Clinical Systemic Lupus Erythematosus Disease Research Articles

Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort

ObjectiveTo determine the independent impact of different definitions of remission and low disease activity (LDA) on damage accrual.MethodsPatients with ≥2 annual assessments from a longitudinal multinational inception lupus cohort were...

2021 DORIS definition of remission in SLE: final recommendations from an international task force

ObjectiveTo achieve consensus on a definition of remission in SLE (DORIS).BackgroundRemission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking....

Follow-up and management of serologically active clinically quiescent cases in pediatric systemic lupus erythematosus.

ObjectivesOur aim is to identify the presence of serologically active clinically quiescent (SACQ) episodes in pediatric systemic lupus erythematosus (SLE) patients. We aim to identify serologic biomarkers associated with SACQ episodes and discuss risks and benefits of escalating treatments.Material and methodsWe evaluated 25 pediatric SLE patients, 13 of whom experienced SACQ episodes. Serologically active clinically quiescent was defined as two consecutive clinic visits without any clinical symptoms or clinical examination findings of a lupus flare with a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of zero, but either elevated anti-ds-DNA antibodies or low complement (C3 and/or C4) levels.ResultsAmong the 13 patients who experienced a SACQ episode, there were a total of 24 episodes, with each patient experiencing 1–4 SACQ episodes. Erythrocyte sedimentation rate (ESR) was the most commonly elevated laboratory marker in a SACQ episode, followed by low hemoglobin levels, and then elevated anti-dsDNA antibodies. Of the 17 episodes treated during a SACQ episode, 15 (88%) did not progress to a clinical flare within six months, while two did. Furthermore, of the 7 patients who were not treated during their SACQ episode, 2 (29%) continued to be SACQ without flare, whereas 5 led to a clinical flare within six months.ConclusionsSerologically active clinically quiescent episodes were identified in pediatric SLE patients, suggesting that the presence of SACQ is not limited to adults with SLE. Serologic markers such as increased ESR, hemoglobin, and elevated anti-dsDNA antibodies are preliminarily associated with pediatric SACQ episodes. Treating these SACQ episodes in pediatric SLE patients was less likely to lead to a clinical flare within six months when compared to not treating (p < 0.05). More research with a larger sample size is needed to define SACQ episodes, determine the prevalence in pediatric SLE patients, and establish SACQ treatment guidelines.

Disease Activity and Rate and Severity of Flares During Peripartum Period in Thai Patients With Systemic Lupus Erythematosus: An Age at Diagnosis and Disease Duration Matched Controlled Study.

The aim of this study was to compare disease activity and rate and severity of flares between pregnant and nonpregnant systemic lupus erythematosus (SLE) patients. Medical records of pregnant SLE patients seen between January 1993 and June 2017 were reviewed. Nonpregnant SLE controls were matched by age at diagnosis and disease duration before pregnancy. Systemic lupus erythematosus disease activity and flares were determined by the cSLEDAI (clinical Systemic Lupus Erythematosus Disease Activity Index) and Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI Flare Index, respectively. Disease activity was measured from 6 months before conception (-6 months) until the postpartum period. The repeated measures mixed model, Cox regression, and cumulative hazard plots were used for statistical analysis. Ninety pregnancies occurred in 77 patients. The cSLEDAI scores from -6 months to the postpartum period were comparable between the pregnancy and control group, but slightly yet significantly higher in the controls at conception (mean ± SEM, 3.57 ± 0.45 vs 1.90 ± 0.36; p = 0.019). When compared with the controls, during the pregnancy and postpartum period, the pregnancy group did not have significantly higher incidence of flare (41.11% vs 28.89%, p = 0.086 and 7.78% vs 11.11%, p = 0.445, respectively) or flare category (severe flare) (75.68% vs 53.85%, p = 0.070 and 85.71% vs 70.00%, p = 0.603, respectively). The flare incidence rate (95% confidence interval)/100 patient-months in the pregnancy and control group was 6.75 (4.89-9.32) and 4.34 (2.96-6.38), respectively, giving the adjusted hazards for flare (95% confidence interval) of 1.54 (0.91-2.61) (p = 0.110). There was no overall significant increase in SLE disease activity, flare incidence, and flare severity in pregnant SLE patients when compared with their properly matched nonpregnant SLE controls.

Increased levels of anti-dsDNA antibodies in immune complexes before treatment with belimumab associate with clinical response in patients with systemic lupus erythematosus

IntroductionImmune complexes are of importance in systemic lupus erythematosus pathogenesis, and autoantibodies are believed to participate in immune complex formation. Quantification of autoantibody levels in circulating IC might be of prognostic value.MethodsA C1q-binding-eluting technique was applied to purify immune complexes from 55 belimumab-treated systemic lupus erythematosus patients during a 24-month follow-up. Autoantibodies in serum and in solubilized immune complexes were quantified using addressable laser bead immunoassay. We investigated whether levels of autoantibodies in immune complexes associate with disease activity and response to belimumab treatment.ResultsHigh baseline anti-double-stranded DNA and anti-histone levels in immune complexes associated with attainment of zero scores in clinical systemic lupus erythematosus disease activity index 2000 during the 24-month follow-up (p = 0.003 and p = 0.048, respectively). Low complement levels associated with high serum anti-double-stranded DNA and anti-ribosomal P levels (p = 0.003 and p = 0.008, respectively) and high anti-double-stranded DNA (p = 0.002) but not anti-ribosomal P levels in immune complexes. Anti-SSA/SSB serum levels were lower in patients attaining lupus low disease activity state at month 6; these associations were stronger for corresponding immune complex levels. Serum levels of most autoantibodies had declined at month 3, whereas autoantibody levels in immune complexes, except for anti-double-stranded DNA, showed a more gradual decline over 1–2 years. Serum anti-double-stranded DNA levels decreased in all patients irrespective of systemic lupus erythematosus disease activity index 2000=0 attainment, whereas immune complex levels decreased only in achievers.ConclusionImmune complex levels of autoantibodies against double-stranded DNA and the SSA/SSB complex show more specific associations with treatment outcome compared with serum levels in belimumab-treated systemic lupus erythematosus patients. Characterization of autoantibody content in circulating immune complexes could prove useful in treatment evaluation in systemic lupus erythematosus and other immune complex-associated diseases.

Definitions of remission in systemic lupus erythematosus: a post-hoc analysis of two randomised clinical trials.

The Definitions Of Remission In Systemic Lupus Erythematosus (DORIS) international task force has proposed remission definitions that are amenable to scientific testing. In this study, we aimed to evaluate their suitability as outcome measures in studies of systemic lupus erythematosus. In this post-hoc study, we applied remission definitions as specified by DORIS criteria at multiple timepoints in the BLISS-52 (n=865) and BLISS-76 (n=819) clinical trials. All definitions required physician's global assessment scores less than 0·5 (possible range 0-3). The DORIS 1 definitions required clinical systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K)=0 (with serological items excluded). The DORIS 2 definitions required a score of D or E in all British Isles Lupus Assessment Group (BILAG) domains. The definitions were assessed in the trial populations both with (on therapy) and without (off therapy) treatment allowance-ie, low-dose glucocorticoids (prednisone ≤5 mg/day) and maintenance immunosuppressive and biological agents. Antimalarial agents were allowed in all definitions. The definitions were applied irrespective of serological activity (anti-double stranded DNA positivity, or low C3 or C4) and with normal serology. Finally, we applied modifications similar to DORIS on therapy but allowing higher prednisone doses (≤10 mg/day). In the pooled dataset, the remission definition most frequently attained was the modified (prednisone ≤10 mg/day) DORIS 1a on therapy definition, which required a SLEDAI-2K score of 0 and permitted serological activity (237 [17·8%] of 1333 participants at week 52), followed by the unmodified (predisone ≤5 mg/day) DORIS 1 on therapy definition (140 [10·5%] of 1336 participants at week 52) based on these two definitions. We detected no significant difference between the placebo and belimumab groups. Proportions of patients achieving off therapy and BILAG-based definitions were low (≤0·9% at all timepoints). Sustained attainment of certain on therapy definitions showed an ability to discriminate between patients who received belimumab 10 mg/kg and patients who received placebo. Attainment of DORIS remission definitions was infrequent overall. Use of clinical SLEDAI-2K=0 in the definitions yielded higher proportions of attainment than did use of BILAG D or E. Attainment was also higher using definitions that allowed for serological activity and maintenance treatment. Addition of the durability aspect to on therapy definitions led to an ability to discriminate between belimumab and placebo. Swedish Rheumatism Association, Professor Nanna Svartz Foundation, Ulla and Roland Gustafsson Foundation, Region Stockholm, and Karolinska Institutet Foundations.

Clinical Remission and Low Disease Activity Outcomes Over 10 Years in Systemic Lupus Erythematosus.

A recent study conducted by our clinical group demonstrated that low disease activity (LDA), defined as a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≤2, maintained for 12 months, confers the same risk for damage accrual as complete remission after 2 years. The aim of the present study was to assess the validity of these findings in the long term (10 years). Patients in the inception cohort of the Toronto Lupus Clinic, who had a minimum follow-up of 10 years and no interval >18 months between consecutive visits, were included in the analysis. Prolonged clinical remission was defined based on a SLEDAI-2K score of 0 (serology excluded), achieved within the first 5 years of enrollment and maintained for ≥10 years. Prolonged LDA was defined as SLEDAI-2K score ≤2 (serology excluded) with the same time frame restrictions. Of 267 patients, 27 (10.1%) achieved prolonged clinical remission and 48 (18%) attained prolonged LDA. There were no differences regarding demographic, clinical, and immunologic variables at any time. The mean prednisone dose at enrollment was higher in patients in whom remission was achieved, while patients with prolonged LDA were taking antimalarials more frequently, both at enrollment and after the 10-year time period. Cumulative damage and flare rate after 10 years, and mortality throughout follow-up were comparable. SLE in patients in the prolonged LDA group was in complete remission for 76% of the follow-up time. Prolonged clinical remission and LDA were demonstrated in 10.1% and 18% of our patients, respectively, and comparable outcomes were demonstrated in the long term, rendering sustained LDA an acceptable treat-to-target outcome in SLE.

Disease course patterns in systemic lupus erythematosus.

Disease activity in systemic lupus erythematosus follows three different courses: long quiescent, relapsing remitting and persistently active. However, the patterns of disease course since diagnosis are not known. This study aimed to assess the prevalence and characteristics of such patterns over 10 years. The inception cohort of the Toronto Lupus Clinic (≥10 year follow up, between visit interval ≤18 months) was investigated. Prolonged remission was defined as a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 = 0 achieved within 5 years of enrolment and maintained for ≥10 years. The relapsing-remitting pattern was defined based on ≥2 remission periods (clinical Systemic Lupus Erythematosus Disease Activity Index 2000 = 0 for two consecutive visits). Patients with no remission were categorized as persistently active. Groups were compared for baseline characteristics, cumulative damage, flare rate, mortality and certain co-morbidities. Of 267 patients, 27 (10.1%) achieved prolonged remission, 180 (67.4%) relapsing-remitting and 25 (9.4%) persistently active. In total, 35 (13.1%) had only one remission period (hybrid). At enrollment, there were no differences regarding clinical and immunological variables. At 10 years, persistently active patients had accumulated significantly more damage than the prolonged remission and relapsing-remitting patients. Being of Black race and higher adjusted mean Systemic Lupus Erythematosus Disease Activity Index 2000 over the first 2 years were associated with a more severe disease course. Relapsing-remitting and persistently active patients had an increased flare rate and accrued more osteoporosis, osteonecrosis and cardiovascular events. Approximately 70% of systemic lupus erythematosus patients followed a relapsing-remitting course, whereas 10% displayed prolonged remission and another 10% a persistently active course. Early response to treatment was associated with a less severe course and better prognosis.

Cell-bound complement activation products (CB-CAPs) have high sensitivity and specificity in pediatric-onset systemic lupus erythematosus and correlate with disease activity.

Elevated levels of cell-bound complement activation products (CB-CAPs) (C4d deposition on B lymphocytes (BC4d) and/or erythrocytes (EC4d)) are sensitive and specific in diagnosis and monitoring of adult systemic lupus erythematosus (SLE). Our objective was to evaluate the role of CB-CAPs for diagnosis and monitoring of pediatric-onset SLE (pSLE). A prospective cohort study of 28 pSLE and 22 juvenile arthritis patients was conducted. SLE disease activity was determined using a clinical Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) that excluded serologies. Autoantibodies were measured using solid-phase immunoassays, C3 and C4 using immunoturbidimetry, and CB-CAPs using quantitative flow cytometry. Abnormal CB-CAPs were defined as EC4d or BC4d above the 99th percentile for healthy adults (>14 and > 60 net mean fluorescence intensity (MFI), respectively). Performance characteristics of CB-CAPs were assessed using area under the curve (AUC) for receiver operating characteristics. Linear mixed effect models evaluated the correlation between CB-CAPs and clinical SLEDAI over 6 months. BC4d yielded higher AUC (0.91 ± 0.04) than C3 (0.63 ± 0.08) and C4 (0.67 ± 0.08) ( p < 0.05). Abnormal CB-CAPs were 78% sensitive and 86% specific for diagnosis of pSLE (Youden's index = 0.64 ± 0.11). In contrast to BC4d, EC4d levels correlated with clinical SLEDAI ( p < 0.01). CB-CAPs (EC4d and BC4d) have higher sensitivity and specificity than low complement in pSLE, and may help with diagnosis of pSLE. EC4d could provide a useful biomarker for disease activity monitoring.

A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS)

ObjectivesTreat-to-target recommendations have identified ‘remission’ as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to...

Studies of Filipino patients with systemic lupus erythematosus: Autoantibody profile of first-degree relatives

This study surveyed the frequency of autoantibodies among un-affected first-degree relatives (FDRs) of Filipino systemic lupus erythematosus (SLE) patients compared with healthy un-related Filipino controls. The sensitivity, specificity and predictive value of the autoantibodies for SLE diagnosis were also assessed in this Filipino cohort. Filipino patients included in the University of Santo Tomas (UST) Lupus Database and un-affected FDRs were recruited. Healthy controls included those with no known personal or family history of autoimmune disease. The following autoantibodies were tested in all subjects: anti-nuclear antibody (ANA), anti-dsDNA, anti-Ro/SSA, anti-chromatin, anti-thyroid microsome, and anti-cardiolipin antibodies. Participants included 232 SLE patients, 546 FDRs, and 221 healthy controls. Median age of patients was 27 (range 8-66) years with median disease duration of 27.5 (range 1-292) months. Median age of FDRs was 42.0 (range 5-87) years. Compared with healthy controls, there were significantly more FDRs with positive ANA at titers 1 : 40 to 1 : 160 (p < 0.001) and 1 : 320 (p = 0.003), anti-Ro/SSA (4.94% versus 0.45%, p = 0.003), and anti-dsDNA ≥ 5.0 IU/ml (4.58% versus 1.36%, p = 0.031). ANA titer ≥1 : 160, anti-dsDNA, anti-Ro/SSA and anti-chromatin had the highest predictive value for SLE diagnosis. These findings reinforce the role of genetic influence in SLE risk among Filipinos, with a significant proportion of un-affected FDRs of SLE patients testing positive for autoantibodies compared with healthy Filipino controls. A longitudinal observational study in this same cohort will determine which proportion of these un-affected FDRs will evolve into clinical SLE disease in the future.