Mean SLEDAI-2K Scores Research Articles

The efficacy of rituximab plus belimumab or telitacicept in refractory lupus nephritis.

Lupus nephritis is a severe and common complication of systemic lupus erythematosus (SLE). The pathogenesis of lupus nephritis is characterized by B-cell activation and autoantibody formation. Rituximab and belimumab, as well as telitacicept, target B cells through different mechanisms, potentially exerting a synergistic effect in the treatment of lupus nephritis. This study aims to investigate the efficacy and safety of treatment with rituximab followed by belimumab or telitacicept in the management of refractory lupus nephritis. We conducted a single-center, open-label, retrospective study, including 25 patients with refractory lupus nephritis. All patients received combination therapy with rituximab in individualized dosages to achieve peripheral B-cell depletion, and then followed by belimumab or telitacicept. The follow-up period was at least 12 months, and the primary end point was renal remission rate at the last follow-up. During a median follow-up of 19 (13, 29) months, 20 of 25 (80%) patients achieved objective remission (OR), including 19 (76%) patients achieved complete renal response (CRR). After rituximab (712 ± 416mg in average), 18 patients received belimumab and seven patients received telitacicept. In the rituximab plus telitacicept group, all patients achieved CRR; while in the rituximab plus belimumab group, 12 (66.7%) patients achieved CRR and 13 (72.2%) patients achieved OR. The mean SLEDAI-2K score decreased from 15 ± 6 to 6 ± 6, representing an average reduction of 60%. At the last follow-up, 18/25 (72%) had prednisone ≤ 5mg/d or even discontinued prednisone use. Adverse effects were mainly immunoglobulin deficiency, respiratory tract infection, urinary tract infections, and rash. No death occurred. Rituximab followed by belimumab or telitacicept may be effective in inducing remission in refractory lupus nephritis, with tolerable adverse effects.

Remission and low disease activity in Polish patients with systemic lupus erythematosus - real-life, five-year follow-up outcomes.

Remission in systemic lupus erythematosus (SLE) or Lupus Low Disease Activity State (LLDAS) are associated with less organ damage and thus create new perspectives for effective damage-limiting treatment. The aim of this study was to assess the occurrence of remission defined by The Definition of Remission In SLE (DORIS) and of LLDAS as well as their predictors in the Polish SLE cohort. In this retrospective study data were collected on patients with SLE that achieved at least one year of DORIS remission or LLDAS and were followed up for 5 years. Clinical and demographic data were gathered; DORIS and LLDAS predictors were determined by univariate regression analysis. The full analysis set included 80 patients at baseline and 70 at follow-up. Over half of patients with SLE (39; 55.7%) fulfilled the DORIS remission criteria. In this group, 53.8% (21) of patients were in remission on-treatment and 46.1% (18) in remission off-treatment. LLDAS was fulfilled by a cohort of 43 (61.4%) patients with SLE. Among patients that achieved DORIS or LLDAS at follow-up, 77% were not treated with glucocorticoids (GCs). The most important predictors for DORIS and LLDAS off-treatment were mean SLEDAI-2K score with cut-off of ≤8.0, treatment with mycophenolate mofetil or antimalarials, and the age at disease onset above 43 years. Remission and LLDAS are achievable goals in treating SLE as over half of study patients fulfilled the DORIS remission and LLDAS criteria. The identified predictors for DORIS and LLDAS indicate the importance of effective therapy leading to reduction of GC use.

Factors associated with poor outcomes in SLE patients with COVID-19: Data from ReumaCoV-Brazil register.

ObjectivesTo evaluate factors associated with COVID-19 severity outcomes in patients with systemic lupus erythematosus (SLE).MethodsThis was a cross-sectional analysis of baseline data of a prospective, multi-stage cohort study—“The ReumaCoV Brazil”—designed to monitor patients with immune-mediated rheumatologic disease (IMRD) during the SARS-CoV-2 pandemic. SLE adult patients with COVID-19 were compared with those without COVID-19. SLE activity was evaluated by the patient global assessment (PGA) and SLE Disease Activity Index 2000 (SLEDAI-2K).Results604 SLE patients were included, 317 (52.4%) with COVID-19 and 287 (47.6%) in the control group. SLE COVID-19 patients reported a lower frequency of social isolation and worked more frequently as health professionals. There was no difference in the mean SLEDAI-2K score between groups in the post–COVID-19 period (5.8 [8.6] vs. 4.5 [8.0]; p = 0.190). However, infected patients reported increased SLE activity according to the Patient Global Assessment (PGA) during this period (2.9 [2.9] vs. 2.3 [2.6]; p = 0.031. Arterial hypertension (OR 2.48 [CI 95% 1.04–5.91], p = 0.041), cyclophosphamide (OR 14.32 [CI 95% 2.12–96.77], p = 0.006), dyspnea (OR: 7.10 [CI 95% 3.10–16.23], p < 0.001) and discontinuation of SLE treatment medication during infection (5.38 [CI 95% 1.97–15.48], p = 0.002), were independently associated with a higher chance of hospitalization related to COVID-19. Patients who received telemedicine support presented a 67% lower chance of hospitalization (OR 0.33 [CI 95% 0.12–0.88], p = 0.02).ConclusionHypertension and cyclophosphamide were associated with a severe outcome, and telemedicine can be a useful tool for SLE patients with COVID-19.

Relationship of Socioeconomic Status, Depression and Disease Activity in Patients with Systemic Lupus Erythematosus

Systemic lupus erythematosus has different presentations and the outcome of this illness is variable. It is associated with significant psychological distress and the outcome of this disease has been shown to be influenced by socioeconomic factors. Objective: To determine the association between socioeconomic status, depression and disease activity in patients with systemic lupus erythematosus. Methodology: It was a cross sectional study carried out at department of Rheumatology, Mayo Hospital, Lahore. 150 patients with systemic lupus erythematosus who fulfilled the inclusion criteria were enrolled. Demographic detail, clinical history and examination findings were noted down. Socioeconomic status was assessed by history, depression was assessed by Beck Depression Inventory and disease activity was assessed by SLEDAI-2K and findings were noted down and was subjected to statistical analysis. Results: The mean age of the patients was 29.12±7.44, mean BDI score was 19.2±10.7 and mean SLEDAI-2K score was 9.94±4.91. There were 33.7% males and 66.3% females. Depression was present in 32% of the patients. Depression was more common in patients with higher scores of disease activity. This association between depression and its severity and the disease activity was found to be statistically significant as indicated by a p value of 0.04. The scores of disease activity were found to be higher in patients who were of middle socioeconomic status and low socioeconomic status i.e. in 48% and 34% respectively and the association was statistically significant (p-value 0.000). Conclusion: Depression, socioeconomic status and disease activity are significantly associated with each other in patients with systemic lupus erythematosus and must be screened in every patient. Keywords: Systemic Lupus Erythematosus, Depression, Socioeconomic status, disease activity

A cluster of type II interferon-regulated genes associates with disease activity in patients with systemic lupus erythematosus

Upregulation of interferon-regulated genes (IRGs), denoted IFN signature, in peripheral blood has been used as an indirect measure of IFN pathway activation in patients with systemic lupus erythematosus (SLE). However, it has not been determined, which IFN signatures that optimally reflect clinical disease activity.In this study, we determined an IFN signature based on the expression of 128 IRGs in whole blood from 34 SLE patients in a cross-sectional (CS) study, 11 with active lupus nephritis followed longitudinally (LS) and 15 healthy controls. Blood samples were collected in PAXgene tubes and RNA was extracted and purified using a PAXgene blood RNA kit (Qiagen). Gene expression was measured using the NanoString nCounter Gene Expression platform.The CS SLE patients with higher disease activity displayed thrice as many upregulated IRGs (n = 46) as the rest. These IRGs clustered in three groups, consisting of IRGs known to be predominantly stimulated by type I (gene cluster K1) and type II (gene clusters K2 and 3) IFNs. SLEDAI-2K scores associated with the K2 and K3 gene scores (β = 0.372 and β = 0.419, both p < 0.015) but not with K1. In the longitudinal study, the mean SLEDAI-2K score decreased after an average follow-up of 360 days (β = −2.08, P = 5.09 × 10−12). The mean K1, K2 and K3 gene scores did not change over time, however longitudinal changes in SLEDAI-2K and K3 scores were associated (β = 0.814, p = 0.007).This study validates the presence of type I IRG subsets that do not associate with disease activity in SLE patients. The novel finding in this study is the association between a type II IRG subset and disease activity. Both findings may have significant implications for choosing IRGs defining clinically relevant IFN signatures.

Utilization of glucocorticoids among White and Black patients with systemic lupus erythematosus: Observations from the enrollment visit of a prospective registry.

Black patients with systemic lupus erythematosus (SLE) face higher rates of morbidity and mortality compared to White patients. Long-term glucocorticoid use has been associated with worse health outcomes among patients with SLE. We sought to quantify chronic glucocorticoid use among Black and White patients with SLE within a prospective registry. Using enrollment data from a registry at a large academic institution, we compared glucocorticoid use among Black and White patients with SLE. Multivariable logistic regression of race and glucocorticoid use was performed, adjusting for covariates exhibiting a bivariate association with glucocorticoids at significance level p < 0.10. 114 White participants (mean age 45; standard deviation (SD) 15) and 59 Black participants (mean age 42; SD 14) were analyzed. White participants had mean SLEDAI-2K score of 3.7 (SD 5.2). Black participants had mean SLEDAI-2K scores of 6.3 (SD 6.0). Among Black participants, 43 (72%) utilized glucocorticoids compared to White participants 39 (34%) (unadjusted odds ratio (OR) 5.17; 95% confidence interval (CI) 2.59-10.33). We did not observe differences between unadjusted hydroxychloroquine (OR 0.69; 95% CI 0.28-1.65) or conventional disease-modifying anti-rheumatic drug (cDMARD) (OR 1.07; 95% CI 0.57-2.01) utilization among Black and White participants. SLEDAI-2K, disability, recent hospitalization, and past or present hydroxychloroquine or cDMARD use were included in a logistic regression model. Adjusting for covariates, Black participants were more likely to be on glucocorticoids (adjusted OR 5.69; 95% CI 2.17-14.96); p = 0.0004). Adjusting for disease activity and other medications, Black patients had more exposure to chronic glucocorticoids than White patients in the Cleveland Clinic SLE registry. These patients may face increased glucocorticoid-related morbidity, which could contribute significantly to long-term health outcomes and utilization of health care resources. Future research in larger, more diverse registries should be conducted to further characterize patterns of glucocorticoid use.

AB0653 COURSE OF COVID-19 INFECTION IN A SERIES OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Background:Infection is a remarkable cause of morbidity and mortality in patients with SLE.Objectives:We aimed to determine the clinical course of COVID-19 infection in our patients with SLE and the factors affecting this courseMethods:SLE patients (2012 SLICC criteria) diagnosed with COVID-19 infection by a positive PCR test and/or typical findings of lung involvement in CT (computed tomography) imaging were included. Data regarding cumulative clinical and laboratory characteristics, histopathology results, autoantibody profiles, immunsuppressives and damage (SLICC damage index/SDI)) were retrieved from the existing database and revised. SLE Disease Activity Index (SLEDAI-2K) was determined at the time of infection.Results:Sixteen SLE patients with COVID-19 infection were identified. Most (87.5%) of these patients were female. Seventy % (n=11) had lupus nephritis. Twenty-five % had thrombotic antiphospholipid syndrome.PCR was positive in 70% (n=11) of the patients. Pulmonary parenchymal findings compatible with COVID-19 were observed in 56% (n=9) of those patients. Regarding complaints upon admission, 50% (n=8) had fever, 44% (n=7) cough, 44% (n=7) dyspnea, 19% (n=3) myalgia, 12.5% (n=2) headache, 12.5% (n=2) nausea /vomiting, 6% (n=1) diarrhea, and 6 % (n=1) had anosmia. Eight patients were hospitalized. Six of these patients needed oxygen therapy via nasal cannula. None needed a follow-up in the intensive care unit. The mean hospitalization duration was 14 ± 5 (8-25) days.Regarding disease activity at the time of infection, 9 had inactive disease with a SLEDAI-2K score of 0 whilst in 5 patients SLEDA-2K score was ≥4. The mean SLEDAI-2K score at the time of infection was 1.7 ± 2.3 (0-6). System/organwise, 1 patient with chronic thrombocytopenia presented with a worsening platelet count accompanied by serologic activity. This patient was a non-adherent to treatment who had stopped taking mycophenolic acid months before COVID19. Three patients 2 of whom had proliferative nephritis experienced nephritic flares.1 patient who had a history of cutaneous lupus and was in remission presented with oral ulcer, leukopenia and hypocomplementemia during infection. Of 16 patients, 7 had system damage at the time of infection. The mean SDI score of the patients was 1.4±1.8. Comparison of patients with and without damage revealed no significant differences in disease activity, symptoms associated with COVID, in the need for hospitalization, hospitalization duration, and the requirement for oxygen therapy. However,CT findings compatible with COVID19, were more common in patients with damage (87% vs.33%,p=0.04) and their mean CRP levels were higher at diagnosis (65 ± 47 vs.22 ± 48 mg/l;p=0.032).All patients received similar treatment for COVID-19 except active patients who required high dose steroids (2 with active renal, 1 with thrombocytopenia and 1 with oral ulcer, leukopenia and hypocomplementemia).The patient with thrombocytopenia also received intravenous immunoglobulin and 1 with cutaneous active disease received tocilizumab as she developed macrophage activation syndrome. Six patients (37.5%) had received rituximab (RTX) in the last 6 months before COVID. No significant difference, in terms of hospitalization and need for oxygen therapy due to COVID19 was found between patients who had received RTX vs who had not. No hypogammaglobulinemia was detected in patients who received RTX despite lower levels of IgG (998 ± 184 vs 1481± 51 mg/dl, p=0.02)Conclusion:Although half of the patients in our series of COVID19 infected SLE patients required hospitalization, there were no mortalities. More patients with damage (none pulmonary) displayed CT findings compatible with COVID19 and further follow up will reveal whether they will suffer from fibrotic lung disease. Patients can experience disease flares during COVID. But it is also important to consider that some manifestations such as thrombocytopenia may also be a sign of severe infection. Immunosupressive agents may not have a negative impact on the course of infection.*the first two authors contributed equallyDisclosure of Interests:None declared.

High disease activity status suggests more severe disease and damage accrual in systemic lupus erythematosus

ObjectiveDisease severity in SLE is an important concept related to disease activity, treatment burden and prognosis. We set out to evaluate if high disease activity status (HDAS), based on ever...

Juvenile systemic lupus erythematosus in Turkey: demographic, clinical and laboratory features with disease activity and outcome.

Objectives This paper aims to assess in a retrospective fashion the clinical and laboratory features, severity and outcome of juvenile systemic lupus erythematosus (jSLE) from a referral center in Turkey. Methods We have included all jSLE patients ( n = 92) diagnosed according to the revised American College of Rheumatology 1997 criteria between January 2004 and January 2017. Results The most prevalent clinical feature in our cohort was mucocutaneous manifestations (97.8%), followed by constitutional (81.5%), hematological (59.8%) and musculoskeletal manifestations (56.5%). Renal involvement was observed in 38% ( n = 35) of the patients, whereas biopsy-proven lupus nephritis was detected in 29.3% ( n = 27) of the cohort. Neurologic involvement was seen in 15 (16.3%) individuals. Among the patients positive for anticardiolipin IgM and/or IgG ( n = 11, 12%), only three developed antiphospholipid antibody syndrome. The mean SLEDAI-2K scores at disease onset (10.5 ± 4.8) showed a substantial decrease at last visit (4.3 ± 4.6). One-quarter of the patients (26.1%, n = 24) had damage according to the PedSDI criteria with a mean score of 0.45 ± 1.0 (range 0-7). When the PedSDI damage items were evaluated individually, growth failure was the most frequent damage criterion ( n = 6), followed by seizure ( n = 5). Two patients died during the designated study period of end-stage renal disease. The five-year and 10-year survival rate of our cohort was 100% and 94.4%, respectively. Conclusions Given the lower frequency of nephritis and central nervous system disease and lower basal disease activity and damage scores, we could conclude that children with jSLE in Turkey have a more favorable course compared to Asian and African American children, as expected from Caucasian ethnicity.

Defining Low Disease Activity in Systemic Lupus Erythematosus.

To define and identify a group of systemic lupus erythematosus patients with low disease activity (LDA) and to examine whether LDA is similar to patients in remission and different from a high disease activity group (HDA) in short-term outcomes. The LDA group was defined as Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) <3, including only 1 clinical manifestation of rash, alopecia, mucosal ulcers, pleurisy, pericarditis, fever, thrombocytopenia, or leukopenia. The patients could be taking antimalarials. Remission was defined as no clinical manifestation from taking antimalarials alone, and the HDA group was defined as SLEDAI-2K >6. The time frame for inclusion in each group was at least 1 year. Of 620 patients with active disease who were seen between 1970 and 2015, 80 patients (12.9%) fulfilled the criteria for LDA, 191 (30.8%) for remission, and 349 (56.3%) for HDA. The LDA patients with and without positive serology results were similar at baseline and with prior disease characteristics. After 2 years of followup, the LDA and remission groups were similar in their adjusted mean SLEDAI-2K score, organ involvement, The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score, mortality, and therapies. After 2 and 4 years of followup, the HDA group had a higher adjusted mean SLEDAI-2K score, more major organ involvement, a higher SDI score, higher mortality, and more therapy compared to the combined LDA/remission groups. LDA and remission groups had similar short-term outcomes, and both had better outcomes and prognosis than the HDA group. LDA may be used as an outcome measure in therapeutic trials or in treat-to-target regimens.

ASYMPTOMATIC VERTEBRAL COMPRESSION FRACTURES IN POSTMENOPAUSAL WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that most commonly occurs in women. Improved treatments for SLE have led to a substantial increase in the life expectancy of patients, so the problems of complications of both the disease itself and its therapy have come to be top priority. The most common complications of SLE among the musculoskeletal system lesions are osteoporosis and related vertebral compression fractures (VCFs). However, only one third of these fractures has clinical manifestations and causes the patient to seek medical advice. More VCFs remain undetected because they have no or scarce symptoms. The question of the influence of various factors (gender, age, menopause, etc.) on the incidence of VCFs in patients with SLE remains open. It should be expected that in postmenopausal women with SLE, the incidence of VCFs may be considerably higher than that in the population. Objective : to determine the frequency of and to evaluate the role of various factors in the development of asymptomatic vertebral fractures in postmenopausal women with SLE (a retrospective study). Subjects and methods . A total of 86 postmenopausal women (mean age, 59±7.9 years) with a diagnosis of SLE, which met the 2012 Systemic Lupus Collaborating Clinics (SLICC) criteria, were examined. The mean duration of the disease and menopause was 15±8.3 and 12.8±7 years, respectively. All the patients with SLE were treated with glucocorticoids (GC) at a dose of 15±5 mg/day calculated with reference to prednisolone for more than 12 months (mean, 159.7±90.9 months) and had a low disease activity (the mean SLEDAI-2K score was 5.1±3.9). The ACR damage index for SLE averaged 5.5±2.6. All the patients underwent vertebral fracture assessment (VFA) using a Hologic Explorer bone densitometer to identify VCFs in the thoracic and lumbar spine. The anterior, middle, and posterior heights of ТhIV–LV, and the height of each vertebra as well as the underlying vertebra were calculated and compared. If the differences in the anterior, middle, or posterior vertebral heights were >20–25%, this deformation was regarded as VCFs. Bone mineral density (BMD) in the hip and spine was measured with an X-ray bone densitometer. Results. VFA revealed VCFs in 40 (46.5%) patients with SLE; these were detected for the first time in 22 (55%) patients since they had no significant clinical manifestations. VCFs happened most commonly in the mid-thoracic spine (ThVI–IX). All the patients with asymptomatic VCFs had a fracture of only one vertebra. The patients with VCFs had a longer duration of SLE and menopause, more frequently received cytostatic therapy, and had a higher cumulative dose and a longer duration of GC therapy. They also had a higher damage index and lower BMD values in LI–IV than patients without VCFs (p 0.05). Conclusion. The detection rate for VCFs is nearly 50% in postmenopausal women with SLE, and about every two VCFs remain undetected. The long duration of SLE, menopause, and GC treatment, a high cumulative dose, a high damage index and low BMD values in LI–IV were associated with VCFs. VFA is an effective screening method to detect asymptomatic VCFs.

Adrenocorticotropic hormone gel in the treatment of systemic lupus erythematosus: A retrospective study of patients.

Acthar Gel is a long-acting formulation of adrenocorticotropic hormone (ACTH) with anti-inflammatory effects thought to be mediated in part through melanocortin receptor activation. This study was initiated to understand the role of Acthar Gel in SLE treatment in rheumatology practices. This is a retrospective case series of nine adult female patients treated with Acthar Gel for at least six months at five academic centers. Treating physicians completed a one-page questionnaire on lupus medications, disease activity, and outcomes. Clinical response was defined using SLEDAI 2K and improvement in the clinical manifestation(s) being treated. The most common clinical SLE manifestations/indications requiring therapy with Acthar Gel were arthritis, rash, and inability to taper corticosteroids. The mean SLEDAI 2K score at baseline was 5.8 ± 5.0 (range 0-16). Six patients were concomitantly treated with corticosteroids (mean dose 18.3mg/day). All patients were on background SLE medications including immunosuppressives. Seven of nine patients had an overall improvement, with a decrease in SLEDAI 2K from 5.8 ± 5.0 at baseline to 3.5 ± 2.7 (range 0-8); four of five patients had improvement or resolution in arthritis, and one of two patients had resolution of inflammatory rash. Four patients discontinued corticosteroids and one patient tapered below 50% of the initial dose by 3 months of treatment with Acthar Gel. No adverse events were reported. This study suggests a role for Acthar Gel as an alternative to corticosteroids in the treatment of SLE. Acthar Gel appears to be safe and well-tolerated after 6 months of treatment, with a significant reduction in disease activity.

Adrenocorticotropic hormone gel in the treatment of systemic lupus erythematosus: A retrospective study of patients.

Objectives: Acthar Gel is a long-acting formulation of adrenocorticotropic hormone (ACTH) with anti-inflammatory effects thought to be mediated in part through melanocortin receptor activation. This study was initiated to understand the role of Acthar Gel in SLE treatment in rheumatology practices. Methods: This is a retrospective case series of nine adult female patients treated with Acthar Gel for at least six months at five academic centers. Treating physicians completed a one-page questionnaire on lupus medications, disease activity, and outcomes. Clinical response was defined using SLEDAI 2K and improvement in the clinical manifestation(s) being treated. Results: The most common clinical SLE manifestations/indications requiring therapy with Acthar Gel were arthritis, rash, and inability to taper corticosteroids. The mean SLEDAI 2K score at baseline was 5.8 ± 5.0 (range 0-16). Six patients were concomitantly treated with corticosteroids (mean dose 18.3mg/day). All patients were on background SLE medications including immunosuppressives. Seven of nine patients had an overall improvement, with a decrease in SLEDAI 2K from 5.8 ± 5.0 at baseline to 3.5 ± 2.7 (range 0-8); four of five patients had improvement or resolution in arthritis, and one of two patients had resolution of inflammatory rash. Four patients discontinued corticosteroids and one patient tapered below 50% of the initial dose by 3 months of treatment with Acthar Gel. No adverse events were reported. Conclusions: This study suggests a role for Acthar Gel as an alternative to corticosteroids in the treatment of SLE. Acthar Gel appears to be safe and well-tolerated after 6 months of treatment, with a significant reduction in disease activity.

Adrenocorticotropic hormone gel in the treatment of systemic lupus erythematosus: A retrospective study of patients.

Objectives: Acthar Gel is a long-acting formulation of adrenocorticotropic hormone (ACTH) with anti-inflammatory effects thought to be mediated in part through melanocortin receptor activation. This study was initiated to understand the role of Acthar Gel in SLE treatment in rheumatology practices.Methods: This is a retrospective case series of nine adult female patients treated with Acthar Gel for at least six months at five academic centers. Treating physicians completed a one-page questionnaire on lupus medications, disease activity, and outcomes. Clinical response was defined using SLEDAI 2K and improvement in the clinical manifestation(s) being treated.Results: The most common clinical SLE manifestations/indications requiring therapy with Acthar Gel were arthritis, rash, and inability to taper corticosteroids. The mean SLEDAI 2K score at baseline was 5.8 (range 0-16). Six patients were concomitantly treated with corticosteroids (mean dose 18.3mg/day). All patients were on background SLE medications including immunosuppressives. Seven of nine patients had an overall improvement, with a decrease in SLEDAI 2K to 3.5; four of five patients had improvement or resolution in arthritis, and one of two patients had resolution of inflammatory rash. Four patients discontinued corticosteroids and one patient tapered below 50% of the initial dose by 3 months of treatment with Acthar Gel. No adverse events were reported.Conclusions: This study suggests a role for Acthar Gel as an alternative to corticosteroids in the treatment of SLE. Acthar Gel appears to be safe and well-tolerated after 6 months of treatment, with a significant reduction in disease activity.

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

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

Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort

We describe disease activity, damage, and the accrual of key autoantibodies in an inception systemic lupus erythematosus (SLE) cohort. The Systemic Lupus International Collaborating Clinics (SLICC) International Research Network, comprising 27 centers from 11 countries, has followed an inception cohort of SLE patients yearly according to a standardized protocol. Of these patients, 298 were followed for a minimum of 5 years and constitute the study population. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K) and damage was assessed using the SLICC/American College of Rheumatology Damage Index (SDI). Antinuclear antibody (ANA), anti-DNA, and anticardiolipin antibody (aCL) levels and lupus anticoagulant were assessed yearly. Descriptive statistics were generated and repeated-measures general linear models were used to evaluate SLEDAI-2K and SDI over time between whites and nonwhites. Of the 298 patients, 87% were women, 55% were white, 12% were African American, 14% were Asian, 16% were Hispanic, and 2% were categorized as "other." At enrollment, the mean age was 35.3 years, the mean SLEDAI-2K score was 5.9, and the mean disease duration was 5.5 months. Mean SLEDAI-2K scores decreased in the first year and then remained low. SLEDAI-2K scores were significantly lower at each year in whites compared to nonwhites. Mean SDI scores increased progressively over 5 years; there was no significant difference between whites and nonwhites. As expected, ANA positivity was high and anti-DNA positivity was relatively low at enrollment, and both increased over 5 years. Although lupus anticoagulant increased slightly over 5 years, aCL positivity did not. Disease activity in newly diagnosed patients decreases over their first 5 years, while damage increases. Antibody positivity ran variable courses over this period.