Lupus Erythematosus Disease Activity Index Research Articles

Comparison of Responsiveness of British Isles Lupus Assessment Group 2004 Index, Systemic Lupus Erythematosus Disease Activity Index 2000, and British Isles Lupus Assessment Group 2004 Systems Tally.

To compare the responsiveness of the British Isles Lupus Assessment Group 2004 index (BILAG-2004) and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity indices and to determine whether there was any added value in combining BILAG-2004, BILAG-2004 system tally (BST), or simplified BST (sBST) with SLEDAI-2K. This was a multicenter longitudinal study of SLE patients. Data were collected on BILAG-2004, SLEDAI-2K, and therapy on consecutive assessments in routine practice. The external responsiveness of the indices was assessed by determining the relationship between change in disease activity and change in therapy between 2 consecutive visits. Comparison of indices and their derivatives was performed by assessing the main effects of the indices using logistic regression. Receiver operating characteristic curves analysis was used to describe the performance of these indices individually and in various combinations, and comparisons of area under the curve were performed. There were 1,414 observations from 347 patients. Both BILAG-2004 and SLEDAI-2K maintained an independent relationship with change in therapy when compared. There was some improvement in responsiveness when continuous SLEDAI-2K variables (change in score and score of previous visit) were combined with BILAG-2004 system scores. Dichotomization of BILAG-2004 or SLEDAI-2K resulted in poorer performance. BST and sBST had similar responsiveness as the combination of SLEDAI-2K variables and BILAG-2004 system scores. There was little benefit in combining SLEDAI-2K with BST or sBST. The BILAG-2004 index had comparable responsiveness to SLEDAI-2K. There was some benefit in combining both indices. Dichotomization of BILAG-2004 and SLEDAI-2K leads to suboptimal performance. BST and sBST performed well on their own; sBST is recommended for its simplicity and clinical meaningfulness.

Novel immunoprofiling method for diagnosing SLE and evaluating therapeutic response

ObjectiveDiagnosis of SLE is based on clinical manifestations but is heterogeneous in early onset. Hence, we aimed to evaluate the feature of the immunoprofiling in patients with SLE and apply...

Changes in the expression of T-cell factor-1 in follicular helper T cells reflect the condition of systemic lupus erythematosus patients

ObjectiveThis study aimed to identify changes in T-cell factor-1 (TCF1) in circulating T-cell subsets of systemic lupus erythematosus (SLE) patients and to explore their significance in SLE. MethodsPeripheral blood was collected from 41 SLE patients and 45 healthy controls (HCs). TCF1 in follicular helper T (TFH), follicular regulatory T (TFR) and regulatory T (Treg) cells was analyzed by flow cytometry. Interleukin-21 (IL-21), programmed death receptor 1 (PD-1) and killer cell lectin-like receptor G1 (KLRG1) were detected and compared among TFH subsets sorted according to TCF1 and CD62L expression. Correlation analyses were conducted between TCF1-related TFH cell subsets and autoantibody levels, systemic lupus erythematosus disease activity index (SLEDAI), and plasmablast levels of SLE patients. ResultsAbsolute numbers of TCF1- TFH and TCF1+ Treg cells were increased in SLE patients. According to TCF1 and CD62L expression, circulating TFH cells and Tregs were sorted into four subsets. CD62L+TCF1+ TFH cell percentages were decreased, and CD62L-TCF1- TFH cells were increased. CD62L+TCF1+ Treg cell percentages were increased, and CD62L-TCF1- Treg cell percentages were decreased. KLRG1+ percentages in CD62L-TCF1-TFH were higher in SLE patients than in HCs. Functionally, CD62L+TCF1+ TFH cells had stronger IL-21 secretion, while CD62L-TCF1-TFH cells had weaker IL-21 secretion and lower PD-1 expression. TCF1- and CD62L-TCF1- TFH numbers were positively correlated with anti-ribosomal P, anti-dsDNA and SLEDAI. ConclusionThe increased TFH cells in SLE patients were mostly TCF1-negative subsets with weakened function. Changes in TCF1-related subsets can reflect the condition and abnormal humoral immunity of SLE patients.

Characteristics and renal survival of patients with lupus nephritis with glomerular immunoglobulin G4 deposition: a single-centre retrospective analysis

ObjectiveRenal injury is common in SLE. Immune complex deposition plays an important role in the development of lupus nephritis (LN), while little is known about glomerular IgG4 deposition in patients...

Mechanism of action of baricitinib and identification of biomarkers and key immune pathways in patients with active systemic lupus erythematosus

ObjectivesTo elucidate the mechanism of action of baricitinib, a Janus kinase (JAK) 1/2 inhibitor, and describe immunological pathways related to disease activity in adults with systemic lupus erythematosus (SLE) receiving...

POS0190 EFFICACY AND SAFETY OF BARICITINIB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS FROM TWO RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, PHASE 3 STUDIES

BackgroundIn a 24-week, phase 2 clinical study (NCT02708095) in patients with systemic lupus erythematosus (SLE), baricitinib (BARI), an oral selective inhibitor of Janus kinase 1 and 2 approved for the treatment of rheumatoid arthritis and atopic dermatitis, inhibited the type l interferon gene signature, multiple other cytokine pathways, and improved disease activity (1) (2).ObjectivesTo further evaluate the efficacy and safety of BARI in patients with SLE.MethodsPatients with active SLE receiving stable background therapy were randomised 1:1:1 to BARI 2-mg, 4-mg, or placebo (PBO) once daily in two identically designed, 52-week, phase 3 randomised, PBO-controlled studies. In SLE-BRAVE-I (NCT03616912) and -II (NCT03616964), 760 and 775 patients, respectively were enrolled in a balanced manner across regions, although different countries per region participated in each study. The primary endpoint for both studies was the proportion of patients achieving an SLE Responder Index-4 (SRI-4) response at week 52. Glucocorticoid tapering was encouraged but not required per protocol.ResultsThe mean Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) at baseline was 10.1 for both SLE-BRAVE-I and -II participants; musculoskeletal and mucocutaneous domains were the most common domains involved at baseline. In SLE-BRAVE-I, the proportion of SRI-4 responders at week 52 among patients treated with BARI 4-mg (56.7%), but not BARI 2-mg (49.8%), was significantly greater than in patients treated with PBO (45.9%, p = 0.016) (Table 1). No difference was seen in SLE-BRAVE-II (47.1%, 46.3%, and 45.6%, BARI 4-mg, 2-mg, and PBO, respectively). None of the key secondary endpoints, including glucocorticoid tapering or time to first severe flare (SFI), were met in either study. The proportions of patients with serious adverse events (SAEs) were 7.1% and 8.6% for PBO, 9.4% and 13.4% for BARI 2-mg and 10.3% and 11.2% for BARI 4-mg in SLE-BRAVE-I and II, respectively.Table 1.Efficacy and safety of baricitinib in patients with SLE-BRAVE-I and -IISLE-BRAVE-ISLE-BRAVE-IIEfficacy measurePBO (N=253)BARI 2-mg (N=255)BARI 4-mg (N=252)PBO (N=256)BARI 2-mg (N=261)BARI 4-mg (N=258)SRI-4 (W52)116 (45.9)126 (49.8)142 (56.7)*116 (45.6)120 (46.3)121 (47.1)SRI-4 (W24)99 (39.1)114 (44.8)117 (46.5)98 (38.6)104 (40.0)108 (42.1)Severe Flares (n, events)38 (15.0)34 (13.3)26 (10.3)26 (10.2)29 (11.1)29 (11.2)HR for time to first severe flare (SFI) HR [CI]NA0.8 [0.52, 1.32]0.65 [0.40, 1.08]NA1.1 [0.65, 1.89]1.1 [0.67, 1.94]Glucocorticoid sparing36 (30.8)31 (29.2)36 (34.0)33 (31.7)34 (29.8)36 (34.3)LLDAS (W52)66 (26.2)65 (25.7)74 (29.7)59 (23.2)62 (24.0)65 (25.4)Safety measureTEAE210 (83.0)210 (82.4)208 (82.5)198 (77.3)199 (76.2)200 (77.5)SAE18 (7.1)24 (9.4)26 (10.3)22 (8.6)35 (13.4)29 (11.2)Data are n (%) patients, unless otherwise indicated. BARI=baricitinib; CI=confidence interval; HR=hazard ratio compared with PBO; LLDAS=lupus low disease activity state; N=number of patients in the analysis population; n=number of patients in the specified category; PBO=placebo; TEAE=treatment-emergent adverse event; SAE=serious adverse event; W=week. *p≤0.05 vs PBO.ConclusionAlthough phase 2 data suggested BARI as a potential treatment for patients with SLE (2), the SLE-BRAVE-I and -II phase 3 study results were discordant for the primary outcome measure, with only SLE-BRAVE-I positive, making it difficult to elucidate benefit. Additional analyses are being performed to understand this discordance. No new safety signals were observed.

AB0428 TREATMENT PATTERNS OF SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS IN TAIWAN – A POPULATION-BASED ANALYSIS

BackgroundSystemic lupus erythematosus (SLE) is a chronic, autoimmune disease of an unknown etiology with a broad spectrum of organ manifestations, and patients with SLE have limited treatment options to NSAIDS, glucocorticoids, hydroxychloroquine and immunosuppressants. There is a lack of real-world evidence related to treatment patterns of SLE patients in Taiwan.ObjectivesTo describe the real-world patient demographics, clinical characteristics, and treatment patterns of patients with SLE in Taiwan.MethodsA retrospective observational study using Taiwan’s National Health Insurance Research Database (NHIRD) from 1/1/2014 to 12/31/2019 was undertaken. Patients holding catastrophic illness certificates for SLE in 2015-2017 were identified. Enrolled patients aged ≥ 18 years were then divided into three groups (mild, moderate, and severe) based on the highest severity patients experienced in the one year following the enrollment date using a published claims-based algorithm (Garris et al 2013) that incorporates the Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, British Isles Lupus Assessment Group Index and expert clinical opinion, and indexed upon the first date of entering the severity group. Baseline patient characteristics and treatment patterns during the follow-up period were measured. The types of treatment considered were NSAIDs, glucocorticoids, hydroxychloroquine and immunosuppressants.ResultsA total of 20,181 patients with catastrophic illness certificates for SLE were included in this study. The mean age of all SLE patients was 46.5 years and patients were mostly female (89.1%). The mean Charlson Comorbidity Index (CCI) score of all SLE patients was 1.5 (SD 1.3). Of these patients, 29.3% (n=5,918) had mild SLE activity, 60.7% (n=12,253) moderate and 10.0% (n=2,010) severe. During the one-year follow-up period, moderate to severe patients had numerically higher utilization rate of all types of treatment compared with mild patients (Table 1). Of all oral glucocorticoid users,27.8% of severe patients used high-dose glucocorticoids (> 15 mg/day) compared to <0.1% for mild and 9.7% for moderate patients. More than 70.0% of moderate to severe patients were prescribed 2 or more types of treatment at the same point of time. Of these patients having concomitant treatment of glucocorticoids with immunosuppressants, glucocorticoid dosage increased with the number of immunosuppressant used, especially in severe patients. 80.4% of moderate to severe patients received glucocorticoid-based therapy as the first-line treatment and the median treatment duration was 3.1 months. The median treatment duration of each first-line immunosuppressant ranged from 0.9 to 4.8 months in moderate to severe patients.Table 1.SLE treatment utilization during the 1-year follow-up periodTotal (n=20,181)`Mild (n=5,918)Moderate (n=12,253)Severe (n=2,010)n%n%n%n%NSAID7,21235.71,40523.74,98340.782441.0Glucocorticoid14,01969.52,01534.110,29784.01,70784.9Hydroxychloroquine13,27865.82,86748.58,97073.21,44171.7Immunosuppressant7,63037.800.06,31951.61,31165.2Methotrexate8984.500.07866.41125.6Azathioprine5,64228.000.04,84339.579939.8Leflunomide1320.700.01171.0150.8Cyclosporin8544.200.07155.81396.9Mycophenolate9594.800.07746.31859.2Cyclophosphamide7903.900.0170.177338.5ConclusionThe complexity and intensity of therapeutic approaches in SLE were associated with increased disease severity and patients were often resistant to treatment. These findings reflect the disease burden in SLE patients and suggest there is a substantial unmet need in the SLE treatment paradigm for moderate to severe SLE patients.

B-cell activating factor and A proliferation-inducing ligand in relation to intima-media thickness as biomarkers of premature atherosclerosis in systemic lupus erythematosus patients

BackgroundThe aim of this study was to assess the correlation of the serum B-cell activating factor (BAFF), A proliferation-inducing ligand (APRIL) and interleukin (IL)-21 with carotid intima-media thickness (cIMT) to evaluate their efficacy as non-invasive biomarkers for the risk of premature development of atherosclerosis. MethodsELISA test was used to quantify serum BAFF, APRIL and IL-21 in 40 patients with systemic lupus erythematosus (SLE) and 20 healthy controls (HCs). The obtained results were correlated with disease duration, anti-double stranded DNA, complement proteins levels, lipid profile, cIMT and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). ResultsSerum BAFF, APRIL and IL-21 were significantly increased in SLE compared to HCs. Positive correlation was recorded between BAFF (r = 0.51) and APRIL (r = 0.52) with the cIMT. IL-21 correlated positively with SLEDAI (r = 0.33) and negatively with BAFF (r = -0.37) and APRIL (r = -0.44). According to the multiple logistic regression analysis, we found that low-density lipoprotein, serum BAFF and APRIL values were independent factors for cIMT in SLE. To discriminate premature atherosclerosis in patients with SLE, BAFF ≥455 pg/ml yielded 88.9% sensitivity with 100% specificity while APRIL ≥600 pg/ml yielded 95% sensitivity with 100% specificity. IL-21 ≥240 pg/ml yielded 66.7% sensitivity and 100% specificity. ConclusionsCirculating BAFF and APRIL in patients with SLE were correlated to disease activity and cIMT, suggesting that they could be used as a peripheral blood biomarker for the occurrence of premature atherosclerosis in SLE.

A novel circRNA, circRACGAP1, hampers the progression of systemic lupus erythematosus via miR-22-3p-mediated AKT signalling

Background Systemic lupus erythematosus (SLE) is defined as a multisystem autoimmune disease involving various organs, of which exact molecular mechanisms remain elusive. Here, we aimed to investigate a novel circular RNA (circRNA), circRACGAP1, abnormally expressed in SLE and explored its underlying regulatory network. Methods The expression patterns of circRACGAP1 were determined in patients diagnosed with SLE by using a qRT-PCR assay. Spearman correlation analysis was employed to evaluate the correlation between circRACGAP1 and clinicopathological variables in patients with SLE. Flow cytometry and TUNEL assays were subjected to assess the cell apoptosis. Nuclear-cytoplasmic fractionation and luciferase reporter assay was used to verify the circRACGAP1/miR-22-3p/PTEN axis. Western blot analysis was performed to measure the PTEN/AKT signalling-related proteins and apoptotic-related biomarkers. Results Down-regulated circRACGAP1 was observed and correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, anti-double-stranded (ds) DNA, and complement C3 level in patients with SLE. Overexpression of circRACGAP1 significantly alleviated cell apoptosis in Jurkat cells within UVB exposure. Mechanistic investigation revealed that circRACGAP1 could serve as a sponge of miR-22-3p to regulate PTEN/AKT signalling. Conclusions Collectively, circRACGAP1 regulated the AKT signalling pathway via binding to miR-22-3p in the progression of SLE, suggesting therapeutic targets for SLE treatment.

Treatment Patterns and Clinical Characteristics of Patients with Systemic Lupus Erythematosus and Musculoskeletal Symptoms: A Retrospective, Observational Study.

IntroductionMusculoskeletal (MSK) symptoms, including arthritis and arthralgia, are common manifestations of systemic lupus erythematosus (SLE); definitions of activity patterns in SLE differ across studies. This study described clinical characteristics and treatment patterns of patients with SLE-MSK over time and by disease activity patterns from a real-world setting.MethodsThis retrospective descriptive analysis includes a subset of patients with SLE from the Hopkins Lupus Cohort with identified MSK involvement by scores on the arthritis domain of the Safety of Estrogens in Systemic Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) or Lupus Activity Index. Clinical characteristics and treatment patterns were described for patients with at least two visits over the observation period (2010–2019) for the SLE-MSK population based on three disease activity patterns: chronically active (MSK-CA), relapsing–remitting (MSK-RR), and long quiescence (MSK-LQ).ResultsThe SLE-MSK subpopulation included 664 patients (4069 person-years). The most frequently used medications over the observation period were antimalarials (95%), corticosteroids (92%), immunosuppressants (58%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (48%); 7% of patients used biologics. The highest use of corticosteroids was in the MSK-CA group (90.5% of follow-up time), followed by MSK- RR (83.9%), and MSK-LQ (46.5%). Mean prednisone dose was significantly higher in MSK-RR (8.5 mg) compared to MSK-CA (6.5 mg).ConclusionsThis descriptive analysis highlights the impact of prevalent manifestations such as arthritis on the chronic use of corticosteroids, immunosuppressants, and NSAIDs to manage disease activity in patients with SLE, suggesting there is a need for new therapeutic options that enable a lower use of medication when treating lupus.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02148-8.

α-2,6-sialic acid/IgG anti-dsDNA ratios correlate with human lupus disease activity and possible mechanisms: A pilot study.

To study the association of α2,6-sialic acid (SIA) content in serum IgG anti-dsDNA with human systemic lupus erythematosus disease activity index (SLEDAI) and the effect of sialylated and desialylated (deSIA) IgG anti-dsDNA on lupus B cells. Blood from lupus patients was collected to determine the ratio of SIA in isolated IgG anti-dsDNA over serum IgG anti-dsDNA (SIA/IgG anti-dsDNA) ratios, which were plotted against SLEDAI using a receiver-operating-characteristics curve. Lupus B cells were cultured in vitro with chimeric sialylated IgG anti-dsDNA and its deSIA form. Culture supernatants were assayed for anti-inflammatory IL-10 and SIA/IgG anti-dsDNA ratios, which were compared among different pre-treatment groups using t-tests. The area-under-the-curve (AUC) for anti-dsDNA levels against SLEDAI was 0.791 positively (95% confidence interval [C.I.]: 0.699-0.884) and SIA/IgG anti-dsDNA ratios against SLEDAI yielded an AUC of 0.705 inversely (95% C.I: 0.601-0.809): not significantly different. SIA/IgG anti-dsDNA ratios discriminated significantly between patients without and patients with proteinuria (p = .046). SIA/IgG anti-dsDNA ratios correlated significantly and positively with serum C3c and C4 levels. Pre-treatment with IgG anti-dsDNA and its immune complexes (dsDNA/IgG anti-dsDNA IC) induced higher IL-10 from lupus B cells than medium pre-treatment (most p < .01 from day 2 to day 5 culture). DeSIA IgG anti-dsDNA IC induced lower IL-10 (p < .05) and lower SIA/IgG anti-dsDNA ratios (p < .001) from lupus B cells than medium and dsDNA pre-treatment. α2,6-SIA/IgG anti-dsDNA ratios inversely forecasted SLEDAI scores. Possible mechanisms may be due to the different effects of sialylated and deSIA IgG anti-dsDNA on lupus B cells in terms of IL-10 secretion and SIA/IgG anti-dsDNA ratios.

The association of urinary plasmin level with renal involvement and disease flare among systemic lupus erythematosus patients.

To explore the ability to use urinary level of plasmin as an indicator for renal affection and activity in systemic lupus erythematosus (SLE) patients. Between April 2020 and October 2020, urine samples from 50 SLE patients (2 males, 48 females; mean age: 35.5±8.1 years; range, 22 to 39 years) and 20 age- and sex-matched healthy controls (2 males, 18 females; mean age: 34.1±6.5 years; range, 27 to 38 years) were collected. The patients were divided into two groups according to the presence or absence of renal manifestations as those with renal disease (n=28) and those without renal disease (n=22). The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), renal activity (rSLEDAI), and Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) scores were calculated. Renal biopsy was performed to patients with active lupus nephritis (LN). The activity index (AI) and Chronicity Index (CI) were scored. There was a highly statistically significant difference in the mean urinary plasmin levels between SLE cases and the control group (88.9±42.6 ng/mL vs. 21.3±26.8 ng/mL, respectively; p<0.001). A significant elevation was observed (p<0.05) in patients with LN (97.9±46.6 ng/mL) than without (42.7±12.7 ng/mL), particularly in patients with active renal involvement (82.9±26.6 ng/mL) than patients with inactive renal disease (63.2±15.5 ng/mL). There were significant positive correlations between the mean urinary plasmin levels and inflammatory markers, SLEDAI, and rSLEDAI scores. Urinary level of plasmin is significantly elevated among SLE cases, particularly in those with active LN. The remarkable association between urinary plasmin level and various activity status implies that urinary plasmin can be used as a beneficial marker to monitor lupus nephritis flare.

Early assessment of subclinical myocardial injury in systemic lupus erythematosus by two-dimensional longitudinal layer speckle tracking imaging.

To investigate the feasibility of quantitatively assessing left ventricular function and synchronization and diagnose subclinical myocardial injury in patients with systemic lupus erythematosus (SLE) using two-dimensional (2D) longitudinal layer speckle tracking imaging (STI). This was a single-center prospective study. A total of 69 patients with SLE were included in the case group and further divided into 2 subgroups, a nonactive and an active group, according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 scoring standard. We selected 30 healthy volunteers as the control group. The global longitudinal strain (GLSglobal), global endocardial longitudinal strain (GLSendo), global epicardial longitudinal strain (GLSepi), and peak strain dispersion (PSD) were obtained. The transmural gradient of longitudinal strain (TGLS) was calculated for the difference in strains between the inner and outer membranes. (I) Compared with the control group, decreased speckle strain parameters and elevated PSD were observed in patients with SLE (GLSglobal: -18.80%±2.41% vs. -21.19%±2.16%, GLSendo: -21.15%±2.47% vs. -24.09±2.49%; GLSepi: -16.58%±2.39% vs. -18.50±1.77%; TGLS: -4.56%±1.24% vs. -5.59%±1.39%; and PSD: 36.61±10.85 vs. 30.00±8.54 ms). More severely impaired layer strains were observed in active-stage patients. Compared with the nonactive group, GLSendo, GLSglobal, GLSepi, TGLS, complement C3, and complement C4 were decreased in the active group, while SLEDAI, erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein (Hs-CRP) were elevated. (II) Receiver operating characteristic (ROC) analysis demonstrated that subendocardial myocardial longitudinal strain was the most powerful tool for detecting myocardial insufficiency early in patients with SLE [area under the curve (AUC) =0.809], especially in patients in the active stage (AUC =0.734), and the optimal cut-off point was -21.35%, with a sensitivity of 71.9% and a specificity of 62.2%. (III) Correlation analysis revealed that GLSendo was moderately correlated with PSD, SLEDAI, ERS, Hs-CRP, and complement C3 (correlation coefficients: 0.535, 0.428, 0.659, 0.559, and -0.440, respectively). Subclinical myocardial injury in patients with SLE can be assessed early using 2D longitudinal STI, and the injury is more obvious in active-stage patients. Endocardial longitudinal strain is a more sensitive index than epicardial longitudinal strain for the early detection of subclinical myocardial injury in patients with SLE, which is a potentially valuable clinical tool to assist in the early detection of myocardial damage.

Clinical Efficacy of Gandakang Tablets plus Methylprednisolone in Patients with Systemic Lupus Erythematosus.

Objective To evaluate the clinical efficacy of Gandakang tablets plus methylprednisolone in patients with systemic lupus erythematosus (SLE). Methods From February 2015 to February 2019, 60 eligible patients with SLE were recruited and assigned via the random number table method at a ratio of 1 : 1 to receive either methylprednisolone (control group) or Gandakang tablets plus methylprednisolone (observation group). The primary endpoint was clinical efficacy, and the secondary endpoints included Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, immunoglobulin (Ig), inflammatory factor levels, and adverse events. Results Gandakang tablets plus methylprednisolone were associated with a significantly higher treatment efficacy versus methylprednisolone alone (P < 0.05). Gandakang tablets plus methylprednisolone resulted in significantly lower SLEDAI scores and lower levels of IgG, IgM, IgA, tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and interleukin-6 (IL-6) versus single medication of methylprednisolone (P < 0.05). The two groups showed a similar incidence of adverse events (P > 0.05). Patients given Gandakang tablets plus methylprednisolone had higher mental health, emotional role, physical role, social functioning, and bodily pain scores versus those receiving the monotherapy of methylprednisolone (P < 0.05). Conclusion Gandakang tablets plus methylprednisolone is effective in the treatment of SLE by enhancing the patients' immunity, mitigating the inflammatory response, eliminating negative emotions, and improving their quality of life.

Prognostic Factors at Diagnosis Associated With Damage Accrual in Childhood-Onset Systemic Lupus Erythematosus Patients.

ObjectivesTo associate prognostic factors present at diagnosis with damage accrual in childhood-onset systemic lupus erythematosus (cSLE) patients.MethodsWe designed a cohort study of eligible children age 16 or younger who fulfilled the 1997 American College of Rheumatology (ACR) classification criteria for SLE. Excluded were those with previous treatment of steroids or immunosuppressants. The diagnosis date was cohort entry. We followed up on all subjects prospectively for at least 2 years. Two experts assessed the disease activity with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Mexican-SLEDAI (MEX-SLEDAI) every 3–6 months. Damage was measured annually, applying Pediatric Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) to their last visit. We analyzed prognostic factors by relative risks (RR) and used logistic regression to construct the clinimetric table.ResultsNinety patients with a median age of 11.8 years at diagnosis had a SLEDAI score of 15.5 (2–40) and a MEX-SLEDAI score of 12 (2–29); and of them, forty-eight children (53%) had SDI ≥ 2. The associated variables to damage (SDI ≥ 2) are as follows: neurologic disease RR 9.55 [95% CI 1.411–64.621]; vasculitis RR 2.81 [95% CI 0.991–7.973], and hemolytic anemia RR 2.09 [95% CI 1.280–3.415]. When these three features are present at diagnosis, the probability of damage ascends to 98.97%.ConclusionAt diagnosis, we identified neurologic disease, vasculitis, and hemolytic anemia as prognostic factors related to the development of damage in cSLE. Their presence should lead to a closer follow-up to reduce the likelihood of damage development.

High Disease Severity Among Asian Patients in a US Multiethnic Cohort of Individuals With Systemic Lupus Erythematosus.

Knowledge about systemic lupus erythematosus (SLE) outcomes among US Asian patients is lacking. The present study was undertaken to examine SLE disease activity, severity, and damage among Asian patients of primarily Chinese and Filipino descent in a multiethnic cohort. California Lupus Epidemiology Study (n = 328) data were analyzed. Data were collected in English, Cantonese, Mandarin, or Spanish using validated instruments for disease activity (Systemic Lupus Erythematosus Disease Activity Index), disease severity (Lupus Severity Index [LSI]), and disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). We assessed differences in SLE outcomes among racial/ethnic groups using multivariable linear regression including interaction terms for age at diagnosis and race/ethnicity. Asian was the largest racial/ethnic group (38% [Chinese = 22%; Filipino = 9%; Other = 7%]). Average age at diagnosis was younger among Asian patients (27.9 years), particularly Filipino patients (22.2 years), compared with White (29.4 years) and Black patients (34.0 years). After adjustment, disease activity and damage were not significantly different across groups. Disease severity among Asian patients was significantly higher than among White patients (LSI score 7.1 versus 6.5; P < 0.05) but similar among Black and Hispanic patients. Early age at diagnosis was associated with greater organ damage among Asian, Black, and Hispanic patients, but not White patients. SLE was more severe among US Asian patients compared to White patients. Filipinos were affected at strikingly young ages. Asian patients and non-White groups with younger age at diagnosis had greater organ damage than White patients. Such racial/ethnic distinctions suggest the need for heightened clinical awareness to improve health outcomes among Asian patients with SLE. Further study of SLE outcomes across a range of US Asian subgroups is important.

Predictors of Unsuccessful Hydroxychloroquine Tapering and Discontinuation: Can We Personalize Decision-Making in Systemic Lupus Erythematosus Treatment?

ObjectiveHydroxychloroquine (HCQ) is a key systemic lupus erythematosus (SLE) drug, making concerns of drug shortages grave. Our objective was to evaluate factors associated with poor outcomes after HCQ taper or discontinuation in SLE.MethodsWe studied 5 Canadian SLE cohorts between 1999 and 2019, following patients from the date of HCQ tapering (cohort 1) or discontinuation (cohort 2). A composite outcome was defined as any of the following: a need for therapy augmentation, an increase (of at least 4 points) in the Systemic Lupus Erythematosus Disease Activity Index 2000 score, or hospitalization for SLE. In each cohort, multivariable Cox regression was used to identify demographic and clinical factors associated with time to the earliest of these events. A third cohort continuing to receive HCQ was also studied, to assess whether the same factors influenced the outcome even when the HCQ dose was unchanged.ResultsThe poor outcome rate, per 100 person‐years, was 35.7 (95% confidence interval [95% CI] 31.6–40.3) in the HCQ taper cohort (n = 398), 29.0 (95% CI 25.5–33.0) in the discontinuation cohort (n = 395), and 16.1 (95% CI 13.2–19.6) in the maintenance cohort (n = 395). In patients tapering HCQ, baseline prednisone use was independently associated with greater risk of poor outcomes. In the discontinuation cohort, the risk of poor outcomes was greater for Black patients and those diagnosed with SLE at age ≤25 years. Among those maintaining HCQ, baseline immunosuppressive use and First Nations ethnicity were associated with poor outcomes.ConclusionWe identified demographic and clinical factors associated with poor outcomes after HCQ taper/discontinuation. This information is critical in the current setting of potential shortages, but over the long term, such information could inform personalized therapies.

Hematologic manifestations of juvenile systemic lupus erythematosus: An emphasis on anemia.

Anemia is common in patients with juvenile systemic lupus erythematosus (jSLE). While autoimmune hemolytic anemia (AIHA) is the only etiology included in the classification criteria, the etiology of anemia in jSLE may be diverse. We aimed to investigate the etiology of anemia in jSLE and the relationship between anemia and disease characteristics at onset and during the follow-up period. Patients diagnosed with jSLE who met the Systemic Lupus Erythematosus International Collaborating Clinics classification criteria between January 2012 and December 2020 were retrospectively analyzed. Hematologic involvement was observed in 70% of the patients. Anemia was the most common cytopenia among patients (60%). Anemia of chronic disease (ACD) and AIHA were the most common etiological factors, both observed in 23% of patients. Patients with anemia had a significantly higher rate of positive ds-DNA antibody and higher erythrocyte sedimentation rate (ESH) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. ESH, serum ferritin, and SLEDAI scores negatively correlated with hemoglobin levels in patients with anemia. Iron deficiency was the sole etiology of new-onset anemia. Patients with new-onset anemia during the follow-up period had significantly lower hemoglobin values at onset and a higher rate of renal involvement. Anemia in jSLE is mostly AIHA and ACD, but iron deficiency is not rare. The severity of inflammation is associated with the severity of anemia. During the follow-up period, iron deficiency was the predominant cause of anemia, especially in patients with lower hemoglobin concentrations at onset and renal involvement.

Reproductive concerns and contributing factors in women of childbearing age with systemic lupus erythematosus.

Reproductive concerns are common in women of childbearing age with systemic lupus erythematosus (SLE) with inadequate disclosure. This study aimed to investigate the contributing factors of reproductive concerns and to evaluate their impact on health-related quality of life. One hundred eighty women of childbearing age with SLE were enrolled in this cross-sectional study in Affiliated Hospital of Nantong University from March 2021 to December 2021. A series of questionnaires were conducted: Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the Hospital Anxiety and Depression Scale (HADS), the Multidimensional Fatigue Inventory (MFI-20), Female Sexual Distress Scale-Revised (FSDS-R), Family Assessment Device (APGAR), the Medical Coping Modes Questionnaire (MCMQ), the Short-Form 36 (SF-36), and the Chinese version of Reproductive Concerns After Cancer (RCAC). Independent t test, one-way ANOVA, Mann-Whitney U test, Pearson/Spearman, and multiple linear stepwise regression were used to analyze the data. The results indicated that female SLE patients were more concerned about the child's health and personal health than becoming pregnant, fertility potential, partner disclose and acceptance; SLE patients with the characteristics of living in rural residence, having no reproductive history, fearing unexpected pregnancy, sexual distress, and depression showed more serious fertility concerns. Meanwhile, most female SLE patients adopted active confrontation when facing reproductive concerns, and these patients were significantly lower in the dimension score of mental related quality of life. Our study demonstrated that female SLE patients should be paid more attention to their fertility concerns and effective intervention measures should be carried out to relieve their reproductive concerns, so as to improve their long-term quality of life if their disease condition permits.

Frequency of anti-neutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus

IntroductionSystemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Patients with SLE exhibit multiple serum autoantibodies, including anti-neutrophil cytoplasmic antibodies (ANCAs). There are two main techniques to detect ANCAs: indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA). In this study, an attempt was made to determine the frequency and clinical associations of ANCAs in patients with SLE. MethodsA cross-sectional study was conducted in a tertiary care hospital in Colombia that included 74 patients with SLE. The presence of ANCAs was assessed using IIF with ethanol-fixed slides, and ELISA was used to detect antibody specificities for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA. ResultsOf the 74 patients with SLE evaluated, 60 (81.1%) of them were ANCA-positive by IIF. By contrast, only one patient showed specificity for PR3-ANCA by ELISA. The relevance of ANCA positivity by IIF and clinical and serological features was significant for renal involvement (p=.0174), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p=.0308). ConclusionANCAs are common in the serum of patients with SLE, as detected by ethanol-fixed slides with IIF staining. However, detection of specificity to PR3 and/or MPO is rare, thus highlighting the importance of detecting these autoantibodies by different techniques.