Safety Of Estrogens In Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index Research Articles

Effect of belimumab in patients with systemic lupus erythematosus treated with low dose or no corticosteroids.

Systemic lupus erythematosus (SLE) responder index (SRI)-4 response has been achieved with belimumab treatment in patients with moderate disease activity in cornerstone clinical trials and following studies. However, most studies involved patients treated with a mean prednisolone-equivalent dose of approximately 10 mg/d and focused on the steroid-sparing effect of belimumab. We aimed to identify the effect of belimumab in patients with mild-to-moderate SLE who were treated with low-dose or no corticosteroids. We retrospectively reviewed the electronic medical records of patients treated with belimumab for at least 6 months between May 2021 and June 2022. The primary endpoint was SRI-4 response at 6 months. Thirty-one patients were included (13 low dose- and 18 steroid non-users). The mean age was 39.2 ± 11.4 years, and 90.3% of patients were female. The baseline Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 6.0 (4.0-9.0). The primary endpoint was achieved in 32.3% (10/31) of patients. Significant improvements in anemia, C4 levels, and SELENA-SLEDAI score were observed during treatment. Univariate analysis showed that the baseline SELENA-SLEDAI and arthritis were significantly associated with SRI-4 response at 6 months, and only the SELENA-SLEDAI remained significant (p = 0.014) in multivariate analysis. This cohort study is the first to report the efficacy of belimumab after minimizing the effect of corticosteroids. Belimumab showed efficacy in improving the SELENA-SLEDAI score, anemia, and low C4 in patients who did not receive corticosteroids or received only low doses.

#4516 CLINICAL CHARACTERISTICS OF PATIENTS WITH LUPUS NEPHRITIS CLASS III–V: ANALYSIS OF INTERNATIONAL REAL-WORLD DATA

Abstract Background and Aims Lupus nephritis (LN) is a severe renal manifestation of systemic lupus erythematosus (SLE) that negatively impacts morbidity and mortality; however, real-world data for LN is scarce. This study describes: the proportion of patients with SLE managed by rheumatologists (rheum-managed) and by nephrologists (neph-managed) with LN class III–V; the proportion of patients with a Safety of Estrogens in Lupus Erythematosus National Assessment - SLE Disease Activity Index (SELENA-SLEDAI) score ≥8 by region; extra-renal organ systems involvement by region; flaring by region; and EQ-5D and EQ-visual analogue scale (VAS) scores by estimated glomerular filtration rate (eGFR). Method Data were drawn from the Adelphi Lupus Disease Specific Programme, a cross-sectional, multi-subscriber survey of physicians and their consulting patients conducted April 2021–May 2022 in China, Japan, EU5 (France, Germany, Italy, Spain and the UK) and the USA. Physicians provided demographic and clinical data for 5–6 consecutive adult patients consulting for SLE/LN. LN class III–V was assessed by the physician at data collection. SELENA-SLEDAI scores were derived by physician assessment of patients’ current clinical manifestations. Patients had the opportunity to complete an EQ-5D form. All analyses were descriptive. Results Overall, 9% (183/2148) of rheum- and 48% (364/766) of neph-managed patients had LN. Most patients with LN had a SELENA-SLEDAI score ≥8 (70% of rheum- and 76% of neph-managed; Table 1), compared with 48% (1032/2148) of rheum-managed patients with SLE alone. The proportion of neph-managed patients with LN with a SELENA-SLEDAI score ≥8 varied by region, from 58% in the USA to 87% in China. In total, 62% of rheum- and 43% of neph-managed patients with LN had ever flared (any organ system; Table 1). The proportion of rheum-managed patients with LN who had ever flared ranged from 52% in China + Japan to 75% in EU5. The proportion of patients with LN currently experiencing a flare was similar between rheum- (31%) and neph-managed (35%) patients, but varied by region, with the highest proportion for rheum-managed patients in China (59%) and lowest in the USA (18%). In subgroups with ≥15 patients, EQ-5D and EQ-VAS scores generally worsened as eGFR lowered (Figure 1). Conclusion Patients with LN class III–V had high disease burden (SELENA-SLEDAI scores ≥8) and flaring that varied by region, suggesting a need for more efficacious treatments for patients with LN.

Fatigue is independently associated with disease activity assessed using the Physician Global Assessment but not the SLEDAI in patients with systemic lupus erythematosus

ObjectivesTo analyse whether reported fatigue, one of the most challenging manifestations of systemic lupus erythematosus (SLE), may bias the assessment of disease activity in SLE according to the Physician Global...

Subclinical left ventricular dysfunction during systemic lupus erythematosus activity with follow-up after remission – A speckle tracking echocardiographic study

Aim of the workTo investigate the subclinical left ventricular (LV) dysfunction in patients with active systemic lupus erythematosus (SLE) using speckle tracking echocardiography (STE). The echocardiographic parameters were followed up when the disease activity was controlled. Patients and methodsThis prospective study included 63 patients with active SLE and LV ejection fraction (EF) ≥50%.Safety of Estrogens in Lupus Erythematosus: National Assessment – Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) was assessed and categorized as mild/moderate (≤12) or severe (>12). Fifty SLE patients continued follow-up after 3–6 months of the disease remission. Fifty age- and gender-matched healthy individuals acted as the control group. The measured STE parameters included LV deformation (global longitudinal strain [GLS] and global circumferential strain [GCS]) and rotational parameters (rotation, twist, and torsion). ResultsThe patients were 56 females and 7 males (F:M 8:1) and median age 26 years (IQR: 21–31 years) and a disease duration of 3 years (IQR 2–5 years. Active SLE patients showed worse strain parameters than controls (mean GLS −19.9%±2.1 vs −22.7%±1.3 and mean GCS −21.2 ± 2.5% vs −25.1 ± 1.7% respectively; p < 0.001 for both). Patients had lower LV rotational parameters (p < 0.001 for all). STE parameters were similar in patients with mild-moderate and severe activity and improved after remission in both groups. ConclusionActive SLE patients had modest LV dysfunction by STE despite having normal function by traditional echocardiography. Disease remission resulted in the improvement of STE parameters. STE is a simple tool to use in SLE activity scores to detect early cardiac dysfunction.

Low-dose belimumab for patients with systemic lupus erythematosus at low disease activity: protocol for a multicentre, randomised, double-blind, placebo-controlled clinical trial

IntroductionSLE is a chronic inflammatory systemic autoimmune disease with relapsing–remitting pattern. B-lymphocyte stimulator was involved in the pathogenesis of SLE. The humanised monoclonal antibody belimumab with 10 mg/kg was effective...

Efficacy and safety of belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison

ObjectiveTo assess the efficacy and safety of belimumab in paediatric versus adult patients with systemic lupus erythematosus (SLE).MethodsWe performed across-study comparisons of patients with active SLE who received belimumab or...

Psychometric properties of FACIT-Fatigue in systemic lupus erythematosus: a pooled analysis of three phase 3 randomised, double-blind, parallel-group controlled studies (BLISS-SC, BLISS-52, BLISS-76)

BackgroundFatigue is a key symptom in patients with systemic lupus erythematosus (SLE), and regulatory bodies recommend its assessment in clinical trials of SLE therapies.MethodsThis post hoc pooled analysis of the three BeLimumab In Subjects with Systemic lupus erythematosus (BLISS) Phase 3 randomised, double-blind, parallel-group controlled trials evaluated the measurement properties of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue. Patients (N = 2520) completed the FACIT-Fatigue every 4 weeks from baseline until the end of each study period. Internal consistency, test–retest reliability, convergent validity, and ability to detect changes in SLE were evaluated for the FACIT-Fatigue.ResultsThe FACIT-Fatigue showed good internal consistency reliability (Cronbach’s alpha > 0.90), very good test–retest reliability (0.76 ≤ intraclass correlation coefficient ≤ 0.92), and moderate-strong convergent validity (0.49 ≤ |r| ≤ 0.86) against scale and summary measure scores from the Short Form 36 Health Survey Version 2. Correlations between FACIT-Fatigue and British Isles Lupus Assessment Group (BILAG) General/Musculoskeletal scores (0.24 ≤ |r| ≤ 0.43) supported convergent validity. Correlations between FACIT-Fatigue and the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores and SLE annualised flare rate were weak but in the expected direction (ranging from − 0.02 to − 0.25). Known-groups validity testing showed that the FACIT-Fatigue can significantly discriminate between patient groups with differing scores for SELENA-SLEDAI, BILAG (General and Musculoskeletal) ratings, and Physician’s Global Assessment (PGA). Patients showing improvement in PGA and meeting the BILAG responder criteria had significantly higher mean improvement in FACIT-Fatigue scores than those without improvements in either measure (Week 52 mean score difference [95% confidence interval]: − 4.0 [− 5.0, − 3.0] and −2.2 [−3.1, −1.2], respectively; both p < 0.0001). The range of important (i.e. meaningful) change in FACIT-Fatigue, based on multiple anchors, was 3–6 points.ConclusionsThe FACIT-Fatigue demonstrated adequate psychometric properties in patients with SLE. The body of evidence from the three BLISS trials (both pooled and individually) supports the FACIT-Fatigue as a reliable and valid measure of SLE-related fatigue in clinical trials.Clinical trial identifiersBLISS-SC (NCT01484496), BLISS-52 (NCT00424476), and BLISS-76 (NCT00410384).

The Arabic LupusPRO: A Cross-Cultural Validation of a Disease-Specific Patient-Reported Outcome Tool for Quality of Life in Lupus Patients.

To translate and cross-culturally adapt the Arabic version of LupusPRO v.1.8 and to test its reliability and validity. LupusPRO was translated into the Arabic language following a standard procedure with forward-backward translation and was tested in patients with systemic lupus erythematosus (SLE) before use. The Arabic version was administered to 107 Egyptian SLE patients, along with a validated Arabic version of RAND 36-Item Health Survey 1.0 (SF-36). The internal consistency and test-retest reliability were determined. Validity was assessed by correlating LupusPRO scores with SF-36, Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). The conceptual framework of the Arabic LupusPRO was evaluated using confirmatory factor analysis (CFA). Among the 107 SLE patients, 95% were women with a median (range) age of 32 (18-55) years, median (range) SELENA-SLEDAI of 6 (0-23) and median (range) SDI of 0 (0-6). The Cronbach's alpha for the Arabic LupusPRO ranged from 0.71 to 0.98, except for the social support domain (0.65). Test-retest reliability ranged from 0.95 to 0.99. Convergent validity with corresponding domains of SF 36 was satisfactory. For criterion validity, there was a weak but significant correlation between several LupusPRO domains with SELENA-SLEDAI. CFA showed a good model fit. The Arabic version of LupusPRO v1.8 is a reliable and valid tool for measuring quality of life among Arabic speaking SLE patients.

Safety and efficacy of metformin in systemic lupus erythematosus: a multicentre, randomised, double-blind, placebo-controlled trial.

Immunometabolism is involved in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to repurpose metformin, an anti-diabetic drug that regulates systemic and cellular metabolism, and assess its effects in Chinese patients with SLE without diabetes. We did a multicentre, randomised, double-blind, placebo-controlled trial in three hospitals in Shanghai, China. We enrolled adult patients with SLE, without diabetes, who had Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores no higher than 6; with no A score or no more than one B score on the British Isles Lupus Assessment Group (BILAG) scale at screening; who had had at least one lupus flare; and were treated with prednisone (≥20 mg per day) within the preceding 12 months. Patients were randomly assigned (1:1) in blocks of four by a computer algorithm to add metformin tablets (250 mg per tablet with a target dose of 0·5 g three times per day; metformin group) or placebo tablets (placebo group) to their standard therapy, for a maximum of 12 months. Patients, assessment staff, and statisticians were masked to group assignment. The primary endpoint was a composite index of major or mild-to-moderate disease flares (SELENA-SLEDAI Flare Index) at 12 months. The full analyses were done in all patients who received at least one dose of the study drug using the χ2 test. Adverse events were recorded during the 12-month follow-up. This study is registered with ClinicalTrials.gov, NCT02741960. Between May 24, 2016, and Dec 13, 2017, 180 patients were screened, of whom 140 (78%) of them were enrolled. 31 (17%) did not meet the inclusion criteria and nine (5%) withdrew informed consent without treatment after randomisation. 67 patients were assigned to the metformin group and 73 to the placebo group. By 12 months of follow-up, there was no significant difference in the incidence of lupus flares, which occurred in 14 (21%) patients in the metformin group versus 25 (34%) in the placebo group (relative risk 0·68, 0·42-1·04, p=0·078). Patients receiving metformin experienced more gastrointestinal adverse events (three [4%] discontinued for this reason vs one [1%] for placebo; overall 26 [39%] vs 11 [15%], p=0·0015), but the incidence of non-flare serious adverse events was similar between groups (one [1%] vs three [4%], p=0·35). The frequency of infection events was significantly lower in patients in the metformin group than in the placebo group (17 [25%] vs 32 [44%], p=0·022). No patients died as a result of treatment. This trial was underpowered to draw a sound conclusion on the efficacy of metformin to reduce disease flares as an add-on treatment to standard care in patients with SLE. Nonetheless, metformin had a favourable safety profile and our data present a basis for larger trials to investigate its potential effect on reducing the frequency of flares for patients with SLE with low-grade disease activity who are at risk of relapse. Shanghai Shenkang Promoting Project and the National Key Research and Development Program of China.

Sexual functioning and its correlates in premenopausal married Indian women with systemic lupus erythematosus.

This study aimed to evaluate sexual functioning and its association with disease activity, damage, marital satisfaction, fatigue and psychiatric comorbidity in married women with systemic lupus erythematosus (SLE). One hundred and twelve premenopausal married women with SLE were included in the study. Disease activity and damage were assessed using Safety of Estrogens in Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index (SDI) respectively. Female sexual function index (FSFI) and couple satisfaction index (CSI) were used to evaluate sexual function and marital satisfaction respectively. Depression, anxiety and fatigue were assessed using Patient Health Questionnaire 9 (PHQ9), Generalized Anxiety Disorder 7 (GAD7) and fatigue severity scale (FSS) respectively. The mean age of the study group was 34.0 (SD 6.8) years. Mean SELENA-SLEDAI was 3.67 (SD 4.2) and mean SDI was 0.25 (SD 0.62). Median steroid dose at the time of evaluation was 7.5mg/d of prednisolone. Based on FSFI total score, impaired sexual functioning was found in 60.7%. However, when the cut-off of different domains was considered, more than 90% of the participants reported problems in desire, arousal and lubrication. The mean CSI score was 130.39±26.17. Eighteen patients (16.1%) had CSI lower than the cut-off score (104.5) suggestive of marital distress. On univariate analysis sexual function showed a correlation with marital satisfaction (r=.34, P<.001), dose of steroids(r=-.26, P=.008), disease activity (r=-.21, P=.027), depression (r=-.19, P=.039) and anxiety (r=-.201, P=.034). Sexual dysfunction is highly prevalent in premenopausal married females with SLE. Higher dose of steroids, disease activity, depression,anxiety and marital satisfaction were associated with poor sexual functioning in one or more domains.

Validity and Reliability of Patient Reported Outcomes Measurement Information System Computerized Adaptive Tests in Systemic Lupus Erythematosus.

The aims of this study were to assess the construct validity and the test-retest reliability of Patient Reported Outcomes Measurement Information System (PROMIS) computerized adaptive tests (CAT) in patients with systemic lupus erythematosus (SLE). Adults with SLE completed the Medical Outcomes Study Short Form-36, LupusQoL-US version ("legacy instruments"), and 14 selected PROMIS CAT. Using Spearman correlations, PROMIS CAT were compared with similar domains measured with legacy instruments. CAT were also correlated with the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) disease activity and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) scores. Test-retest reliability was evaluated using ICC. There were 204 outpatients with SLE enrolled in the study and 162 completed a retest. PROMIS CAT showed good performance characteristics and moderate to strong correlations with similar domains in the 2 legacy instruments (r = -0.49 to 0.86, p < 0.001). However, correlations between PROMIS CAT and the SELENA-SLEDAI disease activity and SDI were generally weak and statistically insignificant. PROMIS CAT test-retest ICC were good to excellent, ranging from 0.72 to 0.88. To our knowledge, these data are the first to show that PROMIS CAT are valid and reliable for many SLE-relevant domains. Importantly, PROMIS scores did not correlate well with physician-derived measures. This disconnect between objective signs and symptoms and the subjective patient disease experience underscores the crucial need to integrate patient-reported outcomes into clinical care to ensure optimal disease management.

Associations of the Levels of C4d-bearing Reticulocytes and High-avidity Anti-dsDNA Antibodies with Disease Activity in Systemic Lupus Erythematosus.

There are no laboratory tools that detect early flares in systemic lupus erythematosus (SLE). Our aim was to validate in our population the previous findings of the association of C4d-bearing reticulocytes (R-C4d) compared to anti-dsDNA antibodies, with disease activity assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) 2004 scales. All patients who met the 1987 American College of Rheumatology classification criteria and were seen consecutively in 2013 at a specialized SLE care clinic were included. Disease activity was established by the SELENA-SLEDAI and BILAG 2004. Anti-dsDNA and R-C4d were quantified in peripheral blood. Comparisons were made between values of active and inactive patients, and the correlations between the SELENA-SLEDAI and serum levels of anti-dsDNA and R-C4d were measured. Sixty-two patients (83.9% women) were included. A total of 32.3% had active disease according to the SELENA-SLEDAI. There was a significant statistical difference (p = 0.0001) in the distribution of R-C4d between disease activity groups. The correlation coefficient between R-C4d and the SELENA-SLEDAI score was rs = 0.738 (p = 0.0001). R-C4d differed between patients with and without activity in the BILAG 2004 constitutional, mucocutaneous, gastrointestinal, renal, and hematological domains. R-C4d showed a higher correlation with SLE activity measured by the SELENA-SLEDAI and BILAG 2004 than anti-dsDNA did, suggesting a possible involvement in diagnosing disease activity. Prospective studies that confirm these findings and evaluate its involvement in followup are needed.

A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study

ObjectiveTo evaluate the efficacy and safety of subcutaneous blisibimod, an inhibitor of B cell activating factor, in patients with systemic lupus erythematosus (SLE) in a dose-ranging Phase 2b clinical trial.Methods547...

Turkish lupusPRO: cross-cultural validation study for lupus

LupusPRO is a disease-targeted patient-reported outcome measure that was developed and validated from and among US patients with systemic lupus erythematosus (SLE). We herein report the results of the cross-cultural adaptation and validation study of the Turkish translated version of the LupusPRO. Turkish LupusPRO and the Medical Outcomes Study Short Form (SF-36) (Turkish) were administered to the Turkish lupus patients. Disease activity was ascertained using the physician global assessment (PGA), Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI), and flare (defined by LFA-Lupus Foundation of America). Disease damage was assessed with Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). Also, second Turkish LupusPRO tests were given to the patients to be completed within 2-3days and sent back to us. Internal consistency reliability, test-retest reliability, and convergent and criterion validity (against disease activity or health status) were tested. All reported p values are two-tailed. The conceptual framework of the LupusPRO was evaluated using confirmatory factor analysis appropriate for categorical data. One hundred two SLE subjects (94% women) were enrolled. The median (IQR) age and mean disease duration (±SD) were 38.5 (18) years and 60.3 (±56.3) months, respectively. The mean ± SD, SLEDAI, and SDI scores were 3.1 ± 3.7 and 0.52 ± 0.75, respectively. There were 25 patients who had flares at the time of study. Forty-two patients with no change in their health status completed and sent back the second LupusPRO test and were included in the test-retest analysis. Test-retest reliability of LupusPRO domains ranged from 0.87 to 0.97, while internal consistency reliability of the domains ranged from 0.63 to 0.94. Convergent validity with corresponding domains of SF-36 was present. Health-related quality-of-life domains performed well against disease activity measures (PGA, total SLEDAI, LFA flare, and SF-6D-overall health status), establishing its criterion validity. Item-to-factor loadings representing the hypothesized item-to-scale relationships were satisfactory. The model fit for the hypothesized item-to-scale relationships was also satisfactory. The Turkish version of the LupusPRO is valid and appears to perform comparably to the English and Spanish language versions. It can be used as a patient-reported outcome parameter in clinical trials, as well as longitudinal studies for testing responsiveness to change.

Cross-cultural Validation of a Disease-specific Patient-reported Outcome Measure for Systemic Lupus Erythematosus in Canada

The LupusPRO, a disease-targeted patient-reported outcome measure, was developed and validated in US patients with systemic lupus erythematosus (SLE). We report the results of the cross-cultural validation study of the English version of the LupusPRO among patients in Canada with SLE. The LupusPRO was administered to English-speaking Canadian patients with SLE. Demographic, clinical, and serological characteristics were obtained, and the Medical Outcomes Study Short Form-36 (SF-36) and LupusPRO were administered. Disease activity was ascertained using the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the Lupus Foundation of America definition of flare (Yes/No). Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Physician disease activity and damage assessments were also ascertained using visual analog scales. A mail-back LupusPRO form was completed within 2-3 days of the index visit. Items tested were internal consistency reliability (ICR), test-retest reliability (TRT), convergent and discriminant validity (against corresponding domains of the SF-36), criterion validity (against disease activity or health status), and known-groups validity. Participants were 123 Canadian patients with SLE (94% women); mean age was 47.7 (SD 14.8) years. The median (interquartile range) SELENA-SLEDAI and SDI were 4 (6) and 1 (3), respectively. The ICR of the LupusPRO domains ranged from 0.60 to 0.93, while the TRT range was 0.62-0.95. Measures observed were convergent and discriminant validity with corresponding domains of SF-36, criterion validity, and known-groups validity against disease activity, damage, and health status. Confirmatory factor analysis showed a good fit. The LupusPRO has fair psychometric properties among Canadian patients with SLE, and prospective studies to establish minimally important difference are continuing.

Seasonal Variation in the Activity of Systemic Lupus Erythematosus

To determine whether there is any seasonal variation in the activity of systemic lupus erythematosus (SLE) overall and by individual organs. The study group comprised 2102 patients with SLE who were followed in a prospective longitudinal cohort study. In this cohort, 92.3% of the patients were women. The mean ± SD age of the patients was 47.9 ± 13.9 years, 56.3% were white, 37.1% were African American, and 3.1% were Asian. Global disease activity was recorded by the Safety of Estrogens in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the physician's global assessment. Activity of each organ was also recorded using SLEDAI terms and a visual analog scale (VAS; 0 to 3). There was significant seasonal variation in photosensitive rash (p < 0.0001), which was more frequent in the spring and summer months (p < 0.0001). There was significantly more arthritis activity in spring and summer, as measured by both SELENA-SLEDAI (p = 0.0057) and the joint VAS (p = 0.0047). A decrease in renal activity was found in the summer months compared to the rest of the year (p = 0.0397). Serositis recorded by VAS had higher activity from August to October (p = 0.0392). Anti-dsDNA levels were significantly higher during October and November (p < 0.0001). There was significant seasonal variation in antiphospholipid antibody levels (p < 0.0001) and lupus anticoagulant (p = 0.0003). We found a significant variation in activity through the year in global disease activity as measured by SELENA-SLEDAI (p = 0.048). In the Hopkins Lupus Cohort, skin and joint activity is increased during the spring and summer, but other organs have different patterns. These seasonal variations likely reflect environmental factors that influence disease activity, including ultraviolet light and infections.

Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial

Systemic lupus erythematosus is a heterogeneous autoimmune disease that is associated with B-cell hyperactivity, autoantibodies, and increased concentrations of B-lymphocyte stimulator (BLyS). The efficacy and safety of the fully human monoclonal antibody belimumab (BLyS-specific inhibitor) was assessed in patients with active systemic lupus erythematosus. Patients (aged ≥18 years) who were seropositive with scores of at least 6 on the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) were enrolled in a multicentre phase 3 study, which was done in Latin America, Asia-Pacific, and eastern Europe. Patients were randomly assigned by use of a central interactive voice response system in a 1:1:1 ratio to belimumab 1 mg/kg or 10 mg/kg, or placebo by intravenous infusion in 1 h on days 0, 14, and 28, and then every 28 days until 48 weeks, with standard of care. Patients, investigators, study coordinators, and sponsors were masked to treatment assignment. Primary efficacy endpoint was improvement in the Systemic Lupus Erythematosus Responder Index (SRI) at week 52 (reduction ≥4 points in SELENA-SLEDAI score; no new British Isles Lupus Assessment Group [BILAG] A organ domain score and no more than 1 new B organ domain score; and no worsening [<0·3 increase] in Physician's Global Assessment [PGA] score) versus baseline. Method of analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00424476. 867 patients were randomly assigned to belimumab 1 mg/kg (n=289) or 10 mg/kg (n=290), or placebo (n=288). 865 were treated and analysed in the belimumab (1 mg/kg, n=288; 10 mg/kg, n=290) and placebo groups (n=287). Significantly higher SRI rates were noted with belimumab 1 mg/kg (148 [51%], odds ratio 1·55 [95% CI 1·10-2·19]; p=0·0129) and 10 mg/kg (167 [58%], 1·83 [1·30-2·59]; p=0·0006) than with placebo (125 [44%]) at week 52. More patients had their SELENA-SLEDAI score reduced by at least 4 points during 52 weeks with belimumab 1 mg/kg (153 [53%], 1·51 [1·07-2·14]; p=0·0189) and 10 mg/kg (169 [58%], 1·71 [1·21-2·41]; p=0·0024) than with placebo (132 [46%]). More patients given belimumab 1 mg/kg (226 [78%], 1·38 [0·93-2·04]; p=0·1064) and 10 mg/kg (236 [81%], 1·62 [1·09-2·42]; p=0·0181) had no new BILAG A or no more than 1 new B flare than did those in the placebo group (210 [73%]). No worsening in PGA score was noted in more patients with belimumab 1 mg/kg (227 [79%], 1·68 [1·15-2·47]; p=0·0078) and 10 mg/kg (231 [80%], 1·74 [1·18-2·55]; p=0·0048) than with placebo (199 [69%]). Rates of adverse events were similar in the groups given belimumab 1 mg/kg and 10 mg/kg, and placebo: serious infection was reported in 22 (8%), 13 (4%), and 17 (6%) patients, respectively, and severe or serious hypersensitivity reactions on an infusion day were reported in two (<1%), two (<1%), and no patients, respectively. No malignant diseases were reported. Belimumab has the potential to be the first targeted biological treatment that is approved specifically for systemic lupus erythematosus, providing a new option for the management of this important prototypic autoimmune disease. Human Genome Sciences and GlaxoSmithKline.

Association of increased interferon‐inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus

To study 5 type I interferon (IFN)-inducible genes (LY6E, OAS1, OASL, MX1, and ISG15) in patients with systemic lupus erythematosus (SLE) and to correlate expression levels with disease activity and/or clinical manifestations. Peripheral blood cells were obtained from 48 SLE patients, 48 normal controls, and 22 rheumatic disease controls, and total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real-time polymerase chain reaction, standardized to a housekeeping gene, and summed to an IFN score. Disease activity was determined by the Safety of Estrogens in Lupus Erythematosus: National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) composite. Each gene was highly expressed in SLE patients compared with normal controls (P < or = 0.0003) or disease controls (P < or = 0.0008 except for MX1). IFN scores were positively associated with the SELENA-SLEDAI instrument score (P = 0.001), the SELENA-SLEDAI flare score (P = 0.03), and the physician's global assessment score (P = 0.005). Compared with patients without nephritis, lupus nephritis patients had higher IFN scores (overall P < 0.0001), especially during active renal disease. IFN scores were weakly associated with neurologic manifestations. Elevated IFN scores were positively associated with the current presence of anti-double-stranded DNA (anti-dsDNA) antibodies (P = 0.007) or hypocomplementemia (P = 0.007). LY6E expression levels distinguished active from inactive lupus nephritis (P = 0.02) and were positively associated with proteinuria (P = 0.009). The 5 IFN-inducible genes were highly expressed in SLE patients, and increased levels were correlated with disease activity defined by several methods. IFN scores, or LY6E levels, were elevated in lupus nephritis patients, especially during active renal disease, and in patients with anti-dsDNA antibody positivity and hypocomplementemia. IFN scores, or LY6E levels, may be useful as a biomarker for lupus nephritis therapy.

Raloxifene for postmenopausal women with systemic lupus erythematosus: A pilot randomized controlled study

To study the effects of raloxifene on disease activity and bone mineral density (BMD) in postmenopausal women with systemic lupus erythematosus (SLE). Postmenopausal women with osteopenia and inactive SLE were randomly assigned to receive either raloxifene (60 mg/day) plus elemental calcium (1,200 mg/day) or elemental calcium alone (control). Patients with a history of thromboembolism or antiphospholipid antibody positivity were excluded. BMD at various sites was serially measured, and lupus activity was serially assessed using the Safety of Estrogens in Lupus Erythematosus: National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI). The study group comprised 33 patients (16 assigned to receive raloxifene and 17 controls, mean +/- SD age 53.8 +/- 5.3 years). Age, body mass index, and baseline BMD values did not differ significantly between the 2 groups of patients. All patients were receiving low-dose prednisolone. After 12 months, femoral neck BMD (mean +/- SD -2.6 +/- 1.0%; P = 0.02) and lumbar spine BMD (-3.3 +/- 0.8%; P = 0.001) decreased significantly in the controls but not in the raloxifene group. No patient had a major flare of lupus, but mild/moderate flares occurred in 4 raloxifene-treated and 6 control patients (P = 0.79). The total area under the curve of SELENA-SLEDAI scores was not significantly different between the 2 groups. A significant increase in the high-density lipoprotein cholesterol level and a reduction in the low-density lipoprotein cholesterol level were observed in the raloxifene group but not in controls. One patient in the raloxifene group (6%) withdrew from the study because of hot flushes. No thromboembolic events were reported. Raloxifene was well tolerated in Chinese patients with SLE who had inactive disease and in whom hypercoagulability was not identified. Raloxifene maintained femoral neck and spinal BMD in patients receiving corticosteroids.