Objective
One objective in the treatment of systemic lupus erythematosus (SLE) disease activity is to reduce long‐term rates of organ damage. We undertook this study to analyze data from a large ...clinical SLE cohort to compare patients achieving different levels of disease activity with respect to rates of long‐term damage.
Methods
We analyzed data from 1,356 SLE patients in the Hopkins Lupus Cohort, followed up quarterly, with 77,105 person‐months observed from 1987 to 2016. Three outcome measures were considered: clinical remission with no treatment, clinical remission on treatment, and lupus low disease activity state (LLDAS).
Results
Patients achieved LLDAS in 50% of their follow‐up months. They achieved clinical remission with no treatment or clinical remission on treatment in only 13% and 27%, respectively, of their follow‐up visits. The rates of damage consistently declined with increased percentage of prior time in either LLDAS or clinical remission on treatment. Spending a short proportion of prior time (<25%) in clinical remission on treatment was associated with a relatively low rate of damage compared to never achieving that condition (1.01 events per 10 person‐years versus 1.82 events per 10 person‐years; rate ratio 0.54, P < 0.0001). Those patients who experienced LLDAS at least 50% of the time had relatively low rates of damage (rate ratio 0.39–0.47, P < 0.0001).
Conclusion
LLDAS is an easier target to achieve than clinical remission on treatment and results in reduced risk of long‐term damage. However, even a small percentage of time in clinical remission on treatment was associated with reduced damage.
Patients with systemic lupus erythematosus (SLE) are at excess risk of cardiovascular events (CVEs). There is uncertainty regarding the relative importance of SLE disease activity, medications, or ...traditional risk factors in this increased risk. To gain insight into this, the authors analyzed data from a cohort of 1,874 patients with SLE who were seen quarterly at a single clinical center (April 1987-June 2010) using pooled logistic regression analysis. In 9,485 person-years of follow-up, the authors observed 134 CVEs (rate = 14.1/1,000 person-years). This was 2.66 times what would be expected in the general population based on Framingham risk scores (95% confidence interval: 2.16, 3.16). After adjustment for age, CVE rates were not associated with duration of SLE. However, they were associated with average past levels of SLE disease activity and recent levels of circulating anti-double-stranded DNA. Past use of corticosteroids (in the absence of current use) was not associated with CVE rates. However, persons currently using 20 mg/day or more of corticosteroids had a substantial increase in risk even after adjustment for disease activity. Thus, consistent with findings in several recent publications among cohorts with other diseases, current use of corticosteroids was associated with an increased risk of CVEs. These results suggest a short-term impact of corticosteroids on CVE risk.
Objective
In 2016, the American Academy of Ophthalmology (AAO) changed the recommended daily dose of hydroxychloroquine (HCQ) from 6.5 mg/kg to <5 mg/kg. However, it is not clear that the lower ...prescribed dose of HCQ will have the same efficacy for systemic lupus erythematosus (SLE) activity or the same role in protecting against cardiovascular risk factors and thrombosis. This study was undertaken to address the frequency of HCQ retinopathy and the role of HCQ blood levels in identifying those individuals who are at a greater future risk of retinopathy.
Methods
HCQ blood levels in 537 patients with SLE from a large clinical cohort were repeatedly measured, and patients were tested for HCQ retinopathy. We assessed the risk of retinopathy according to clinical characteristics and blood levels of HCQ.
Results
The overall frequency of retinopathy was 4.3% (23 of 537 patients). There was a 1% risk of retinopathy in the first 5 years of HCQ treatment, 1.8% from 6 to 10 years, 3.3% from 11 to 15 years, 11.5% from 16 to 20 years, and 8.0% after 21 years of use. We found that older age (P < 0.0001), higher body mass index (P for trend = 0.0160), and longer duration of HCQ intake (P = 0.0024 and P for trend = 0.0006) were associated with a higher risk of HCQ toxicity. Higher blood levels of HCQ predicted later HCQ retinopathy (P = 0.0124 and P = 0.0340 for mean and maximum HCQ blood levels, respectively).
Conclusion
Our data prove the utility of assessing blood levels of HCQ in the prediction of retinopathy. This would allow clinicians to either decrease the dose or increase monitoring in those patients with high HCQ blood levels.
Hydroxychloroquine (HCQ) is used for its effect on systemic lupus erythematosus (SLE) disease activity and longterm benefits. This can be limited by adherence. One way to assess adherence is to ...measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is disagreement about dosing; rheumatologists recommend weight-based dosing while some other specialists advocate height-based "ideal body weight" dosing.
Patients were prescribed HCQ not exceeding 6.5 mg/kg (max 400 mg/day). In hemodialysis, the dose was 200 mg after each session, and in renal insufficiency it was 200 mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the effect of measurement and counseling on adherence, we compared the proportion of patients with a level of 500 ng/ml or higher based on the number of prior assessments.
The proportion of patients with HCQ levels in the therapeutic range differed significantly by age, sex, and Vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, subtherapeutic, and therapeutic levels, disease activity decreased (SLE Disease Activity Index 2.92, 2.36, and 2.20, p = 0.04 for trend). At first, 56% were therapeutic, and by the third measurement this increased to 80% (p ≤ 0.0001).
There was a trend toward higher disease activity with lower HCQ levels. Renal failure dosing led to suboptimum levels. We show that weight-based dosing (max 400 mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling, and repeated testing can increase adherence rates.
The frequency of endstage renal disease (ESRD) from systemic lupus erythematosus (SLE) in the United States has not improved over the last few decades in large population datasets. Understanding the ...risk factors for renal failure in SLE could lead to earlier detection of lupus nephritis and potentially more effective treatments in those with markers of poor prognosis.
The Hopkins Lupus Cohort, comprising 2528 patients was used. One hundred fifty-one patients experienced renal failure after SLE diagnosis, defined as dialysis or renal transplant. We estimated the risk of renal failure in subgroups defined by demographics, laboratory tests, and the American College of Rheumatology/Systemic Lupus International Collaborating Clinics (ACR/SLICC) classification criteria satisfied within 1 year of SLE diagnosis.
The overall incidence of renal failure within 20 years of SLE diagnosis was 8.4%. The risk was much higher (20.0%) among those who experienced proteinuria within the first year of diagnosis. Demographic predictors included African American ethnicity rate ratio (RR) 1.82,
= 0.0012 and age ≥ 40 years at SLE diagnosis (RR 0.51 vs those with diagnosis at < 30 yrs of age,
= 0.019). Among immunologic markers, low C3 was a strong predictor of renal failure (RR 2.00,
= 0.0011).
Proteinuria within the first year of diagnosis of SLE is one of the most important predictors of ESRD. Our data also confirm African American ethnicity, younger age at SLE diagnosis, and low C3 as strong predictors of renal failure.
The relationship between common patient characteristics, such as sex and metabolic comorbidities, and mortality from coronavirus disease 2019 (COVID-19) remains incompletely understood. Emerging ...evidence suggests that metabolic risk factors may also vary by age. This study aimed to determine the association between common patient characteristics and mortality across age-groups among COVID-19 inpatients.
We performed a retrospective cohort study of patients discharged from hospitals in the Premier Healthcare Database between April-June 2020. Inpatients were identified using COVID-19 ICD-10-CM diagnosis codes. A priori-defined exposures were sex and present-on-admission hypertension, diabetes, obesity, and interactions between age and these comorbidities. Controlling for additional confounders, we evaluated relationships between these variables and in-hospital mortality in a log-binomial model.
Among 66 646 (6.5%) admissions with a COVID-19 diagnosis, across 613 U.S. hospitals, 12 388 (18.6%) died in-hospital. In multivariable analysis, male sex was independently associated with 30% higher mortality risk (aRR, 1.30, 95% CI: 1.26-1.34). Diabetes without chronic complications was not a risk factor at any age (aRR 1.01, 95% CI: 0.96-1.06), and hypertension without chronic complications was a risk factor only in 20-39 year-olds (aRR, 1.68, 95% CI: 1.17-2.40). Diabetes with chronic complications, hypertension with chronic complications, and obesity were risk factors in most age-groups, with highest relative risks among 20-39 year-olds (respective aRRs 1.79, 2.33, 1.92; P-values ≤ .002).
Hospitalized men with COVID-19 are at increased risk of death across all ages. Hypertension, diabetes with chronic complications, and obesity demonstrated age-dependent effects, with the highest relative risks among adults aged 20-39.
Remission is the ultimate goal in systemic lupus erythematosus (SLE). In this study, we applied four definitions of remission agreed on by an international collaboration (Definitions of Remission in ...SLE, DORIS) to a large clinical cohort to estimate rates and predictors of remission.
We applied the DORIS definitions of Clinical Remission, Complete Remission (requiring negative serologies), Clinical Remission on treatment (ROT) and Complete ROT. 2307 patients entered the cohort from 1987 to 2014 and were seen at least quarterly. Patients not in remission at cohort entry were followed prospectively. We used the Kaplan-Meier approach to estimate the time to remission and the time from remission to relapse. Cox regression was used to identify baseline factors associated with time to remission, adjusting for baseline disease activity and baseline treatment.
The median time to remission was 8.7, 11.0, 1.8 and 3.1 years for Clinical Remission, Complete Remission, Clinical ROT and Complete ROT, respectively. High baseline treatment was the major predictor of a longer time to remission, followed by high baseline activity. The median duration of remission for all definitions was 3 months. African-American ethnicity, baseline low C3 and baseline haematological activity were associated with longer time to remission for all definitions. Baseline anti-dsDNA and baseline low C4 were associated with longer time to Complete Remission and Complete ROT. Baseline low C4 was also negatively associated with Clinical Remission.
Our results provide further insights into the frequency and duration of remission in SLE and call attention to the major role of baseline activity and baseline treatment in predicting remission.
Male patients with systemic lupus erythematosus (SLE) are thought to be similar to female patients with SLE, but key clinical characteristics may differ. Comparisons were made between male and female ...patients with SLE in the Hopkins Lupus Cohort.
A total of 1979 patients in the Hopkins Lupus Cohort were included in the analysis.
The cohort consisted of 157 men (66.2% white, 33.8% African American) and 1822 women (59.8% white, 40.2% African American). The mean followup was 6.02 years (range 0-23.73). Men were more likely than women to have disability, hypertension, thrombosis, and renal, hematological, and serological manifestations. Men were more likely to be diagnosed at an older age and to have a lower education level. Women were more likely to have malar rash, photosensitivity, oral ulcers, alopecia, Raynaud's phenomenon, or arthralgia. Men were more likely than women to have experienced end organ damage including neuropsychiatric, renal, cardiovascular, peripheral vascular disease, and myocardial infarction, and to have died. In general, differences between males and females were more numerous and striking in whites, especially with respect to lupus nephritis, abnormal serologies, and thrombosis.
Our study suggests that there are major clinical differences between male and female patients with SLE. Differences between male and female patients also depend on ethnicity. Future SLE studies will need to consider both ethnicity and gender to understand these differences.
We evaluated which aPL combinations increase the risk of future thrombosis in patients with SLE.
This prospective cohort study consisted of SLE patients who had been tested for all seven aPL (LA, aCL ...isotypes IgM, IgG and IgA, and anti-β2-glycoprotein I isotypes IgM, IgG and IgA). Pooled logistic regression was used to assess the relationship between aPL and thrombosis.
There were 821 SLE patients with a total of 75 048 person-months of follow-up. During the follow-up we observed 88 incident cases of thrombosis: 48 patients with arterial, 37 with venous and 3 with both arterial and venous thrombosis. In individual models, LA was the most predictive of any age-adjusted rate ratio 3.56 (95% CI 2.01, 6.30), P < 0.0001, venous 4.89 (2.25, 10.64), P < 0.0001 and arterial 3.14 (1.41, 6.97), P = 0.005 thrombosis. Anti-β2-glycoprotein I IgA positivity was a significant risk factor for any 2.00 (1.22, 3.3), P = 0.0065 and venous 2.8 (1.42, 5.51), P = 0.0029 thrombosis. Only anti-β2-glycoprotein I IgA appeared to add significant risk to any 1.73 (1.04, 2.88), P = 0.0362 and venous 2.27 (1.13, 4.59), P = 0.0218 thrombosis among those with LA. We created an interaction model with four categories based on combinations of LA and other aPL to look at the relationships between combinations and the risk of thrombosis. In this model LA remained the best predictor of thrombosis.
Our study demonstrated that in SLE, LA remained the best predictor of thrombosis and adding additional aPL did not add to the risk, with the exception of anti-β2-glycoprotein I IgA.
Despite the high prevalence of cardiovascular (CV) disease among patients with systemic lupus erythematosus (SLE), the relationship between age, blood pressure (BP), and BP variability (BPV) is not ...well understood. We studied visit-to-visit BPV, its relationship to age, clinical, and demographic characteristics, and its potential role as a CV risk factor in patients with SLE.
We analyzed systolic (SBP) and diastolic BP (DBP) measures in our cohort using mixed-effects regression models. From these models, we then obtained estimates of the mean BP, the visit-to-visit SD, and the between-person SD. The estimated means were compared to the general population using data from the National Health Statistics Reports from 2001 to 2008. In addition, we examined the relationship between BP (means, variances), patient demographic and clinical characteristics, and subsequent CV events.
The mean SBP in SLE increased with age and was significantly higher in younger patients compared to the general population. BPV in SLE was elevated across all ages. BPV was significantly higher in African Americans, in patients with traditional CV risk factors, those with high disease activity, and in patients taking prednisone. Hydroxychloroquine was associated with significantly lower BPV. Within-person variability in DBP of ≥ 9 mmHg was highly associated with CV events in a multivariate analysis.
Age-related BP patterns in SLE differ from the general population. Increased visit-to-visit BPV is affected by many disease-specific and traditional CV factors. Increased DBP variability is highly associated with CV events in SLE.
PDF
