Immunotherapy Ruxolitinib Cream Improves Facial Vitiligo

MedicalResearch.com Interview with:

David Rosmarin, MD Dermatologist; Assistant Professor Tufts University School of Medicine

Dr. Rosmarin

David Rosmarin, MD
Dermatologist; Assistant Professor
Tufts University School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Vitiligo is a disease where the immune system causes depigmentation of the skin. We performed a pilot study to evaluate the use of a new class of medication for the treatment of vitiligo.


MedicalResearch.com: What should readers take away from your report?

Response: After applying topical ruxolitinib cream twice a day, patients had significant repigmentation, particularly those with facial vitiligo.

This treatment holds promise as a potential new treatment for vitiligo. Because it is a topical, it spares many side effects of taking a medication orally.

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Secukinumab Provides Sustained Improvements in Dermatology-Specific Quality of Life in Moderate to Severe Psoriasis Patients Through 3 Years of Treatment

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.

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Safer Immunotherapy Dupilumab (Dupixent) FDA Approved For Atopic Dermatitis

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

Dr. Guttman

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.

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Secukinumab (Cosentyx) Provides Greater Improvement in Quality of Life, Work Productivity, and Daily Activity Than Ustekinumab (Stelara) in Moderate To Severe Psoriasis

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.

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Newly Recognized Connection Between Immune System and Sperm Opens Window to Some Male Infertility and Cancer Vaccine Failures

MedicalResearch.com Interview with:
Kenneth S. K. Tung, M.D.
Professor of Pathology and Microbiology
Director of UVA Research Histology Core
Beirne B. Carter Center for Immunology Research
University of Virginia

MedicalResearch.com: What is the background for this study?

Response: The immune system needs to see tissue antigens to avoid responding to them in order to prevent autoimmune disease development. The current dogma, stated in all Immunology and Reproductive Biology textbooks, considers the sperm antigens in the testis to be exempted from this process. They are considered totally hidden behind a tissue barrier, and are invisible to the immune system.

Because sperm antigens are treated as foreign molecules, they should stimulate strong immune response when employed in cancer vaccines against antigens common to sperm and cancers. It is also believed that sperm molecules are protected by local factors that inhibit inflammation, whereas systemic mechanisms such as regulatory T cells would not exist.

The paradigm has restrained ongoing research on systemic tolerance to sperm, and the need to understanding systemic regulation in infertility research

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Effects of Riociguat in Treatment-Naïve vs Pretreated Patients With Pulmonary Arterial Hypertension

MedicalResearch.com Interview with:

Prof. Hossein-Ardeschir Ghofrani University of Giessen and Marburg Lung Center Giessen, Germany, and Member of the German Center of Lung Research and Department of Medicine Imperial College London London, UK

Prof. Ghofrani

Prof. Hossein-Ardeschir Ghofrani
University of Giessen and Marburg Lung Center
Giessen, Germany, and
Member of the German Center of Lung Research
and Department of Medicine
Imperial College London
London, UK

MedicalResearch.com: What is the background for this study?

Response: Pulmonary arterial hypertension (PAH) is characterised by increased pulmonary vascular resistance (increased resistance to blood flow in the pulmonary circulation), which can lead to right heart failure and death. Riociguat is the first of a new class of drugs – the soluble guanylate cyclase stimulators. It has been approved for the treatment of PAH based on the impressive efficacy and safety results from two pivotal Phase III studies: PATENT-1 and its long-term extension phase, PATENT-2. PATENT-1 was a 12-week, double-blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of riociguat in patients with PAH. Patients who completed PATENT-1 without ongoing riociguat-related serious adverse events (AEs) could enter PATENT-2, in which they received open-label riociguat. PATENT-1 admitted patients whether they were treatment-naïve or already receiving targeted PAH therapies, such as endothelin receptor antagonists (ERAs) and prostanoids. This current analysis compared the safety and efficacy of riociguat between treatment-naïve and pretreated patients in the PATENT-2 long-term extension study.

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Ibalizumab Immunotherapy Decreased Viral Load In Resistant HIV

MedicalResearch.com Interview with:

Brinda Emu MD Assistant Professor of Medicine (Infectious Diseases Yale University New Haven, CT

Dr. Brinda Emu

Brinda Emu MD
Assistant Professor of Medicine (Infectious Diseases
Yale University
New Haven, CT 

MedicalResearch.com: What is the background for this study?

Response: Ibalizumab is a fully humanized monoclonal antibody that targets the CD4 receptor.  This Phase III registrational study enrolled individuals with HIV infection that harbor high levels of multi-drug resistance, with limited treatment options.  At IDWeek in October, 2016, data was presented that demonstrated patients experienced a significant decrease in viral load after receiving a single loading dose of ibalizumab 2,000 mg intravenously (IV) in addition to their failing antiretroviral therapies (ART) (or no therapy). Seven days after this loading dose, 83% of patients achieved a ≥ 0.5 log10 decrease from baseline compared with 3% during the seven-day control period .These results were statistically significant (p<0.0001).

At CROI, additional data on the Week 24 results from this study are now presented.

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Allergic Rhinitis: Three Years of Immunotherapy Gives Longer Lasting Symptom Control

MedicalResearch.com Interview with:
Stephen R. Durham, MD

Imperial College, London, and Royal Brompton and Harefield Hospitals
NHS Foundation Trust
London, United Kingdom

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Allergic rhinitis affects 1 in 4 the UK population and may compromise sleep and work/school performance and be associated with bronchial asthma. When nasal steroids and antihistamines do not work or cause side effects, allergen immunotherapy is an alternative. Immunotherapy using high doses of grass pollen allergen as monthly injections or daily tablets under the tongue are highly effective. Treatment for 3 years not only gives sustained improvement on treatment but also long-term benefits and disease remission for at least 2-3 years after stopping treatment.

This single centre study at Imperial College London and Royal Brompton Hospital London included 106 adults with severe Hayfever followed up for 3 years, 2 years on treatment and 1 year after stopping treatment. In this double-blind trial, 3 randomised groups took sublingual immunotherapy, subcutaneous immunotherapy and placebo treatment. 92 completed the trial. Results showed that 2 years treatment with both modalities did not result in persistent benefit at year 3, although the researchers found that both treatments were effective compared to placebo during years 1 and 2.

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PCSK9 Inhibition with Alirocumab Increases Removal of LDL Cholesterol

MedicalResearch.com Interview with:
Henry N. Ginsberg, MD

Irving Institute for Clinical and Translational Research
Columbia University
Columbia College of Physicians and Surgeons
New York, NY

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies in mice and cells have identified increased hepatic low density lipoprotein (LDL) receptors as the basis for LDL lowering by PCSK9 inhibitors, but there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism, particularly effects on very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) or LDL metabolism.

This study in 18 healthy subjects, found that alirocumab decreased the number of IDL and LDL particles in the circulation, and their associated cholesterol and apoB levels by increasing efficiency of the clearance of IDL and LDL. There were not effects on VLDL metabolism. The increased clearance of IDL meant that less LDL was produced from IDL, which is the precursor of LDL. Thus, the dramatic reductions in LDL cholesterol resulted from both less LDL being produced and more efficient clearance of LDL. These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition.

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Imatinib Revolutionizes Treatment of Unresectable/Metastatic GI Stromal Tumors

MedicalResearch.com Interview with:

Michael C. Heinrich, MD Professor of Medicine and Cell and Developmental Biology Oregon Health & Sciences University

Dr. Michael Heinrich

Michael C. Heinrich, MD
Professor of Medicine and Cell and Developmental Biology
Oregon Health & Sciences University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Prior to 2000, there were no effective medical treatments for advanced GI stromal tumor and patients faced an average life expectancy of 18 months or less.  In our study of the  long-term treatment results using imatinib (Gleevec),  we found that approximately 7% of patients were still on front-line therapy at 10 years without any evidence of tumor progression.  More importantly, the estimated 10 year survival was 23%.   Progression-free and overall survival rates were significantly higher for patients with KIT exon 11-mutant GIST when compared with patients with KIT exon 9-mutant or “wild-type” GIST (no KIT/PDGFRA mutations).

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Cancer Killed While Preserving A Kidney Transplant

MedicalResearch.com Interview with:

Kenar D. Jhaveri, MD Professor of Medicine Division of Kidney Diseases and Hypertension Hofstra Northwell School of Medicine, 100 Community Drive, Great Neck, NY 11021

Dr. Kenar Jhaveri,

Kenar D. Jhaveri, MD
Professor of Medicine
Division of Kidney Diseases and Hypertension
Hofstra Northwell School of Medicine,
100 Community Drive, Great Neck, NY 11021

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The immune check point inhibitors are novel anti cancer agents being used rapidly in various cancers. Many cancers don’t allow our natural immune system to attack the cancer. These immunotherapy agents “activate” the immune system to attack the cancer. These agents have been reported to cause multiple end organ side effects as noted by this recent NYT article. We also recently reported the known renal effects of immunotherapy.

In the kidney transplant patient who is on immunosuppressive agents, the physicians need to keep the immune system suppressed to preserve the kidney. When one of these agents are used for a cancer in a kidney transplant patient, prior reports have suggested severe rejection episodes and loss of the transplanted kidney. Our case in the NEJM is the first report of a preventive strategy used to allow for simultaneous treatment of cancer and preventive rejection of the kidney. We used a regimen of steroids and sirolimus( an anti-proliferative agent that is used to treat cancer and also is an immunosuppresant) along with the immunotherapy. The cancer started regressing and the kidney did not reject.

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Vaccine Nanodiscs Can Trigger More Cancer Fighting Immune Cells

MedicalResearch.com Interview with:

James Moon, PhD John Gideon Searle Assistant Professor University of Michigan Dept. of Pharmaceutical Sciences and Biomedical Engineering Biointerfaces Institute Ann Arbor, MI, 48109

Dr. James Moon

James Moon, PhD
John Gideon Searle Assistant Professor
University of Michigan
Dept. of Pharmaceutical Sciences and Biomedical Engineering
Biointerfaces Institute
Ann Arbor, MI, 48109

MedicalResearch.com: What is the background for this study?

Response: The field of cancer immunotherapy has recently made a breakthrough with the clinical success of immune checkpoint inhibitors, which work by removing the brakes on immunosuppressed T-cells. However, these approaches generally work by augmenting pre-existing T-cell immunity and benefit only a subset of patients. In addition, because the majority of somatic mutations in cancer cells are unique to each patient, cancer immunotherapy may benefit from a personalized approach.

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