Author Interviews, COVID -19 Coronavirus, Dermatology, Respiratory / 06.10.2021

MedicalResearch.com Interview with: Lara van der Schoot  MD, PhD candidate Department of Dermatology Radboud University Medical Center Nijmegen, The Netherlands MedicalResearch.com: What is the background for this study? Response: Psoriasis is a chronic, immune mediated skin disease for which effective targeted biological agents have become available the past years. Inherent to their immunomodulatory mechanism of action, biologics might increase infections risk. We know from clinical trial data that respiratory tract infections are among the most common adverse events during biologic treatment, but real-world data is sparse. Regarding the risk of serious infections among biologic users, mostly defined as infections requiring hospitalization, previous studies provided different results and there is limited comparative data for the newer biologics available. The COVID-19 pandemic turned attention to the risk of infections among biologic users, especially for respiratory tract infections, as they might relate to susceptibility for viral respiratory tract infections such as COVID-19. In our study, the primary aim was to determine the risk of respiratory tract infections among real-world psoriasis patients treated with biologics, including the newer IL-17 and IL-23 inhibitors. The secondary aim was to assess risk of serious infections in this cohort. Additionally, rates of SARS-CoV-2 infections were assessed. (more…)
Author Interviews, Dermatology, Heart Disease, JACC, NYU / 17.05.2021

MedicalResearch.com Interview with: Michael S. Garshick, MD Assistant Professor Department of Medicine Grossman School of Medicine NYU MedicalResearch.com: What is the background for this study? Response: Patients with psoriasis have a 50% higher risk of cardiovascular disease when compared to patients without psoriasis, the mechanisms of which are still under investigation Dyslipidemia is also highly prevalent in psoriasis including elevation in a variety of lipoproteins causal in atherosclerosis. Lipoprotein(a) is an LDL like particle which is associated with atherosclerosis, atherothrombosis, and the development of clinical cardiovascular disease. Traditionally lipoprotein(a) is felt to be inherited rather than acquired, but some evidence suggest that lipoprotein(a) is elevated in those with underlying inflammatory conditions and associated with systemic inflammation including circulating IL-6. We therefore aimed to determine if lipoprotein(a) is elevated in psoriasis and associated with underlying systemic inflammatory profiles and biomarkers of cardiovascular risk.  (more…)
Author Interviews, Dermatology, NEJM / 28.04.2021

MedicalResearch.com Interview with: Prof. Kristian Reich, MD, PhD Professor for Translational Research in Inflammatory Skin Diseases Institute for Health Services Research in Dermatology and Nursing University Medical Center Hamburg-Eppendorf MedicalResearch.com: What is the background for this study? What are the main findings? Response: Complete skin clearance is an important treatment goal for patients with psoriasis and is closely associated with treatment satisfaction and improved quality of life. However, it remains an unmet need for many patients. The interleukin (IL)-17 isoforms IL-17A and IL-17F play central roles in psoriasis pathophysiology and are overexpressed in psoriatic tissues. Existing biologic therapies, such as secukinumab, inhibit IL-17A only. However, increasing evidence indicates that IL-17F contributes independently to the pathobiology of plaque psoriasis, and that blocking both IL-17A and IL-17F may lead to more complete suppression of inflammation and superior clinical outcomes, compared with blocking IL‑17A alone. Bimekizumab is a humanized monoclonal IgG1 antibody that has been designed to selectively inhibit IL-17F in addition to IL-17A. (more…)
Author Interviews, Dermatology, Inflammation / 30.10.2020

MedicalResearch.com Interview with: Dr. Douglas Maslin, MPhil, MB BCHir Dermatologist and Pharmacologist Addenbrooke's Hospital Cambridge, UK   MedicalResearch.com: What is the background for this study? Response: I’d like to answer this question in three parts: EVELO BIOSCIENCESFirstly, the background to Evelo and the therapeutic EDP1815: Evelo is developing orally administered biologic medicines based on a new understanding of how systemic inflammation is controlled. Evelo’s medicines are selected for their ability to modulate the small intestinal axis, or SINTAX, a network of anatomical and functional connections that has evolved to connect the small intestine with the rest of the body. SINTAX links small intestinal mucosal immunology with systemic inflammation and is now accessible with oral medicines. This inflammatory control pathway may enable a new class of products which are effective, safe, and can be manufactured affordably at large scale. EDP1815 is a non-live pharmaceutical preparation of a strain of the bacterium Prevotella histicola isolated from the duodenum of a human donor. Its pharmacodynamic effect is through interactions with the immune cells within the small intestine and it has no systemic absorption. These local interactions in the small intestine then downregulate systemic inflammation. In fact, the inflammatory control afforded by targeting the small intestinal axis appears to result in the coordinated downregulation of multiple inflammatory pathways without immunosuppression, mimicking the body’s normal physiological processes of inflammation resolution. Secondly, there is the key and exciting background pre-clinical data on EDP1815 – the details of which have been published today at the EADV conference. For example, oral administration of EDP1815 to mice has been shown to lead to striking therapeutic effects in in vivo models of delayed-type hypersensitivity, imiquimod-induced skin inflammation, fluorescein isothiocyanate cutaneous hypersensitivity, collagen-induced arthritis, and experimental acute encephalomyelitis (EAE). The consistency of effect and dose shows that EDP1815 can coordinately resolve systemic inflammation across TH1, TH2 and TH17 pathways. This suggests the potential for clinical benefit across multiple diseases. And, thirdly, there is the clinical unmet need for an oral, safe, effective treatment specifically for mild and moderate psoriasis patients, who have very limited treatment options outside of the poorly tolerated topical therapies, and these patients are reported to be dissatisfied with treatment options and therefore are often under-treated. These three points explain the background to EDP1815 and the reason for progressing forward into the phase 1b in psoriasis. (more…)
Author Interviews, Dermatology / 28.10.2020

MedicalResearch.com Interview with: Dr. Linda Stein Gold MD Director of Dermatology Clinical Research at Henry Ford Health System Detroit, Michigan Division Head of Dermatology Henry Ford Health System in West Bloomfield, Michigan MedicalResearch.com: What is the background for this study? Response: Halobetasol and Tazarotene work by complimentary mechanisms of action in treating psoriasis and also have been shown to counteract the side effects associated with the other medications. In prior studies using tazarotene as monotherapy, there was a maintenance of effect even after the drug was discontinued. We investigated to see if there was a maintenance of treatment effect in patients who achieved clear skin after using the fixed combination of halobetasol propionate 0.01%/tazarotene 0.045% lotion for 8 weeks of daily treatment. 

I served as lead author on the study, which was presented Fall Clinical Dermatology Conference this weekend in a poster titled, “Long-term management of moderate-to-severe plaque psoriasis: maintenance of treatment success following cessation of halobetasol propionate 0.01%/tazarotene 0.045% lotion.”

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Allergies, Author Interviews, Dermatology / 22.07.2020

MedicalResearch.com Interview with: Emma Guttman-Yassky, MD, PhD Professor of Dermatology and Immunology Vice Chair of the Department of Dermatology Icahn School of Medicine MedicalResearch.com: What is the background for this study? What is the importance of differentiating these two skin conditions?   Response: The background is that up to now skin biopsies were considered the gold standard for obtaining skin biomarkers of atopic dermatitis/AD and psoriasis that are linked to disease activity in skin and for obtaining the cutaneous gene and protein expression fingerprint of each individual disease. Biopsies are also used in clinical trials to obtain the skin phenotype. However biopsies are invasive, painful and scarring. Thus we need less invasive means to profile diseases and obtain biomarkers. Tape strips is a minimally invasive approach to sample and study the skin. However, prior studies using tape strips could not fully capture the phenotype of the diseases and also sampling the recovery rate was less than optimal, not allowing this approach to be widely used. Psoriasis and AD are the most common inflammatory skin diseases, but these diseases are treated very differently and in some cases are very difficult to differentiate between them clinically and even in biopsies.  (more…)
Author Interviews, Cancer Research, Dermatology, JAMA / 19.02.2020

MedicalResearch.com Interview with: Nikolai Dyrberg Loft MD, Ph.D.-fellow Department of Dermatology and Allergy Gentofte Hospital Hellerup MedicalResearch.com: What is the background for this study? Response: Epidemiological studies examining the association between psoriasis or psoriatic arthritis and cancer have reported conflicting results. Some studies report an increased risk of cancer in individuals with psoriasis or psoriatic arthritis and others do not. Whether individuals with psoriasis or psoriatic arthritis have an increased risk of cancer is important as this might help guiding in clinical practice. In order to determine if there is an increased risk of cancer and the magnitude of this risk, a systematic review of the literature and meta-analysis is needed.  (more…)
Author Interviews, Dermatology, Weight Research / 12.08.2019

MedicalResearch.com Interview with: Prof Ching-Chi Chi, MD, MMS, DPhil (Oxford) Department of Dermatology Chang Gung Memorial Hospital, Linkou Taiwan MedicalResearch.com: What is the background for this study?   Response: Psoriasis has been associated various inflammatory comorbidities including diabetes mellitus, coronary artery disease, etc. Moreover, obesity is prevalent among psoriasis patients and has been considered as an independent risk factor for occurrence and worsening of psoriasis by promoting systemic inflammation. Notably, body weight (BW) gain of psoriasis patients after biologics use has been observed. However, there are inconsistent reports on whether biological therapy relates to BW gain.  (more…)
Author Interviews, Brigham & Women's - Harvard, Dermatology, Heart Disease, JAMA / 27.03.2019

MedicalResearch.com Interview with: Seoyoung C. Kim, MD, ScD, MSCE Director, Program in Rheumatologic, Immunologic, and Musculoskeletal PharmacoEpidemiology Associate Professor of Medicine Division of Pharmacoepidemiology & Pharmacoeconomics Division of Rheumatology, Immunology and Allergy Brigham and Women's Hospital Harvard Medical School MedicalResearch.com: What is the background for this study? Response: Given a high cardiovascular (CV) risk among patients with psoriasis and psoriatic arthritis, it is important to have more information with regard to potential effect of different treatment agents on CV risk. As the number of treatment options for psoriasis and psoriatic arthritis has been rising over the few decades, it is even more crucial to have high-quality evidence on comparative safety of different treatment options so physicians and patients can choose an agent based on the benefit-risk profile of each drug they are considering. (more…)
Abbvie, Author Interviews, Dermatology, Immunotherapy / 11.03.2019

MedicalResearch.com Interview with: Anne Robinson, Pharm D Executive Scientific Director AbbVie MedicalResearch.com: What is the background for the risankizumab data presented at the American Academy of Dermatology 2019 Annual Meeting? Response: Abstracts presented by AbbVie at the American Academy of Dermatology (AAD) 2019 Annual Meeting highlight additional data from the Phase 3 clinical trial program evaluating the safety and efficacy of risankizumab, an investigational interleukin-23 (IL-23) inhibitor. The registrational program for risankizumab evaluated more than 2,000 adult patients with moderate to severe plaque psoriasis across four pivotal studies. (more…)
Author Interviews, Dermatology, Heart Disease, JAMA, Race/Ethnic Diversity / 04.03.2019

MedicalResearch.com Interview with: Francis Alenghat, MD, PhD Assistant Professor of Medicine Section of Cardiology University of Chicago MedicalResearch.com: What is the background for this study? What are the main findings? Response: Psoriasis has been associated with higher rates of atherosclerotic cardiovascular disease (ASCVD), potentially due to higher-than-normal levels of systemic inflammation. Whether this association varies by race was unknown. Also, it was unclear whether patients with psoriasis have more frequent ASCVD because of higher rates of traditional cardiovascular risk factors (smoking, diabetes, hypertension, hyperlipidemia) or because of components intrinsic to psoriasis itself. We found that, amongst a large population of patients with psoriasis, patients of both sexes and most ages had elevated ASCVD rates compared to those without psoriasis. Overall, African American patients with psoriasis had a 15% ASCVD prevalence, whereas it was 10% in white patients with psoriasis. Increased ASCVD associated with psoriasis occurred at earlier ages in African American patients compared to white patients. Traditional cardiovascular risk factors were common in patients with psoriasis and appeared to play a large role in the driving the higher rates of ASCVD in these patients, but even in patients with psoriasis but without any documented traditional risk factors, ASCVD rates were elevated compared to patients without psoriasis.  (more…)
Author Interviews, Dermatology, Lipids / 04.12.2018

MedicalResearch.com Interview with: Wendy Bollag, PhD, FAHA Professor of Physiology VA Research Career Scientist Augusta University, Georgia MedicalResearch.com: What is the background for this study? Response: We have previously shown that the lipid (fat) phosphatidylglycerol (PG) is able to inhibit rapidly growing keratinocytes (skin cells) and promote their maturation. We also found that PG can suppress skin inflammation. Since the common skin disease psoriasis is characterized by inflammation and excessive growth and abnormal maturation of skin cells, we believed that PG might be useful as a treatment. However, the mechanism of its anti-inflammatory effect was unknown. PG in the lung has been found to inhibit inflammation induced by microbes or their components, which work by activating the innate immune system via binding to proteins called toll-like receptors (TLRs); however, psoriasis is not considered to be an infectious disease. We hypothesized that PG would also inhibit inflammation induced by anti-microbial peptides that activate TLRs. Anti-microbial peptides, produced normally by the skin to protect against infection, are known to be excessively up-regulated in psoriatic skin.  (more…)
Author Interviews, Dermatology, Gastrointestinal Disease, JAMA / 25.10.2018

MedicalResearch.com Interview with: Prof Ching-Chi Chi, MD, MMS, DPhil  Department of Dermatology Chang Gung Memorial Hospital, Linkou Guishan Dist, Taoyuan MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies have shown common genotypes, clinical course, and immunological features shared by psoriasis and inflammatory bowel disease. However, the relationship between psoriasis and inflammatory bowel disease was largely unclear. In this study, we found when compared to the general population, psoriatic patients are more likely to have concomitant inflammatory bowel disease.  (more…)
Author Interviews, Dermatology, Eli Lilly / 25.09.2018

MedicalResearch.com Interview with: Lotus Mallbris, M.D., Ph.D., Vice president, Immunology Development Lilly Bio-Medicines  MedicalResearch.com: What is the background for this study? What are the main findings? Response: By exploring creative clinical approaches and patient-centric pathways to more thoroughly address the key aspects of treating these complex conditions, Lilly is bringing innovation forward in hopes of reducing the burden of dermatologic disease for people around the world. The results of the IXORA-S study suggest that Taltz may provide significantly greater clearance of nail psoriasis than ustekinumab. This is significant because nail lesions are a common feature of psoriasis. It’s often associated with discomfort, which can lead to functional impairment and distress, further supporting the importance of complete clearance.   (more…)
Author Interviews, Dermatology, JAMA, Nutrition, UCLA / 27.06.2018

MedicalResearch.com Interview with: Adam Ford, BS Research fellow with Dr. April Armstrong Keck School of Medicine University of Southern California MedicalResearch.com: What is the background for this study? Response: Our psoriasis patients have long asked us about the role of diet on psoriasis. Previously, there was a lack of evidence synthesis on the relationship between psoriasis and diet. As such, providers were mostly unable to address their patients questions on the role of diet on psoriasis. This pivotal effort from the National Psoriasis Foundation has been a few years in the making. We looked at the role of diet on psoriasis and psoriatic arthritis based on a careful synthesis of the scientific studies available to us currently. (more…)
Author Interviews, Dermatology, JAMA / 30.05.2018

MedicalResearch.com Interview with: Andrew Blauvelt, M.D., M.B.A. President Oregon Medical Research Center  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: This new paper focuses on treatment of psoriasis in classically difficult-to-treat areas of the body, which include the scalp, the palms/soles, and the fingernails. We show that guselkumab, which is a new biologic therapy that selectively targets IL-23 (a key pro-inflammatory cytokine in psoriasis pathogenesis), works well in these areas affected by psoriasis. More specifically, after 6 months of treatment with guselkumab, approximately 85%, 80%, and 60% of patients achieved complete or near complete clearance of psoriasis in their scalp, palms/soles, and fingernails, respectively.  (more…)
Author Interviews, Dermatology, UT Southwestern / 06.05.2018

MedicalResearch.com Interview with: Richard Wang, M.D., Ph.D.  Assistant Professor Dermatology UT Southwestern Medical Center  Richard Wang, M.D., Ph.D.  Assistant Professor Dermatology UT Southwestern Medical Center  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Targeting cellular metabolism is currently being explored as a new way to diagnose and treat diseases. In particular, there has been increasing interest in specifically targeting metabolic pathways are preferentially altered in disease states, like cancer.  Although an increased dependence on glucose transport and metabolism has been well established for rapidly proliferating cells, attempts to target this conserved pathway have been limited by concerns about the high potential for side effects from the systemic inhibition of glucose transport. To investigate the feasibility of targeting glucose transport in skin diseases, we investigated the effect of inhibiting glucose transport in the skin by deleting the primary glucose transporter in the skin, Glut1, in mouse keratinocytes. We confirmed that the Glut1-deficient keratinocytes showed metabolic and oxidative stress and impaired proliferation. However, the keratinocyte-specific ablation of Glut1 did not compromise mouse skin development and barrier function. Metabolomic profiling revealed sphingolipid, hexose, amino acid, and nucleotide adaptations in Glut1-deficient keratinocytes. However, Glut1 deficient skin did show defects in both proliferation and migration after physiologically relevant stressors like excisional wounds and UV-B irradiation. Given its importance during stressors, we further tested whether Glut1 was important in the pathogenesis of psoriasis models. Notably, both the genetic and pharmacological inhibition of Glut1 decreased hyperplasia in mouse and human organic models of psoriasis. Moreover, the topical application of a Glut1 inhibitor further decreased inflammation in these models. The ability to deliver glucose transport inhibitors specifically to the skin may limit the adverse effects from the systemic inhibition of glucose transport and suggests that the topical inhibition of glucose transport may be a novel approach to treat hyperproliferative and inflammatory skin diseases.  (more…)
Author Interviews, Dermatology, Eli Lilly, Sexual Health / 07.03.2018

MedicalResearch.com Interview with: Dr. Jennifer Cather MD Medical Director at Modern Dermatology and Modern Research Associate Dallas, Texas  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Genital psoriasis can be an uncomfortable and burdensome condition that many people living with moderate-to-severe plaque psoriasis experience. Due to the significant impact, Lilly conducted a 12-week Phase 3b clinical trial with patients with moderate-to-severe genital psoriasis treated with ixekizumab, which found that patients had a greater decrease in the impact of their condition on sexual activity compared to placebo as early as one week. Specifically, trial patients were randomized to receive ixekizumab (80 mg every two weeks, following a 160-mg starting dose) or placebo and researchers measured pre-specified patient-reported outcomes, including the Genital Psoriasis Sexual Impact Scale (GPSIS), which is composed of the Sexual Activity Avoidance (Avoidance) and Impact of Sexual Activity on Genital Psoriasis Symptoms (Impact) subscales. Patient-reported outcomes were also measured by the Sexual Frequency Questionnaire (SFQ) item 2, evaluating the impact of genital psoriasis on the frequency of sexual activity, and the Dermatology Life Quality Index (DLQI) item 9, evaluating the impact of skin symptoms on sexual difficulties. At 12 weeks, patients reported the following outcomes:
  • DLQI Item 9 0/1: 92.0 percent of patients treated with ixekizumab compared to 56.8 percent of patients treated with placebo reported no (0) or little (1) sexual difficulties caused by skin symptoms.
  • SFQ Item 2 0/1:  78.4 percent of patients treated with ixekizumab compared to 21.4 percent of patients treated with placebo (reported the frequency of sexual activity was either never (0) or rarely (1) limited by genital psoriasis.
  • GPSIS-Avoidance 1/2:  76.7 percent of patients treated with ixekizumab compared to 25.7 percent of patients treated with placebo reported never (1) or rarely (2) avoiding sexual activity due to genital psoriasis.
  • GPSIS-Impact 1/2:  85.7 percent of patients treated with ixekizumab compared to 52.9 percent of patients treated with placebo reported worsening of genital psoriasis symptoms during or after sexual activity was very low/none at all (1) or low (2). 
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Author Interviews, Dermatology, J&J-Janssen, Pharmaceutical Companies, Rheumatology / 13.11.2017

MedicalResearch.com Interview with: Atul A. Deodhar, MD, MRCP, FACP, FACR Professor of Medicine Division of Arthritis & Rheumatic Diseases Medical Director, Rheumatology Clinics Medical Director, Immunology Infusion Center Oregon Health & Science University (OHSU)  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Phase 2, randomized, double-blind, placebo–controlled, multicenter trial was designed to evaluate the efficacy and safety of guselkumab (Tremfya®) compared with placebo in adults with active psoriatic arthritis, despite having received treatment with standard-of-care therapies, including anti-tumor necrosis factor (TNF)-alpha agents. In an observed analysis presented at ACR 2017, more than 70 percent of patients receiving guselkumab achieved at least a 20 percent improvement in signs and symptoms of disease (ACR 20) at week 56.  Findings also showed that improvements in tender and swollen joints, skin clearance, pain and physical function, and patient-reported quality of life outcomes reported at week 24, were maintained through week 56 in patients receiving guselkumab maintenance therapy (subcutaneous injections every eight weeks).  (more…)
Author Interviews, Dermatology, University of Pennsylvania / 03.09.2017

MedicalResearch.com Interview with: Megan H. Noe MD, MPH Clinical Instructor and Post-Doctoral Research Fellow University of Pennsylvania, Department of Dermatology Perelman Center for Advanced Medicine Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous research has shown that patients with psoriasis have higher rates of hypertension, diabetes, cardiovascular disease and chronic kidney disease that may put them at an increased risk of death. Our research found that patients with psoriasis covering more than 10% of their body had almost double the risk of death than people of the same age with similar medical conditions, but without psoriasis. (more…)
Author Interviews, Dermatology, Heart Disease / 21.08.2017

MedicalResearch.com Interview with: Alexander Egeberg, MD PhD Gentofte Hospital Department of Dermatology and Allergy Kildegårdsvej 28 2900 Hellerup Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: The majority cardiovascular events in psoriasis occur in patients at low risk by traditional cardiovascular risk calculators. It has been speculated that long-term exposure to systemic inflammation may increase the risk of adverse cardiovascular outcomes. Therefore, clinically available historical features such as disease duration may identify those at higher risk for cardiovascular disease. Using a translational epidemiological approach, combining 18F-fluorodeoxyglucose positron emission tomography computed tomography scanning with nationwide epidemiological data of more than four million individuals, we provide the first convincing evidence to suggest a detrimental effect of psoriasis duration on cardiovascular disease beyond traditional cardiovascular risk factors, even in patients deemed “low-risk” by conventional risk scores. We found a 1% increase in future major adverse cardiovascular event risk per additional year of disease duration. This finding has an effect size similar to smoking, a well-established cardiovascular risk factor. (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, 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…)
Author Interviews, Dermatology, Orthopedics / 26.03.2017

MedicalResearch.com Interview with: Dr. Jonathan L. Silverberg MD PhD MPH Assistant Professor in Dermatology Medical Social Sciences and Preventive Medicine Northwestern University, Chicago, Illinois Response: Psoriasis is associated with a number of potential risk factors for developing osteoporosis and pathological fractures, including including low vitamin D, chronic inflammation, higher rates of cigarette smoking and systemic corticosteroid usage. We hypothesized that adults with psoriasis have higher rates of osteoporosis and pathological fractures. We examined data from the 2002-2012 National Inpatient Sample, which contains a representative 20% sample of all hospitalizations in the United States. We found that psoriasis was associated with higher odds of osteopenia, osteoporosis, osteomalacia, ankylosing spondylitis, and pathological fractures. In particular, psoriasis was associated with vertebral, pelvic, femoral and tibial/fibular fractures. The associations between psoriasis and pathological fractures were more pronounced in women than men. (more…)
Author Interviews, Boehringer Ingelheim, Dermatology, Pharmacology / 08.03.2017

MedicalResearch.com Interview with: Andrew Blauvelt, M.D., M.B.A. President and Investigator Oregon Medical Research Center  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Findings from the Phase 3 VOYAGE 1 study showed that patients with moderate to severe plaque psoriasis receiving guselkumab, an human anti-interleukin (IL)-23 monoclonal antibody, achieved significant improvement in skin clearance and in comparison with Humira® (adalimumab), a TNF blocker.  The Phase 3 study and head-to-head analysis of guselkumab vs. adalimumab showed the significant and durable efficacy of guselkumab as maintained through one year when compared with adalimumab, and the robust efficacy of this novel IL-23 targeted therapy in meeting all primary and major secondary endpoints. (more…)
Author Interviews, Dermatology, Rheumatology / 01.03.2017

MedicalResearch.com Interview with: Lihi Eder MD PhD Rheumatologist, Women’s College Hospital Scientist, Women’s College Research Institute Assistant Professor of Medicine, University of Toronto Toronto, ON, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: There significant delays in the diagnosis of psoriatic arthritis (PsA) among patients with psoriasis. Many patients with psoriasis experience musculoskeletal symptoms. The majority of them do not have PsA, but other non-inflammatory conditions such as fibromyalgia or osteoarthritis. In this study, we aimed to assess whether the presence and the degree of musculoskeletal symptoms in psoriasis patients predict the development of psoriatic arthritis. We analyzed a cohort of 410 psoriasis patients who were followed over a period of 9 years. These patients did not have arthritis at baseline. The patients were assessed annually by a rheumatologist for signs of PsA. A total of 57 patients developed psoriatic arthritis during the follow-up period. (more…)
Author Interviews, Dermatology, Pharmacology / 24.02.2017

MedicalResearch.com Interview with: Prof. Dr. med. Kristian Reich Dermatologie, Allergologie Psoriasis- und Neurodermitis-Trainer Hamburg MedicalResearch.com: What is the background for this study? What are the main findings? Response: Ustekinumab is an antibody against the p40 molecule shared by IL-12 and IL-23. The antibody shows a favorable benfit-risk profile in the treatment of psoriasis. IL-23 is regarded a key driver in psoriasis pathology. It is speculated that antibodies against the IL-23-specific subunit p19 may produce even higher levels of clinical response than ustekinumab or the anti-TNF antagonist adalimumab. Guselkumab is the first IL-23p19 antibody to publish phase III data in psoriasis.    (more…)
Author Interviews, Boehringer Ingelheim, Dermatology / 05.01.2017

MedicalResearch.com Interview with: Andrew Blauvelt, M.D., M.B.A. President and Investigator Oregon Medical Research Center Portland, OR 97223 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Findings from the guselkumab Phase 3 VOYAGE 1 study showed that patients with moderate to severe plaque psoriasis receiving the anti-interleukin (IL)-23 monoclonal antibody (mAb) achieved significant improvements in skin clearance compared with patients receiving placebo and patients receiving Humira® (adalimumab), a TNF blocker. The Phase 3 study and head-to-head analysis of guselkumab vs. adalimumab in the treatment of moderate to severe plaque psoriasis also showed the significant efficacy of guselkumab maintained through week 48 compared with adalimumab, and the robust efficacy of guselkumab in meeting all primary and major secondary endpoints. (more…)
Author Interviews, Dermatology, Orthopedics / 02.01.2017

MedicalResearch.com Interview with: Hsien-Yi Chiu, MD/ Tsen-Fang Tsai, MD Department of Dermatology, National Taiwan University Hospital Taipei, Taiwan MedicalResearch.com: What is the background for this study? What are the main findings? Response: Psoriasis is a chronic, immune-mediated disorder, characterized by red, itchy and scaly skin patches. Over the past several years, accumulating research had shown the effects of psoriasis go far deeper than the skin and psoriasis is associated with multiple comorbidities. Psoriasis shares the inflammatory pathways and several contributing factors with avascular necrosis (AVN), a bone disease presented with death of trabecular bone and collapse of the bony structure. However, previous studies mostly focus on evaluation the increased risk of cardiovascular diseases in patients with psoriasis. No large scale studies have previously explored a potential association between psoriasis and AVN. Our nationwide population-based cohort study investigated this risk in 28268 patients with psoriasis registered in the Taiwan National Health Insurance Research Database. The patients were matched, by age and sex, with 113072 controls without psoriasis. Both the patients and controls were followed to identify those who subsequently diagnosed with an AVN. The results showed that psoriasis was associated with a disease severity–dependent increase in avascular necrosis risk. Moreover, AVN risk was positively associated with male sex, age younger than 30 years, corticosteroid use, severe psoriasis, and concomitant psoriatic arthritis. People with severe psoriasis were 3 times more likely to develop AVN compared with the control group. (more…)