Accidents & Violence, Author Interviews, Dermatology, JAMA, UCSF, Urology / 17.08.2017

MedicalResearch.com Interview with:
Thomas W. Gaither, BS Department of Urology University of California, San Francisco General Hospital, San Francisco
MedicalResearch.com: What is the background for this study? What are the main findings? Response: We study genitourinary trauma and reconstruction. This study was motivated from a previous study showing that Emergency Room visits due to grooming were increasing over the past nine year. We sought to better characterize who was at most risk for grooming injuries. We found that grooming is extremely common in both men and women and minor injuries occur in about 25% of groomers. Surprisingly, a little over one percent sought medical care due to their injury. Participants at most risk our those who remove all of their pubic hair frequently ( as opposed to those who just trim). We did not find any instruments that were necessarily putting participants at risk for injury. (more…)
Author Interviews, Cancer Research, Dermatology / 17.08.2017

MedicalResearch.com Interview with: Prof. Gary M. Halliday Discipline of Dermatology, Bosch Institute Central Clinical School University of Sydney Sydney, NSW, Australia MedicalResearch.com: What is the background for this study? What are the main findings? Response: The recently published article is a review paper- we reviewed previous laboratory studies of the effects of nicotinamide on normal pigment cells and on melanoma, and also the previous studies showing that nicotinamide can reduce rates of non-melanoma skin cancer (basal cell and squamous cell carcinoma) in high risk patients. We have not done any clinical investigations of nicotinamide as a preventive agent for melanoma. (more…)
Author Interviews, Cost of Health Care, Dermatology, JAMA / 16.08.2017

MedicalResearch.com Interview with: Kyle T. Amber, MD Department of Dermatology UC Irvine Health Irvine, CA 92697-2400  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The use of IVIg has been shown in randomized controlled trials to be safe and highly effective in the treatment of both pemphigus and bullous pemphigoid. Despite its efficacy, its cost remains a deterrent to its use. Cost studies in the United States point towards IVIg being an overall cost-saving therapy in the treatment of  Autoimmune Blistering Diseases when compared to traditional immunosuppressive treatment due to the decrease in associated infections, complications, and hospitalizations. (more…)
Author Interviews, Cancer Research, Dermatology, Ophthalmology / 24.07.2017

MedicalResearch.com Interview with: Dr.med.univ. Christoph Schwab Departement of Ophthalmology Medical University of Graz Graz, Austria  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Knowledge about risk factors and/or pathways involved in pathogenesis is from special importance in order of preventing diseases. The role of sunlight in several eye diseases is unclear. In our study we found a close relation between sun light exposure - evaluated by a full body skin examination and a personal questionnaire - and iris freckles. Therefore we suggest the presence of iris freckles as a novel biomarker indicating high ocular sun exposure. (more…)
Author Interviews, Dermatology / 21.07.2017

MedicalResearch.com Interview with: Dr Jean Fletcher Assistant Professor Schools of Medicine and Biochemistry & Immunology Trinity College Dublin, the University of Dublin Dublin, Ireland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Hidradenitis suppurativa (HS) is an inflammatory skin disease which causes deep, painful lesions in areas such as the underarms and groin. 1-4% of people are thought to suffer from the disease, however as it is under recognised and often misdiagnosed these may be conservative estimates. The pain and distress associated with HS leads to a poor quality of life with many patients experiencing depression. Current interventions include combinations of antibiotics, surgery to remove lesions and more recently the use of the biologic therapies such as TNF inhibitors; however these are often ineffective and there is a pressing need for more effective treatments. The cause of Hidradenitis suppurativa is unknown, however there are known risk factors which include smoking and obesity, and there is an association with inflammatory bowel disease, which suggests that dysregulation of the immune system may play a role. (more…)
Author Interviews, Dermatology, Immunotherapy, JAMA, Lung Cancer / 14.07.2017

MedicalResearch.com Interview with: Dr. Noelia Rivera MD Dermatologist Hospital Universitari Germans Trias i Pujol, Badalona Universitat Autònoma de Barcelona MedicalResearch.com: What is the background for this study? Response: In the last few years some new therapies targeting immune checkpoints have been developed. The programmed death receptor-1 (PD-1) are immune checkpoints that prevent the immune system to act against own tissues. By blocking these mediators it is possible to prevent tumors to escape from the immune system. About half of the patients receiving these therapies will develop mild to moderate cutaneous adverse events. In the pre-authorization studies for malignant melanoma these include rash, vitiligo, and pruritus. "Rash" has commonly been reported as an adverse event in many oncologic trials evaluating the drugs, without providing further information about the clinical or histological details. Lately, lichenoid eruptions associated to these therapies have been reported and it suggests that an important percentage of these reactions present lichenoid histological features. (more…)
Author Interviews, Dermatology, Melanoma / 14.07.2017

MedicalResearch.com Interview with: Maryam M. Asgari, MD, MPH Department of Dermatology Massachusetts General Hospital, Department of Population Medicine Harvard Medical School, Boston, Massachusetts Division of Research, Kaiser Permanente Northern California, Oakland  MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Laboratory studies show lithium, an activator of  the Wnt/ß-catenin signaling pathway, slows melanoma progression, but no published epidemiologic studies have explored this association. We conducted a retrospective cohort study of adult white Kaiser Permanente Northern California members (n=2,213,848) from 1997-2012 to examine the association between lithium use and melanoma risk. Our main finding is that lithium-exposed individuals had a reduced incidence of melanoma, did not develop very thick tumors (> 4 mm Breslow depth) or extensive disease at presentation, and had decreased melanoma-specific mortality compared to unexposed individuals suggesting a possible role for lithium in altering melanoma risk. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Dermatology, HIV, JAMA, Kaiser Permanente, Merck / 13.07.2017

MedicalResearch.com Interview with: Maryam M. Asgari, MD, MPH Department of Dermatology Massachusetts General Hospital, Department of Population Medicine Harvard Medical School, Boston, Massachusetts Division of Research, Kaiser Permanente Northern California, Oakland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nonmelanoma skin cancer – defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) – is a common malignant condition, affecting more than 2 million Americans every year. BCCs are more common than SCCs among individuals with healthy immune systems, while SCCs are more predominate than BCCs among people who are immunocompromised. We examined how laboratory markers used to evaluate HIV disease progression may be associated with subsequent nonmelanoma skin cancer risk in white patients previously diagnosed with at least one such cancer from 1996 to 2008.  We measured CD4 count, viral load and subsequent nonmelanoma skin cancer. The study included 455 participants with HIV and 1,952 without HIV. All were members of the Kaiser Permanente Northern California health care plan. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Dermatology, JAMA / 07.07.2017

MedicalResearch.com Interview with: Dr. Chrysalyne D. Schmults, MD, MSCE Associate Professor of Dermatology, Harvard Medical School Director, Mohs and Dermatologic Surgery Center and Mr. Pritesh S. Karia, MPH Department of Epidemiology Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland Department of Dermatology Brigham and Women's Faulkner Hospital Harvard Medical School, Boston, Massachusetts Jamaica Plain, MA 02130-3446  MedicalResearch.com: What is the background for this study? Response: Perineural nerve invasion (PNI) is a well-recognized risk factor for poor prognosis in patients with cutaneous squamous cell carcinoma (CSCC). Most cases of CSCC with PNI are identified on histologic examination at the time of surgery and the patient has no clinical symptoms or radiologic evidence of PNI. These cases are classified as incidental PNI (IPNI). However, some patients with PNI present with clinical symptoms and/or radiologic evidence of PNI. These cases are classified as clinical PNI (CPNI). A few studies have shown differences in disease-related outcomes between CSCC patients with IPNI and CPNI but consensus regarding adjuvant treatment and detailed guidelines on follow-up schedules have not yet materialized. (more…)
Author Interviews, Cancer Research, Dermatology, JAMA, University of Pennsylvania / 06.07.2017

MedicalResearch.com Interview with: Mackenzie R. Wehner, MD, MPhil Department of Dermatology University of Pennsylvania Philadelphia, PA MedicalResearch.com: What is the background for this study? Response: For some diseases, we have national registries, in which information about every person with that disease is entered for research purposes. For other diseases, unfortunately, we do not have such registries. There are growing opportunities to use information like internet searches to better understand behaviors and diseases, however. Our study was a proof-of-concept: we aimed to find out whether internet searches for diseases correlated with known incidence (how many people are diagnosed with the disease) and mortality (how many people die of the disease) rates. E.g. does the number of people who searched 'lung cancer' online correlate with the number of people who we know were diagnosed with or who died of lung cancer during that same time period? This is important to know if researchers in the future want to use internet search data for diseases where we lack registry information. (more…)
Author Interviews, BMJ, Dermatology / 03.07.2017

MedicalResearch.com Interview with: Joann G. Elmore M.D., M.P.H. Professor of Medicine, Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499 MedicalResearch.com: What is the background for this study? JE: Previous studies on diagnostic accuracy in interpreting melanocytic lesions exist but have small sample size, inclusion of experts only, or small numbers of specimens. We sought to examine accuracy and reproducibility in melanocytic skin lesions by improving upon the methodological limitations of previous studies. Specifically, we recruited a large national sample of practicing community and academic pathologists with a wide range of experience, and we utilized a large sample of biopsy cases that were carefully selected. Given that diagnostic errors can lead to patient deaths and invasive melanoma kills more than 9,000 Americans each year, we wanted to study the issue of diagnostic accuracy in interpreting melanocytic skin lesions in a very robust fashion. (more…)
Author Interviews, Dermatology, UCSF / 26.06.2017

MedicalResearch.com Interview with: Dr. Katrina Abuabara MD, MA, MSCE University of California San Francisco MedicalResearch.com: What is the background for this study? Response: Atopic dermatitis (synonymous with atopic eczema or just “eczema”) is a common and burdensome condition that often presents in childhood but can occur in individuals of any age. It is episodic, meaning that it waxes and wanes over time, and many patients will have periods without signs or symptoms of the disease. Conventional wisdom suggests that “most children” improve by adolescence, but prior studies have not had sufficiently frequent follow-up to detect episodic disease beyond childhood. (more…)
Author Interviews, Dermatology, Infections / 22.06.2017

MedicalResearch.com Interview with: Dr. Sue Cammarata, MD Chief Medical Officer Melinta Therapeutics MedicalResearch.com:   Would you explain what is meant by MRSA? Response: MRSA is methicillin-resistant Staphylococcus aureus, a type of staph bacteria that is  resistant to many antibiotics. MRSA is noted by the CDC as one of the top 18 drug-resistant bacteria threats to the United States.  (from CDC https://www.cdc.gov/drugresistance/biggest_threats.html  )  MedicalResearch.com:   Why is infection with MRSA so serious? Response:  MRSA can cause skin infections, lung infection and other issues. If left untreated, MRSA infections can become severe and cause sepsis - a life-threatening reaction to severe infection in the body - and even death.  MRSA can also cause major issues, such as bloodstream infections, pneumonia and surgical site infections in a healthcare setting, such as a hospital or nursing home. “Resistance to first-line drugs to treat infections caused by Staphlylococcus aureus—a common cause of severe infections in health facilities and the community—is widespread. People with MRSA (methicillin-resistant Staphylococcus aureus) are estimated to be 64% more likely to die than people with a non-resistant form of the infection.”  (quote from WHO website http://www.who.int/mediacentre/factsheets/fs194/en/  )   (more…)
Author Interviews, Dermatology, HPV, PLoS / 22.06.2017

MedicalResearch.com Interview with: Prof. Dr. med. Sigrun Smola Institute of Virology, Saarland University Homburg/Saar, Germany MedicalResearch.com: What is the background for this study? Response: Non-melanoma skin cancer (NMSC), the most common cancer in humans, is caused by UV-irradiation. The potential co-factor role of cutaneous genus beta-human papillomaviruses (beta-HPV) in skin carcinogenesis, particularly in immunosuppressed patients, has become a major field of interest. However, the underlying mechanisms were unclear. The skin has natural mechanisms providing protection against UV-induced damage. One important factor suppressing UV-induced skin carcinogenesis is the transcription factor C/EBPα belonging to the CCAAT/enhancer binding protein family. C/EBPα can induce cellular differentiation and is regarded as a tumor suppressor in various tissues. When C/EBPα expression is blocked in these tissues, tumorigenesis is enhanced. Another important factor is the microRNA-203. It has been shown to control “stemness” in normal skin by suppressing a factor called p63. In many tumors miR-203 expression is shut off releasing this “brake”. In our study we demonstrate that cutaneous beta-HPV interferes with both protective factors providing an explanation how cutaneous beta-HPV enhances the susceptibility to UV-induced carcinogenesis. Moreover, we provide evidence that these viruses regulate miR-203 via C/EBPα. We have investigated this mechanism in Epidermodysplasia verruciformis (EV) patients that serve as a human model disease for studying the biology of genus beta-HPVs. They are highly susceptible to persistent genus beta-HPV infection, such as HPV8, and have an increased risk to develop non-melanoma skin cancer at sun-exposed sites. (more…)
Author Interviews, Brigham & Women's - Harvard, Dermatology, Melanoma / 22.06.2017

MedicalResearch.com Interview with: David E. Fisher MD, PhD Edward Wigglesworth Professor & Chairman Dept of Dermatology Director, Melanoma Program MGH Cancer Center Director, Cutaneous Biology Research Center Massachusetts General Hospital Harvard Medical School Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study grew from an interest to mimic the dark pigmentation patterns in human skin which are known from epidemiology to be associated with low skin cancer risk. In the current work, a molecular inhibitor of the SIK enzyme was used to block the inhibitory action of SIK relative to melanin synthesis. The result was stimulation of dark pigmentation within human skin. (more…)
Author Interviews, Dermatology, Genetic Research, Yale / 05.06.2017

MedicalResearch.com Interview with: Keith Adam Choate, MD, PhD, FAAD Associate Professor of Dermatology, Genetics and Pathology Director of Research, Dermatology Yale University School of Medicine New Haven, CT MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Over the last 10 years, we have systematically been examining patients with ichthyosis to identify new genetic causes of this group of disorders.  We found that autosomal recessive mutations in KDSR cause ichthyosis and that the resulting skin disease is effectively treated with isotretinoin. (more…)
Author Interviews, Dermatology / 01.06.2017

MedicalResearch.com Interview with: Jean-François Cailhier, M.D., Ph.D., FRCP(c) Professeur Agrégé de Clinique/ Associate Professor Département de Médecine, Faculté de Médecine Université de Montreal MedicalResearch.com: What is the background for this study? What are the main findings? Response: Milk Fat Globule Epidermal Growth Factor-8 (MFG-E8) is released by apoptotic cells and activated cells in the skin. Its effect on endothelial cells and pericytes was previously reported to accelerate wound healing. In our wound healing model, we demonstrated that MFG-E8 was important to reprogram skin macrophages into pro-repair cells. Moreover, we demonstrated that administration of exogenous MFG-E8 was able to accelerate wound healing in WT and MFG-E8 KO mice by generating M2 macrophages. Furthermore, to highlight to importance of MFG-E8 on macrophage reprogramming, adoptive transfer of MFG-E8-treated macrophages also promoted wound healing. These pro-repair effects seem to be dependent on the production of a crucial fibroblast growth factor, basic Fibroblast Growth Factor (bFGF), by macrophages which promoted fibroblast migration and proliferation. (more…)
Author Interviews, Dermatology, OBGYNE / 16.05.2017

MedicalResearch.com Interview with: Alexander Egeberg, MD PhD Gentofte Hospital Department of Dermatology and Allergy Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: An issue that frequently arise in clinical practice is the question from patients whether they should discontinue their therapy if they want to have children. Since immunosuppressant agents are frequently used for a number of conditions, and discontinuation could lead to disease flaring, assessment of the potential impact of such drugs on birth outcomes is important. In our study, we examined birth outcomes in children whose father had received treatment with methotrexate, azathioprine, cyclosporine, and mycophenolate mofetil in the time leading up to conception. Importantly, we found no increased risk of congenital abnormalities, low birth weight, or preterm birth associated with paternal treatment with these drugs. (more…)
Allergies, Asthma, Author Interviews, Dermatology, PLoS, Vitamin D / 10.05.2017

MedicalResearch.com Interview with: Brent Richards, MD, MSc Associate Professor of Medicine William Dawson Scholar / FRQS Clinical Research Scholar Departments of Medicine, Human Genetics, Epidemiology and Biostatistics McGill University Senior Lecturer, King's College London (Honorary) MedicalResearch.com: What is the background for this study? What are the main findings? Response: Some previous epidemiological studies have suggested that low vitamin D levels are associated with increased rates of asthma, atopic dermatitis—an itchy inflammation of the skin—and elevated levels of IgE, an immune molecule linked to atopic disease (allergies). In our study, we looked at genetic and health data on more than 100,000 individuals from previous large studies to determine whether genetic alterations that are associated with vitamin D levels predispose people to the aforementioned conditions. We found no statistically significant difference between rates of asthma (including childhood-onset asthma), atopic dermatitis, or IgE levels in people with and without any of the four genetic changes associated with lower levels of 25-hydroxyvitamin D, the form of vitamin D routinely measured in the blood. (more…)
Author Interviews, Dermatology, JAMA, Melanoma, Technology / 27.04.2017

MedicalResearch.com Interview with: Laura Korb Ferris, MD, PhD Associate Professor, University of Pittsburgh Clinical and Translational Science Institute Director of Clinical Trials Department of Dermatology University of Pittsburgh Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: We found that a non-invasive adhesive patch applied to the skin over a pigmented skin lesion allowed us to capture enough genetic material from the lesion to analyze and predict if that lesion is likely to be melanoma, meaning a biopsy is warranted, or if it is likely benign, meaning the patient would not need a skin biopsy. In this study, we asked dermatologists to use their clinical judgement to decide if they would recommend biopsying a skin lesion based on photos and information about the lesion and the patients, such as the patient's age, personal and family history of skin cancer, and if the lesion was new or changing. We then provided them the read out of the gene test and asked them how this influence their decision. We found that with this test result, dermatologists were more accurate in their decision making, meaning they were more likely to recommend biopsy of melanomas and less likely to biopsy harmless moles than they were without the test. This is important as it means this test has the potential to reduce the number of unnecessary skin biopsies performed, saving patients from undergoing a procedure and having a scar as a result, without increasing the risk of missing a melanoma. (more…)
Author Interviews, Dermatology, Orthopedics, Stem Cells / 22.04.2017

MedicalResearch.com with: Lee Buckler, CEO RepliCel Life Sciences MedicalResearch.com: What is the background for this your company, RepliCel.com? Response: RepliCel Life Sciences is a Canadian regenerative medicine company based in Vancouver, British Columbia that was founded in 2006. The company focuses on the development of cell therapies using a patient's own cells (autologous cell therapy). It is developing treatments targeted at healing chronic tendon injuries that have failed to heal properly, hair restoration, and the treatment of damaged and aged skin. (more…)
Author Interviews, Cannabis, Dermatology / 21.04.2017

MedicalResearch.com Interview with: Jessica S. Mounessa, BS University of Colorado School of Medicine Aurora, Colorado and Robert Dellavalle, MD, PhD, MSPH Professor of Dermatology and Public Health University of Colorado School of Medicine Colorado School of Public Health Chief, Dermatology Service US Department of Veterans Affairs Eastern Colorado Health Care System Denver, CO 80220  MedicalResearch.com: What is the background for this study? What are the main findings? Response: One in 10 adult cannabis users in the U.S. use it for medicinal purposes. Medicinal cannabis is well studied for its uses in chronic pain, anorexia, and nausea. Numerous recent studies have highlighted other medicinal uses for cannabinoids and related compounds. We conducted a comprehensive review of the literature on the potential role of cannabinoids in conditions affecting the skin. Our study reveals the potential benefit of topically prepared cannabinoid compounds, especially for pruritus and eczema.  For example, creams containing Palmitoylethanolamide (PEA), which enhances cannabinoid-receptor binding, have been successful in relieving itch both in the literature, and anecdotally in our clinics. Though not strictly considered an endocannabinoid, as it does not directly bind to CB1 and CB2 receptors, PEA works by enhancing endocannabinoid binding to these receptors.** Furthermore, the majority of the cannabinoid compounds we studied did not contain psychoactive effects. (more…)
Author Interviews, Dermatology, Technology / 17.04.2017

MedicalResearch.com Interview with: Paul J.D. Whiteside, doctoral candidate and Dr. Heather Hunt, assistant professor of bioengineering University of Missouri MedicalResearch.com: What is the background for this technology? What are the barriers to the use of conventional laser treatment of tattoos? Response: Traditional laser treatments rely on the concept of selective photothermolysis (laser-induced heating) to specifically target certain structures for treatment, while leaving other parts of the skin unaffected. The problem with traditional laser treatments is that the laser needs to transmit through the epidermis, which acts as a barrier to laser transmission both due to its reflective properties and because it is filled with light-absorbing melanin, the pigment that gives our skin its color. Sonoillumination acts to change the properties of the epidermis temporarily using painless ultrasound technology, thereby allowing more laser light to penetrate deeper into the skin to impact desired targets, such as hair follicles, tattoos, and blood vessels. Funding for clinical trials is currently being sought to provide evidence for what we surmise may be benefits of this technology relative to traditional laser treatments. These benefits may include being able to treat darker-skinned people more effectively, being able to provide laser therapy with less risk of scarring or pigment changes, and being able to do treatments with less discomfort, fewer treatments, and lower laser energy settings. (more…)
Author Interviews, Dermatology, Genetic Research / 17.04.2017

MedicalResearch.com Interview with: Akio Kihara, PhD. Laboratory of Biochemistry Faculty of Pharmaceutical Sciences, Hokkaido University Sapporo, Japan MedicalResearch.com: What is the background for this study? What are the main findings? Response: The skin barrier is the most powerful defensive mechanism terrestrial animals possess against pathogens and harmful substances such as allergens and pollutants. Recent studies indicate that lipids play a central role in skin barrier formation. Multi-lamellar structures consisting of lipids are formed extracellularly in the stratum corneum, the outermost layer of epidermis, and their high hydrophobicity prevents the invasion of external pathogens and compounds. The stratum corneum-specific lipid acylceramide is especially important for skin barrier formation. Decreases in acylceramide levels are associated with cutaneous disorders such as ichthyosis and atopic dermatitis. However, the mechanism behind acylceramide production is poorly understood, especially regarding the last step of acylceramide production: i.e., esterification of ω-hydroxyceramide with linoleic acid. This means that the broader picture of the molecular mechanisms behind skin barrier formation still remained unclear. Although PNPLA1 has been identified as an ichthyosis-causative gene, its function in skin barrier formation remains unresolved. In the present study, we revealed that PNPLA1 catalyzes the last step of acylceramide synthesis. Our finding completes our knowledge of the entire pathway of the acylceramide production, providing important insights into the molecular mechanisms of skin barrier formation. (more…)
Author Interviews, Dermatology, Smoking / 11.04.2017

MedicalResearch.com Interview with: Jacob P. Thyssen MD, PhD, DmSci Department of Dermatology and Allergy Herlev and Gentofte Hospital University of Copenhagen Hellerup, Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: Atopic dermatitis has been associated with various comorbidities. With the emergence of biologics for the treatment of atopic dermatitis, the hypothesis has been raised that atopic dermatitis is a systemic immune disease affecting more than just the skin. (more…)
Author Interviews, Boehringer Ingelheim, Dermatology, Eli Lilly, Immunotherapy, J&J-Janssen, Merck / 30.03.2017

MedicalResearch.com Eric Hughes Global Development Franchise Head Immunology & Dermatology Novartis MedicalResearch.com: What is the background for this study? What are the main findings? Response: Psoriasis is a chronic immune-mediated inflammatory disease that negatively impacts patients’ quality of life (QOL); therefore QOL outcomes are increasingly recognized as an important measure of efficacy in psoriasis, complementing traditional measures of severity such as the Psoriasis Area and Severity Index (PASI). Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), exhibits significant efficacy in the treatment of moderate-to-severe psoriasis, ankylosing spondylitis and psoriatic arthritis, demonstrating a rapid onset of action and a favorable safety profile. Biologic therapies for psoriasis have previously been associated with a fall-off in efficacy over time; accordingly, extended follow-up is required to adequately evaluate novel therapeutic strategies like IL-17A inhibition. Recently, results from the extension of the SCULPTURE secukinumab trial showed that high responses initially achieved with secukinumab at year 1 in the SCULPTURE study were sustained over time up to 3 years with no new or unexpected safety concerns. In this analysis, we examined whether the sustained efficacy observed in SCULPTURE up to 3 years was translated into sustained effect of secukinumab on patient’s QOL measured by the Dermatology Life Quality Index (DLQI) questionnaire. SCULPTURE, a multi-center extension study, was conducted with subjects who completed 52 weeks of treatment. Subjects were randomized into two maintenance dosing regimens; a fixed-interval schedule of secukinumab 300 mg every 4 weeks (Fixed interval dosing regimen (FI) cohort), and secukinumab retreatment-as-needed (Retreatment as needed (RAN) cohort), in which subjects received placebo until start of relapse, at which time secukinumab 300 mg every 4 weeks was re-initiated. The analysis using as-observed data showed that at Year 3, improvements in the total score on DLQI was well sustained in both FI and RAN cohorts. Approximately two-thirds of the subjects in the FI cohort reported no impact of skin disease on QOL (corresponding to a score of 0 or 1 on DLQI). The proportion of patients in the RAN cohort reporting no impact of the disease on their QOL was well sustained through 3 years but remained consistently lower than those observed in the FI cohort. The results for each subscale of the DLQI questionnaire were consistent with those with DLQI total score i.e. showing high and sustained proportions of patients reporting no impact of the disease on different domains of health-related QOL in the two secukinumab cohorts with greater effect in the FI cohort compared to the RAN cohort. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Dermatology, JAMA / 30.03.2017

MedicalResearch.com Interview with: Prof. Dr. Maja Mockenhaupt Dept. of Dermatology Medical Center - University of Freiburg Deutschland / Germany MedicalResearch.com: What is the background for this study? Response: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse reactions that are associated with high morbidity and mortality. Primarily due to their rareness, therapeutic effects are often studied in observational settings. An evidence-based standardized treatment protocol for SJS/TEN is still missing. (more…)
Author Interviews, Dermatology, Immunotherapy / 29.03.2017

MedicalResearch.com Interview with: Emma Guttman, MD, PhD Professor, Dermatology, Medicine and Clinical Immunology Vice Chair of Research in the Dermatology Department Director of the center for Excellence Eczema in the Occupational/Contact Dermatitis clinic Director of the Laboratory of Inflammatory Skin Diseases Icahn School of Medicine at Mount Sinai Medical Center New York MedicalResearch.com: Would you briefly explain what is meant by atopic dermatitis? How many people are affected by this disorder? Response: Atopic dermatitis or eczema as most people know it is an itchy red scaly skin disorder characterized by a very severe itch, that disrupts daily activities, and sleep and severely impairs the quality of life of patients. In the US 30 million people are affected by it, and 1/3 of these we expect to be moderate to severe. MedicalResearch.com: What is the background for Dupilumab therapy? How does it differ from emollients, steroids or topical immunomodulator treatments for eczema ie Protopic? Response: The background is that we currently do not have good treatments for long term use for our moderate to severe patients. The only approved drug by the FDA for atopic dermatitis in the US is oral prednisone, that has many long term side effects and causes disease rebound upon discontinuation. Other treatments with many side effects are broad immune suppressants--Cyclopsorin A, Mycophenolate mofetyl and phototherapy that is not feasible for most patients. Thus there is a large unmet need for safer and better treatments for moderate to severe atopic dermatitis patients. Dupilumab is different since it only targets one immune axis--Th2 axis, providing a safer alternative, with high efficacy, that is equal or even better than cyclosporin A, that is the current gold standard immune suppressant, and harbors many side effects including permanent effects on the kidneys after long term use. Topical treatments, while useful for mild patients, are often not adequate or sufficient to control moderate to severe patients that usually have more than 10% body surface area involved and need a systemic treatment. (more…)
Author Interviews, Boehringer Ingelheim, Dermatology, Immunotherapy / 29.03.2017

MedicalResearch.com Interview with: Eric Hughes, Global Head of Development, Immunology & Dermatology Novartis Pharma AG Basel, Switzerland MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is well established that psoriasis negatively affects quality of life and work productivity. However, how the treatments affect psoriasis severity (based on skin clearance, itch, pain and scaling symptoms), health-related quality of life (HRQOL), work productivity, and daily activity directly or indirectly (via other factors) are still largely unknown. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), exhibits significant efficacy in the treatment of moderate-to-severe psoriasis, ankylosing spondylitis, and psoriatic arthritis, demonstrating a rapid onset of action and a favorable safety profile. In CLEAR, a Phase 3b head-to-head study versus ustekinumab, secukinumab demonstrated sustained superior efficacy in clearing skin through Week 52, greater improvement in symptoms and HRQOL, greater relief of work and activity limitations, and a comparable safety profile. In this sub-analysis of the CLEAR study, Novartis was interested in examining the relationships among multiple variables that are thought to be important to patients with psoriasis. The direct and indirect (i.e. mediated) effects of treatment (secukinumab or ustekinumab) on psoriasis severity and patients’ HRQOL, work productivity, and daily activity were examined. The evaluation was conducted using structural equation modeling (or path analysis) and compared these relationships for secukinumab versus ustekinumab at 16 and 52 weeks. Structural equation modeling or path analysis is a statistical method that models the direct and indirect relationship between multiple patient-relevant outcomes simultaneously. Goodness-of-fit statistics for all models were excellent confirming the robustness of the results. Results at Week 16 and at Week 52 for different Psoriasis Area and Severity Index (PASI) response categories (e.g. PASI 75, PASI 90, PASI 100) indicated that psoriasis treatment indirectly affected HRQOL and work productivity and daily activity, measured with the Dermatology Life Quality Index (DLQI) and the Work Productivity and Activity Impairment (WPAI) questionnaires, respectively. Actually, greater effect of secukinumab over ustekinumab on DLQI was mediated by greater improvement of secukinumab in PASI response as well as by greater improvement in psoriasis-related symptoms (itch, pain and scaling). Greater effect of secukinumab over ustekinumab on work productivity and daily activity was mediated by greater improvement of secukinumab in psoriasis-related symptoms. (more…)