAI-2K and generates a total score reflecting disease activity overall. The SLE Responder Index (SRI) has been successfully used to identify responders in recent trials. This is the first study to evaluate the ability of SRI-50 to identify responders, defined as patients who had a clinically important improvement over their baseline value over 12 months. We compared the performance of SRI-50 with that of SLEDAI-2K and SRI at 6 and 12 months in identifying responders. METHODS: Patients with active disease were followed for 6-12 months and assessed using SLEDAI-2K, British Isles Lupus Assessment Group and Physician Global Assessment. We identified SLEDAI-2K responders, SRI-50 responders and SLE responders at 6 and 12 months. We determined whether patients who are defined as SRI-50 responders are true responders when SRI is considered the gold standard. RESULTS: Among the 103 patients studied, the percentage of responders at 6 and 12 months was 44 and 51% when determined by SLEDAI-2K and 43 and 51% by SRI, respectively. The percentage of SRI-50 responders at 6 and 12 months was 51 and 58%, respectively. CONCLUSION: SRI-50 identified more responders compared with SLEDAI-2K and SRI at 6 and 12 months. SRI-50 is a valid responder index that can be used independently to identify patients with true clinically important improvement.

Long-term outcome of early neuropsychiatric events due to active disease in systemic lupus erythematosus.

OBJECTIVE: Neuropsychiatric (NP) manifestations attributable to active disease affect up to 30% of individuals with systemic lupus erythematosus (SLE). The short-term impact of NP events includes increased organ damage, fatigue, and mortality, and lower health-related quality of life. We investigated the impact of NP events attributable to active SLE at presentation on long-term disease activity, organ damage, and health-related quality of life. METHODS: Seventy-two NP cases and 144 matched controls from the University of Toronto Lupus Cohort, enrolled between 1970 and 2005, were included in the study. NP cases had at least 1 NP event attributable to active SLE at the first clinic visit. Controls did not have NP events at the first clinic visit and were matched to cases on age, sex, disease duration, and decade. Paired case-control analyses were performed on measures of disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000), disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), and health-related quality of life (Short Form 36) at 1 year, 3 years, and 5 years after the first clinic visit. RESULTS: NP cases showed greater disease activity than controls at the first clinic visit (P < 0.0001) and greater cumulative organ damage at 1-year followup (P = 0.01). No statistically significant differences were found on 3-year or 5-year outcomes. Mean scores showed a decreasing trend of disease activity, increasing organ damage, and persistently low quality of life for both cases and controls. CONCLUSION: This study shows that early NP events due to active SLE are not major contributors to long-term disease activity, accumulation of damage, or health-related quality of life. The long-term prognosis and patterns of disease in SLE patients with early NP events are similar to those of SLE patients without these events.

Outcomes in patients with systemic lupus erythematosus with and without a prolonged serologically active clinically quiescent period.

OBJECTIVE: Serologically active clinically quiescent (SACQ) systemic lupus erythematosus (SLE) patients' discordance presents a clinical dilemma. Does active serology alone warrant treatment? We explore outcomes in patients with and without a prolonged SACQ period, comparing the rate of damage accrual by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) and incidences of renal damage and coronary artery disease (CAD) over a decade. METHODS: SACQ was defined as a ≥2-year sustained period without clinical activity, with persistent serologic activity (increased anti-double-stranded DNA and/or hypocomplementemia). Antimalarials were permissible and corticosteroids/immunosuppressives were not. The SACQ patients were matched for relevant variables with SLE controls. Change in the SDI and incidences of CAD and renal damage were compared. Descriptive statistics were used; comparisons were made using t-tests and McNemar's tests. RESULTS: Fifty-five SACQ patients and 110 controls were identified. The mean ± SD SDI score at 3 years from the start of the SACQ period was 0.70 ± 1.27 in the SACQ patients versus 1.13 ± 1.54 in controls (P < 0.0001), and by 10 years was 1.26 ± 1.68 versus 2.26 ± 2.23 (P = 0.001); the intergroup difference in damage significantly increased over 10 years. Initially, 2 (3.6%) of the SACQ patients had CAD versus 7 (6.4%) of the controls (P = 0.32), with 1 (1.8%) new case in SACQ patients versus 8 (7.3%) new cases in controls over 10 years (P = 0.06). Baseline serum creatinine level did not differ between the groups. By definition, the SACQ patients had no baseline proteinuria versus 13 (12.3%) of the controls (P < 0.0001). By year 10, 2 (3.6%) SACQ patients versus 26 (23.6%) controls had renal damage (P < 0.0001). CONCLUSION: Patients with a prolonged SACQ period accrued less damage over a decade compared to matched controls, supporting management with active surveillance without treatment during an SACQ period.

Ability of non-fasting and fasting triglycerides to predict coronary artery disease in lupus patients.

OBJECTIVES: To test whether non-fasting and fasting triglyceride (TG) levels differ in individual patients and whether TG (non-fasting and fasting) levels predict coronary artery disease (CAD) in lupus patients. METHODS: Using predefined criteria for a patient's inclusion in this study, we identified the first available set of non-fasting and fasting TG measurements on each individual lupus patient seen in the clinic since 1996. We dichotomized TG values as normal/abnormal and determined whether non-fasting and fasting TG levels differ in each individual patient. We determined whether TG levels (non-fasting and fasting) predict CAD in all consecutive lupus patients seen in the clinic since 1973 using time-dependent time-to-event analysis and stepwise reduction analysis. RESULTS: Part 1: 514 patients were identified. The time between first non-fasting and fasting TG measurements available was 3.2 months. Examining dichotomized TG values as normal/abnormal, there was concordance between fasting and non-fasting TG in 92% of the visits. Non-fasting TG levels were 0.16 (0.75) higher than fasting TG levels (P < 0.001). Part 2: among 1289 patients, 638 had at least one elevated TG level and the length of follow-up from the first TG level recorded to CAD or last clinic visit was 8.82 years. One hundred and four patients developed CAD. TG (non-fasting and fasting) levels predicted CAD with a hazard ratio of 1.15 (95% CI 1.02, 1.29). CONCLUSIONS: Although non-fasting TG levels were statistically higher than the fasting TG levels, the clinical significance of this difference is uncertain. TG (non-fasting and fasting) levels can predict CAD in lupus patients.