Outcome Of Systemic Lupus Erythematosus Research Articles

Impact of Joint Involvement on Patients Reported Outcomes in Systemic Lupus Erythematosus.

Joint involvement is common among patients with systemic lupus erythematosus (SLE). Aim of this work was to evaluate the correlation between the presence of joint involvement and patient-reported pain, perception of disease activity, general health and quality of life. Fifty consecutive SLE patients were enrolled in the study. All patients underwent a complete clinical evaluation including a 44-joint count; in addition, an ultrasound evaluation of joint involvement of hands and wrists was performed. The following patients reported outcomes (PROs) were completed: Visual Analog Scales 0-100 mm (VAS) evaluating patients reported pain, patient's perception of global disease activity and general health (GH) and a validated Italian version of the Health Assessment Questionnaire (HAQ). Fourteen patients (28%) reported a significant morning stiffness lasting for more than 30 minutes; hand or wrist arthritis was clinically detectable in 10 (20%) patients, while the US evaluation exhibited at least one joint or tendon pathology in 18 patients (36%). The mean VAS score for pain and disease activity perception was 27 (±27.7) mm and 25.3 (±25.2) mm, respectively, the mean of GH score was 33.2 (±24.3) mm, and the mean HAQ score was 0.34 (±0.5). A significant correlation was observed between VAS score for pain, patient's perception of disease activity and GH and the presence of arthritis. PROs may play an important role in guiding therapeutic decisions and suggest the utility of ultrasound evaluation in patients reporting articular symptoms.

Predictive value of the neutrophil-to-lymphocyte ratio and hemoglobin insystemic lupus erythematosus.

The aim of the present study was to evaluate the association of the neutrophil-to-lymphocyte ratio (NLR) and hemoglobin levels with disease activity in patients with systemic lupus erythematosus (SLE) and to explore their clinical significance in predicting SLE. The present study included 212 patients with SLE and 201 healthy controls. All the clinical characteristics were collected from their medical records. The results revealed that the NLR was elevated and the hemoglobin level was markedly decreased in the patients with SLE compared with the healthy controls. NLR was positively correlated with the SLE Disease Activity Index 2000 (SLEDAI-2K), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), whereas it was not correlated with C3 or C4. The hemoglobin level was negatively correlated with SLEDAI-2K, ESR and CRP and positively correlated with C3 and C4. In addition, NLR [EXP(B)=1.986; 95% confidence interval (CI), 1.432-2.753; P=0.001] and hemoglobin [EXP(B)=0.947; 95% CI, 0.929-0.965; P=0.001] were independent predictive factors of SLE. The optimal NLR cut-off value for predicting SLE was 2.075, with 71.14% sensitivity and 69.57% specificity, whereas the optimal hemoglobin cut-off value was 131.5 mg/l, with 75.79% sensitivity and 77.98% specificity. In addition, high NLR together with low hemoglobin levels and high NLR or low hemoglobin levels had increased positive predictive values (86.05 and 66.95, respectively). High NLR with low hemoglobin levels and high NLR or low hemoglobin levels also had higher sensitivity (64.91 and 92.40, respectively) and specificity (64.91 and 18.95, respectively), compared with high NLR alone or low hemoglobin alone. In conclusion, NLR and hemoglobin may reflect SLE disease activity and may be used as markers for predicting the outcome of SLE.

Musculoskeletal involvement and ultrasonography update in systemic lupus erythematosus: New insights and review.

Ultrasonography has been rarely used to measure musculoskeletal and joint activity in systemic lupus erythematosus (SLE). The aim of this review is to discuss the utility and reliability of this non-invasive diagnostic tool for the assessment of joint disease in SLE patients. In the last decade, several reports have highlighted the role of ultrasonography for a better evaluation of SLE-related musculoskeletal symptoms. The symptoms have also been associated with worse outcomes in SLE; therefore, it is essential to seek useful and accessible techniques for better understanding of such patients who are insufficiently assessed by standard physical examination.

Management and outcomes of pregnancy with or without lupus nephritis: a systematic review and meta-analysis.

BackgroundAlthough it is well established that systemic lupus erythematosus (SLE) negatively affects pregnancy outcomes, there is insufficient evidence on the effect of lupus nephritis (LN) on antenatal management and pregnancy outcomes. We performed a systematic review and meta-analysis to determine the association of LN with management and pregnancy outcomes in SLE patients.MethodsEmbase, Medline, Cochrane, and ClinicalTrials.gov were carefully searched for relevant English and Chinese language studies. A total of 2,987 articles were reviewed. Data were extracted that compared management and pregnancy outcomes in SLE pregnant women with LN vs without LN. Risk of bias was assessed by a modified version of the Newcastle-Ottawa Scale and the STROBE checklist. Combined odds ratios (OR) and 95% confidence intervals (CI) were obtained and sensitivity analysis was performed using RevMan 5.3 software.ResultsSixteen studies, including 1,760 pregnant patients with SLE, were included. Gestational hypertension (OR=5.65, 95% CI=2.94–10.84), preeclampsia (OR=2.84, 95% CI=1.87–4.30), SLE flare (OR=2.66, 95% CI=1.51–4.70), renal flare (OR=15.18, 95% CI=5.89–39.14), proteinuria (OR=8.86, 95% CI=4.75–16.52), and hypocomplementemia (OR=2.86, 95% CI=1.68–4.87) were significantly affected in pregnant women with LN. Anti-Sjögren’s syndrome-related antigen A/Ro autoantibodies were negatively associated with pregnant women with LN (OR=0.57, 95% CI=0.33–0.98). Pregnant women with LN presented a significant decrease in live births (OR=0.62, 95% CI=0.49–0.80) and a significant increase in preterm births (OR=1.92, 95% CI=1.49–2.49) and fetal growth restriction (OR=1.43, 95% CI=1.08–1.91). Regarding antenatal management, steroids (OR=2.48, 95% CI=1.59–3.87) and immunosuppressant treatment (OR=6.77, 95% CI=3.30–13.89) were more frequently used in women with LN.ConclusionThis review identified a significant association between the aforementioned outcomes and SLE pregnant patients with LN. In patients with SLE, LN increased the risks for adverse pregnancy outcomes and the use of medication. Therefore, special treatment and close monitoring should be allocated to pregnant women with LN.

Update on the epidemiology, risk factors, and disease outcomes of systemic lupus erythematosus.

Obtaining an updated view of the epidemiology, risk factors, and prognosis of systemic lupus erythematosus (SLE) is pivotal to our understanding of the disease burden. Recent community-based studies with comprehensive methodology provided more accurate disease occurrence estimates and suggested that SLE may be more frequent than previously thought. Gender, race, and socioeconomic status are important disease determinants, and there is increasing appreciation of the contribution of family history and environmental exposures in SLE susceptibility. Owing to its systemic nature, assessment of disease activity is challenging, also pertaining to efforts to improve trial endpoints for better discrimination between active drug and placebo. Notably, emerging evidence supports that remission or low disease activity states and prevention of flares are realistic targets in the management of SLE associated with improved prognosis. For the future, we anticipate that high-throughput analyses in patient cohorts will enhance the identification of robust biomarkers for diagnosis, risk stratification, and personalized treatment.

Features, Treatment, and Outcomes of Macrophage Activation Syndrome in Childhood-Onset Systemic Lupus Erythematosus.

To describe the features and treatment of macrophage activation syndrome (MAS) in a single-center cohort of patients with childhood-onset systemic lupus erythematosus (SLE), and to compare childhood-onset SLE manifestations and outcomes between those with and those without MAS. We included all patients with childhood-onset SLE followed up at The Hospital for Sick Children from 2002 to 2012, and identified those also diagnosed as having MAS. Demographic, clinical, and laboratory features of MAS and SLE, medication use, hospital and pediatric intensive care unit (PICU) admissions, as well as damage indices and mortality data were extracted from the Lupus database. Student's t-tests and Fisher's exact tests were used to compare continuous and categorical variables, respectively. We calculated incidence rate ratios of hospital and PICU admissions comparing patients with and those without MAS, using Poisson models. Kaplan-Meier survival analysis was used to examine the time to disease damage accrual. Of the 403 patients with childhood-onset SLE, 38 (9%) had MAS. The majority (68%) had concomitant MAS and SLE diagnoses. Fever was the most common MAS clinical feature. The frequency of renal and central nervous system disease, hospital admissions, the average daily dose of steroids, and time to disease damage were similar between those with and those without MAS. We observed a higher mortality rate among those with MAS (5%) than those without MAS (0.2%) (P = 0.02). MAS was most likely to develop concomitantly with childhood-onset SLE diagnosis. The majority of the MAS patients were successfully treated with corticosteroids with no MAS relapses. Although the numbers were small, there was a higher risk of death associated with MAS compared to SLE without MAS.

Outcomes of multitarget therapy using mycophenolate mofetil and tacrolimus for refractory or relapsing lupus nephritis.

Objectives Outcomes of systemic lupus erythematosus (SLE) have significantly improved over the years. However, when there is major organ involvement, the outcomes can still be unfavorable. Outcomes of multitarget therapy using mycophenolate mofetil (MMF) and tacrolimus in patients with SLE who were refractory to standard therapy were assessed. Methods We retrospectively reviewed the Hanyang BAE lupus cohort to identify patients with biopsy-confirmed lupus nephritis (classes III, IV, or V) who failed to either achieve complete response with standard induction therapy or those who had a lupus flare after achieving a complete response with conventional induction therapy and subsequently were switched to multitarget combination therapy with MMF and tacrolimus. Outcomes, including renal response, proteinuria, glomerular filtration rate, serum albumin, anti-dsDNA antibody level, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and complements, were assessed at six and 12 months. Results Twenty-nine patients, including 12 who failed to achieve a complete response at 12 months after initial conventional induction therapy and 17 with lupus flare after achieving a complete response at 12 months and treated with multitarget therapy, were included in the analysis. At six months, 53.9% of the patients showed a response, with 15.4% of patients showing a complete response and 38.5% of patients showing a partial response. At 12 months, 55.5% of patients exhibited a response (with complete and partial response in 25.9% and 29.6%, respectively). The dosage of steroids was significantly decreased at six months compared with baseline and was maintained at 12 months. Proteinuria, anti-double-stranded DNA antibody positivity, as well as C3 and C4 levels improved after treatment and persisted until 12 months, but were not significant. SLEDAI also improved. Outcomes were significantly better in patients who had a complete response but later had a flare, resulting in the use of multitarget therapy and achieving a subsequent complete response. Conclusions Multitarget therapy with MMF and tacrolimus can be a reasonable option in refractory lupus nephritis patients who failed to show adequate response to conventional induction therapy or who had flares during maintenance therapy. This treatment can help patients achieve a renal response and reduce the use of steroids.

Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: post-hoc analysis of the Phase IIb MUSE trial of anifrolumab

ObjectivesIn a post-hoc analysis, we aimed to validate the Lupus Low Disease Activity State (LLDAS) definition as an endpoint in an systemic lupus erythematosus (SLE) Phase IIb randomised controlled trial...

The mediational role of helplessness in psychological outcomes in systemic lupus erythematosus.

Objective Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can result in disability and psychological distress. Although pain has been associated with depressive symptomatology and stress in SLE, a paucity of theoretical models have been used to explain the relationship between pain and psychological distress in this population. Thus, the present study examined helplessness as a mediator of the relationship between pain and psychological distress among patients with SLE. Methods Multiple mediation analysis was used to examine the hypothesis that learned helplessness mediates the relationship between pain and symptoms of anxiety, depression, and stress in a sample of patients with SLE ( N = 136) receiving medical care at Cedars Sinai Medical Center. Results The mean score on the Helplessness subscale was 14.5 ( SD = 5.4). Helplessness fully mediated the relationship between pain vitality and symptoms of anxiety (BCa 95% CI (-0.073, -0.015)), depression (BCa 95% CI (-0.502, -0.212)), and stress (BCa 95% CI (-0.063, -0.027)). Conclusion Participants reported a high level of perceived inability to control one's disease. Helplessness fully mediated the relationship between pain and measures of anxiety, depression, and perceived stress among patients with SLE.

Incidence and outcome of lupus nephritis in French Polynesia .

Outcomes of systemic lupus erythematosus (SLE) and lupus nephritis (LN) are highly heterogeneous among some populations because of interactions between genetic, epigenetic, environmental, and socioeconomic factors. A better characterization of social and ethnic disparities in mixed populations may thus help to develop individualized treatment regimens. Retrospective observational study including all patients with LN diagnosed between January 1993 and January 2014 in the only Nephrology Department of French Polynesia. The annual incidence of SLE and LN in French Polynesia was 3.6 and 0.96 per 100,000, respectively. Among the 45 patients with biopsy-proven LN (pediatric onset, 26.7%), LN occurred during the first SLE flare-up in 68.8%. At presentation, median eGFR was 72mL/min/1.73m² (31-105), 32 patients had class-III/IV active glomerulonephritis (GN), and 10 had pure or mixed class-V GN. During the follow-up, 5 patients died (11.1%) and 2 reached end-stage renal disease (4.4%). Cumulative incidences of complete and partial renal responses were 31.1% and 40% at 12 months. Complete renal response (CR)<bold> </bold>was only predicted by renal presentation (lack of leukocyturia, low proteinuria). Among the 36 patients with renal response, 18 relapsed. Maintenance treatment (mycophenolate mofetil) and place of residence (Windward Islands as compared to remote islands) were the only factors that protected from relapse. Renal presentation was the main predictive factor for a renal response whereas geographical residence and maintenance-treatment regimen were predictive of LN relapses in patients from French Polynesia, an area characterized by a specific genetic background and including several isolated islands that have limited access to healthcare. .

Predictors and outcome of systemic lupus erythematosus (SLE) admission rates in a large teaching hospital in sub-Saharan Africa.

Although it was previously believed that systemic lupus erythematosus was uncommon among Africans, it has become increasingly apparent that the incidence is higher, and socioeconomic challenges such as physician shortages, poor medical facility access, and poor health literacy may worsen prognosis. This retrospective study examines characteristics and outcomes of hospitalized systemic lupus erythematosus patients over a two-year period and serves as a baseline for comparison for future studies to examine the outcomes with the provision of more dedicated care. There were 51 patient admissions over a two-year period, with a mean duration from start of illness to admission of approximately two years. Duration of admission ranged from one to 140 days with a mean period of 26.12 days (SD ± 26.6). There were 22 deaths (43.1% of admissions), which were mainly due to infections and renal complications. Factors associated with risk of death in regression analysis were: infections, fever, disease flare, musculoskeletal involvement, amenorrhea, depression, a clinical finding of hepatomegaly, and chest infection. Understanding the effect and outcome of systemic lupus erythematosus across different countries can elucidate the role of genetic, environmental, and other causative factors in the progression of the disease.

The Role of Patient-Reported Outcomes in Systemic Lupus Erythematosus

Purpose of review The use of patient-reported outcomes (PROs) is increasing in rheumatology and other chronic diseases, with growing evidence of its utility in complementing physical and biochemical assessments to guide management of complex conditions, such as systemic lupus erythematosus (SLE). This review describes currently utilized PROs and their use in SLE, and highlights areas of unmet need that require further attention. Recent findings Existing PRO instruments, both generic and SLE-specific, assess a variety of health-related quality of life (HRQoL) and, to a lesser extent, non-HRQoL domains that are frequently reported health issues in SLE patients – although there remain other important aspects that are not routinely assessed, including the ability of patients to participate in social roles and relationships. Summary PRO domains pertinent to SLE patients will continue to be identified and these areas of unmet needs will have to be addressed by novel and existing PRO instruments.

Pregnancy outcome of planning pregnancies in patients with SLE

Objectives: To investigate the pregnancy outcomes in systemic lupus erythematosus (SLE) patients with planning pregnancy.And to evaluate the value of fetal umbilical artery Doppler. Methods: A total of 130 SLE patients with planning pregnancy were prospectively recruited from January 2013 to January 2017 at the First Affiliated Hospital of Sun Yat-sen University. Results: Thirty eight (29.2%) patients had active lupus, 30 with mild activity, 5 with moderate activity and 3 with severe activity.Active disease in the first, second and third trimesters occurred in 6, 11 and 21 cases respectively.Lupus nephritis (76.3%) and hematological system involvement (39.5%) were the most common manifestation.Seven cases had pre-eclampsia during pregnancy.One or more adverse outcomes occurred in 40 patients, including 28 with premature, 12 with pregnancy loss, 9 with intrauterine growth restriction, and 8 with fetal distress.All of the pulsatility index, resistance index and S/D value of patients with adverse outcomes were higher than that of patients without adverse outcomes (P<0.05). Conclusions: In SLE patients with planning pregnancy, disease flares were infrequent, and outcomes were favorable. Fetal umbilical artery Doppler can be used as a noninvasive monitoring method for SLE patients at late pregnancy.

Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus

BackgroundLupus pathogenesis is closely associated with interferon gamma (IFN-γ), which plays a central role in innate and adaptive immunity. The aim of this study was to evaluate the ex vivo production of IFN-γ after stimulation of peripheral blood mononuclear cells with phytohemagglutinin (PHA) in patients with lupus, according to disease activity.MethodsThis study included 118 patients with lupus who had undergone IFN-γ-releasing assays (IGRAs) to screen for tuberculosis. Data on IFN-γ production in negative (nil) and positive (mitogen with PHA) controls were collected and analysed. The difference (mitogen minus nil) was used to calculate ex vivo IFN-γ production. Disease activity was evaluated using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K). Poor hospitalisation outcome was defined as in-hospital mortality or intensive care unit admission. Associations among disease activity, poor hospitalisation outcome, and ex vivo IFN-γ production were assessed.ResultsThe level of ex vivo IFN-γ production was significantly lower in patients with active systemic lupus erythematosus (SLE) (n = 64) than in those with inactive SLE (n = 54) (median 0.92 vs. 11.06 IU/mL, p < 0.001). Ex vivo IFN-γ production was correlated with the SLEDAI-2 K (r = − 0.587, p < 0.001). Results of multivariate logistic regression analysis showed that ex vivo IFN-γ production ≤ 7.19 IU/mL was an independent predictor for discriminating active and inactive lupus. In addition, patients with ex vivo IFN-γ production ≤ 0.40 IU/mL had more frequent poor hospitalisation outcomes than those with ex vivo IFN-γ production > 0.40 (40.0% vs. 9.3%, p = 0.001). The proportion of indeterminate IGRA results was higher in patients with active lupus than in those with inactive lupus (45.3% vs. 0.0%, p < 0.001) because of decreased ex vivo IFN-γ production.ConclusionsEx vivo IFN-γ production is a useful biomarker for assessing disease activity and predicting poor clinical outcomes of SLE.

Basophils contribute to pristane-induced Lupus-like nephritis model

Lupus nephritis (LN), one of the most severe outcomes of systemic lupus erythematosus (SLE), is initiated by glomerular deposition of immune-complexes leading to an inflammatory response and kidney failure. Autoantibodies to nuclear antigens and autoreactive B and T cells are central in SLE pathogenesis. Immune mechanisms amplifying this autoantibody production drive flares of the disease. We previously showed that basophils were contributing to LN development in a spontaneous lupus-like mouse model (constitutive Lyn−/− mice) and in SLE subjects through their activation and migration to secondary lymphoid organs (SLOs) where they amplify autoantibody production. In order to study the basophil-specific mechanisms by which these cells contribute to LN development, we needed to validate their involvement in a genetically independent SLE-like mouse model. Pristane, when injected to non-lupus-prone mouse strains, induces a LN-like disease. In this inducible model, basophils were activated and accumulated in SLOs to promote autoantibody production. Basophil depletion by two distinct approaches dampened LN-like disease, demonstrating their contribution to the pristane-induced LN model. These results enable further studies to decipher molecular mechanisms by which basophils contribute to lupus progression.

Malignancy in Pediatric-onset Systemic Lupus Erythematosus.

To determine cancer incidence in a large pediatric-onset systemic lupus erythematosus (SLE) population. Data were examined from 12 pediatric SLE registries in North America. Patients were linked to their regional cancer registries to detect cancers observed after cohort entry, defined as date first seen in the clinic. The expected number of malignancies was obtained by multiplying the person-years in the cohort (defined from cohort entry to end of followup) by the geographically matched age-, sex-, and calendar year-specific cancer rates. The standardized incidence ratio (SIR; ratio of cancers observed to expected) was generated, with 95% CI. A total of 1168 patients were identified from the registries. The mean age at cohort entry was 13 years (SD 3.3), and 83.7% of the subjects were female. The mean duration of followup was 7.6 years, resulting in a total observation period of 8839 years spanning the calendar period 1974-2009. During followup, fourteen invasive cancers occurred (1.6 cancers per 1000 person-yrs, SIR 4.13, 95% CI 2.26-6.93). Three of these were hematologic (all lymphomas), resulting in an SIR for hematologic cancers of 4.68 (95% CI 0.96-13.67). SIR were increased for both male and female patients, and across age groups. Although cancer remains a relatively rare outcome in pediatric-onset SLE, our data do suggest an increase in cancer for patients followed an average of 7.6 years. About one-fifth of the cancers were hematologic. Longer followup, and study of drug effects and disease activity, is warranted.

Comparison of Disease Characteristics, Organ Damage, and Survival in Patients with Juvenile-onset and Adult-onset Systemic Lupus Erythematosus in a Combined Cohort from 2 Tertiary Centers in Turkey

Age at onset has been shown to affect the clinical course and outcome of systemic lupus erythematosus (SLE). Herein, we aimed to define the differences in clinical characteristics, organ damage, and survival between patients with juvenile-onset (jSLE) and adult-onset SLE (aSLE). For the study, 719 patients (76.9%) with aSLE and 216 (23.1%) with jSLE were examined. Comparisons between the groups were made for demographic characteristics, clinical features, auto-antibody profiles, damage, and survival rates. These results were significantly more frequent in jSLE: photosensitivity, malar rash, oral ulcers, renal involvement, neuropsychiatric (NP) manifestations, and autoimmune hemolytic anemia (AIHA). Of the autoantibodies, a higher frequency of anti-dsDNA and anticardiolipin IgG and IgM were observed in the jSLE group. A significant proportion of patients with aSLE had anti-Sm positivity and pleuritis. The proportion of patients with jSLE who developed organ damage was comparable to that of patients with aSLE (53% vs 47%) and the mean damage scores were similar in both groups. Renal damage was significantly more frequent in jSLE while musculoskeletal and cardiovascular system damage and diabetes mellitus were more prominent in aSLE. Comparison of survival rates of the 2 groups did not reveal any significant differences. We report a higher frequency in the jSLE group of renal involvement, cutaneous symptoms, oral ulcers, NP manifestations, AIHA, and anti-dsDNA positivity. A significant proportion of patients in the jSLE group had damage, most prominently in the renal domain. Our findings might support different genetic/environmental backgrounds for these 2 subgroups.

Outcomes in Children Born to Women with Rheumatic Diseases.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are the most prevalent autoimmune rheumatic diseases, predominantly occurring in women during childbearing years. Research has focused on assessing the risk of immediate complications during SLE and RA pregnancies, with studies documenting a higher risk of adverse obstetric outcomes, such as preterm births and infants small for gestational age. Until recently, little was known regarding the long-term health of children born to affected women. We present a review of the current evidence regarding the risk of adverse health outcomes in SLE and RA offspring, and potential mechanisms involved in their pathogenesis.

Failure of a systemic lupus erythematosus response index developed from clinical trial data: lessons examined and learned.

Background Our primary goal was to create an outcome change score index similar to a standard rheumatoid arthritis (RA) model utilizing real-world data in systemic lupus erythematosus (SLE) patients that occurred during their phase 3 trials with a Food and Drug Administration-approved drug. Methods We utilized raw data from trials of belimumab for the treatment of SLE. Data were split 80/20 into training/validation sets. Index variables present in a majority of patients and with face validity were selected. Variables were scored for each patient as percentage improvement from baseline after one year. The percentage of placebo- and drug-treated patients considered improved after the application of various criteria was ascertained. Logistic regression was employed to determine the ability of the new index to predict treatment assignment. Results A total of 1693 subjects had data for analyses. Eight variables were chosen: arthritis, rash, physician global assessment, fatigue, anti-double stranded DNA antibodies, C3, C4 and C-reactive protein. In the training dataset, ≥20% improvement in ≥4 of eight variables produced the largest difference between placebo- and drug-treated patients (22.1%) with an acceptable rate of improved placebo-treated patients (25%). This resulted in an odds ratio for belimumab (10 mg/kg) vs placebo of 2.7 (95% CI: 2.0-3.6; p < 0.001). However, in the validate dataset the odds ratio was not significant at 1.3 (95% CI: 0.8-2.2; p = 0.863). Conclusions The index created from training data did not achieve statistical significance when tested in the validation set. We have speculated why this happened. Is the lack of success of therapeutics for SLE caused by ineffective medications, study design and outcome instruments that fail to inform us, or is the heterogeneity of the disease too daunting? The lessons learned here can help direct future endeavors intended to improve SLE outcome instruments.

Does treatment with vitamin D supplementation improve patient outcomes in systemic lupus erythematosus?

Does treatment with vitamin D supplementation improve patient outcomes in systemic lupus erythematosus?