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Objective: This integrated analysis evaluates the efficacy and safety of voclosporin, a novel calcineurin inhibitor, at 23.7 mg twice daily in combination with mycophenolate mofetil (MMF) and oral glucocorticoids in lupus nephritis (LN) using pooled data from two large phase II and phase III clinical trials. The purpose was to expand the pool of patients for safety analyses and to increase power for efficacy analyses in patient subpopulations. Methods: Aurinia Urinary Protein Reduction in Active Lupus with Voclosporin (AURA-LV) (phase II) and Aurinia Renal Response in Active Lupus With Voclosporin (AURORA 1) (phase III) were randomized, placebo-controlled, double-blind trials with similar designs and end points comparing voclosporin to control in combination with MMF and oral glucocorticoids for the treatment of LN. The primary efficacy outcome of the integrated analysis was complete renal response (CRR) at approximately one year (Week 48 data from AURA-LV and Week 52 from AURORA 1). Safety was assessed throughout the trials. Results: Overall, 534 patients (268 voclosporin; 266 control) were included in the integrated analysis. Significantly more patients achieved a CRR at one year in the voclosporin group than in the control group (43.7% vs. 23.3%; OR 2.76; 95% CI 1.88, 4.05 P < 0.0001). The incidence of adverse events (AEs) was similar (91.4% voclosporin; 87.2% control). Most AEs were mild to moderate in severity; the most commonly reported AEs were classified as infections and infestations (62.2% voclosporin; 54.9% control) and gastrointestinal disorders (45.3% voclosporin; 35.3% placebo). No new or unexpected safety signals were detected. Conclusions: This integrated analysis demonstrates the efficacy and safety of voclosporin in the treatment of LN across the diverse racial and ethnic groups studied.

Introduction We conducted post hoc analyses of biomarker results from a multicenter, randomized, double-blind, placebo-controlled study of repository corticotropin injection (RCI; Acthar® Gel) in patients with persistently active systemic lupus erythematosus (SLE) despite treatment with moderate-dose glucocorticoids. Methods Adults with active SLE and moderate to severe rash and/or arthritis were enrolled in the primary study. Patients had active SLE despite treatment with stable glucocorticoids, antimalarials, and nonsteroidal anti-inflammatory drugs and/or immunosuppressants. Patients were randomly assigned to 80 U of RCI or placebo subcutaneously every other day for 4 weeks and then twice weekly through week 24. Blood samples were analyzed for serum cytokines and complement proteins using enzyme-linked immunosorbent or Luminex assays and for circulating leukocytes using flow cytometry. Biomarker levels were reported as percentages of the baseline and were further evaluated in subgroups stratified by baseline SLE Disease Activity Index-2000 (SLEDAI-2K) scores (

ObjectiveThe Lupus Foundation of America Rapid Evaluation of Activity in Lupus (LFA-REAL) system is a novel and simple SLE disease activity instrument, consisting of a tandem clinician-reported (ClinRO) and patient-reported (PRO) outcome measure. The aim of this study was to compare the LFA-REAL system with other SLE activity measures in the phase III trial of ustekinumab in patients with active SLE.MethodsThis was a prespecified analysis of data from a randomised, double-blind, placebo-controlled, parallel-group trial conducted at 140 sites in 20 countries. Correlations were evaluated between the LFA-REAL ClinRO and PRO with a panel of clinician-reported and patient-reported disease activity measures commonly used in SLE clinical trials at baseline, week 24 and week 52. All p values are reported as nominal.ResultsTrial participants included 516 patients with SLE with a mean (SD) age of 43.5 (8.9), of whom 482 (93.4%) were female. The LFA-REAL ClinRO correlated with Physician Global Assessment (r=0.39, 0.65 and 0.74, pConclusionsThe LFA-REAL ClinRO and PRO showed varied levels of correlations (weak to strong) with existing physician-based lupus disease activity measures and patient-reported outcome instruments, respectively and were able to more accurately capture organ-specific mucocutaneous and musculoskeletal manifestations. More analyses are needed to determine areas in which patient-reported outcomes are most similar or different to physician-reported end points and the basis for differences.

Objective To assess the safety, mechanism of action, and preliminary efficacy of rituximab followed by belimumab in the treatment of refractory lupus nephritis (LN). Methods In a multicenter, randomized, open-label clinical trial, 43 patients with recurrent or refractory LN were treated with rituximab, cyclophosphamide (CYC), and glucocorticoids followed by weekly belimumab infusions until week 48 (RCB group), or treated with rituximab and CYC but no belimumab infusions (RC group). Patients were followed up until week 96. Percentages of total and autoreactive B cell subsets in the patients' peripheral blood were analyzed by flow cytometry. Results Treatment with belimumab did not increase the incidence of adverse events in patients with refractory LN. At week 48, a complete or partial renal response occurred in 11 (52%) of 21 patients receiving belimumab, compared to 9 (41%) of 22 patients in the RC group who did not receive belimumab (P = 0.452). Lack of improvement in or worsening of LN was the major reason for treatment failure. B cell depletion occurred in both groups, but the percentage of B cells remained lower in those receiving belimumab (geometric mean number of B cells at week 60, 53 cells/μl in the RCB group versus 11 cells/μl in the RC group; P = 0.0012). Percentages of total and autoreactive transitional B cells increased from baseline to week 48 in both groups. However, percentages of total and autoreactive naive B cells decreased from baseline to week 48 in the belimumab group compared to the no belimumab RC group (P = 0.0349), a finding that is consistent with the observed impaired maturation of naive B cells and enhanced censoring of autoreactive B cells. Conclusion The addition of belimumab to a treatment regimen with rituximab and CYC was safe in patients with refractory LN. This regimen diminished maturation of transitional to naive B cells during B cell reconstitution, and enhanced the negative selection of autoreactive B cells. Clinical efficacy was not improved with rituximab and CYC in combination with belimumab when compared to a therapeutic strategy of B cell depletion alone in patients with LN.

We read with great interest the paper by Putman et al.(1). The publication reviews data from 45 studies evaluating hydroxychloroquine (HCQ), chloroquine (CQ), anakinra and anti-IL-6 therapies in COVID-19. Except anakinra, none of the other therapies decreased the risk of death in hospitalized COVID-19 patients. We would like to discuss the evidence evaluating the role of HCQ in the prophylaxis of SARS-CoV-2 infections. The in-vitro antiviral effect of antimalarials suggested a role in preventing disease progression(2).

Introduction We assessed the efficacy and safety of repository corticotropin injection (RCI; Acthar® Gel) for persistently active systemic lupus erythematosus (SLE) despite use of moderate-dose glucocorticoids. Methods This multicenter, double-blind, randomized, placebo-controlled study enrolled patients ≥ 18 years with active SLE and moderate to severe rash and/or arthritis despite stable glucocorticoid doses (7.5–30 mg/day prednisone equivalent) and antimalarials for ≥ 4 weeks and/or immunosuppressants for ≥ 8 weeks before screening. Stable glucocorticoid doses were required through week 16 with optional taper from weeks 16 to 24. Patients were randomized (1:1) to 80 U RCI subcutaneously or placebo every other day to week 4, then twice weekly to week 24. Endpoints included the proportion of SLE Responder Index (SRI)-4 responders at week 16; changes from baseline to week 16 in 28 Swollen Joint Count/Tender Joint Count (28 SJC/TJC) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-Activity score; and changes from baseline to week 24 in inflammatory cytokines. Safety was assessed by adverse events. Results In the modified intention-to-treat population (RCI, n = 84; placebo, n = 85), the proportion of SRI-4 responders at week 16 was not significantly different between groups (RCI, 47.6%; placebo, 43.5%; OR [95% CI] 1.2 [0.6 to 2.2]; p = 0.5762). RCI treatment resulted in a reduction from baseline to week 16 in 28 SJC/TJC and CLASI-Activity score and from baseline to week 8 in a proliferation-inducing ligand cytokine. Post hoc analyses demonstrated a greater proportion of BILAG-based Combined Lupus Assessment responders for RCI than placebo at weeks 4, 12, and 20 and greater SRI-4 response in RCI-treated patients with baseline SLE Disease Activity Index-2000 ≥ 10 and CLASI-Activity ≥ 11. No new safety signals were identified. Conclusions Despite failure to achieve the primary endpoint, these results support the utility of RCI for treating persistently active SLE. Trial Registration ClinicalTrials.gov identifier NCT02953821. Electronic Supplementary Material The online version of this article (10.1007/s40744-020-00236-1) contains supplementary material, which is available to authorized users.

Drug development in lupus has improved over the past 10 years but still lags behind that of other rheumatic disease areas. Assessment of prospective lupus therapies in clinical trials has proved challenging for reasons that are multifactorial including the heterogeneity of the disease, study design limitations and a lack of validated biomarkers which greatly impacts regulatory decision-making. Moreover, most composite outcome measures currently used in trials do not include patient-reported outcomes. Given these factors, the Addressing Lupus Pillars for Health Advancement Global Advisory Committee members who serve on the drug development team identified an opportunity to convene a meeting to facilitate information sharing on completed and existing outcome measure development efforts. This meeting report highlights information presented during the meeting as well as a discussion on how the lupus community may work together with regulatory agencies to simplify and standardise outcome measures to accelerate development of lupus therapeutics.

Funder: Lupus Foundation of America, Inc, Objective: In systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence. Methods: We conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966���October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with

Disease modification has become a well-established concept in several therapeutic areas; however, no widely accepted definition of disease modification exists for SLE.We reviewed established definitions of disease modification in other conditions and identified a meaningful effect on ‘disease manifestations’ (ie, signs, symptoms and patient-reported outcomes) and on ‘disease outcomes’ (eg, long-term remission or progression of damage) as the key principles of disease modification, indicating a positive effect on the natural course of the disease. Based on these findings and the treatment goals and outcome measures for SLE, including lupus nephritis, we suggest a definition of disease modification based on disease activity indices and organ damage outcomes, with the latter as a key anchor. A set of evaluation criteria is also suggested.Establishing a definition of disease modification in SLE will clarify which treatments can be considered disease modifying, provide an opportunity to harmonise future clinical trial outcomes and enable comparison between therapies, all of which could ultimately help to improve patient outcomes. This publication seeks to catalyse further discussion and provide a framework to develop an accepted definition of disease modification in SLE.

Signaling lymphocyte activation molecule family member 6 (SLAMF6) is a T cell co-receptor. Previously, we showed that SLAMF6 clustering was required for T cell activation. To better understand the relationship between SLAMF6 location and function and to evaluate the role of SLAMF6 as a therapeutic target, we investigated how its compartmentalization on the cell surface affects T cell functions. We used biochemical and co-culture assays to show that T cell activity is enhanced when SLAMF6 colocalizes with the CD3 complex. Mechanistically, co-immunoprecipitation analysis revealed the SLAMF6-interacting proteins to be those essential for signaling downstream of T cell receptor, suggesting the two receptors share downstream signaling pathways. Bispecific anti-CD3/SLAMF6 antibodies, designed to promote SLAMF6 clustering with CD3, enhanced T cell activation. Meanwhile, anti-CD45/SLAMF6 antibodies inhibited SLAMF6 clustering with T cell receptor, likely because of the steric hindrance, but nevertheless enhanced T cell activation. We conclude that SLAMF6 bispecific antibodies have a role in modulating T cell responses, and future work will evaluate the therapeutic potential in tumor models.

ObjectiveTo evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.MethodsData were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity.ResultsWe studied 1460 patients (89% female, 52% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95% CI 1.01 to 1.09).ConclusionsThis is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis.

ObjectiveWe conducted an international survey of patients with SLE to assess their access, preference and trust in various health information sources pre-COVID-19 and during the COVID-19 pandemic.MethodsPatients with SLE were recruited from 18 observational cohorts, and patients self-reporting SLE were recruited through five advocacy organisations. Respondents completed an online survey from June 2020 to December 2021 regarding the sources of health information they accessed in the 12 months preceding (pre-11 March 2020) and during (post-11 March 2020) the pandemic. Multivariable logistic regressions assessed factors associated with accessing news and social media post-11 March 2020, and self-reporting negative impacts from health information accessed through these sources.ResultsSurveys were completed by 2111 respondents; 92.8% were female, 76.6% had postsecondary education, mean (SD) age was 48.8 (14.0) years. Lupus specialists and family physicians were the most preferred sources pre-11 March 2020 and post-11 March 2020, yet were accessed less frequently (specialists: 78.5% pre vs 70.2% post, difference −8.3%, 95% CI −10.2% to −6.5%; family physicians: 57.1% pre vs 50.0% post, difference −7.1%, 95% CI −9.2% to −5.0%), while news (53.2% pre vs 62.1% post, difference 8.9%, 95% CI 6.7% to 11.0%) and social media (38.2% pre vs 40.6% post, difference 2.4%, 95% CI 0.7% to 4.2%) were accessed more frequently post-11 March 2020 vs pre-11 March 2020. 17.2% of respondents reported negative impacts from information accessed through news/social media. Those outside Canada, older respondents or with postsecondary education were more likely to access news media. Those in Asia, Latin America or younger respondents were more likely to access social media. Those in Asia, older respondents, males or with postsecondary education in Canada, Asia or the USA were less likely to be negatively impacted.ConclusionsPhysicians, the most preferred and trusted sources, were accessed less frequently, while news and social media, less trusted sources, were accessed more frequently post-11 March 2020 vs pre-11 March 2020. Increasing accessibility to physicians, in person and virtually, may help reduce the consequences of accessing misinformation/disinformation.

Background/purpose The LFA REAL™ is a measurement system for evaluating lupus disease activity from both clinician and patient perspectives. Patients’ viewpoints are captured using a patient-reported outcome (PRO) questionnaire. A series of visual analog scales are designed to rate disease severity and progress over the past 4 weeks. Brief instructions guide the patient to distinguish between active, potentially reversible symptoms and chronic pain or discomfort that are more likely due to damage. Beyond its simplicity and efficiency, the PRO can provide versatile assessments from a global, organ-based, and symptom-specific level. This paper describes the patient-centered approach used to evaluate the content validity of the LFA-REAL PRO. Methods The PRO was developed in accordance with FDA guidance. A two-phase qualitative study was performed with 25 lupus patients, 10 who participated in concept elicitation (Phase 1) and 15 in cognitive debriefing interviews (Phase 2). Qualitative data were analyzed using ATLAS.ti software v7.5. Upon completion of the interviews, participants completed the draft PRO and additional measures to characterize the sample. Results The mean age of participants was 45.6 and 88% were female, as expected in a lupus population. The mean SF-36 physical component score was 29.8 and the mean mental component score was 46.4. Phase 1 elicited symptom saturation and mapping of the draft PRO. Fatigue was reported by 100% of patients, highlighting its importance as a measurable domain. Additionally, 100% of patients spontaneously mentioned arthritis, which may be more important to this group than previously estimated, substantiating the approach of this PRO to break down components of arthritis into joint pain, stiffness, and swelling. Shortness of breath and fever were reported more frequently than expected. Phase 2 data demonstrated that participants found the instrument easy to use and offered recommendations to improve clarity, leading to adjustments in wording and formatting. Conclusions Results suggest that the LFA-REAL PRO has content validity and, with some modifications suggested by participants, is ready for quantitative validation, including tests of reliability, validity, responsiveness to change, and performance relative to other PROs used in lupus trials. After validation, the LFA-REAL system is intended for use in clinical practice and research. Electronic supplementary material The online version of this article (10.1186/s12955-019-1151-8) contains supplementary material, which is available to authorized users.

Objectives To assess the prevalence of combined hormonal contraceptives (CHCs) in reproductive-age women with SLE with and without possible contraindications and to determine factors associated with their use in the presence of possible contraindications. Methods This observational cohort study included premenopausal women ages 18–45 years enrolled in the SLICC Registry ⩽15 months after SLE onset, with annual assessments spanning 2000–2017. World Health Organization Category 3 or 4 contraindications to CHCs (e.g. hypertension, aPL) were assessed at each study visit. High disease activity (SLEDAI score >12 or use of >0.5 mg/kg/day of prednisone) was considered a relative contraindication. Results A total of 927 SLE women contributed 6315 visits, of which 3811 (60%) occurred in the presence of one or more possible contraindication to CHCs. Women used CHCs during 512 (8%) visits, of which 281 (55%) took place in the setting of one or more possible contraindication. The most frequently observed contraindications were aPL (52%), hypertension (34%) and migraine with aura (22%). Women with one or more contraindication were slightly less likely to be taking CHCs [7% of visits (95% CI 7, 8)] than women with no contraindications [9% (95% CI 8, 10)]. Conclusion CHC use was low compared with general population estimates (>35%) and more than half of CHC users had at least one possible contraindication. Many yet unmeasured factors, including patient preferences, may have contributed to these observations. Further work should also aim to clarify outcomes associated with this exposure.

T cell activation is the result of the integration of signals across the T cell receptor and adjacent co-receptors. The signaling lymphocyte activation molecules (SLAM) family are transmembrane co-receptors that modulate antigen driven T cell responses. Signal transduction downstream of the SLAM receptor is mediated by the adaptor protein SLAM Associated Protein (SAP), a small intracellular protein with a single SH2 binding domain that can recruit tyrosine kinases as well as shield phosphorylated sites from dephosphorylation. Balanced SLAM-SAP signaling within T cells is required for healthy immunity, with deficiency or overexpression prompting autoimmune diseases. Better understanding of the molecular pathways involved in the intracellular signaling downstream of SLAM could provide treatment targets for these autoimmune diseases.

Introduction We assessed patient-reported outcomes from a multicenter, randomized, double-blind, placebo-controlled study of repository corticotropin injection (RCI; Acthar® Gel) in patients with persistently active systemic lupus erythematosus (SLE) despite treatment with moderate-dose glucocorticoids. Methods The trial enrolled adults with active SLE and moderate-to-severe rash and/or arthritis despite use of stable glucocorticoids (7.5 mg/day to 30 mg/day prednisone equivalent), antimalarials, and nonsteroidal anti-inflammatory drugs for ≥ 4 weeks and/or immunosuppressants for ≥ 8 weeks before screening. Patients were randomly assigned to 80 U of RCI or placebo subcutaneously every other day through week 4, then twice weekly through week 24. Primary analyses evaluated the change from baseline to week 24 in the Lupus Quality of Life (QoL) and Work Productivity and Activity Impairment (WPAI)-Lupus questionnaires. Post hoc analyses stratified results by baseline disease activity (SLE Disease Activity Index-2000 [SLEDAI-2K]

ObjectiveThe Lupus Foundation of America Rapid Evaluation of Activity in Lupus (LFA-REAL) clinician-reported outcome (ClinRO) and the LFA-REAL patient-reported outcome (PRO) were developed in order to capture manifestations of SLE from the perspective of both the clinician and the patient. The aim of this study is to compare the LFA-REAL ClinRO and PRO with other lupus disease activity measures.MethodsA cross-sectional analysis of patients from a single-centre cohort was performed using Spearman’s correlation. Disease activity measures included were LFA-REAL ClinRO (range 0–1400), LFA-REAL PRO (range 0–1200), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), clinical SLEDAI-2K and Physician Global Assessment (PGA, range 0–100).ResultsTwo hundred and twenty-seven patients with SLE were studied. The mean age was 46.3 (SD: 13.8); 212 (93.4%) were female. The mean (SD) LFA-REAL ClinRO was 25.4 (34.7), LFA-REAL PRO was 241.1 (187.6), PGA was 11.9 (15.4), SLEDAI-2K was 2.3 (3.3) and clinical SLEDAI-2K was 1.6 (2.9). The LFA-REAL ClinRO correlated with PGA (r=0.758, pConclusionsThe LFA-REAL ClinRO and the LFA-REAL PRO had good and weak correlations, respectively, with several physician-based disease activity measures in a cross-sectional study, suggesting their potential usefulness in establishing disease severity. Longitudinal studies will be required to determine their value in monitoring patients with SLE.

ObjectivesLupus nephritis (LN) requires renal replacement therapy in 10%–30% of patients. About 30% of these patients receive a kidney transplant. Belatacept is a second-generation, selective, T-cell co-stimulator blocker (inhibits cytotoxic, T-lymphocyte antigen 4, CTLA-4) used as an alternative to calcineurin inhibitors (CNI) for maintenance regimens after kidney transplantation. The pathogenic relevance of CTLA-4 inhibition and the favourable cardiovascular profile of belatacept make it an attractive therapeutic option in systemic lupus erythematosus (SLE). Intravenous administration of belatacept ensures therapeutic adherence.MethodsThis retrospective, single-centre study evaluates the outcomes of LN kidney transplant recipients treated with belatacept for reasons not related to SLE at the Columbia University Lupus and Renal Transplant Cohort.ResultsBelatacept was started in six patients on CNI regimens at 15.5±17.1 months following transplantation for LN. In five patients, creatinine levels stabilised 6 months after belatacept, one returned to haemodialysis due to CNI toxicity and pyelonephritis and one relisted for a kidney transplant following acute cellular rejection and cortical necrosis. Five patients are followed for extrarenal lupus; no extrarenal manifestations were documented in the other two patients. Data on SLE disease activity pre-belatacept and post-belatacept were available and scored in three patients using the SLE Disease Activity Index Glucocorticosteroid Index (SLEDAI-2KG), which accounts for clinical and laboratory manifestations, as well as steroid dose. Mean SLEDAI-2KG decreased from 13 to 7.6.ConclusionBelatacept in LN kidney transplant recipients may decrease extrarenal manifestations, attenuate CNI toxicity and stabilise allograft function, providing a better alternative to CNI regimens. Furthermore, these data suggest that belatacept, although initiated for reasons not related to SLE, might have a beneficial effect in SLE.

Lupus disease measures such as the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group (BILAG) index are challenging to interpret. The Lupus Foundation of America-Rapid Evaluation of Activity in Lupus (LFA-REAL) is intended to provide an efficient application of anchored visual analog scores, each representing the individual severity of active symptoms, with the sum of individual scores deriving an overall disease activity assessment. Our objective was to compare the performance of LFA-REAL to systemic lupus erythematosus disease activity assessments and compare scores between trained lupus clinical investigators and clinicians.Investigators scored the SLEDAI, BILAG, physician's global assessment (PGA), and LFA-REAL, while the clinicians scored the LFA-REAL. The level of agreement between physicians and instruments was determined.The study included 99 patients (93% women, 31% white, mean ± SD ages 43.4 ± 13.2 years). At the first visit, the mean ± SD SLEDAI score was 5.5 ± 4.5, BILAG score 6.7 ± 7.8, and PGA score 33.6 ± 24.5. The mean ± SD investigator LFA-REAL score was 46.2 ± 42.9, and clinician LFA-REAL score 56.1 ± 53.6. At the second visit, the mean ± SD investigator LFA-REAL score was 41.3 ± 36.7, and clinician LFA-REAL score 48.3 ± 42.6. Total LFA-REAL scores correlated positively with PGA, SLEDAI, and BILAG (ρ = 0.58-0.88, P0.001). LFA-REAL scores produced correlation coefficients of ρ0.7 for musculoskeletal, mucocutaneous, and renal BILAG domains. The intraclass correlation coefficient between the LFA-REAL scores of investigators and clinicians was 0.79 for visit 1 (P0.001) and 0.86 for visit 2 (P0.001).The LFA-REAL provides a reliable surrogate for more complicated disease activity measures when used by lupus clinical investigators or clinicians.

Background Comprehensive assessment of systemic lupus erythematosus (SLE) and its treatment requires patient-reported outcome (PRO) measures to capture impacts and fluctuating symptoms. The objective of this study was to develop PROs, in accordance with the Food and Drug Administration (FDA) PRO Guidance, to assess fluctuations in SLE symptoms and its impact. Methods Following independent review board approval, six US rheumatology practices recruited patients with SLE to participate in concept elicitation (CE) interviews, in order to identify important SLE symptoms and their impacts. The SLE Symptom Severity Diary (SSD) and SLE Impact Questionnaire (SIQ) were drafted based on CE interview results and clinician input. The PROs were revised based on patient feedback from cognitive debriefing (CD) interviews, clinician feedback, and a translatability assessment. Results Forty-one patients completed CE interviews. Commonly-reported symptoms included fatigue (98%), joint pain (93%), and rash (88%). The most frequently reported impact was difficulty with chores/housework (61%). Eighteen patients completed CD interviews. The PROs were considered comprehensive, clear, and relevant. The SSD contains 17 items assessing energy/vitality, joint and muscle pain/stiffness/swelling, flu-like symptoms, cognition, numbness/tingling, skin symptoms and hair loss using an 11-point numeric response scale and a 24-h recall period (with the exception of hair loss). It also evaluates steroid status and dose. The SIQ contains 50 items, uses a 5-point Likert scale and a 7-day recall period, to assess disease impacts including patients’ ability to make plans, work, and physical/social/emotional functioning. Conclusion The SSD and SIQ are comprehensive SLE-specific PROs developed in accordance with the FDA PRO Guidance. Following assessment of their measurement properties, they may be useful in clinical studies and clinical practice to measure fluctuations in, and the impact of, symptoms in patients with SLE.

Platelet-bound complement activation products (PC4d) are associated with thrombosis in Systemic Lupus Erythematosus (SLE). This study investigated the effect of PC4d on platelet function, as a mechanistic link to arterial thrombosis. In a cohort of 150 SLE patients, 13 events had occurred within five years of enrollment. Patients with arterial events had higher PC4d levels (13.6 [4.4–24.0] vs. 4.0 [2.5–8.3] net MFI), with PC4d 10 being the optimal cutoff for event detection. The association of arterial events with PC4d remained significant after adjusting for antiphospholipid status, smoking, and prednisone use (p=0.045). PC4d levels correlated with lower platelet counts (r=−0.26, p=0.002), larger platelet volumes (r=0.22, p=0.009) and increased platelet aggregation: the adenosine diphosphate (ADP) concentration to achieve 50% maximal aggregation (EC(50)) was lower in patients with PC4d 10 compared with PC4d

Objective The aim of this study was to develop a patient-reported outcome measure specific for systemic lupus erythematosus (SLE) to assess patient satisfaction with treatment, treatment options, and medical care. Methods Patients with SLE were recruited from four US rheumatology practices. Concept elicitation interviews identified aspects that patients considered important and relevant regarding satisfaction with treatment and medical care. Concept elicitation interviews and clinical input were used to draft the Lupus Satisfaction Questionnaire (LSQ). A second cohort of patients with SLE participated in combined concept elicitation/cognitive debriefing interviews, after which the LSQ was revised. Results Fourteen patients completed concept elicitation interviews: 93% were female, 57% were white, and 85% had moderate/severe SLE. Current treatments included hydroxychloroquine (93%), steroids (79%), and belimumab (57%), and 43% were biologic naive. Patients were generally satisfied with their treatment and medical care; however, they were dissatisfied with treatment adverse effects and the number of available treatment options. Cognitive debriefing interviews (n = 8) demonstrated that the LSQ was comprehensive, clear, and relevant; therefore, only minor revisions were made to the questionnaire. The LSQ assesses satisfaction with current SLE treatments (25 items), medical care (11 items), and insurance coverage (3 items). The draft LSQ was evaluated in 195 adults with SLE. Fifty-eight percent of patients reported that they were "somewhat satisfied" with their SLE treatment. Conclusions The LSQ has been developed to assess treatment satisfaction among patients with SLE. Following further testing to support its validity and reliability, it will provide a useful tool to facilitate assessment of satisfaction with treatments for SLE and help inform treatment decisions.

Background: XmAb5871 is a humanized anti-CD19 antibody Fc-engineered for increased affinity to FcγRIIb. Co-ligation of CD19 and FcγRIIb inhibits B lineage cells key to SLE pathogenesis. Objectives: This Phase 2 study was designed to minimize background medications and placebo responses to improve interpretation of a small trial in a complex, heterogenous disease. Methods: SLE patients were enrolled with active disease, ameliorated during screening with ≥160 mg of IM Depo-Medrol. Improvement was required before randomization, defined by decrease in SLEDAI ≥4 points or ≥1 grade in a BILAG A or B score. Immunosuppressive drugs were stopped except antimalarials and/or ≤10 mg/day prednisone or equivalent. Subjects were randomized to IV XmAb5871 (5 mg/kg) or placebo and given Depo-Medrol 80 mg IM on Days 1 and 15, after which, steroid impact was expected to withdraw gradually. Study treatments were given Q14 days for up to 16 doses or loss of improvement (LOI), defined as SLEDAI increase ≥4 points OR new BILAG A or B, with investigator-determined significance. At LOI, patients could receive immediate standard treatments. The primary endpoint was the proportion with no LOI by Day 225 in the efficacy evaluable group (those completing Day 225 or withdrawn for LOI or drug-related adverse event). Results: 104 subjects were randomized: 99 female, median age 45 (20-65). The primary endpoint was met by 21 (42%) of XmAb5871-treated patients vs 12 (28.6%) of the placebo group (p=0.18). All but one responder also fulfilled the SRI-4 response definition from screening to completion. Results did not differ in those with or without anti-dsDNA and/or ENA antibodies. Time to flare was significantly longer in the XmAb5871 group (p=0.025) (figure 1). XmAb5871-treated patients with LOI had less recurrent disease after IM steroid cessation than those in the placebo group; 6 (20%) of placebo patients developed BILAG A scores vs 3 (13%) in the active arm. 9 (30%) of worsening placebo patients had SLEDAI increase ≥7 vs 0 in the XmAb5871 group. SLEDAI scores were higher and increased sooner after disease nadir with placebo vs XmAb5871 (figure 2); 16 (30.8%) of XmAb5871 patients vs 7 (13.5%) placebo patients sustained LLDAS (low disease) during months 6-8 (p=0.0453). Transient, infusion-related gastrointestinal side effects occurred in XmAb5871-treated patients during the 1st or 2nd infusion. There were 8 SAEs in 7 XmAb5871-treated subjects, 5 in 4 placebo patients, no opportunistic infections, and no deaths. Infection rate was low compared to other SLE trials. Conclusion: XmAb5871 was well-tolerated. Preliminary data from this small trial indicates suppression of disease recurrence after treatment withdrawal, supporting further evaluation of XmAb5871 in SLE. Disclosure of Interests: Joan Merrill Grant/research support from: Genentech, UCB, GSK, EMD Serono, Pfizer, Celgene, Exagen, Bristol Myers Squibb, Medimmune/Astra Zeneca, Lilly, Amgen, Xencor, Neovacs, Consultant for: Genentech, UCB, GSK, EMD Serono, Pfizer, RemeGen, Celgene, Exagen, Bristol Myers Squibb, Medimmune/Astra Zeneca, Lilly, Immupharma, Amgen, Janssen, Sanofi, Neovacs, Anthera, Speakers bureau: UCB, GSK, EMD Serono, Bristol Myers Squibb, Medimmune/Astra Zeneca, Janssen, Joshua June: None declared, Fotios Koumpouras: None declared, Wambui Machua: None declared, Mohammad Faisal Khan: None declared, Anca Askanase: None declared, Arezou Khosroshahi: None declared, Saira Sheikh: None declared, Judith A. James: None declared, Joel Guthridge: None declared, Gaurav Rathi Shareholder of: Xencor Inc, Employee of: Xencor Inc, Bart Burington Shareholder of: Xencor Inc, Employee of: Xencor Inc, Paul Foster Shareholder of: Xencor Inc, Employee of: Xencor Inc, Debra Zack Shareholder of: Xencor Inc, Employee of: Xencor Inc