Publications by authors named "Eric F Morand"

Objective: High disease activity status (HDAS) in patients with systemic lupus erythematosus (SLE) is associated with adverse long-term outcomes. We examined the frequency of lupus low disease activity state (LLDAS) and remission (REM) attainment in HDAS patients and whether their attainment was associated with improved patient outcomes.

Methods: Demographic, clinical and outcomes data, collected prospectively from a multinational cohort between 2013 and 2020, were analysed.

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To evaluate experience in a tertiary rheumatology service with melanoma differentiation-association-protein-5 (MDA5) disease and testing, patients with positive autoantibody results were reviewed for the presence of clinical disease. Anti-MDA5 positivity was detected in 2% of myositis-specific antibody tests. Of these, 29% did not have features consistent with anti-MDA5 disease.

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  • Systemic lupus erythematosus (SLE) primarily affects women around their childbearing years, and this study focuses on the risk factors and frequency of adverse pregnancy outcomes (APOs) in an Australian group of female SLE patients.
  • The research included a review of pregnancy histories from 278 participants, revealing a 44.3% rate of APOs, most commonly involving prematurity and associated with younger ages at SLE diagnosis and specific antibody presence.
  • The findings highlight the importance of pre-pregnancy counseling and collaboration among healthcare specialists for women with SLE, particularly those diagnosed at a younger age, to manage the risks of pregnancy effectively.
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Objectives: Anti-Ro60 and anti-Ro52 autoantibodies are frequently used as diagnostic biomarkers for Sjogren's disease, but their clinical significance in systemic lupus erythematosus (SLE) is not well characterised.

Methods: Patients fulfilling SLE classification criteria were studied according to their anti-Ro status. We defined Ro positivity (Ro+) as those who have either anti-Ro60 or anti-Ro52 positivity.

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The first inhabitants of Australia and the traditional owners of Australian lands are the Aboriginal and Torres Strait Islander peoples. Aboriginal and Torres Strait Islander peoples are two to four times more likely to have systemic lupus erythematosus (SLE) than the general Australian population. Phenotypically, SLE appears distinctive in Aboriginal and Torres Strait Islander peoples and its severity is substantially increased, with mortality rates up to six times higher than in the general Australian population with SLE.

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Background: Validation of protective associations of the lupus low disease activity state (LLDAS) against flare, irreversible damage, health-related quality of life, and mortality has enabled the adoption of treat-to-target strategies in patients with systemic lupus erythematosus (SLE). Previous validation studies were of short duration, limiting the ability to detect longer term signals in flare rate and irreversible damage. In addition, previous studies have focused on percent time at target, rather than actual periods of time that are more useful in clinical practice and trials.

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  • New medicines for systemic lupus erythematosus (SLE) have been slow to develop, with only three drugs approved in the last 60 years, showing a big need for better treatments.
  • Scientists discovered that a part of the immune system called type 1 interferons (IFNs) plays an important role in SLE, leading to attempts to create drugs that target these molecules.
  • The antibody anifrolumab successfully blocked IFN and got approved in 2021 after some testing, showing that targeting IFN might be a good way to develop new treatments for SLE and helping future drug development.
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  • This study looked at how standard medications for systemic lupus erythematosus (SLE) affect important health outcomes like disease activity, flare-ups, and damage over time, using a substantial patient data set from the Asia Pacific Lupus Collaboration (APLC).
  • Findings showed that a significant percentage of patients reached low disease activity levels, but many also had flares, with variations in medication use across different countries; specifically, some medications appeared to have a steroid-sparing effect.
  • Key results revealed that patients on specific medications like tacrolimus had better odds of achieving low disease activity, while those taking azathioprine and methotrexate were less likely to reach that outcome; however
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Introduction: Anifrolumab is a type I interferon (IFN) receptor 1 (IFNAR1) blocking antibody approved for treating patients with systemic lupus erythematosus (SLE). Here, we investigated the immunomodulatory mechanisms of anifrolumab using longitudinal transcriptomic and proteomic analyses of the 52-week, randomised, phase 3 TULIP-1 and TULIP-2 trials.

Methods: Patients with moderate to severe SLE were enrolled in TULIP-1 and TULIP-2 and received intravenous anifrolumab or placebo alongside standard therapy.

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  • The study aimed to determine if achieving Lupus Low Disease Activity State (LLDAS) leads to better outcomes for patients with newly diagnosed systemic lupus erythematosus (SLE).
  • Data was collected from a longitudinal SLE cohort in 13 countries, focusing on patients diagnosed within the last year, revealing that these patients had higher disease activity and use of glucocorticoids, but less organ damage initially compared to older patients in the study.
  • Results showed that while fewer patients in the recent onset group were in LLDAS at the start, they were more likely to achieve it during follow-up and LLDAS attainment was linked to a lower risk of disease flare-ups.
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  • * Data from a large international cohort of 1,850 mSACQ patients revealed that reducing GCs by 1 mg/day did not increase the risk of overall or severe flares; in fact, the use of antimalarials was linked to a lower risk of flares.
  • * Tapering GCs was found to reduce the risk of damage accrual for patients starting with higher prednisolone doses (over 5 mg/day
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Antigen-specific regulatory T cells (Tregs) suppress pathogenic autoreactivity and are potential therapeutic candidates for autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis is associated with autoreactivity to the Smith (Sm) autoantigen and the human leucocyte antigen (HLA)-DR15 haplotype; hence, we investigated the potential of Sm-specific Tregs (Sm-Tregs) to suppress disease. Here we identify a HLA-DR15 restricted immunodominant Sm T cell epitope using biophysical affinity binding assays, then identify high-affinity Sm-specific T cell receptors (TCRs) using high-throughput single-cell sequencing.

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Background: Targets of treatment for systemic lupus erythematosus (SLE) include the Lupus Low Disease Activity State (LLDAS), remission, and complete remission. Whether treatment can be tapered after attaining these targets and whether tapering is safer in patients in complete remission compared with LLDAS are unknown. We aimed to assess the odds of disease flares after treatment tapering in stable disease, versus continuing the same therapy.

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Autoimmune rheumatic disease (AIRD) is a collective term, which comprises a group of multisystem inflammatory autoimmune diseases, including connective tissue disease, chronic inflammatory arthritis, sarcoidosis and systemic vasculitis. Some AIRD are prevalent in the general population, and all can cause significant morbidity and reduced quality of life, with some increasing the risk of premature mortality, such as systemic lupus erythematosus (SLE), a connective tissue disease that is more prevalent and severe in Australian Aboriginal and Torres Strait Islander Peoples with high mortality rates. To ensure that management of AIRD can be optimised for all Australians, it is important that we understand the prevalence and potential phenotypic variations of AIRD across the Australian population.

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Objective: The longitudinal Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS) aims to assess SLE disease course overall and according to type I interferon 4 gene signature (IFNGS). Here, we describe SPOCS patient characteristics by IFNGS and baseline disease activity.

Methods: SPOCS (NCT03189875) is an international study of patients with SLE according to Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) criteria.

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Systemic lupus erythematosus (SLE) is a severe multisystem autoimmune disease that can cause injury in almost every body system. While considered a classic example of autoimmunity, it is still relatively poorly understood. Treatment with immunosuppressive agents is challenging, as many agents are relatively non-specific, and the underlying disease is characterized by unpredictable flares and remissions.

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Objectives: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.

Methods: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation.

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Remission is the established therapeutic goal for patients with systemic lupus erythematosus (SLE) and is currently defined by the widely adopted Definition Of Remission In SLE (DORIS) criteria. Attainment of remission is rare in the clinical setting, thus an alternative, pragmatic treatment target of low disease activity, as defined by the Lupus Low Disease Activity State (LLDAS), provides a less stringent and more attainable treatment goal for a wider proportion of patients compared with DORIS remission. Randomized controlled trials and real-world analyses have confirmed the positive clinical benefits of achieving either DORIS remission or LLDAS.

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  • The study aimed to identify which patients with systemic lupus erythematosus (SLE) are most likely to benefit from the treatment atacicept using gene signatures from immune cells.
  • Researchers used a specialized algorithm to analyze blood gene expression data and discovered five distinct patient clusters with different immune cell characteristics.
  • The findings suggest that patients in certain clusters showed higher flare rates when treated with placebo, while atacicept had a more significant positive effect on reducing these flares in specific clusters, indicating potential for targeted treatment strategies.
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  • TLR7 and TLR8 are receptors that help the immune system fight viral infections but can also contribute to autoimmune diseases like lupus when activated incorrectly.
  • * Research indicates that inhibiting TLR7/8 can enhance the effectiveness of lower doses of glucocorticoids (GCs), a common treatment for autoimmune conditions, reducing potential side effects.
  • * In studies, combining TLR7/8 inhibitors with GCs showed improved outcomes in inflammatory responses and in a lupus mouse model, highlighting a promising new treatment approach for autoimmune diseases.
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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.

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Systemic lupus erythematosus (SLE) is a disease of high unmet therapeutic need. The challenge of accurately measuring clinically meaningful responses to treatment has hindered progress towards positive outcomes in SLE trials, impeding the approval of potential new therapies. Current primary end points used in SLE trials are based on legacy disease activity measures that were neither specifically designed for the clinical trial context, nor developed according to contemporary recommendations for clinical outcome assessments (COAs), such as that substantial patient input should be incorporated into their design.

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