SLE Duration Research Articles

Burden of systemic lupus erythematosus in clinical practice: baseline data from the SLE Prospective Observational Cohort Study (SPOCS) by interferon gene signature

ObjectiveThe longitudinal Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS) aims to assess SLE disease course overall and according to type I interferon 4 gene signature (IFNGS). Here, we describe...

The characteristics and risk factors of cerebrovascular events in young systemic lupus erythematosus patients: A case-control study

We clarified the characteristics and risk factors of CVEs in young SLE patients. We retrospectively reviewed the medical records of patients younger than 50 years of age diagnosed with SLE and first CVEs from 1995 to 2020 in a tertiary medical center in Taiwan. We collected data on the patient characteristics before the CVE and reviewed the laboratory data obtained during the period. At a ratio of 1:3, cases and controls were matched with sex, SLE diagnosis age, diagnosis year, and SLE duration. We enrolled 43 CVE SLE patients and matched 129 non-CVE SLE controls. The median age at the time of the CVE was 39 years. Around 70% of young-aged CVE involved the cerebral lobes of frontal (∼30%), parietal (∼20%), occipital (∼10%), and temporal (∼10%). The peak incidence period for hemorrhagic CVE was within 1st year of SLE diagnosis (37%); in contrast, during the 2nd to 5th year of SLE diagnosis (25%) for ischemia CVEs. Hyperlipidemia (odds ratio [OR]=19.36, p=0.002), anti-phospholipid syndrome (APS) (OR=41.9, p=0.0068), a lower hemoglobin level (OR=0.66, p=0.0192), and a higher SLE Disease Activity Index (SLEDAI-2k) score (OR=1.22, p=0.0019) were independent risk factors for CVEs in young SLE patients. Hyperlipidemia, APS, low Hb level, and high SLEDAI-2k significantly increase the risk of young-aged SLE patients developing CVE.

P164 An emerging role of interferon targeted therapy in mucocutaneous SLE: a prospective real-world evaluation of anifrolumab for refractory cutaneous lupus

Abstract Background/Aims Advances in rational drug design and recent clinical trials are leading to emergence of a range of novel therapies for SLE and therapeutic options in clinical practice are expected to broaden rapidly. The optimal real-world place of emerging and established agents will be guided by understanding their differential efficacy on specific SLE manifestations as well as efficacy for more resistant disease. Anifrolumab, a type-I interferon receptor blocking monoclonal antibody, showed efficacy in SLE in phase III trials with a notable effect on mucocutaneous disease although specific lesion subtypes and chroncicity were not explored. Severe refractory mucocutaneous SLE such as scarring discoid lesions are an important and common clinical challenge in current practice. We therefore prospectively evaluated the real-world efficacy and quality of life impact of anifolumab for active mucocutaneous SLE, recalcitrant to multiple biologic and immunosuppressant therapies. Methods Seven patients commenced anifrolumab (300 mg by monthly iv infusion) following application to the manufacturer’s early access programme (NCT 04750057). Prior biologic therapies were discontinued at least 5 half-lives in advance. Mucocutaneous disease activity was captured by Cutaneous Lupus Disease Area and Severity Index (CLASI) activity score and medical photography. Patient reported health-related quality of life comprising the Dermatology Life Quality Index (DLQI); Lupus-QoL and EQ5D-5L were evaluated at baseline, three and six months. Results Seven female patients with active mucocutaneous SLE (Discoid LE n = 5, chilblain LE n = 1, subacute cutaneous LE n = 1) and median disease duration of 17 years were evaluated. Median baseline CLASI activity score was 17 (range 10-26; higher scores indicating severe disease). Median number of previously failed therapies was 7 and included rituximab in 6/7, belimumab in 2/7 and thalidomide in 4/7. Rapid resolution of scale and erythema in DLE was established within 1 month of anifrolumab treatment. Improvements to chilblain lupus were evident by three months. CLASI activity score was improved ≥75% in all patients at 3 months. Clinical responses were associated with significant improvements in DLQI (p < 0.001) and EQ5D-VAS (p = 0.002) by three months. Lupus-QoL trended toward improvement across all domains but most strongly for fatigue (p = 0.01) and pain (p = 0.002) by 6 months. One patient discontinued treatment after 4 months due to polydermatomal shingles complicated by sensorineural hearing loss. Infection coincided with background prednisolone dose >15 mg daily, recent COVID-19 infection and new on-treatment hypogammaglobulinaemia (IgG <5 g/L). Prolonged aciclovir treatment was required for lesion resolution. Conclusion We report rapid real-world efficacy and quality of life impact of anifrolumab on highly refractory mucocutaneous SLE, which exceeded that anticipated from existing clinical trial data. Findings suggest a unique role for emerging interferon targeting therapies in management of mucocutaneous SLE but emphasize need for enhanced VZV precautions among higher risk patients. Disclosure L. Carter: Consultancies; UCB. Z. Wigston: None. P. Laws: Consultancies; Amgen, Celgene, Janssen, Leo, Lilly and Sanofi. Member of speakers’ bureau; AbbVie, Actelion and BMS. Grants/research support; UCB, Almirall, and Novartis. E.M. Vital: Consultancies; Roche, GSK, AstraZeneca, Aurinia Pharmaceuticals, Lilly and Novartis. Grants/research support; Roche, AstraZeneca and Sandoz.

Response to therapy at 6 months predicts long-term renal outcome in lupus nephritis with poor kidney function

ObjectiveIt is unclear whether aggressive treatment would benefit lupus nephritis (LN) with poor renal function, which has been excluded from most clinical trials. We aimed at demonstrating their clinicopathological features...

Pattern and clinical phenotype of systemic lupus erythematosus among male patients: Hospital‐based study

AbstractBackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown aetiology. SLE is mostly considered a disease of women, though men may also be affected, and this may lead to a delay in diagnosis in men. The result is a greater burden of inflammation and subsequent organ damage over time. This study aims to assess the pattern, clinical phenotype and organ damage in male patients with SLE.MethodsA descriptive cross‐sectional study enrolled 30 male SLE patients in Omdurman Military Hospital, Khartoum, Sudan, during the period of December 2019 to May 2020. Data were collected by designated questioner containing demographics, age at diagnosis, clinical manifestations at onset and during the disease course and immunological assays. The data were analyzed by Statistical Package for Social Studies Program.ResultsThe mean age of 35.7 years ranged and the mean age at diagnosis was 32 years, and a third of the patients were found in the age group (30–39 years). The origin distribution showed that 50% of the patients were from central areas, and most of the patients were university graduates, the mean SLE duration was 5 years. Constitutional symptoms were the major manifestation at the onset of SLE in 56.7% of the patients. SLE manifestations during the course of the disease were mainly musculoskeletal manifestations in 87.7% of patients.ConclusionThe mean duration of the disease is 5 years, and the mean age of the patients is in the middle of their thirties, the constitutional symptoms were the major manifestation and musculoskeletal manifestations came second to that and almost all of them have positive antinuclear antibodies and anti‐dsDNA.

Serologic phenotypes distinguish systemic lupus erythematosus patients developing interstitial lung disease and/or myositis.

ObjectivesTo determine if serologic phenotypes could be identified in systemic lupus erythematosus patients developing interstitial lung disease (ILD) and/or myositis.MethodsAdult SLE patients (without myositis/ILD at baseline) had annual assessments and serum sampling between 2000 and 2017. New-onset ILD was identified using the SDI pulmonary fibrosis item. New-onset myositis was identified using the SLICC Damage Index muscle atrophy/weakness item, the SLEDAI-2K item for myositis, and annual creatinine kinase testing. Chart review confirmed ILD/myositis cases and randomly sampled SLE patients from baseline formed our sub-cohort (N = 72). Cases and sub-cohort were compared regarding myositis-related biomarkers at baseline and at a randomly selected follow-up between baseline and end of observation (date of ILD/myositis diagnosis or Dec. 31, 2017). Descriptive analyses and hazards ratios (HRs) were generated for ILD/myositis incidence, focusing on baseline serology and adjusting for sex, race/ethnicity, age at SLE diagnosis, and SLE duration.ResultsFourteen SLE patients developed ILD (N = 9), myositis (N = 3), and/or both (N = 2). Thirteen of those (92.9%) developing ILD/myositis had at least one biomarker at baseline, versus 47 (65.3%) SLE patients who never developed myositis/ILD. The most common biomarkers in myositis/ILD were KL-6, anti-Ro52, and anti-Ku. Baseline biomarkers tended to remain positive in follow-up. In multivariate Cox regressions, SLE patients had higher risk of developing myositis/ILD with elevated baseline KL-6 (adjusted hazard ratio 3.66; 95% confidence interval 1.01, 13.3). When updating biomarkers over time, we also saw correlations between anti-Smith and ILD/myositis.ConclusionsBaseline myositis-related biomarkers were highly associated with ILD/myositis incidence. This is the first identification of biomarker phenotypes with ILD/myositis risk in SLE.

One-year renal outcome in lupus nephritis patients with acute kidney injury: a nomogram model.

To develop a short-term renal outcome prediction model for acute kidney injury (AKI) in patients with LN. Two lupus AKI cohorts from two independent centres during 2013-2019 were included: a derivation cohort from a rheumatology centre and a validation cohort from a nephrology centre. Clinical characteristics and renal histologic features were obtained. The outcome measurement was the recovery of kidney function within 12 months. Lasso regression was used for feature selection. Prediction models with or without pathology were built and a nomogram was plotted. Model evaluation including calibration curve and decision curve analysis was performed. A total of 130 patients were included in the derivation cohort and 96 patients in the validation cohort, of which 82 and 73 patients received a renal biopsy, respectively. The prognostic nomogram model without pathology included determinants of SLE duration, days from AKI onset to treatment and baseline creatinine level [C-index 0.85 (95% CI 0.78, 0.91) and 0.79 (95% CI 0.70, 0.88) for the two cohorts]. A combination of histologic tubulointerstitial (TI) fibrosis in the nomogram gave an incremental predictive performance (C-index 0.93 vs 0.85; P = 0.039) in the derivation cohort but failed to improve the performance in the validation cohort (C-index 0.81 vs 0.79; P = 0.78). Decision curve analysis suggested clinical benefit of the prediction models. The predictive nomogram models might facilitate more accurate management for lupus patients with AKI.

Treatment outcomes in refractory lupus nephritis: Data from an observational study.

Despite current advances in treatment, refractory lupus nephritis (RLN) continues to pose a challenge. The present paper studies the clinical profile and treatment outcomes in patients with RLN. This observational, bidirectional study enrolled consecutive lupus nephritis (LN) patients from August 2018 to January 2019, who either failed to improve within three months, did not achieve partial renal response (PR) at six months, or did not achieve complete renal response (CR) after two years of treatment. Patients were followed every three months; treatment details and outcomes [CR, PR, no renal response (NR)], doubling serum creatinine, and death were recorded. Group comparisons were made using ANOVA and chi-square test. Factors affecting renal response were studied using linear regression. Forty-five of forty-eight enrolled patients completed at least nine months of follow-up and were included in outcome analysis. The median (IQR) SLE duration was three years (2-6 years). The majority of patients (n = 25) had proliferative LN (ISN/RPS class III/IV), with nine patients having pure membranous LN (class V). The mean activity and chronicity indices were 8 and 0. Over a median (IQR) follow-up period of 15 (12-27) months, 28 had CR, 9 had PR, and 8 showed no response to a switch in an immunosuppressive (IS) agent. Repeat renal biopsy (n = 8) with a mean (±SD) biopsy interval of 2 (±1) years showed histological class transformation in more than half of the patients. There was no significant difference in treatment outcome and time to attain response based on individual IS agent or sequence of IS agents used. None of the variables (duration of SLE or nephritis, baseline SLEDAI, leukopenia, hypertension, elevated anti-dsDNA, low complements, serum albumin, 24-hour urinary protein, biopsy class) predicted renal response on univariate analysis. No patient had a doubling of serum creatinine or progression to end-stage renal disease. There were three deaths, all related to infection. A change in immunosuppression produces response in most RLN patients while a fifth of them showed no response to therapy. No predictor of renal response was identified. Histologic class switch was frequent. Renal function did not decline over a year of follow-up.

Quantitative MRI adds to neuropsychiatric lupus diagnostics.

Attributing neuropsychiatric manifestations to SLE is often challenging. Brain white matter lesions are frequent in SLE at MRI, but their diagnostic role is unclear. Here, we assessed whether white matter lesions count, volume and distribution measurement can help in the diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE). Brain dual-echo and 3D T1-weighted sequences were acquired from 32 patients with SLE and 32 healthy controls with a 3 T-scanner and employed to derive T2-hyperintense lesion volume (T2LV), number (T2LN) and probability maps (LPM) using a semi-automatic local thresholding segmentation technique. NPSLE was classified as per the ACR nomenclature, the Italian Society for Rheumatology algorithm and by clinical impression. Clinical descriptors including the SLE International Collaborating Clinics/ACR damage index (SDI) were also recorded. Higher T2LV were observed in SLE vs healthy controls (P<0.001) and in NPSLE vs other SLE (P=0.006). Patients with NPSLE also had higher T2LN (P=0.003) compared with other SLE. In SLE, T2LPM revealed a high prevalence of lesions in the splenium of the corpus callosum, right superior longitudinal fasciculus and right corona radiata. T2LV and T2LN correlated with SLE duration (rho = 0.606; P<0.001 and rho = 0.483; P=0.005, respectively) and age (rho = 0.478; P=0.006 and rho = 0.362; P = 0.042, respectively). T2LV also correlated with SDI (rho = 0.352; P=0.048). SLE patients with fatigue had lower T2LN (P=0.038) compared with patients without fatigue. Thresholds of T2LV ≥ 0.423 cm3 or of T2LN ≥ 12 were associated with definite NPSLE and improved the classification of patients with possible NPSLE per clinical impression. Brain white matter lesions (WML) quantitation adds to NPSLE diagnostics.

LESIONS OF RESPIRATORY SYSTEM IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS:

Introduction. The respiratory system lesions in patients with systemic lupus erythematosus have not been properly addressed by both clinicians and scientists yet, since the progression of these lesions is often asymptomatic. Objective. To identify and determine the nature and prevalence of respiratory system lesions in patients with systemic lupus erythematosus; to distinguish syntropic comorbid lesions, to determine their prevalence and their relationship with the age of patients, disease duration, and the severity of respiratory failure. Materials and methods. 370 patients (331 women and 39 men) with SLE were enrolled. They underwent comprehensive examinations and were stratified by age, duration, and the activity of SLE. The obtained data were processed in Microsoft Excel by means of descriptive statistics, χ2 test, and z-test for comparisons of two proportions; the relationships were considered to be statistically significant when p &lt; 0.05. Results. 67.57% of patients with SLE had respiratory system lesions. Pneumosclerosis, pulmonary hypertension, pneumonitis, and pulmonary fibrosis were found to be syntropic comorbid lesions, i.e. pathogenetically associated with SLE. The prevalence of syntropic comorbid respiratory system lesions in patients with systemic lupus erythematosus depends on the age of patients, duration of the disease, and the severity of respiratory failure. Pneumosclerosis is more prevalent in elderly patients and patients with the SLE duration of more than 6 years. It was the cause of respiratory failure in 43.02% of patients; the condition was of the first degree of severity. Pulmonary hypertension is more prevalent in elderly patients and patients with the SLE duration of less than one year. It led to respiratory failure in 16.13% of patients; the respiratory failure was predominantly mild. Pneumonitis is more prevalent in young patients and patients with SLE duration of more than 10 years. It led to respiratory failure in 52.00% of patients, while 64.10% out of them had degree I respiratory failure. Pulmonary fibrosis is more prevalent in elderly patients and patients with the SLE duration of 1-5 years. It led to respiratory failure in 62.50% of patients, while 80.00% out of them had the first degree of this condition).

Retinal Complications in Patients with Systemic Lupus Erythematosus Treated with Antimalarial Drugs.

Hydroxychloroquine (HCQ) and chloroquine (CQ) are key drugs in systemic lupus (SLE) and related diseases. Retinal toxicity remains the most worrisome complication. We studied factors potentially associated with retinal toxicity, using case-control analyses. Within our SLE clinic cohort, we identified patients with retinal changes using the Systemic Lupus International Collaborating Clinics Damage Index. We confirmed HCQ/CQ retinopathy with chart review, and selected up to 3 SLE controls for each case, matched by age at SLE diagnosis and SLE duration. Over an average 12.8 years of followup, within 326 patients exposed to antimalarial drugs, 18 (5.5%) developed retinal toxicity. The minimum number of years of HCQ/CQ exposure before retinopathy developed was 8 years (maximum 33 yrs). Median HCQ/CQ duration was statistically similar in cases [19 yrs, interquartile range (IQR) 14-20] and controls (16 yrs, IQR 11-22), likely due to our matching on SLE duration. Versus controls, cases tended to have more renal disease (cases 22.2%, controls 14.8%) and were slightly less likely to be white (cases 61.1%, controls 74.1%), but neither variable reached statistical significance. Among patients with retinal toxicity, the number previously exposed to CQ was more than 3 times that in controls. Just over 5% of patients developed antimalarial retinal complications, over an average of 12.8 years. No cases were detected in the first 5 years of therapy. Past CQ use was more common in cases versus controls. Future studies using larger cohorts are under way to better define the roles of therapy duration, race/ethnicity, and other factors.

Cell of origin in diffuse large B-cell lymphoma in systemic lupus erythematosus: molecular and clinical factors associated with survival

BackgroundSLE is associated with increased risk of diffuse large B-cell lymphoma (DLBCL). DLBCL is routinely classified by cell of origin (COO), with germinal centre B-cell (GCB) being more common and...

Role of long non-coding RNAs expression (ANRIL, NOS3-AS, and APOA1-AS) in development of atherosclerosis in Egyptian systemic lupus erythematosus patients.

To quantify the expression level of three lncRNAs which are known to be relevant to atherosclerosis (ANRIL, NOS3-AS, and APOA1-AS) in SLE patients and to assess their relationship with atherogenic and inflammatory biomarkers. The circulating levels of these lncRNAs were assessed using RT-PCR, in addition to measurement of E-selectin, V-CAM1, oxidized low-density lipoprotein (oxLDL), total nitric oxide (NOx), and lipid profile in 65 SLE patients (35 atherosclerotic and 30 non-atherosclerotic) and 35 healthy subjects. The expression levels of these lncRNAs were higher in SLE patients than in healthy controls. Importantly, a higher overexpression of these lncRNAs was noticed in atherosclerotic SLE patients than in non-atherosclerotic ones. In atherosclerotic SLE patients, level of ANRIL was positively associated with menopause, SLE duration, SLEDAI, and SLICC and negatively correlated with C3. Moreover, NOS3-AS expression was negatively correlated with total NOx level and HDL, while it was positively correlated with TC, LDL-C, hypertension, metabolic syndrome, obesity and dyslipidemia, CIMT, VCAM-1, E-selectin, oxLDL, SLEDAI, and SLICC. With respect to APOA1-AS, its expression was negatively correlated with HDL-C, whereas it was positively correlated with TC, LDL-C, hypertension, dyslipidemia, obesity, metabolic syndrome, menopause, CIMT, RI, V-CAM1, E-selectin, oxLDL, and SLICC. ANRIL, NOS3-AS, and APOA1-AS could be used as predictive biomarkers for atherosclerosis in SLE. Multivariate analyses identified these lncRNAs as independent predictors for atherosclerosis in SLE. These lncRNAs play a pivotal role in development of atherosclerosis via their significant repercussions atherogenic and inflammatory indices.

The frequency and outcome of lupus nephritis: results from an international inception cohort study

To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort. Patients in the Systemic Lupus International Collaborating Clinics inception cohort (≤15 months of SLE diagnosis) were assessed annually for estimated glomerular filtration rate (eGFR), proteinuria and end-stage renal disease (ESRD). Health-related quality of life was measured by the Short Form (36 questions) health survey questionnaire (SF-36) subscales, mental and physical component summary scores. There were 1827 patients, 89% females, mean (s.d.) age 35.1 (13.3) years. The mean (s.d.) SLE duration at enrolment was 0.5 (0.3) years and follow-up 4.6 (3.4) years. LN occurred in 700 (38.3%) patients: 566/700 (80.9%) at enrolment and 134/700 (19.1%) during follow-up. Patients with nephritis were younger, more frequently men and of African, Asian and Hispanic race/ethnicity. The estimated overall 10-year incidence of ESRD was 4.3% (95% CI: 2.8%, 5.8%), and with nephritis was 10.1% (95% CI: 6.6%, 13.6%). Patients with nephritis had a higher risk of death (HR = 2.98, 95% CI: 1.48, 5.99; P = 0.002) and those with eGFR <30 ml/min at diagnosis had lower SF-36 physical component summary scores (P < 0.01) and lower Physical function, Physical role and Bodily pain scores. Over time, patients with abnormal eGFR and proteinuria had lower SF-36 mental component summary (P ≤ 0.02) scores compared to patients with normal values. LN occurred in 38.3% of SLE patients, frequently as the initial presentation, in a large multi-ethnic inception cohort. Despite current standard of care, nephritis was associated with ESRD and death, and renal insufficiency was linked to lower health-related quality of life. Further advances are required for the optimal treatment of LN.

Systemic lupus erythematosus and malignancies risk.

To evaluate the risk of site-specific and overall malignancies after SLE and explore the potential influencing factors. We searched electronic databases for articles that assessed the risk of malignancies after SLE through February 2015. We extracted the incidence rates (IRs) and corresponding 95 % confidence intervals (CIs). We used random effects models to calculate the pooled IRs and assessed the impact of study designs, region, gender, age and duration of follow-up. Eighteen studies were included, giving a pooled IR of 1.44 (95 % CI 1.23-1.69). Europeans, Americans and Asians showed a IR of 1.56 (95 % CI 1.07-2.28), 1.18 (95 % CI 1.01-1.39) and 1.62 (95 % CI 1.38-1.89), respectively. Males and females (eight studies) demonstrated a IR of 1.34 (95 % CI 1.07-1.67) and 1.51 (95 % CI 1.20-1.90), respectively. Prospective and retrospective studies showed a IR of 1.55 (95 % CI 0.97-2.47) and 1.44 (95 % CI 1.21-1.73), respectively. An increment of 10 years of age conferred a decrease in IR of 0.6. An increment of 5 years of SLE duration conferred a decrease in IR of 2.5. An increased IR of malignancies was observed in NHL, vagina/vulva, hematology, head/neck, leukemia, thyroid, liver/gallbladder, kidney, anal, cervix, esophagus, lung and pancreas. A decreased IR of malignancies was observed in ovary and colon/rectum. SLE patients had an increased risk of developing overall malignancies, particularly among Asians and females. Age and SLE duration are inversely associated with the risk of overall malignancies. SLE patients showed a different role in the onset of various site-specific malignancies.

THU0027 Cardiovascular Risk Profile in Systemic Lupus Erythematosus

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune inflammatory disease characterized by the presence of a plethora of autoantibodies and immune complex formation. Virtually every system and organ can be affected...

THU0032 Fibromyalgia Prevalence and Related Factors in A Large Spanish Cohort of Patients with Systemic Lupus Erythematosus

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease that may affect multiple organs. Fibromyalgia (FM) is a physical, mental and social impairing disease. FM has been observed in SLE patients....

THU0300 Serum Mercury Level and Disease Activity of Systemic Lupus Erythematosus (SLE): A Case-Control Study

BackgroundEnvironmental contamination with mercury is linked to increased incidence of autoimmune diseases. Exposure to low-dose non-organic mercury has been reported to exacerbate murine SLE.ObjectivesTo study the serum mercury(Hg) levels in...

THU0299 Factors Associated with Long-Term Renal Function Deterioration in Lupus Nephritis Treated Initially with Combined Prednisolone and Mycophenolate Mofetil (MMF) or Tacrolimus (TAC)

ObjectivesTo study the risk factors for renal function decline in patients with lupus nephritis treated initially with combined steroid and MMF or Tac.MethodsData were extracted from a randomized controlled trial...

SAT0215 Clinical presentation, treatment and outcome of membranous nephropathy in SLE: A comparison with proliferative lupus glomerulonephritis in 141 patients

ObjectivesTo study the presentation and outcome of membranous nephropathy in SLE in comparison with proliferative lupus glomerulonephritis.MethodsPatients with biopsy firmed active lupus nephritis who were recruited in a randomized trial...