Subcutaneous immunoglobulin for patients with idiopathic inflammatory myopathies: a real-world single centre experience.

OBJECTIVES: Idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases characterized by skeletal muscle inflammation associated with cutaneous, pulmonary, and/or other visceral organ involvement. Intravenous immunoglobulin (IVIG) has been recommended as an adjunct therapy for IIM patients refractory to conventional therapy. However, IVIG has high resource needs and increased risk of adverse reactions. Subcutaneous immunoglobulin (SCIG) therapy has been used as an alternative to IVIG in primary immunodeficiencies and neuroinflammatory disorders. We assessed the satisfaction, patient preference and effectiveness in IIM patients transitioned from IVIG to SCIG. METHODS: We retrospectively reviewed consecutive 20 patients with IIM who were transitioned from IVIG to SCIG therapy for >12 months. Patient preference between IVIG vs SCIG was surveyed using a questionnaire previously used in studies with neuroinflammatory conditions. In addition, disease flares, changes in immunosuppression, cumulative prednisone doses and global disease activity were evaluated using the Myositis Intention to Treat Index (MITAX) 12-months prior to- and post-SCIG initiation. RESULTS: Most patients (78.9%) preferred SCIG over IVIG and preferred home-based therapies to hospital-based therapies. There was no significant difference in global disease activity (MITAX 3.31 vs 3.02) nor in cumulative steroid doses 12-months prior to- or post-SCIG initiation. Three patients experienced disease flares, 5 escalated in immunosuppression, while 4 patients deescalated in immunosuppressive medications. CONCLUSIONS: SCIG is preferred by most patients over IVIG without a substantial increased disease activity or need for additional corticosteroids. Future cost effectiveness studies may provide an additional rationale for utilizing SCIG over IVIG for maintenance therapy for IIM.

Reduction in Racial and Ethnic Disparity in Survival Following Liver Transplant for Hepatocellular Carcinoma in the Direct-acting Antiviral Era.

BACKGROUND & AIMS: Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct-acting antiviral (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for candidates with HCC. METHODS: Using the United Network for Organ Sharing registry, we identified patients with HCC who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into 2 era-based cohorts: the pre-DAA era (LT between 2009 and 2011) and DAA era (LT between 2015 and 2017, with follow-up through 2020). Kaplan-Meier and Cox proportional hazards analyses were used to compare post-LT survival, stratified by era and race and ethnicity. RESULTS: Annual wait list additions for HCV-related HCC decreased significantly in White and Hispanic patients during the DAA era, with no change (P = .14) in Black patients. Black patients had lower 3-year survival than White patients in the pre-DAA era (70.6% vs 80.1%, respectively; P < .001) but comparable survival in the DAA era (82.1% vs 85.5%, respectively; P = .16). 0n multivariable analysis, Black patients in the pre-DAA era had a 53% higher risk (adjusted hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.28-1.84), for mortality than White patients, but mortality was comparable in the DAA era (adjusted HR, 1.23; 95% CI, 0.99-1.52). In a stratified analysis in Black patients, HCV-related HCC carried more than a 2-fold higher risk of mortality in the pre-DAA era (adjusted HR, 2.86; 95% CI, 1.50-5.43), which was reduced in the DAA era (adjusted HR, 1.34; 95% CI, 0.78-2.30). CONCLUSIONS: With the availability of DAA therapy, racial disparities in post-LT survival have improved.

Is Liver Transplant Justified at Any MELD Score?

BACKGROUND: Assessing the survival benefit of transplantation in patients with end-stage liver disease is critical in guiding the decision-making process for liver allocation. Previous studies established increased mortality risk for those transplanted below Model for End-Stage Liver Disease (MELD) 18 compared with candidates who remained on the waitlist; however, improved outcomes of liver transplantation and a changing landscape in the donor supply warrant re-evaluation of this idea. METHODS: Using the United Network for Organ Sharing database, we analyzed 160 290 candidates who were waitlisted for liver transplantation within MELD cohorts. We compared patients who were transplanted in a MELD cohort with those listed but not transplanted in that listed MELD cohort with an intent-to-treat analysis. RESULTS: Those transplanted at a MELD between 6 and 11 showed a 31% reduction in adjusted mortality (HR = 0.69 [95% confidence interval [CI], 0.66-0.75]; P < 0.001) compared with the intent-to-treat cohort in a Cox multivariate regression. This mortality benefit increased to a 37% adjusted reduction for those transplanted at MELD between 12 and 14 (HR = 0.63 [95% CI, 0.60-0.66]; P < 0.001) and a 46% adjusted reduction for those transplanted at a MELD between 15 and 17 (HR = 0.54 [95% CI, 0.52-0.57]; P < 0.001), effects that remained in sensitivity analyses excluding patients with hepatocellular carcinoma, encephalopathy, ascites, and variceal bleeds. A multivariate analysis of patients transplanted at MELD < 18 found younger age and cold ischemia time were protective, whereas older age, lower functional status, and socioeconomic factors increased mortality risk. CONCLUSIONS: These findings challenge the current practice of deferring liver transplants below a particular MELD score by demonstrating survival benefits for most transplant patients at the lowest MELD scores and providing insight into who benefits within these subgroups.

Measuring the Impact of MyLupusGuide in Canada: Results of a Randomized Controlled Study.

OBJECTIVE: This study was undertaken to assess the effects of a web-based program, MyLupusGuide, developed to facilitate self-management in systemic lupus erythematosus (SLE). METHODS: In this randomized controlled online study, participants received either immediate access to the MyLupusGuide site or delayed access starting on month 3. The primary outcome was the patient activation measure (PAM) score. Secondary outcomes included measurements of health status, self-efficacy, coping, perceived patient-physician relationship, and medication adherence. Outcomes were measured at the baseline visit and at the 3-month and 6-month follow-up visits. We used linear mixed modeling to compare PAM scores between the 2 groups at months 3 and 6. RESULTS: There were 541 participants included in this study. The mean ± SE age was 50 ± 14 years; 93% were female and 74% were White. The mean ± SE disease duration was 17 ± 12 years, and 56% visited MyLupusGuide at least once. The baseline mean ± SE PAM score was 61.2 ± 13, with 36% scoring low for perceived self-management skills. After 3 months of exposure to MyLupusGuide, there were no differences in terms of PAM scores between groups. In exploratory analyses, we found significant improvement in PAM scores in those who had low PAM scores at baseline and in male individuals. We observed significant improvements in self-efficacy before and after access to MyLupusGuide and delayed improvements at month 6 compared to month 3 in terms of mental health and emotional coping. CONCLUSION: MyLupusGuide increases self-efficacy but not patient activation. A total of 56% of participants visited the MyLupusGuide site during the study period. Individuals with lupus need support to become activated toward self-management behaviors.

Recipient Age Predicts 20-Year Survival in Pediatric Liver Transplant.

Introduction: Pediatric liver transplant recipients have demonstrated excellent long-term survival. The purpose of this analysis is to investigate factors associated with 20-year survival to identify areas for improvement in patient care. Methods: Kaplan-Meier with log-rank test as well as univariate and multivariate logistic regression methods were used to retrospectively analyze 4,312 liver transplant recipients under the age of 18 between September 30, 1987 and March 9, 1998. Our primary endpoint was 20-year survival among one-year survival. Results: Logistic regression analysis identified recipient age as a significant risk factor, with recipients below 5 years old having a higher 20-year survival rate (p < 0.001). A preoperative primary diagnosis of a metabolic dysfunction was found to be protective compared to other diagnoses (OR 1.64, CI 1.20-2.25). African-American ethnicity (OR 0.71, CI 0.58-0.87) was also found to be a risk factor for mortality. Technical variant allografts (neither living donor nor cadaveric) were not associated with increased or decreased rates of 20-year survival. Conclusions: Our analysis suggests that long-term survival is inversely correlated with recipient age following pediatric liver transplant. If validated with further studies, this conclusion may have profound implications on the timing of pediatric liver transplantation.

Do Patients with Autoimmune Conditions Have Less Access to Liver Transplantation despite Superior Outcomes?

Orthotopic liver transplantation (OLT) is a lifesaving therapy for patients with irreversible liver damage caused by autoimmune liver diseases (AutoD) including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Currently, it is unclear how access to transplantation differs among patients with various etiologies of liver disease. Our aim is to evaluate the likelihood of transplant and the long-term patient and graft survival after OLT for each etiology for transplantation from 2000 to 2021. We conducted a large retrospective study of United Network for Organ Sharing (UNOS) liver transplant patients in five 4-year eras with five cohorts: AutoD (PBC, PSC, AIH cirrhosis), alcohol-related liver disease (ALD), hepatocellular carcinoma (HCC), viral hepatitis, and nonalcoholic steatohepatitis (NASH). We conducted a multivariate analysis for probability of transplant. Intent-to-treat (ITT) analysis was performed to assess the 10-year survival differences for each listing diagnosis while accounting for both waitlist and post-transplant survival. Across all eras, autoimmune conditions had a lower adjusted probability of transplant of 0.92 (0.92, 0.93) compared to ALD 0.97 (0.97, 0.97), HCC 1.08 (1.07, 1.08), viral hepatitis 0.99 (0.99, 0.99), and NASH 0.99 (0.99, 1.00). Patients with AutoD had significantly better post-transplant patient and graft survival than ALD, HCC, viral hepatitis, and NASH in each and across all eras (p-values all < 0.001). Patients with AutoD had superior ITT survival (p-value < 0.001, log rank test). In addition, the waitlist survival for patients with AutoD compared to other listing diagnoses was improved with the exception of ALD, which showed no significant difference (p-value = 0.1056, log rank test). Despite a superior 10-year graft and patient survival in patients transplanted for AutoD, patients with AutoD have a significantly lower probability of receiving a liver transplant compared to those transplanted for HCC, ALD, viral hepatitis, and NASH. Patients with AutoD may benefit from improved liver allocation while maintaining superior waitlist and post-transplant survival. Decreased access in spite of appropriate outcomes for patients poses a significant risk for increased morbidity for patients with AutoD.

Significant improvements, but consistent disparities in survival for African Americans after liver transplantation.

Despite improvements in survival across races in the past 20 years, African Americans have worse liver transplant outcomes after orthotopic liver transplantation (OLT). This study aims at quantifying the change in disparities between African Americans and other races in survival after OLT. We retrospectively analyzed the United Network for Organ Sharing (UNOS) database for patient data for candidates who received a liver transplant between January 1, 2007 and December 31, 2017. Multivariate Cox proportional hazards regression indicated similar decreases in mortality over time for each race with a decrease in mortality for African Americans: 2010-2012 (HR = .930), 2012-2015 (HR = .882), and 2015-2017 (HR = .883) when compared to 2007-2010. Risk of mortality for African Americans compared to Caucasians varied across the 4 eras: 2007-2010 (HR = 1.083), 2010-2012 (HR = 1.090), 2012-2015 (HR = 1.070), and 2015-2017 (HR = 1.125). While African Americans have seen increases in survival in the past decade, a similar increase in survival for other races leaves a significant survival disparity in African Americans.

Challenges of Perceived Self-Management in Lupus.

OBJECTIVE: Systemic lupus erythematosus is a chronic autoimmune disease with varied and unpredictable levels of disease activity. The ability to self-manage lupus is important in controlling disease activity. Our objective was to determine levels of patient activation toward self-management in lupus. METHODS: We used baseline results from the MyLupusGuide study, which had recruited 541 lupus patients from 10 lupus centers. We used the Patient Activation Measure (PAM), a validated self-reported tool designed to measure activation toward self-management ability, as our primary variable and examined its association with demographic, disease-related, patient-provider communication and psychosocial variables captured in our study protocol. Univariable and multivariable linear regressions were performed using linear mixed models, with a random effect for centers. RESULTS: The mean ± SD age of participants was 50 ± 14 years, 93% were female, 74% were White, and the mean ± SD disease duration was 17 ± 12 years. The mean ± SD PAM score was 61.2 ± 13.5, with 36% of participants scoring in the 2 lower levels, indicating low activation. Variables associated with low activation included being single, having lower physical health status, lower self-reported disease activity, lower self-efficacy, use of more emotional coping and fewer distraction and instrumental coping strategies, and a perceived lack of clarity in patient-doctor communication. CONCLUSION: Low patient activation was observed in more than one-third of lupus patients, indicating that a large proportion of patients perceived that they are lacking in lupus self-management skills. These results highlight a modifiable gap in perceived self-management ability among patients with lupus.

Nailfold Capillaroscopy Abnormalities Correlate With Disease Activity in Adult Dermatomyositis.

Objectives: The aim of this study was to determine the relationship between disease activity in adult patients with dermatomyositis (DM) and other biomarkers of disease activity such as C-reactive protein creatinine kinase and nailfold video capillaroscopy (NVC). Methods: We performed a prospective single center study of 15 adult patients with DM. Study participants underwent two assessments at least 9 months apart including clinical, laboratory and NVC evaluations. Patients received immunosuppressive medications for their dermatomyositis, and ongoing disease activity was measured by the Myositis Intention to Treat Index (MITAX). NVC evaluation included assessment of capillary density, capillary apical diameter (mm), and the number of microhemorrhages per digit. Results: Microvascular abnormalities were present in most DM patients. Of these, capillary density (4.71 vs. 6.84, p = 0.006) and mean apical diameter (56.09 vs. 27.79 µm, p = 0.003) significantly improved over the study period in concordance with improving disease control (MITAX 8.53 vs. 2.64, p = 0.002). Longitudinal analysis demonstrated that capillary density was independently associated with MITAX (ß = -1.49 [CI -2.49, -0.33], p = 0.013), but not other parameters such as C-reactive protein and creatinine kinase. Conclusions: Nailfold capillary density is a dynamic marker of global disease activity in adult DM. NVC may be utilized as a non-invasive point-of-care tool to monitor disease activity and inform treatment decisions in patients with DM.

Elevated serum sodium in recipients of liver transplantation has a substantial impact on outcomes.

Dysnatremias are a rare but significant event in liver transplantation. While recipient pre-transplant hypernatremia has been demonstrated to increase post-transplant mortality, the degree of hypernatremia and the impact of its resolution have been less well characterized. Here, we used multivariate Cox regression with a comprehensive list of donor and recipient factors in order to conduct a robust multivariate retrospective database study of 54,311 United Network for Organ Sharing (UNOS) liver transplant patients to analyze the effect of pre-transplant serum sodium on post-transplant mortality, post-transplant length of hospitalization, and post-transplant graft survival. Mortality and graft failure increased in a stepwise fashion with increasing pre-transplant hypernatremia: 145 -150 mEq/L (HR = 1.118 and HR = 1.113), 150-155 mEq/L (HR = 1.324 and HR = 1.306), and > 155 mEq/L (HR = 1.623 and HR = 1.661). Pre-transplant hypo- and hypernatremia also increased length of post-transplant hospitalization: < 125 mEq/L (HR = 1.098), 125-130 mEq/L (HR = 1.060), 145 -150 mEq/L (HR = 1.140), and 150-155 mEq/L (HR = 1.358). Resolution of hypernatremia showed no significant difference in mortality compared with normonatremia, while unresolved hypernatremia significantly increased mortality (HR = 1.254), including a durable long-term increased mortality risk for patients with creatinine < 2 mg/dL and MELD < 25. Pre-transplant hypernatremia serves as a morbid prognostic indicator for post-transplant morbidity and mortality.

JAK inhibitors, psoriatic arthritis, and axial spondyloarthritis: a critical review of clinical trials.

INTRODUCTION: Psoriatic arthritis (PsA) and spondyloarthritis (SpA) are inflammatory arthritides associated with progressive damage, deformity and morbidity. Janus kinase (JAK) inhibitors block JAKs, cytoplasmic protein tyrosine kinases important in signal transduction and immune processes that are currently being studied as synthetic disease modifying anti-rheumatic drugs (tsDMARDs) in psoriatic arthritis and spondyloarthritis. AREAS COVERED: This review evaluates published phase 2 and 3 clinical trial data for JAK kinase inhibitors for psoriatic arthritis and spondyloarthritis. A literature search using PubMed was conducted using the following keywords: 'psoriatic arthritis', 'ankylosing spondylitis', 'axial spondyloarthritis', 'non-radiographic axial spondyloarthritis', 'tofacitinib', 'baricitinib', 'filgotinib' and 'upadacitinib'. Mechanism of action, phase 2 and 3 clinical trial data, including efficacy and safety, are discussed. EXPERT OPINION: JAK inhibitors are important orally administered agents conferring different degrees of selectivity toward JAK1, JAK2, and JAK3 which may have implications on efficacy and safety in PsA and SpA. Phase 2 and 3 clinical trials in PsA for tofacitinib and upadacitinib and phase 2 for filgotinib confirmed efficacy comparable to biologic DMARDs. In SpA, phase 2 and 2/3 studies confirmed significant efficacy of tofacitinib, filgotinib and upadacitinib compared to placebo. Safety was comparable to clinical trial, long-term extension, and registry data for rheumatoid arthritis.

RxIALTA: evaluating the effect of a pharmacist-led intervention on CV risk in patients with chronic inflammatory diseases in a community pharmacy setting: a prospective pre-post intervention study.

Patients with inflammatory conditions are at high risk for cardiovascular (CV) disease. Despite such elevated risk, their CV risk factors are suboptimally managed. OBJECTIVE: To evaluate the effect of a pharmacist-led intervention on CV risk in patients with inflammatory conditions. METHODS: DESIGN: Prospective pre-postintervention. SETTING: 17 community pharmacies across Alberta. POPULATION: Adults with inflammatory conditions (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout, systemic lupus erythematosus, psoriasis vulgaris) who had at least one uncontrolled risk factor (A1C, blood pressure, LDL-cholesterol or current tobacco users). INTERVENTION: All patients enrolled in the study received: physical and laboratory assessment, individualised CV risk assessment and education regarding this risk, treatment recommendations, prescription adaptation and prescribing where necessary to meet treatment targets, regular communication with the patient's treating physician(s) and regular follow-up with all patients every month for 6 months. OUTCOMES: Primary: change in estimated CV risk (risk of a major CV event in the next 10 years) after 6 months. Secondary: change in individual risk factors (blood pressure, LDL-cholesterol, A1C and tobacco cessation) over a 6-month period. RESULTS: We enrolled 99 patients. The median age was 66.41 years (IQR 57.64-72.79), More than half of them (61%) were female and more than three-quarters (86%) were Caucasians. After adjusting for age, sex and ethnicity and centre effect, there was a reduction of 24.5% in CV risk (p<0.001); including a reduction of 0.3 mmol/L in LDL-c (p<0.001), 10.7 mm Hg in systolic blood pressure (p<0.001), 1.25% in A1C (p<0.001). There was a non-significant trend towards tobacco cessation. CONCLUSION: This is the first study on CV risk reduction in patients with inflammatory conditions in a community pharmacy setting. RxIALTA provides evidence for the benefit of pharmacist care on global cardiovascular risk reduction as well as the individual cardiovascular risk factors in patients with inflammatory conditions. TRIAL REGISTRATION NUMBER: NCT03152396.

A Population-level Analysis of the Differing Effects of Rheumatoid Arthritis and Spondyloarthritis on Peripartum Outcomes.

OBJECTIVE: The effects of rheumatoid arthritis (RA) and spondyloarthritis (SpA) on maternal and neonatal outcomes at a population level have not previously been well compared. METHODS: A contemporary pregnancy cohort of 312,081 women and corresponding birth events was assembled for the province of Alberta from the random selection of 1 live birth event per woman. We identified 3 groups: (1) no inflammatory arthritis (no IA, n = 308,989), (2) RA (n = 631), and (3) SpA (n = 2461). We compared maternal and neonatal outcomes, comorbid conditions, and medication use among the 3 groups. Multivariable logistic regression models evaluated the independent association between RA and SpA, relative to no IA, and the outcomes of small for gestation age (SGA) and hypertensive disorders during pregnancy. RESULTS: Pregnant women with RA were significantly more likely to have preterm delivery (13.5%), cesarean delivery (33.9%), hypertensive disorders in pregnancy (10.5%), and SGA babies (15.6%), compared to pregnant women with either SpA or no IA. Nonsteroidal antiinflammatory drugs and corticosteroid use were significantly higher in pregnant women with RA compared to the other groups. Women with RA were significantly more likely to have an SGA baby (OR 1.51, 95% CI 1.21-1.88; p < 0.01), and hypertensive disorder in pregnancy (OR 1.51, 95% CI 1.16-1.97; p < 0.01), compared to women with no IA, while no difference was found between women with SpA and those with no IA. CONCLUSION: Women with RA have a higher risk of worse maternal and neonatal outcomes, whereas the risk of these events is similar between women with and without SpA.

Canadian Rheumatology Association Recommendations for the Assessment and Monitoring of Systemic Lupus Erythematosus.

OBJECTIVE: To develop recommendations for the assessment of people with systemic lupus erythematosus (SLE) in Canada. METHODS: Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The Canadian SLE Working Group (panel of Canadian rheumatologists and a patient representative from Canadian Arthritis Patient Alliance) was created. Questions for recommendation development were identified based on the results of a previous survey of SLE practice patterns of members of the Canadian Rheumatology Association. Systematic literature reviews of randomized trials and observational studies were conducted. Evidence to Decision tables were prepared and presented to the panel at 2 face-to-face meetings and online. RESULTS: There are 15 recommendations for assessing and monitoring SLE, with varying applicability to adult and pediatric patients. Three recommendations focus on diagnosis, disease activity, and damage assessment, suggesting the use of a validated disease activity score per visit and annual damage score. Strong recommendations were made for cardiovascular risk assessment and measuring anti-Ro and anti-La antibodies in the peripartum period and conditional recommendations for osteoporosis and osteonecrosis. Two conditional recommendations were made for peripartum assessments, 1 for cervical cancer screening and 2 for hepatitis B and C screening. A strong recommendation was made for annual influenza vaccination. CONCLUSION: These are considered the first guidelines using the GRADE method for the monitoring of SLE. Existing evidence is largely of low to moderate quality, resulting in more conditional than strong recommendations. Additional rigorous studies and special attention to pediatric SLE populations and patient preferences are needed.

Measuring Disease Activity and Damage with Validated Metrics: A Systematic Review on Mortality and Damage in Systemic Lupus Erythematosus.

OBJECTIVE: To identify the effect of disease activity and damage, measured by validated indices, on mortality and damage accrual, in order to inform upcoming Canadian systemic lupus erythematosus (SLE) recommendations. METHODS: Following GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology to fill in evidence-to-decision tables to create recommendations for "minimal investigations needed to monitor SLE patients at baseline and subsequent visits," a systematic literature review was performed. The effect of disease activity and damage, measured by validated metrics, on mortality and damage was systematically reviewed, with metaanalyses performed when available. RESULTS: A title/abstract screen of 5599 articles identified 816 articles for full paper review, with 102 meeting inclusion criteria and 53 with extractable data. Thirty-three articles describing outcomes related to disease activity and 20 articles related to damage were identified. Mortality was associated with higher SLE Disease Activity Index-2000 scores in 6 studies (HR 1.14, 95% CI 1.06-1.22) and higher Systemic Lupus International Collaborating Clinics/ACR Damage Index scores in 6 studies (HR 1.53, 95% CI 1.28-1.83). Higher SLE Activity Measure scores were associated with increased risk of damage in 3 studies (OR 1.06, 95% CI 1.04-1.08). British Isles Lupus Assessment Group was associated with mortality in 1 study with HR of 1.15. CONCLUSION: Active SLE disease and damage are associated with and predict greater mortality and damage. The use of validated disease activity and damage metrics is important in the assessment of disease activity and damage and will inform upcoming Canadian recommendations for the assessment of SLE.

Practice Variations in the Diagnosis, Monitoring, and Treatment of Systemic Lupus Erythematosus in Canada.

OBJECTIVE: To evaluate the diagnosis, monitoring, and treatment of systemic lupus erythematosus (SLE) in Canada. METHODS: A 63-question electronic survey was developed with the Canadian Rheumatology Association and others. Descriptive analyses of responses were performed. RESULTS: Survey respondents (n = 175) reported varying practices in the diagnosis, monitoring, and treatment of SLE. Performance of laboratory investigations for diagnosis and monitoring varied, with 78% of responders performing them at least every 6 months. Validated measures of SLE disease activity and damage were not commonly used. Most common first-line agents besides steroids for induction therapy for class III or IV lupus nephritis included intravenous cyclophosphamide and mycophenolate mofetil. Antimalarial use was common, with 96% of respondents using these in active skin disease. Over 60% of respondents indicated that 80-100% of their patients were taking antimalarials, while another 25% indicated they used these drugs in up to 80% of their patients. There were 71% of responders who reported completing frequent (6-12 mos) ophthalmology screening in patients taking antimalarials. Biologics were infrequently used. Responders were more likely to stop azathioprine and chloroquine than hydroxychloroquine in pregnant patients with SLE. Other aspects of routine care including vaccination and cardiovascular risk management varied considerably. The majority (80%) agreed that a dedicated multidisciplinary care team would improve SLE care. CONCLUSION: Considerable practice variation in SLE management was noted. This may help inform future recommendations for the diagnosis, monitoring, and treatment of SLE in Canada.

Subcutaneous belimumab in the treatment of systemic lupus erythematosus.

Systemic lupus erythematosus is a chronic autoimmune disease with various clinical manifestations, organ involvement and laboratory findings. The disease can involve any organ including skin, joints, kidneys, central and peripheral nervous system, cardiovascular system and more. Currently, the cornerstone of treatment includes antimalarial and immunosuppressive medications and glucocorticosteroids. Recently, great effort has been invested in finding more targeted drugs for achieving better control of the disease with less adverse events. Intravenous belimumab was the first and only biologic drug to be approved by the US FDA and Health Canada for lupus over the last 50 years, and recently was studied in subcutaneous form. This paper will review the major belimumab trials with a focus on the subcutaneous form.

Monitoring of Systemic Lupus Erythematosus Pregnancies: A Systematic Literature Review.

OBJECTIVE: Few data exist to guide the frequency and type of monitoring in systemic lupus erythematosus (SLE) pregnancies. A systematic literature review was performed to address this gap in the literature. METHODS: A systematic review of original articles (1975-2015) was performed using Medline, Embase, and Cochrane Library. We included search terms for SLE, pregnancy, and monitoring. We also hand-searched reference lists, review articles, and grey literature for additional relevant articles. RESULTS: The search yielded a total of 1106 articles. After removing 117 duplicates, 929 articles that were evidently unrelated to our topic based on title and/or abstract, and 7 that were in a language other than English or French, 53 articles were included for full-text review. Following a more in-depth review, 15 were excluded: 6 did not use any measure of SLE activity and 6 did not specifically address SLE monitoring in pregnancy; 1 case series, 1 review, and 1 metaanalysis were removed. Among the 38 included studies, presence of active disease, antiphospholipid (aPL) antibodies positivity, and abnormal uterine and umbilical artery Doppler studies predicted poor pregnancy outcomes. No studies evaluated an evidence-based approach to the frequency of monitoring. CONCLUSION: Few existing studies address monitoring for optimal care during SLE pregnancies. The available data imply roles for aPL antibodies measurement (prior to pregnancy and/or during the first trimester), uterine and umbilical artery Doppler studies in the second trimester, and following disease activity. Optimal frequency of monitoring is not addressed in the existing literature.

Monitoring of Osteonecrosis in Systemic Lupus Erythematosus: A Systematic Review and Metaanalysis.

OBJECTIVE: Nontraumatic osteonecrosis (ON) is a well-recognized complication causing disability and affecting quality of life in patients with systemic lupus erythematosus (SLE). The aim of this study was to identify the risk factors for ON, and to identify the minimal investigation(s) needed to optimally monitor the risk of ON in patients with SLE. METHODS: A systematic review was conducted using MEDLINE and EMBASE. These databases were searched up to January 2016 using the Medical Subject Heading (MeSH) terms "Osteonecrosis," "Systemic lupus erythematosus," and synonymous text words. Randomized controlled trials, case control, cohort, and cross-sectional studies were included. Risk factors for ON in patients with SLE were compiled. The quality of each study was assessed using the Newcastle-Ottawa scale for nonrandomized studies. The quality of evidence of each risk factor was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation method. RESULTS: Of the 545 references yielded, 50 met inclusion criteria. Corticosteroid (CS) use may be strongly associated with ON in patients with SLE. Other clinical variables were moderately associated, including hypertension, serositis, renal disease, vasculitis, arthritis, and central nervous system disease. However, the evidence was low to very low in quality. CONCLUSION: Based on the best evidence available, CS use may be strongly associated with ON in patients with SLE. Results of this review were considered in the development of recommendations for the diagnosis and monitoring of patients with SLE in Canada and will guide clinicians in their assessment of these patients.

Clinical effectiveness and safety of leflunomide in inflammatory arthritis: a report from the RAPPORT database with supporting patient survey.

Leflunomide is indicated for the treatment of adults with rheumatoid arthritis, yet is underutilized. Given the cost of biologic therapy, understanding real-life effectiveness, safety, and sustainability of leflunomide, particularly in patients who have failed methotrexate, would be of value. The primary objective was to assess the proportion of patients achieving clinically meaningful benefit following an adequate trial of leflunomide. A retrospective analysis of a cohort supplemented with patient self-reported data using a standardized questionnaire. Data were analyzed using descriptive statistics, with a database multivariate logistic regression analysis to determine predictors of leflunomide response. Of the cohort available (N = 2591), 1671 patients with confirmed leflunomide use were included in the retrospective analysis, of whom 249 were incident users. Low disease activity (DAS-28 < 3.2) was achieved or maintained by 20% of incident users, with 19% achieving a clinical response (DAS-28 decrease ≥1.2) at 3 months. Adverse effects (AE) were reported by 29% of incident users and after 1 year, 45% remained on leflunomide. Achievement of "minimal or no joint symptoms" was reported by 34% in the 661 analyzable survey responses (39% response rate). AE were reported by 55%, with nuisance (hair loss, nausea, stomach pain) AE and diarrhea being most common. Leflunomide was discontinued by 67% of responders within 1 year. An important proportion of patients, the majority of whom had previously failed methotrexate, achieved disease response with leflunomide with a low risk of serious adverse effects, suggesting that a trial of leflunomide may be a reasonable and cost-effective strategy prior to biologic therapy.