MedicalResearch.com Interview with:
A/Prof. Joshua Ooi, PhD
Head, Regulatory T-cell Therapies
Translational Research Facility
Clinical Sciences at Monash Health,
Monash University
MedicalResearch.com: What is the background for this study?Response: In 2017, we published a landmark Nature paper showing that people who are protected from autoimmune disease have specialized molecules on immune cells. These specific molecules are missing in patients that develop autoimmune disease.
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MedicalResearch.com Interview with:
Raisa Silva, M.D.
Resident physician in Internal medicine
University of Pittsburgh Medical Center
MedicalResearch.com: What is the background for this study?Response: Systemic lupus erythematosus (lupus for short) is a complex disease that significantly affects patients’ lives. Adherence to medications for lupus is known to be suboptimal (it can be as low as 15% in some studies). Multiple social factors may affect treatment adherence. For example, costs of medications (including copayments, deductibles, co-sharing), polypharmacy (patients with lupus often have comorbid diseases that also need medications), and potential side effects are some of the reasons why patients may have difficulty in taking medications for lupus every day. The costs of insurance copayment may represent a major obstacle to adherence. The lack of adherence to lupus medications is associated with poor control of disease, more symptoms, and worse disease outcomes, such as more hospitalizations and more severe disease.
In our study, we examined the association between lupus medications copayment and adherence to these medications (some of the most commonly used medications for lupus).
(more…)
MedicalResearch.com Interview with:
Nathalie Franchimont, M.D., Ph.D.
Senior Vice President, Head of Multiple Sclerosis and Immunology
Head of the Multiple Sclerosis and Immunology Development Unit
Biogen
MedicalResearch.com: What is the background for this study?What are the main findings?Response: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organ systems. Rash and arthritis are among the most frequent manifestations of the disease and severe organ damage can also occur especially when organs like the kidney are affected. Litifilimab (known as BIIB059) is a monoclonal antibody being studied for the potential treatment of SLE and cutaneous lupus erythematosus (CLE).
The Phase 2 LILAC study evaluated litifilimab versus placebo in two parts: Part A in participants who have SLE with active joint and skin manifestations; and Part B in participants with active CLE, including chronic and subacute subtypes, with or without other organ involvement. Results from the SLE portion of the study (Part A) show litifilimab met the study’s primary endpoint by significantly reducing total active joint count compared to placebo. Total active joint count was defined as the total number of tender or swollen joints. Litifilimab was generally well tolerated, with most reported adverse events (AEs) rated as mild or moderate. Note, this Phase 2 trial was not powered to assess secondary endpoints.
Based on these positive Phase 2 results, Biogen is currently enrolling participants into the Phase 3 TOPAZ-1 and TOPAZ-2 studies, which will evaluate the efficacy and safety of litifilimab in participants with active SLE worldwide.
Part B results from LILAC were published separately in NEJMon July 28, 2022 and expand the body of evidence supporting litifilimab as a potential first-in-class therapy for cutaneous lupus erythematosus in addition to SLE.
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Lupus is a rare chronic, hard-to-diagnosis autoimmune disease which disproportionately impacts women of color, particularly Black women, and the implicit...
Stephen Connelly, PhD
Co-founder & Chief Scientific Officer
Equillium, Inc.
San Diego, California
MedicalResearch.com: What is the background for this study? Response: Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that predominantly affects women in the reproductive age range. Approximately 50% of SLE patients experience lupus nephritis (LN), a serious complication that is accompanied by significant morbidity and mortality. Progression of LN to chronic kidney disease is common, with 10% of patients with LN developing end-stage kidney disease.
T cells, play a central role in the pathogenesis of both SLE and LN by mediating tissue damage and enhancing the production of autoantibodies by promoting B cell differentiation, proliferation, and maturation. These T cells express CD6, a costimulatory receptor that through its binding to activated leukocyte cell adhesion molecule (ALCAM), expressed on immune cells and tissues, modulates both the activity and trafficking of effector T cells (Teff). The expression of both CD6 and ALCAM (CD6-ALCAM pathway) have been associated with pathogenic effector T cell activity and trafficking in multiple autoimmune and inflammatory diseases.
Based on a comprehensive screen of more than 1100 urine proteins, soluble urinary ALCAM (uALCAM) was identified as one of only a few molecules that were elevated in the urine of patients with SLE with active renal involvement compared with patients with quiescent or no prior nephritis. However, no studies had been conducted to characterize the cellular sources of the soluble ALCAM and questions remained about the relevance of this protein and whether it was associated with the pathology of the disease.
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MedicalResearch.com Interview with:
Peter Izmirly, M.D.
Associate Professor of Medicine, NYU School of Medicine
Director of Inpatient Rheumatology, Bellevue Hospital Center
co-Director, NYU-Hospital for Joint Diseases Lupus Clinic
Research Office Address:
NYU School of Medicine
New York, NY 10016MedicalResearch.com: What is the background for this study? What are the main findings?Response: Knowing how many people have systemic lupus erythematosus (SLE) is limited, particularly for racial/ethnic subgroups in the United States.
Our work provides accurate estimates of who has (SLE) among the major racial/ethnic groups in the United States and that our estimates for SLE approach the FDA’s definition or a rare disease.
(more…)
MedicalResearch.com Interview with:
Nathalie Franchimont, M.D., Ph.D.
Vice President
Multiple Sclerosis and Immunology Development Unit
Biogen
MedicalResearch.com: What is the background for this study? Response: BIIB059 is an investigational fully humanized IgG1 monoclonal antibody (mAb) targeting blood dendritic cell antigen 2 (BDCA2) expressed on plasmacytoid dendritic cells (pDCs), a protein present in specific cells within the immune system. An antibody against BDCA2 may potentially interrupt production of interferons, which are inflammatory molecules that are increased in patients with lupus and thought to contribute to disease activity.
The LILAC study is two-part, Phase 2, randomized, double-blind trial investigating the efficacy and safety of BIIB059 in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). Data from the CLE portion of the study were recently presented at the European E-Congress of Rheumatology (EULAR) 2020, which was held virtually from June 3-6, 2020.
Overall, study participants with CLE who received BIIB059 demonstrated statistically significant reduction of disease activity compared to those who received placebo, as assessed by the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score. The results were encouraging and it warrants continued evaluation of BIIB059 in patients with CLE.
Cutaneous lupus erythematosus is a chronic autoimmune disease wherein the body’s immune system attacks healthy skin, often causing rashes and skin lesions which can be painful or itchy. There is substantial unmet medical need for people with lupus given the limited number of treatment options available to manage this difficult-to-treat and chronic disease.
Ultimately, we are motivated by the possibility of bringing potential new treatment options to lupus patients in need. (more…)
MedicalResearch.com Interview with:
Richard Alan Furie, MD
Professor, Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases
Feinstein Institutes for Medical Research
Chief, Division of Rheumatology, Northwell Health
Professor of Medicine, Donald and Barbara Zucker School of Medicine
Hofstra/Northwell
MedicalResearch.com: What is the background for this study? Response: It has been known for decades that type I interferons play a role in SLE pathogenesis, and therefore the burning question has been whether inhibitors of these pro-inflammatory cytokines would reduce SLE disease activity and could be used as a therapeutic. There are several strategies for inhibiting the type I interferon pathway, but a conventional approach is to create an antibody against the target protein. The first few clinical trials in SLE evaluated monoclonal antibodies to alpha interferon. Results were modest at best. Since this approach only inhibited one (alpha) of five type I interferon subtypes, there were still four subtypes unaffected that could provoke inflammation. A rather crucial piece of information is that all five subtypes bind to the same receptor. Therefore, if the receptor is blocked as opposed to a single cytokine, the entire type I interferon family of proteins would be prevented from binding the receptor. This was accomplished with anifrolumab.
The phase 2 study in SLE (known as MUSE), which yielded very robust results, was reported several years ago. It served as a foundation for the phase 3 program, which consisted of two pivotal studies known as TULIP-1 and TULIP-2. Both studies were reported at the 2019 American College of Rheumatology meeting in November, 2019. Although TULIP-1 did not achieve the primary endpoint, several secondary endpoints were met. TULIP-2 was successful. Between all three studies, approximately 1000 patients were enrolled. Taking advantage of these large numbers, additional analyses of the combined datasets afforded our ability to answer questions about the effects of anifrolumab that were not previously addressed with greater power.
In the narrative that accompanied my presentation, I stated “In lupus, disease activity begets damage, and damage begets more damage. The long-term sequelae of heightened disease activity, better known as flare, are significant. Regardless of how flare is defined or measured, a major goal is to prevent flare.It is quite justified to think a drug that reduces lupus disease activity should also prevent flares. Well, the proof is in the pudding.In this analysis, we evaluated the effects of anifrolumab on flares. Recall that anifrolumab targets the type I interferon receptor, blocking all 5 type I subtypes. The phase 2 MUSE study yielded robust results as did the phase 3 TULIP-2 study. While, the phase 3 TULIP-1 study did not achieve its primary endpoint, many secondary endpoints showed benefit.In this study, we focused on flare, and examined TULIP-1 and 2 individually as well as pooled data from both studies.” (more…)
MedicalResearch.com Interview with:
Professor Jianmin Fang, Ph.D.
Founder, CEO & CSO
RemeGenMedicalResearch.com: What is the background for this study? Response: Systemic lupus erythematosus (SLE), known more commonly as lupus, is a chronic autoimmune disease in which the immune system mistakenly attacks healthy tissue. SLE can affect tissues like the skin, joints, kidneys, brain and other organs, resulting in a wide variety of signs and symptoms.
With limited treatment options for lupus and the significant unmet medical needs in the treatment of autoimmune diseases, the Phase 2b study evaluated the efficacy and safety of subcutaneous RC18 (telitacicept), a potential new medicine for the treatment of systemic lupus erythematosus (SLE) versus a placebo in combination with standard therapy in patients with SLE at 48 weeks. (more…)
MedicalResearch.com Interview with:
Bella Mehta, MBBS, MS
Assistant Attending Physician, Hospital for Special Surgery
Instructor, Weill Cornell Medical College
MedicalResearch.com: What is the background for this study? What are the main findings?Response: For women with lupus, pregnancy has long been considered high-risk and associated with both medical and obstetric complications. In the 1960s and 1970s, pregnancy was thought to be contraindicated in lupus patients. Beginning in the 1980s, and especially in the 1990s, many studies identified specific risk factors for pregnancy complications and proposed best-practice management guidelines. We wished to see whether these advances improved pregnancy outcomes for lupus patients.
Our study showed a decline in maternal mortality and other outcomes in lupus patients. The improvement in pregnancy outcomes was observed more so in lupus patients than those without lupus.(more…)
MedicalResearch.com Interview with:
Virginia Ladd, CEO American Autoimmune Related Disease Association (AARDA)MedicalResearch.com: Would you briefly explain what is meant by autoimmune disorders?Response: Autoimmune disease is a broad category of related diseases which share both genetic and mechanistic properties. They occur when the person’s immune system attacks the body’s own cell, and tissue. The immune system goes awry and mistakenly attacks the tissues and organs it was designed to protect. Normally the immune system protects the It does this by body by responding to invading microorganisms, such as bacteria, and viruses. Producing antibodies which are special proteins that recognize and destroy the invaders. Autoimmune diseases occur when autoantibodies attack the body’s own cells, tissue and organs. (more…)
MedicalResearch.com Interview with:
Andrea L. Roberts, MPH, PhD
Research Associate, Department of Social and Behavioral Sciences
Harvard T.H. Chan School of Public Health
MedicalResearch.com: What is the background for this study? Response: There is some evidence that depression may increase risk of autoimmune diseases. For example, among people with autoimmune diseases, more people have depression than in the general population. Also, people who have autoimmune diseases who also have depression have more severe disease symptoms.
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MedicalResearch.com Interview with:
Daniel J. Wallace M.D., FACP, MACR
Associate Director, Rheumatology Fellowship Program
Board of Governors, Cedars-Sinai Medical Center
Professor of Medicine, Cedars-Sinai Medical Center
David Geffen School of Medicine Center at UCLA
In affiliation with Attune Health
Beverly Hills, Ca 90211
MedicalResearch.com: What is the background for this study? What are the main findings?Response: This is the first positive study of systemic lupus erythematosus (SLE) using baricitinib, a small oral molecule that blocks the JAK system.
The human kinome consists of 500 genes and helps regulate cell surface receptor interaction. While agents that inhibit certain pathways are approved for rheumatoid arthritis and certain malignancies, this is the first study of its kind in SLE.
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MedicalResearch.com Interview with:
John B. Harley, MD, PhD
Professor and Director
David Glass Endowed Chair
Center for Autoimmune Genomics and Etiology (CAGE)
Department of Pediatrics
University of Cincinnati
Cincinnati Children’s Hospital Medical Center
Cincinnati, Ohio 45229
MedicalResearch.com: What is the background for this study?
Response: Previous work has shown that Epstein-Barr virus infection is associated with systemic lupus erythematosus and studies of the origins of the autoimmune response have also suggested that the autoimmunity of this disease may originate with the immune response against this virus. In the meantime, many investigators have been studying the genetics of lupus over the past 25 years. They have found about 100 convincing genes that alter the risk of developing lupus.
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MedicalResearch.comcom Interview with:
Hui-Wen Lin MD, PHD
Department of Mathematics, Soochow University
Evidence-Based Medicine Center, Wan Fang Hospital, Taipei Medical University
Taipei, Taiwan
MedicalResearch.com: What is the background for this study?
Dr. Hui-Wen Lin: Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder that affects multiple organ systems and it predominantly affects women aged 20 to 40 years, and clinical symptoms caused by autoantibody deposition that triggers subsequent inflammatory reactions vary between individuals. There were 30~80% of SLE patients present neurological symptoms, and it is referred to as neuropsychiatric SLE (NPSLE). However there is no research about risk of dementia for SLE patients. Therefore we investigated this issue by analyzing the National Health Insurance Research Database in Taiwan.
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MedicalResearch.com Interview with:
Jane E. Salmon, MDDivision of Rheumatology
Hospital for Special Surgery, and
Weill Cornell Medical College, New York, NYMedical Research: Background on lupus and antiphospholipid antibodies - what are they?Dr. Salmon: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease that predominantly affects women and presents during their childbearing years. In SLE, the immune system which normally protects one from infection, turns reacts against the self and can cause damage of multiple organs.
Antiphospholipid antibodies (APL) occur in some people with SLE and some without SLE. They are autoantibodies that can damage the placenta and cause arterial and venous thromboses. Patients with APL can have fetal deaths, miscarriages, preeclampsia and/or growth restricted babies.
Pregnancy in patients with SLE, particularly those with antiphospholipid antibodies (APL), and in patients with APL alone, is associated with an increased risk for maternal and fetal morbidity due to preeclampsia (PE) and insufficient placental support of the developing fetus. PE and placental insufficiency are, in turn, associated with adverse pregnancy outcomes (APOs), including maternal complications of PE, intrauterine fetal death, and fetal growth restriction, as well as indicated preterm delivery. Given that APOs affect over one fifth of pregnancies in SLE and/or APL, the ability to identify patients early in pregnancy who are destined for poor outcomes would significantly impact care of this high risk population.
Medical Research: Two bullets about your PROMISSE study:
Dr. Salmon: The PROMISSE Study (Predictors of pRegnancy Outcome: bioMarker In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus). PROMISSE is the largest multi-center, multi-ethnic and multi-racial study to prospectively assess the frequency of APO, clinical, laboratory and biomarker variables that predict APO, in women with SLE and/or APL with inactive or mild/ moderate activity at conception.
Pregnant patients with SLE and/or APL were enrolled at <12 weeks gestation into PROMISSE between September 2003 and August 2013 at 7 sites (n=497) along with matched healthy controls (n=207) and followed every month of pregnancy.(more…)
MedicalResearch.com Interview with:
Dr. Changfu Kuo MD PhD
Division of Rheumatology, Orthopaedics, and Dermatology
School of Medicine, University of Nottingham, Nottingham, England
Division of Rheumatology, Allergy, and Immunology
Chang Gung Memorial Hospital, Taoyuan, Taiwan
Medical Research: What is the background for this study? What are the main findings?
Dr. Kuo: Systemic lupus erythematosus (SLE) is a prototype of autoimmune disease with features like autoantibody production and multiple target organ damage. SLE can affect any part of the body and the course of the disease is highly diverse and unpredictable. SLE can occur at any age and affect both females and males with a sex ratio of 9 to 1.
Familial predisposition has been recognised as a risk factor previously and heritability of SLE has been estimated to be 66%. However, previous reports are often based on less robust sampling strategies and case ascertainment which generally depend on hospital records, self-reported diagnosis and disease registries, therefore limiting generalisability. The previous estimates of heritability are overestimated, due to a lack of consideration of shared environmental contribution.
This study utilised a unique health insurance database that provides information on the whole population of Taiwan and permits determination of spouse and first-degree relatives. Over 23 million people were included in this study. Furthermore, through inclusion of SLE status of the spouse in our analyses the study is also able to examine how much of familial clustering results from genetic versus shared environmental factors. Overall the familial relative risk is 16.92. The genetic contribution to SLE susceptibility is estimated to be 44%. In addition to SLE, other autoimmune diseases are also more prevalent in individuals with a family history of SLE.
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MedicalResearch.com Interview with:
Laura Plantinga, PhD Assistant Professor
Division of Renal Medicine, Department of Medicine
Emory University School of Medicine
Atlanta, GA 30322
Medical Research: What is the background for this study? What are the main findings?
Dr. Plantinga: Quality of care for end-stage renal disease (ESRD), which is treated with dialysis or kidney transplantation, is a high priority for the U.S. healthcare system, given universal coverage of these services. However, quality of ESRD care remains relatively unexplored in lupus patients, who have multiple providers and may have greater access to care. We found that, overall, nearly three-quarters of U.S. ESRD patients with lupus had pre-ESRD nephrology care and about 20% of lupus patients on dialysis were waitlisted for kidney transplant per year; however, fewer than one-quarter of those who started on dialysis had a permanent vascular access in place, which is associated with better outcomes than a temporary catheter. Furthermore, patients who were black or Hispanic were nearly a third less likely to have pre-ESRD care and were also less likely to be placed on the kidney transplant waitlist in the first year of dialysis than white patients. Having Medicaid or no insurance at the start of ESRD were both associated with lower likelihood of quality ESRD care by all measures, despite universal Medicare coverage after the start of ESRD. While there was geographic variation in quality of ESRD care, patterns were not consistent across quality measures.
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Medical Research Interview
Dr Gomez-Puerta MD, PhD, MPH
Division of Rheumatology, Immunology, and Allergy; Brigham and Women's Hospital, Harvard Medical School, Boston, MAMedicalResearch: What is the background for this study? What are the main findings? Dr. Gomez-Puerta: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology which can cause multiorgan system damage and which disproportionately affects women and non- Caucasian minorities. Up to 60% of SLE patients develop renal disease, lupus nephritis (LN), and of these, approximately one fifth progress to end-stage renal disease (ESRD). The risk of cardiovascular (CV) events and mortality is higher in patients with ESRD and in particular in patients suffering SLE. However, information about CV outcomes and mortality is limited in patients with LN associated ESRD.
We observed important variation in cardiovascular outcomes and mortality by race and ethnicity among lupus nephritis related ESRD patients. After adjusting for multiple demographic and clinical factors and accounting for the competing risk of kidney transplantation and loss to follow-up, our results illustrate for the first time that Asian (vs. White) and Hispanic (vs. non-Hispanic) lupus nephritis related ESRD patients have lower mortality risks.
(more…)
Hemodialysis.com Interview with:
Dr. David W. Powell PhD
Associate Director of Clinical Proteomics
Assistant Professor of Medicine Assistant
Professor of Biochemistry and Molecular...
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