Author Interviews, Dermatology / 25.06.2020
Atopic Dermatitis: Study Finds Monoclonal Antibody Tralokinumab + Topical Steroids Effective for Moderate to Severe Disease
MedicalResearch.com Interview with:
[caption id="attachment_24142" align="alignleft" width="128"] Dr. Jonathan Silverberg[/caption]
Dr. Jonathan L. Silverberg MD PhD MPH
Assistant Professor in Dermatology
Medical Social Sciences and Preventive Medicine
Northwestern, Chicago, Illinois
MedicalResearch.com: What is the background for this study?
Response: Topical anti-inflammatory therapy is often inadequate to achieve disease control in patients with moderate-to-severe atopic dermatitis (AD), and systemic therapy is often warranted. Tralokinumab is a fully human immunoglobulin G4 monoclonal antibody that specifically binds to the IL-13 cytokine with high affinity and inhibits downstream IL-13 pro-inflammatory signaling.
Tralokinumab was previously studied as a monotherapy in moderate-severe AD in the ECZTRA1 and ECZTRA2 studies. In this Phase 3 randomized controlled study, ECZTRA3, tralokinumab was studies in combination with topical corticosteroids compared to placebo with topical corticosteroids. The use of topical anti-inflammatory therapy is more akin to the way in which systemic and biologic therapies are typically used in the real-world.
Dr. Jonathan Silverberg[/caption]
Dr. Jonathan L. Silverberg MD PhD MPH
Assistant Professor in Dermatology
Medical Social Sciences and Preventive Medicine
Northwestern, Chicago, Illinois
MedicalResearch.com: What is the background for this study?
Response: Topical anti-inflammatory therapy is often inadequate to achieve disease control in patients with moderate-to-severe atopic dermatitis (AD), and systemic therapy is often warranted. Tralokinumab is a fully human immunoglobulin G4 monoclonal antibody that specifically binds to the IL-13 cytokine with high affinity and inhibits downstream IL-13 pro-inflammatory signaling.
Tralokinumab was previously studied as a monotherapy in moderate-severe AD in the ECZTRA1 and ECZTRA2 studies. In this Phase 3 randomized controlled study, ECZTRA3, tralokinumab was studies in combination with topical corticosteroids compared to placebo with topical corticosteroids. The use of topical anti-inflammatory therapy is more akin to the way in which systemic and biologic therapies are typically used in the real-world.
Dr. Shumel[/caption]
Brad Shumel, MD
Senior Director of Medical Affairs, Immunology
Regeneron
MedicalResearch.com: What is the background for this study?
Response: Atopic dermatitis is a chronic inflammatory disease and one of the most common skin disorders in children. Severe atopic dermatitis is characterized by skin lesions that often cover a large body surface area and can include intense, persistent itch. Uncontrolled moderate-to-severe atopic dermatitis can have a physical, emotional and psychosocial impact on children, resulting in sleep deprivation, activity restriction, poor school performance, depression and anxiety that can have a greater impact on quality-of-life.
The standard of care for this pediatric population has been topical corticosteroids. Children with severe atopic dermatitis who remain uncontrolled with topical therapies have limited treatment options.
This Phase 3 trial was conducted to evaluate the safety and efficacy of dupilumab plus topical corticosteroids (TCS) compared with TCS alone in children with uncontrolled severe atopic dermatitis across two treatment arms – every four weeks and every two weeks (Q4W and Q2W).
Dr. Loewen[/caption]
Shawn Loewen PhD
Professor, Michigan State University
Department of Linguistics & Germanic, Slavic, Asian and African Languages
Second Language Studies Program
Associate Editor, 
Dr. Yosipovitch[/caption]
Gil Yosipovitch, MD, Professor
Miami Itch Center
Lennar Medical Foundation
South Miami Clinic in Coral Gables
University of Miami Health System
MedicalResearch.com: What is the background for this study?
Response: Chronic Pruritus is a common and burdensome condition in patients with end stage chronic kidney disease (CKD). It is Present at all stages of CKD, not only in patients undergoing hemodialysis (including stage 3-5 CKD). There are no approved treatments for this condition in US and Europe. CKD pruritus has significant impact on quality of life of patients with higher mortality rates due to its effect on sleep.
Studies in the last 2 decades have shown that in patients with CKD pruritus there is an imbalance between endogenous mu opioids that are over expressed to Kappa Opioids that are down regulated.
Difelikefalin (DFK) is a novel peripherally selective kappa opioid receptor (KOR) agonist. Study of IV DFK administration in hemodialysis patients has recently been published and showed significant anti Pruritic effect ( NEJM Fishbane et al. 382: 289-290, 2020).
Response: It is well known that marijuana usage impairs driving ability, yet the early studies of the effects of recreational marijuana legalization on traffic fatalities were inconclusive.
MedicalResearch.com: What are the main findings?
Response: By analyzing data over a longer time period, we found that the legalization of recreational marijuana increased traffic deaths in the first four states to legalize. Traffic fatalities increased about 20% in those states. If we apply these numbers to the nation as a whole, nationwide legalization would be associated with about 7,000 excess traffic fatalities each year.
Dr. Factor[/caption]
Stewart A. Factor, D.O.
Professor of Neurology
Director of the Movement Disorders Program
Vance Lanier Chair of Neurology
Emory University School of Medicine
MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by OFF episodes.
Response: Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disease characterized by motor symptoms, including tremor at rest, rigidity and impaired movement, as well as significant non-motor symptoms, such as cognitive impairment, psychiatric symptoms and autonomic symptoms (i.e. urinary issues, constipation, low blood pressure). It is the second-most common neurodegenerative disease after Alzheimer’s disease and it is predicted that the prevalence of Parkinson’s disease will double by the year 2040. The symptoms of PD are in substantial part, due to loss of dopamine nerve cells in the brain. The current standard of care for PD includes replacing the dopamine loss by the use of oral carbidopa/levodopa. Levodopa is a precursor of dopamine, converted in the brain.
OFF episodes have been a significant unmet need in Parkinson’s disease since the emergence of levodopa. Initially, levodopa controls PD symptoms in a continuous fashion throughout the day. With time the response becomes less predictable and patients experience a re-emergence or worsening of PD symptoms. These episodes are what we mean by OFF episodes. OFF episodes can be characterized, in part, by re-emergence of motor symptoms including tremor, stiffness or slowed movement that can happen at any point during the day. OFF episodes typically begin within the first five years of treatment and occur at the end of a dose. This is referred to as end of dose failure or wearing off. Within the first four to six years after diagnosis, regardless of disease severity, up to 60 percent of people with PD experience OFF episodes. With time these episodes become longer, more severe and disabling, more frequent and less predictable as PD progresses. They can take up more than half the day
OFF episodes may alter a persons’ ability to perform everyday activities by slowing or even precluding their completion. The result is significant burden and distress for people living with Parkinson’s disease (PD) and their care partners.
CTH-300 was a Phase 3, 12-week, randomized, double-blind, placebo-controlled, parallel group, study examining the efficacy, safety and tolerability of apomorphine hydrochloride sublingual film (KYNMOBI) in people with levodopa-responsive PD complicated by OFF episodes. The primary endpoint was a mean change in the score from pre-dose in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Motor Examination at 30 minutes after dosing at the 12-week visit of the maintenance treatment phase. The key secondary endpoint was the percentage of people with PD with a patient-rated full ON (or best) response within 30 minutes at the 12-week visit of the maintenance treatment phase.
Dr. Desai[/caption]
Nimesh D. Desai, MD, PhD
Director, Thoracic Aortic Surgery Research Program
Associate Professor of Surgery
Hospital of the University of Pennsylvania
MedicalResearch.com: What is the background for this study?
Dr. Chase Brown: Opioid use in the United States is a public health emergency. We know that opioids prescribed after general surgery operations to patients who never received them within the year prior to their surgery are at increased risk for continuing to take opioids months later. However, this has not been studied in patients undergoing cardiac surgery, who often times have more severe post-operative pain.
Our goal in this study was to determine how many patients after cardiac surgery and are opioid naive are continuing to take opioids within 90-180 days after their surgery. 
Dr. Vandrey[/caption]
Ryan Vandrey, Ph.D.
Associate Professor
Behavioral Pharmacology Research Unit
Johns Hopkins University School of Medicine
Baltimore, MD 21224
MedicalResearch.com: What is the background for this study?
Response: The background for this study is that 33 states in the U.S. have legalized medicinal cannabis use and millions of people are using cannabis for therapeutic purposes, but we have very little data on the broad health impacts of medicinal cannabis use.
We surveyed medicinal cannabis users and non-using controls who had a variety of health problems and found that the cannabis users reported better health, quality of life, and less healthcare utilization compared with controls. Because we worried about group characteristics accounting for the differences observed, we then did an analysis of people who switched groups over time (e.g. non-users who later initiated cannabis use or cannabis users who later quit) and found the same differences emerged in the same individuals over time. Important to note here is that not all individuals who used cannabis benefited from it and that most participants were using high CBD varieties of cannabis in conjunction with more traditional treatments.
Dr. Hänggi[/caption]
MedicalResearch.com: What is the background for this study?
Response: Anti-MAG neuropathy is a rare form of acquired demyelinating neuropathy. The disease onset normally presents after the age of 50 years and is 2.7 times more frequent in men than in women, with a prevalence of about 1 in 100,000. It is caused by the production of monoclonal anti-MAG IgM antibodies that recognize the HNK-1 epitope. The myelin-associated glycoprotein MAG is a mediator for the formation and maintenance of the myelin sheaths. There is strong evidence that the binding and deposition of anti-MAG IgM autoantibodies on myelin sheath is responsible for the demyelination, which clinically manifests itself as a peripheral neuropathy affecting primarily sensory nerves. However, the causes and the exact mechanisms behind the expansion of anti-MAG IgM producing B-cell and plasma cell clones are not fully understood.
Most off-label treatments aim to reduce pathogenic autoantibody titers by depleting autoantibody-producing B cell clones which interfere with antibody-effector mechanisms, or physically remove autoantibodies from the circulation. Most frequently, the anti-CD20 monoclonal antibody rituximab is used to treat anti-MAG neuropathy patients. However, all of these treatment options often lack of selectivity, efficiency, or can induce severe adverse effects in some patients.
Polyneuron has designed PN-1007 to highly selectively target the IgM autoantibodies that cause anti-MAG neuropathy. PN-1007 is a glycopolymer that mimics the natural HNK-1 carbohydrate epitope found on myelin of peripheral nerves and binds to the circulating disease-causing antibodies. By eliminating these pathogenic antibodies, PN-1007 may protect the integrity of the neuronal myelin sheaths of anti-MAG neuropathy patients.
Prof. FAN Zhiyong PhD
University of California, Irvine
HKUST School of Engineering
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: According to the report of The World Health Organization, there are over 252 million people suffering from visual impairment globally and 15 million of them are difficult to cure by conventional medical methods. However, today, even the best bionic eyes have only 200 clinical trials, less than 1 ppm of all the patients, mainly due to their poor performance and high cost. The huge gap in supply and demand triggers the study of bionic eyes with performance comparable to human eyes. One important reason for their poor performance is the mismatch in shape between the flat bionic eyes and concave sclera. To protect the soft tissue in eyes from being damaged by the bionic surface, the implanted bionic eyes have to be small. This has limited the sensing area and further the electrodes number, and finally yielded poor image sensing characters with low resolution and narrow field-of-view.
In this work, we are trying to achieve high performance image sensing by biomimeticing human eyes. The high-density NWs are well aligned and embedded in a hemispherical template to serve as retina. The conformal attachment of bionic eyes with sclera enables the large sensing area and wide visual angle. In addition, each individual high-density nanowires can potentially work as an individual pixel. By addressing these challenges, our device design has huge potential to improve the image sensing performance of bionic eyes.
Dr. Al-Hendy[/caption]
MedicalResearch.com: What is the background for this approval?
Uterine fibroids, commonly referred to as uterine leiomyomas, are the most common type of non-cancerous tumor known to impact women of reproductive age (30-50 years old). In fact, studies show that uterine fibroids can occur in up to 70 percent of European American women and over 80 percent of African American women by age 50. As a result of uterine fibroids, women can experience a range of symptoms, the most common being heavy menstrual bleeding (i.e. prolonged and/or frequent bleeding), which can lead to other health effects such as anemia, fatigue, pelvic pain, urinary frequency etc.
Uterine fibroid treatment recommendations have historically been based on the size and location of the fibroid(s). When treating larger and more complicated fibroids, healthcare providers have typically believed that surgery is their best course of action, which has made uterine fibroids the leading reason for the hysterectomies performed in the U.S. The FDA approval of ORIAHNN was based on improving care for uterine fibroid sufferers who have had a negative impact on their quality of life due to disruptive symptoms. What makes the approval of ORIAHNN so exciting, is that women now have an oral therapy to directly address heavy menstrual bleeding due to uterine fibroids.
Dr. Kempe[/caption]
Allison Kempe, MD, MPH
Ergen Family Endowed Chair in Pediatric Outcomes Research
Professor of Pediatrics, University of Colorado School of Medicine
Director of ACCORDS (Adult and Child Consortium for Health Outcomes Research and Delivery Science)
University of Colorado School of Medicine | Children’s Hospital Colorado
MedicalResearch.com: What is the background for this study?
Response: In 2019 the WHO designated vaccine hesitancy as one of the ten leading threats to global health. Although studies have assessed parental vaccine hesitancy in different localities and estimated vaccine refusals nationally, there is little recent US national data on the prevalence of hesitancy about routine childhood vaccines and national hesitancy rates for influenza vaccine have never been assessed. We used a hesitancy scale developed by the WHO to estimate levels of parental hesitancy for both routine childhood and childhood influenza vaccination 
Dr. Crowley[/caption]
Matthew J. Crowley, MD
Core Investigator, Durham Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT)
Affiliated Investigator, VA Office of Rural Health
Staff Physician, Endocrinology Section, Durham VA Health Care System
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