Lupus Medications Research Articles

A rare presentation of hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening multisystem disorder characterized by immune system dysregulation, hypercytokinemia, and hyperinflammation. This excessive inflammatory response is triggered by the uncontrolled activation of macrophages and T-lymphocytes, leading to widespread tissue damage. Systemic Lupus Erythematosus (SLE), a chronic autoimmune disease, involves the immune system’s loss of tolerance to nuclear self-antigens, resulting in the production of damaging autoantibodies that can affect multiple organ systems. In this case report, we describe a rare presentation of HLH in a young female patient with a known history of SLE. She initially presented with acute respiratory distress syndrome (ARDS), an uncommon but serious manifestation of HLH. The patient, who had discontinued her lupus medications two years prior, developed high-grade fever, generalized myalgia, and progressive respiratory distress, necessitating mechanical ventilation. Her condition rapidly deteriorated despite aggressive supportive measures, with laboratory investigations revealing pancytopenia, hyperferritinemia, and elevated inflammatory markers, ultimately leading to the diagnosis of HLH. This case highlights the diagnostic challenges and the importance of early recognition of HLH in patients with underlying autoimmune conditions, such as SLE, who present with severe systemic inflammation and respiratory failure. Timely intervention is crucial, as delay in diagnosis and treatment can result in fatal outcomes. The case underscores the need for heightened clinical suspicion of HLH in similar presentations, as well as a multidisciplinary approach to management to improve patient prognosis.

Using linked electronic medical record-pharmacy data to examine lupus medication adherence: A retrospective cohort study.

Medication nonadherence is common in systemic lupus erythematosus (SLE) and associated with morbidity and mortality. We explored the reliability of pharmacy data within the electronic medical record (EMR) to examine factors associated with nonadherence to SLE medications. We included patients with SLE who were prescribed ≥1 SLE medication for ≥90 days. We compared two datasets of pharmacy fill data, one within the EMR and another from the vendor who obtained this information from pharmacies and prescription benefit managers. Adherence was defined by medication possession ratio (MPR) ≥80%. In addition to MPR for each SLE medication, we evaluated the weighted-average MPR and the proportion of patients adherent to ≥1 SLE medication and to all SLE medications. We used logistic regression to examine factors associated with adherence. Among 181 patients (median age 36, 96% female, 58% Black), 98% were prescribed hydroxychloroquine, 34% azathioprine, 33% mycophenolate, 18% methotrexate, and 7% belimumab. Among 1276 pharmacy records, 74% overlapped between linked EMR-pharmacy data and data obtained directly from the vendor. Only 9% were available from the vendor but not through linked EMR-pharmacy data. The weighted-average MPR was 57%; 45% were adherent to hydroxychloroquine, 46% to ≥1 SLE medication, and 32% to all SLE medications. Older age was associated with adherence in univariable and multivariable analyses. Our study showed that obtaining linked EMR-pharmacy data is feasible with minimal missing data and can be leveraged in future adherence research. Younger patients were more likely to be nonadherent and may benefit from targeted intervention.

Association of systemic lupus erythematosus standard of care immunosuppressants with glucocorticoid use and disease outcomes: a multicentre cohort study

BackgroundThis study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data.MethodsThe Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes.ResultsAmong 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23–82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53–0.86], p = 0.001) and methotrexate (OR 0.68 [0.47–0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64–0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual.ConclusionsThis study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

An update on clinical trials for cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) comprises dermatologic manifestations that may occur independently or with systemic lupus erythematosus (SLE). Despite advancements in refining CLE classification, establishing precise subtype criteria remains challenging due to overlapping presentations and difficulty in distinguishing morphology. Current treatments encompass preventive measures, topical therapies, and systemic approaches. Hydroxychloroquine and glucocorticoids are the sole US Food and Drug Administration (FDA)-approved medications for CLE, with numerous off-label treatments available. However, these treatments are often not covered by insurance, imposing a significant financial burden on patients. The exclusion of most CLE patients, particularly those without concurrent SLE, from trials designed for SLE has resulted in a lack of targeted treatments for CLE. To develop effective CLE treatments, validated outcome measures for tracking patient responsiveness are essential. The Cutaneous Lupus Erythematosus Disease Area and Severity Index is widely utilized for its reliability, validity, and ability to differentiate between skin activity and damage. In contrast, the FDA mandates the use of the Investigator's Global Assessment, a five-point Likert scale related to lesion characteristics, for skin-related therapeutic trials. It requires the disease to resolve or almost completely resolve to demonstrate improvement, which can be difficult when there is residual erythema or incomplete clearance that is meaningfully improved from a patient perspective. Various classes of skin lupus medications target diverse pathways, allowing tailored treatment based on the patient's lupus inflammatory profile, resulting in improved outcomes. Promising targeted therapeutic drugs include anifrolumab (anti-type 1 interferon), deucravacitinib (allosteric tyrosine kinase 2 inhibitor), litifilimab (plasmacytoid dendritic cell-directed therapy), iberdomide (cereblon-targeting ligand), and belimumab (B-cell directed therapy). Despite the significant impact of CLE on quality of life, therapeutic options remain inadequate. While promising treatments for cutaneous lupus are emerging, it is crucial to underscore the urgency for skin-focused treatment outcomes and the implementation of validated measures to assess therapeutic effectiveness in clinical trials.

Health-related quality of life, remission and low lupus disease activity state in patients with systemic lupus erythematosus.

To measure the association between SLE remission and scores of patients-reported outcome (PRO) measures. We performed a prospective cohort study of SLE patients with a 2-year follow-up, using Lupus Patient-Reported Outcome (LupusPRO), Lupus Quality of Life (LupusQoL), Systemic Lupus Erythematosus Quality of Life (SLEQOL) and 36-item Short Form (SF-36) questionnaires. Remission was defined as remission off treatment (ROFT) and remission on treatment (RONT) according to the definitions of remission in SLE consensus. Mixed models accounting for repeated measures were used to compare groups as follow: ROFT and RONT vs no remission and lupus low disease activity state (LLDAS) vs no LLDAS. A total of 1478 medical visits and 2547 PRO questionnaires were collected during the follow-up from the 336 recruited patients. A between-group difference in PRO scores reaching at least 5 points on a 0-100 scale was obtained in the following domains: lupus symptoms (LLDAS: +5 points on the 0-100 scale, RONT: +9, ROFT: +5), lupus medication (LLDAS: +5, RONT: +8, ROFT: +9), pain vitality (LLDAS: +6, RONT: +9, ROFT: +6) of LupusPRO; role emotional (LLDAS: +5, RONT: +8), role physical (RONT: +7 and ROFT: +7), bodily pain (RONT: +6), mental health (RONT: +5) and social functioning (RONT: +6) of SF-36. In contrast, a between-group difference reaching at least 5 points was not achieved for any of the LupusQoL and SLEQOL domains. RONT, ROFT and LLDAS were associated with significant and clinically relevant higher QoL in most PRO domains of the LupusPRO (disease specific) and SF-36 (generic) questionnaires, but not with LupusQoL and SLEQOL disease-specific questionnaires.

Association of Hurried Communication and Low Patient Self-Efficacy With Persistent Nonadherence to Lupus Medications.

Medication nonadherence is common among patients with systemic lupus erythematosus (SLE), and adherence often fluctuates with time. Underrepresented racial minorities have disproportionately lower rates of medication adherence and more severe SLE manifestations. We aimed to identify modifiable factors associated with persistent medication nonadherence. Patients taking ≥1 SLE medication were enrolled. Adherence data were obtained at baseline and at follow-up roughly 1 year later using both self-reported adherence and pharmacy refill data. Covariates included patient-provider interaction, patient self-efficacy, and clinical factors. We compared characteristics of patients in 3 groups using the Kruskal-Wallis H test: persistent nonadherence (low adherence by self-report and refill rates at both time points); persistent adherence (high adherence by self-report and refill rates at both time points); and inconsistent adherence (the remainder). Among 77 patients (median age 44 years, 53% Black, 96% female), 48% had persistent nonadherence. Compared with other adherence groups, patients with persistent nonadherence were younger and more likely to be Black, have lower income, take ≥2 SLE medications, have higher SLE-related damage at baseline, and have higher physician global assessment of disease activity at follow-up. Persistently nonadherent patients also rated more hurried communication with providers (particularly fast speech and difficult word choice) and had lower self-efficacy in managing medications. Potential avenues to improve medication adherence include optimizing patient-provider communication, specifically avoiding difficult vocabulary and fast speech, and enhancing patient self-efficacy, particularly among younger Black patients with lower income who are at higher risk for nonadherence.

Reconciling Between Medication Orders and Medication Fills for Lupus in Pregnancy.

Most studies consider either medications ordered or filled, but not both. Medication underuse based on filling data cannot necessarily be ascribed to patient nonadherence. Using both data sources, we quantified primary medication adherence in a cohort of prevalent systemic lupus erythematosus (SLE) pregnancies. We identified 419 pregnancies in Kaiser Permanente Northern California in patients with prevalent SLE from 2011 to 2020. We calculated the number of physician-initiated orders or pharmacy-initiated reorders during pregnancy and a comparable 9-month window the year before (prepregnancy) and the proportion of orders ever filled and filled within 30 days for hydroxychloroquine (HCQ), azathioprine, and corticosteroids. For pregnancies without an order or reorder, we identified the proportion with previous prescription fills overlapping into the respective study period. New orders for lupus medications were usually filled. HCQ was prescribed most often (45.8% pregnancies) and usually filled (89.7% in prepregnancy, 93.2% during pregnancy). The majority filled within 30 days (80.5% prepregnancy, 83.3% pregnancy). Some pregnancies without new HCQ orders had continuous refills from prior orders; 53% of 2011-2015 pregnancies either had a new order or fill coverage from a previous period, compared to 63.2% of pregnancies delivering in 2016-2019. Corticosteroid fill frequencies were 90.6% in prepregnancy and 83.6% during pregnancy. Fewer patients used azathioprine; however, most new orders were filled (94.3% prepregnancy, 91.7% pregnancy). For azathioprine and corticosteroids, fill rates were modestly higher in prepregnancy compared to pregnancy. We observed that patients have high adherence to filling new orders for lupus medications, such as HCQ and azathioprine, in pregnancy.

Trust in the attending rheumatologist, health-related hope and medication adherence among Japanese systemic lupus erythematosus patients.

Poor medication adherence among patients with SLE is a critical problem associated with adverse outcomes. This study examined the relationship between trust in one's physician and goal-oriented thinking, hope and medication adherence among Japanese patients with SLE who were ethnically matched to their physicians. This cross-sectional study was conducted in the rheumatology outpatient clinics at five academic centres. Patients with SLE who were prescribed oral medications were included. The main exposures were trust in one's physician measured via the 5-item Japanese version of the Wake Forest Physician Trust Scale and the 18-item Health-related Hope Scale, with each score ranging from 0 to 100 points. Medication adherence was measured using the 12-item Medication Adherence Scale with scores ranging from 5 to 60 points. A general linear model was created after adjusting for demographics, socioeconomic status, disease activity, disease duration, basic health literacy, depression, medication variables, experiencing adverse effects and concerns regarding lupus medications. Altogether, 373 patients with SLE were included. The mean age of the patients was 46.4 years; among them, 329 (88.2%) were women. Both trust in one's physician (per 10-point increase: 0.86, 95% CI 0.49, 1.22) and the Health-related Hope score (per 10-point increase: 0.66, 95% CI 0.35, 0.97) were associated with better medication adherence. This study demonstrated that patients' health-related hope and trust in their rheumatologist were both associated with better medication adherence in SLE.

Prescribing Patterns of Hydroxychloroquine and Glucocorticoids Among Lupus Patients After New-Onset End-Stage Renal Disease.

Optimal strategies for managing lupus medications after end-stage renal disease (ESRD) have not been addressed. The objective was to identify the current US-wide prescribing patterns of hydroxychloroquine (HCQ) and oral glucocorticoids (GS) among systemic lupus erythematosus (SLE) patients with incident ESRD enrolled in the US Renal Data System (USRDS) registry. We identified incident ESRD patients age ≥18 years with SLE as a primary cause of ESRD between January 2006 and June 2013. Patients who were started on dialysis at ESRD onset and enrolled in Medicare Part D within 93 days as required by Medicare were included. Among the 2,654 new-onset ESRD patients with Part D, the median duration of follow-up was 761 days (interquartile range [IQR] 374-1,375). At baseline, 1,076 patients (41%) were not receiving HCQ or GS, 220 (8%) were prescribed HCQ alone, 509 (19%) were prescribed both HCQ and GS, and 849 (32%) were prescribed GS alone. Of the 1,983 patients who either never received or discontinued HCQ after ESRD onset, 667 (34%) continued GS to the end of the follow-up period. The median GS dose was lower for patients taking HCQ (14 mg [IQR 9-21]) compared to patients who were never prescribed HCQ (15 mg [IQR 9-27]) or patients who discontinued HCQ after ESRD (17 mg [IQR 10-27]; P=0.001). Approximately one-third of patients with lupus nephritis and new-onset ESRD received GS monotherapy at high doses. As GS-related complications contribute to hospitalizations and deaths in SLE ESRD, changing these prescribing practices may improve morbidity and mortality outcomes.

HSD46 A Trend Analysis of Lupus Erythematosus Patients' Physician Office Visits and Medications Prescribed

This study aims to identify temporal trends in physician office visits for lupus patients, describe lupus patient visit characteristics and medications prescribed for treatment of lupus and assess comorbidities associated with lupus patients.

Hydroxychloroquine and immunosuppressant adherence patterns and their association with subsequent hospitalization rates among children with systemic lupus erythematosus

ObjectivesUsing a representative sample of children with systemic lupus erythematosus (SLE) in the United States, we characterized prescription claim-based hydroxychloroquine and immunosuppressant adherence estimates and evaluated their concurrent and predictive validity. MethodsWe identified children ages 5–18 with SLE in the Truven Health MarketScan® Commercial and Medicaid claims databases (2013–2018). Among new users of hydroxychloroquine and immunosuppressant medications, we calculated proportion of days covered (PDC) over 365 days to estimate adherence by user group (mycophenolate, azathioprine, methotrexate, and any immunosuppressant use). Agreement between adherence estimates was evaluated with intraclass correlation coefficients (ICC) and kappa statistics. Separate negative binomial regression models were used to estimate associations between (a) hydroxychloroquine, (b) immunosuppressant, or (c) concurrent immunosuppressant/hydroxychloroquine non-adherence and subsequent hospitalizations, adjusted for baseline demographics, disease severity, and healthcare utilization. ResultsAmong 423 new hydroxychloroquine/immunosuppressant users, 63% were Medicaid recipients. Sufficient adherence (PDC≥80%) ranged from 33 to 45% for immunosuppressants vs. 51–52% for hydroxychloroquine. Agreement between hydroxychloroquine and immunosuppressant adherence was modest overall, but better for mycophenolate (ICC 0.55) than methotrexate (0.27). Hydroxychloroquine non-adherence was associated with a 2.9-fold higher incidence of subsequent hospitalizations (95% CI [1.2–7.1]), whereas immunosuppressant and concurrent non-adherence were associated with 5.9 [2.4–14.6] and 5.6-fold [2.0–15.5] increased incidence, respectively. Use of concurrent adherence improved upon estimation of hospitalization risk compared to hydroxychloroquine adherence, but not immunosuppressant adherence alone. ConclusionsHydroxychloroquine adherence is an imperfect proxy for adherence to other lupus medications among children with SLE, and therefore assessing immunosuppressant adherence concurrently adds value to hydroxychloroquine adherence assessments. Prescription claims-based immunosuppressant adherence measures are predictive of acute care utilization and may inform population management strategies.

Cardiovascular disease in systemic lupus erythematosus.

There is a well-known increased risk for cardiovascular disease that contributes to morbidity and mortality in systemic lupus erythematosus (SLE). Major adverse cardiovascular events and subclinical atherosclerosis are both increased in this patient population. While traditional cardiac risk factors do contribute to the increased risk that is seen, lupus disease-related factors, medications, and genetic factors also impact the overall risk. SLE-specific inflammation, including oxidized lipids, cytokines, and altered immune cell subtypes all are likely to play a role in the pathogenesis of atherosclerotic plaques. Research is ongoing to identify biomarkers that can help clinicians to predict which SLE patients are at the greatest risk for cardiovascular disease (CVD). While SLE-specific treatment regimens for the prevention of cardiovascular events have not been identified, current strategies include minimization of traditional cardiac risk factors and lowering of overall lupus disease activity.

Dialysis Outcomes for Children With Lupus Nephritis Compared to Children With Other Forms of Nephritis: A Retrospective Cohort Study

Children with lupus nephritis (LN) are at high risk of developing kidney failure requiring initiation of kidney replacement therapy. This study compared outcomes among children with LN on dialysis with children with non-lupus glomerular disease and investigated risk factors for adverse outcomes among children with LN on dialysis. Retrospective cohort study. Children and adolescents aged 6-20 years with LN (n= 231) and non-lupus glomerular disease (n= 1,726) who initiated maintenance dialysis 1991-2018 and were enrolled in the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry. Lupus nephritis. Hospitalization, mortality, and time to transplant. Contingency tables were used to compare hospitalizations, and multivariable cause-specific hazards models were used to compare rates of death and transplantation in children with LN compared with those with non-lupus glomerular disease. Using data from children with LN, multivariable logistic regression models were fit to evaluate the risk factors for hospitalization, and multivariable Cox regression models were fit to evaluate factors associated with kidney transplantation. Children with LN were more likely to be hospitalized in the first year after dialysis initiation (63.3% vs 48.6%, P< 0.001) and were less likely to receive a kidney transplant in the first 3 years after dialysis initiation (year 0-1: adjusted hazard ratio [AHR], 0.36 [95% CI, 0.23-0.57], P< 0.001; year 1-3: AHR, 0.73 [95% CI, 0.54-0.98], P= 0.04). Anemia was associated with hospitalization after dialysis initiation (adjusted OR, 4.44 [95% CI, 1.44-13.66], P= 0.01). Non-White race was associated with a lower rate of kidney transplantation (AHR, 0.47 [95% CI, 0.27-0.82], P= 0.01). LN was not associated with death while on dialysis (AHR, 1.21 [95% CI, 0.47-3.11], P= 0.7). The NAPRTCS registry does not collect information on lupus disease activity or medication doses and has limited data on medication use. Children and adolescents with LN on dialysis are at higher risk for adverse outcomes including hospitalization and lower rates of kidney transplantation compared with children with non-lupus glomerular disease receiving maintenance dialysis.

OP0132 EFFECT OF IBERDOMIDE ON CUTANEOUS MANIFESTATIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS OF A 24-WEEK, PLACEBO-CONTROLLED, PHASE 2 STUDY

OP0132 EFFECT OF IBERDOMIDE ON CUTANEOUS MANIFESTATIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS OF A 24-WEEK, PLACEBO-CONTROLLED, PHASE 2 STUDY

Hindi LupusPRO: cross cultural validation of disease specific patient reported outcome measure of lupus.

LupusPRO is a SLE specific patient reported outcomes measure developed and validated in the USA. This study aimed to validate the Hindi version of LupusPRO in systemic lupus erythematosus (SLE) patients in India. Disease activity and damage were assessed using SELENA-SLEDAI and SLICC/ACR damage Index respectively. Demographic and clinical features were recorded. The Hindi Version of LupusPRO and 36-Item Short Form Health Survey (SF-36) were administered for assessment of quality of life. Depression, anxiety and fatigue were assessed using Patient Health Questionnaire 9 (PHQ9), Generalized Anxiety Disorder 7 (GAD7) and Fatigue Severity Scale (FSS) respectively. Internal consistency reliability, test-retest reliability, convergent and discriminant validity (against corresponding domains of the SF-36, fatigue, depression and anxiety), criterion validity (against disease activity and damage) and known group validity were tested. A total of 144 (140 females) patients with SLE with a mean age of 32.48 ± 7.26 years participated in the study. The median (interquartile range) SELENA SLEDAI was 2 (5.5). The internal consistency reliability of the LupusPRO domains was >0.7 for most domains (except for lupus symptoms, lupus medication, procreation and social support).We noted good convergent validity of LupusPRO domains with corresponding domains of SF-36, pain vitality with fatigue (FSS) and emotional health domain with depression (PHQ9) and anxiety (GAD7). Criterion validity of lupus symptoms with disease activity was observed. Known group validity of the LupusPRO domains with patient reported health status was observed. Confirmatory factor analysis showed a good fit. The Hindi LupusPRO has fair psychometric properties among Indian patients with SLE.

All-cause hospitalizations in systemic lupus erythematosus from a single medical center in Israel.

Clinical features of systemic lupus erythematosus (SLE) have been described from different geographical regions in the world. The aim of this study was to obtain local and contemporary data on all-cause hospitalizations of SLE patients in an Israeli Medical Center. This is a retrospective observational single-center study. Revision of medical records of hospitalized lupus patients during 5-year period (January 2012-December 2016) was performed. A total of 61 lupus patients and 138 hospitalizations were identified. Female-to-male ratio was 9:1. Average age was 42.5years. Average disease duration was 14.58years. Mean SLICC/ACR damage index was 0.75. The majority of patients were treated with lupus medications (47, 77%). The most common lupus medications were hydroxychloroquine (40, 65.5%), prednisone (25, 40.9%), and azathioprine (9, 14.75%). The most common reasons for hospitalization were disease flare (28, 20.3%), pregnancy and labor (26, 18.9%), and infection (19, 13.8%). The average length of hospitalization for all patients was 6.65days. No fetal morbidity was recorded, and there was one event of maternal morbidity. There were no cases of acute coronary events. There were six ICU admissions (4.35%). Two admissions (1.45%) were complicated by hospital-acquired infection. Three patients died (2.17%) during hospital stay. This survey from a single Israeli medical center revealed low rates of pregnancy complications, coronary events, and nosocomial infections in hospitalized lupus patients. Further studies are required to determine whether these findings reflect local disease expression or it may remark global trend of decrease in lupus complications.

The 2018 pipeline of targeted therapies under clinical development for Systemic Lupus Erythematosus: a systematic review of trials.

Currently, Systemic Lupus Erythematosus (SLE) therapies range from antimalarials to glucocorticoids, in addition to immunosupressive agents or biologics such as rituximab or belimumab, when needed. Several unmet needs remain in the treatment SLE and more targeted drugs with improved safety profiles are expected. Based on recent advances in the understanding of the complex pathogenesis of SLE, several targeted treatments are currently assessed in clinical trials. In this study, we performed a systematic review of all targeted therapies under clinical development in SLE in 17 online registries of clinical trials. The search yielded a total of 1140 trials, from which we identified 74 targeted therapies for SLE. Those treatments target inflammatory cytokines, chemokines, or their receptors (n = 17), B cells or plasma cells (n = 17), intracellular signalling pathways (n = 10), T/B cells costimulation molecules (n = 8), interferons (n = 7), plasmacytoid dendritic cells (pDC) (n = 3), as well as various other targets (n = 12). Not all these candidate drugs will reach phase III, but the broad spectrum of drugs being investigated may satisfy the urgent need for improved lupus medications. The identification of biomarkers that would allow adequate prediction of response-to-therapy remains high, but when solved will allow a more rationale selection of the optimal pharmacological agent at the patient level.

Longitudinal analysis of varicella-zoster virus-specific antibodies in systemic lupus erythematosus: No association with subclinical viral reactivations or lupus disease activity.

Systemic lupus erythematosus (SLE) patients are at high risk of herpes zoster. Previously, we found increased immunoglobulin (Ig)G levels against varicella-zoster virus (VZV) in SLE patients compared to controls, while antibody levels against diphtheria and cellular immunity to VZV were decreased. We aimed to test our hypothesis that increased VZV-IgG levels in SLE result from subclinical VZV reactivations, caused by stress because of lupus disease activity or immunosuppressive drug use.MethodsAntibody levels to VZV (IgG, IgA, IgM), total IgG and VZV-DNA were longitudinally determined in the serum of 34 SLE patients, using enzyme-linked immunosorbent assay and polymerase chain reaction. Clinical data were retrieved from medical records. Reactivation of VZV was defined as an at least fivefold rise in VZV-IgG or presence of VZV-IgM or VZV-DNA. Generalized estimating equations (GEE) were used to longitudinally analyse associations between antibody levels, lupus disease activity and medication use. Systemic Lupus Erythematosus Disease Activity Index, anti-double-stranded DNA and complement levels were used as indicators of lupus disease activity.ResultsA VZV reactivation was determined in 11 patients (33%). In at least five of them, herpes zoster was clinically overt. No association between SLE disease activity or medication use and VZV-specific antibody levels was found. There was a weak association between total IgG and VZV-IgG.ConclusionsOur results indicate that increased VZV-IgG levels in SLE do not result from frequent subclinical VZV reactivations, and are not associated with lupus disease activity. Increased VZV-IgG can only partially be explained by hypergammaglobulinaemia.

A Case of Pneumatosis Intestinalis Caused by Systemic Lupus Erythematous

Introduction: Pneumatosis intestinalis (PI) is a radiographic finding with wide spectrum of presentation, ranging from asymptomatic to perforation and death. There are more than 60 known causes of PI, but systemic lupus erythematous is a rare cause, and infrequently described. Case 42 year old woman was admitted with non-bloody diarrhea and left upper quadrant abdominal cramps for one week. She has a history of GERD (status post fundoplication x3), chronic constipation due to pelvic floor dysfunction, SLE with autonomic instability, resulting in hypotension, syncope, and bradycardia requiring pacemaker placement. Her symptoms occurred in the setting of discontinuing her lupus medications (belimumab and leflunomide), tapering her prednisone, and holding IVIG to repeat testing for autonomic dysfunction, as she had worsening episodes of hypotension and bradycardia in Fall 2016, requiring pacemaker placement. She had a similar presentation in 2015, when she was found to have PI in the splenic flexure. Infectious work up was negative at that time, and symptoms did not improve with a week of IV antibiotics. It then resolved with prednisone taper for presumed SLE exacerbation, resulting in PI. CT abdomen this time showed increased prominence of PI at the splenic flexure, a watershed area. She was placed on bowel rest, given high flow oxygen, and started on metronidazole, but remained symptomatic with nausea, bloating and diarrhea. Colonoscopy showed melanosis coli without evidence of colitis or bowel perforation. Patient then improved with a higher dose of prednisone. Discussion SLE is a rare cause of PI, but could contribute to it through several different mechanisms. A mechanism that was proposed by previous case report was SLE causing enteric vasculitis. Antiphospholipid antibodies and/or lupus anticoagulant may affect the gut mucosa resulting in ischemia, although this patient did not have these antibodies. The patient's autonomic dysfunction may have resulted in hypotensive episodes that could damage the watershed area.

Mapping Perceptions of Lupus Medication Decision-Making Facilitators: The Importance of Patient Context.

Numerous factors can impede or facilitate patients' medication decision-making and adherence to physicians' recommendations. Little is known about how patients and physicians jointly view issues that affect the decision-making process. Our objective was to derive an empirical framework of patient-identified facilitators to lupus medication decision-making from key stakeholders (including 15 physicians, 5 patients/patient advocates, and 8 medical professionals) using a patient-centered cognitive mapping approach. We used nominal group patient panels to identify facilitators to lupus treatment decision-making. Stakeholders independently sorted the identified facilitators (n = 98) based on their similarities and rated the importance of each facilitator in patient decision-making. Data were analyzed using multidimensional scaling and hierarchical cluster analysis. A cognitive map was derived that represents an empirical framework of facilitators for lupus treatment decisions from multiple stakeholders' perspectives. The facilitator clusters were 1) hope for a normal/healthy life, 2) understand benefits and effectiveness of taking medications, 3) desire to minimize side effects, 4) medication-related data, 5) medication effectiveness for "me," 6) family focus, 7) confidence in physician, 8) medication research, 9) reassurance about medication, and 10) medication economics. Consideration of how different stakeholders perceive the relative importance of lupus medication decision-making clusters is an important step toward improving patient-physician communication and effective shared decision-making. The empirically derived framework of medication decision-making facilitators can be used as a guide to develop a lupus decision aid that focuses on improving physician-patient communication.