COPD: FASENRA™ (benralizumab) Did Not Reduce Moderate to Severe Exacerbations

MedicalResearch.com Interview with:

Gerard J. Criner, MD, FACP, FACCPChair and Professor, Thoracic Medicine and SurgeryLewis Katz School of MedicineTemple University

Dr. Criner

Gerard J. Criner, MD, FACP, FACCP
Chair and Professor, Thoracic Medicine and Surgery
Lewis Katz School of Medicine
Temple University 

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

Response: An earlier, Phase II trial of benralizumab found a non-statistically significant reduction in COPD exacerbation rate for patients with eosinophilic inflammation in the airways. In this Phase III trial, the researchers sought to discover whether benralizumab’s ability to deplete the airways of blood eosinophils in patients with eosinophilic inflammation would lead to a reduction in COPD exacerbations.

The Phase III, randomized, double-blind, placebo-controlled, parallel-group clinical trials GALATHEA and TERRANOVA evaluated the efficacy and safety of benralizumab for the prevention of exacerbations in patients with moderate to very severe COPD, eosinophilic inflammation, and increased risk of exacerbations. Benralizumab is a type of drug called an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody. It is approved by the FDA for the treatment of severe eosinophilic asthma.

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Are Commercial Peanut Immunotherapy Products Cost-Effective?

MedicalResearch.com Interview with:

Dr. Marcus Shaker

Dr. Shaker

Marcus S. Shaker, MD
Associate Professor of Pediatrics
Associate Professor of Community and Family Medicine
Dartmouth-Hitchcock Medical Center

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

Response: There are two peanut allergy treatments that are being evaluated for potential FDA approval—an orally administered treatment and an epicutaneous (skin based) treatment.  Both have tremendous potential benefit.  The focus of our study was to explore the range of health and economic benefits in terms of establishing pathways for how each therapy could be cost effective.

We want to be clear that our purpose was not to suggest one therapy is or is not cost effective at present.  That would be a ridiculous statement to make regarding two treatments that not only lack FDA approval, but do not have established pricing.  Rather, we used preliminary inputs that are presently available to create as robust a model as we could to better determine the individual paths that would make them more or less cost-effective.

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Oral Peanut Immunotherapy Evaluated for Preschool Children

MedicalResearch.com Interview with:

Lianne Soller, PhDAllergy Research ManagerUniversity of British ColumbiaVancouver, BC, Canada  

Dr. Soller

Lianne Soller, PhD
Allergy Research Manager
University of British Columbia
Vancouver, BC, Canada  

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

Response: In 2017, a clinical trial of 37 subjects demonstrated that preschool peanut oral immunotherapy was safe, with predominantly mild symptoms reported and only one moderate reaction requiring epinephrine. Our study aimed to examine whether these findings would be applicable in a real-world setting (i.e., outside of research).

We found that peanut oral immunotherapy is safe in the vast majority of preschoolers, with only 0.4% of patients experiencing a severe reaction, and only 12 out of ~40,000 peanut doses needed epinephrine (0.03%).  Continue reading

Walnut Oral Immunotherapy Is Effective For the Treatment of Walnut as well as Additional Tree Nut Allergies

MedicalResearch.com Interview with:

Arnon Elizur MDDirector, The Institute of Allergy, Immunology & Pediatric PulmonologyYitzhak Shamir Medical CenterZerifin, Israel

Dr. Elizur


Arnon Elizur MD

Director, The Institute of Allergy, Immunology & Pediatric Pulmonology
Yitzhak Shamir Medical Center
Zerifin, Israel

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

Response: Tree nuts are among the most common food allergies and are a major cause of fatal and near fatal reactions. Patients with tree nut allergy are often allergic to several nuts, further increasing the risk of accidental exposures, dietary limitations, and the emotional burden and anxiety in affected patients.

In the past 10 years, oral immunotherapy (OIT) has shown promise as a treatment modality for milk, egg and peanut allergies. However, limited data exists on oral immunotherapy for tree nuts and the treatment is complicated by the high prevalence of co-allergy to several nuts.

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Risankizumab for Moderate to Severe Psoriasis: High Rates of Durable Clearance Through One Year

MedicalResearch.com Interview with:

Anne Robinson, Pharm DExecutive Scientific DirectorAbbVie

Dr. Robinson

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. Continue reading

Egg Allergy: Oral Immunotherapy Has Potential for Lasting Benefit

MedicalResearch.com Interview with:

Edward Kim, MD MSAssistant Professor of MedicineDivision of Rheumatology, Allergy and ImmunologyDirector, UNC Allergy and Immunology ClinicUniversity of North Carolina at Chapel HillChapel Hill, NC

Dr. Kim

Edwin Kim, MD MS
Assistant Professor of Medicine
Division of Rheumatology, Allergy and Immunology
Director, UNC Allergy and Immunology Clinic
University of North Carolina at Chapel Hill
Chapel Hill, NC 

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

Response: The background is that egg allergy remains one of the most common food allergies in childhood and although most patients will outgrow the allergy, it seems that many will carry into their teen years. As a result patients still have many years of risk of anaphylaxis, poor quality of life and potential nutritional deficits. The ability to introduce some amount of egg into the diet could have profound benefit to allergy patients.

The main findings are that after completing up to 4 years of egg oral immunotherapy (OIT), most patients are able to introduce at least baked egg products into the diet. The subset of patients who showed a lasting benefit by passing a food challenge 4-6 weeks after stopping the OIT, generally did even better by being able to introduce lightly cooked egg like scrambled, boiled, or fried in addition to baked egg products. This benefit to the diet seemed to last up to 5 years after stopping egg oral immunotherapy. In addition to the safety, quality of life and nutrition benefits, recent data suggesting that bringing baked egg into the diet can speed up outgrowing the allergy provides a further benefit. Continue reading

Viaskin Peanut: Convenient Potential Treatment Option for Peanut Allergy

MedicalResearch.com Interview with:

Dr. Matthew GreenhawtDirector, Food Challenge and Research UnitChildren’s Hospital Colorado

Dr. Greenhawt

Dr. Matthew Greenhawt
Director, Food Challenge and Research Unit
Children’s Hospital Colorado

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

Response: In the US, nearly one million children suffer from a peanut allergy and severe reactions to food allergens are not uncommon – yet there is significant unmet need in the food allergy immunotherapy space, as there are no currently approved treatment options. That being said, we are encouraged by the efficacy and safety data, which support Viaskin Peanut as a convenient and well-tolerated potential treatment option for the peanut allergy.

In the pivotal Phase III clinical trial (PEPITES) just published in The Journal of the American Medical Association (JAMA), Viaskin Peanut – the first epicutaneous immunotherapy (EPIT) in development that leverages the skin to activate the immune system – provided statistically significant desensitization in peanut-allergic children ages 4-11 years old. Patients who were treated with active therapy were more likely to have increased their eliciting dose to peanut (the amount of peanut protein ingested before an objective allergic reaction was seen during a double-blind, placebo-controlled food challenge) by a required amount as compared to patients treated with a placebo patch. The improvement suggests a reduced risk of allergic reaction to accidental peanut ingestion in the group treated with Viaskin Peanut, with no change seen in the placebo group.

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Boiled Peanut Immunotherapy For Peanut Allergy

MedicalResearch.com Interview with:
Dr Paul Turner FRACP PhD
MRC Clinician Scientist and Clinical Senior Lecturer, Imperial College London
Honorary Consultant in Paediatric Allergy & Immunology
Imperial College Healthcare NHS Trust
Hon Consultant, Royal Free Hospital / Royal Brompton & Harefield NHS Foundation Trust
Clinical trials specialist (Paediatrics), Public Health England
Clinical Associate Professor in Paediatrics, University of Sydney, Australia

Dr. Nandinee Patel, MD
Section of Paediatrics
Imperial College London
London, United Kingdom
MRC & Asthma UK Centre in Allergic Mechanisms of Asthma
London, United Kingdom

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

Response: Current desensitisation protocols for peanut allergy use defatted roasted peanut flour, which can be difficult to accurately measure in very low doses needed for desensitisation (and thus has resulted in the development of AR101 by Aimmune which is likely cost many thousands of dollars for a course of treatment).

We have previously observed that some children with food allergy to roasted peanut (such as peanut butter) are nonetheless able to tolerate boiled peanuts without reacting. We performed in vitro protein analysis studies which demonstrated that boiling peanuts resulted in around 50% of protein leaching out of the peanut into the cooking water. Furthermore, we found evidence for preferential leaching of allergen epitopes such as Ara h 2 as well aggregation of proteins resulting in a hypoallergenic peanut product.

We therefore sought to assess whether boiled peanuts could be as effective and safe to induce desensitisation.

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Timing of Immunotherapy Crucial to Outcomes

MedicalResearch.com Interview with:

Tatiana Garcia-Bates, Ph.D. Research Assistant Professor Department of Infectious Diseases and Microbiology Graduate School of Public Health University of Pittsburgh

Dr. Garcia-Bates

Tatiana Garcia-Bates, Ph.D.
Research Assistant Professor
Department of Infectious Diseases and Microbiology
Graduate School of Public Health
University of Pittsburgh

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

Response: Human immunodeficiency virus (HIV) infection is now a manageable disease with the advent and availability of highly effective, combination antiretroviral therapy (ART). Unfortunately, as soon as ART is interrupted, the virus quickly rebounds to high levels and again targets the immune system. Therefore, new immunotherapeutic treatments are sought to re-program the immune system to control the virus after ART interruption.

In many ways, chronic HIV infection, even when controlled, resembles cancer in how it impacts the immune system. Both conditions for example are associated with immune dysfunction, where the immune cells (specifically T cells) that are supposed to protect our bodies against invading microorganisms or cancers become exhausted and fail to respond effectively. In cancer, effective immunotherapies have been developed to reverse this immune exhaustion to extend the fighting capacity of the T cells.

An example of this is drugs that target immune checkpoints, or “shut down” proteins, expressed on activated T cells, such as the programmed death-1 (PD-1) receptor. When engaged, PD-1 sends a negative signal to deactivate the T cell, and this contributes to the immune exhaustion seen in both cancer and in chronic infections. Some cancers express the ligand or the “trigger” for this shut down receptor, called PD-1 ligand (PD-L1). When this interaction between PD-1 and PD-L1 is interrupted, for example by using a blocking antibody, T cells can regain their killing capacity and destroy infected cells or cancer cells. This anti-PD-1 therapy has demonstrated high success against a variety of tumors.

Therefore, we tested this approach in the context of HIV infection using a well-characterized cohort of HIV-positive individuals to see if we could improve their T cell responses to HIV in a laboratory setting.

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Multiple Sclerosis: T Cell Immunotherapy Targeting EBV Infected Cells Shows Promise

MedicalResearch.com Interview with:

Dietmar P. Berger, MD, PhD Head of Global R&D Atara Biotherapeutic

Dr. Berger

Dietmar P. Berger, MD, PhD
Head of Global R&D
Atara Biotherapeutic

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

Response: Epstein-Barr virus (EBV) is present in B lymphocytes, plasma cells and epithelial cells of over 95% of individuals over the age of 40.  Multiple studies have shown that nearly all patients with Multiple Sclerosis (MS) are EBV positive, including a recent presentation at the 2018 ECTRIMS Congress in Berlin that showed 100% of MS patients are positive for EBV (Ruprecht et. al). Current B cell directed therapies such as anti-CD20 therapies have demonstrated an effect on  Multiple Sclerosis activity. These therapies work by depleting B cells including those infected by EBV.

Our belief is that loss of EBV-specific T cell function (e.g., T cell exhaustion) occurs in patients who develop Multiple Sclerosis, which results in the accumulation of EBV infected B and plasma cells in the CNS leading to the autoreactive immune cycle seen in MS patients. The increasing evidence of a link between EBV infection and the development of MS led to the initiation of a Phase 1 study to investigate the use of an autologous T-cell immunotherapy (ATA190) to selectively target and deplete EBV infected cells in patients with progressive MS.

As T cell immunotherapies (like ATA190) are designed to penetrate the central nervous system, this approach was felt to be particularly useful in  Multiple Sclerosis where the inflammatory response and infected B lymphocytes and plasma cells are inaccessible inside the CNS to the vast majority of classic targeted agents.

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Omalizumab (XOLAIR) For Chronic Hives (Urticaria)

MedicalResearch.com Interview with:

Hives - Wikipedia image James Heilman, MD - Own work

Hives – Wikipedia image

Christopher S. Lee, PhD, RN, FAHA, FAAN, FHFSA
Professor and Associate Dean for Research
Boston College William F. Connell School of Nursing
Chestnut Hill, MA 02467

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

Response: Although the efficacy of omalizumab (i.e. can it work?) in the treatment of chronic idiopathic (spontaneous) urticaria has been established in clinical trials, the effectiveness of omalziumab (i.e. does it work?) in the real-world management is less well established.

The purpose of this study was to synthesize what is known about the benefits and harms of omalizumab as used in real-world treatment of Chronic Idiopathic (Spontaneous) Urticaria.

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Novel Immunotherapy Combination Shows Promise in Some with Resistant Metastatic Colon Cancer

MedicalResearch.com Interview with:

Dr James Kuo, MBBS Medical oncologist and Deputy Medical Director Scientia Clinical Research Sydney, Australia 

Dr. Kuo

Dr James Kuo, MBBS
Medical oncologist and Deputy Medical Director
Scientia Clinical Research
Sydney, Australia

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

Response: Immune checkpoint inhibitors (ICI) that have seen success in the treatment of patients with various tumour types have not been as effective in patients with metastatic pancreatic cancer and therefore immune-therapeutic agents of novel mechanism of action, in particular in combination with existing ICI, need to be investigated.

This study set out to test the safety and efficacy of pixatimod, a novel immunomodulatory agent, in combination with nivolumab, firstly in the dose escalation cohorts in patients with any solid tumour for the maximal tolerable dose, and then using this dose to further treat an expansion cohort of patients with pancreatic cancer. Altogether 16 patients had received the combination and in 10 patients in whom treatment response was evaluable, 4 patients experienced a clinical benefit and continued treatment in the trial, with 1 patient having a significant partial response now treated for 48 weeks. Interestingly, all these 4 patients had metastatic colorectal cancer. Side effect profile has been consistent with other immunotherapeutic agent combination and in the patients who had clinical benefit, no treatment related side effects were observed.  Continue reading

Fatal Toxicities Rare With Checkpoint Inhibitors

MedicalResearch.com Interview with:

Douglas B. Johnson, M.D. Assistant Professor of Medicine Clinical Director, Melanoma Research Program Melanoma, clinical and translational studies Vanderbilt University Medical Center

Dr. Johnson

Douglas B. Johnson, M.D.
Assistant Professor of Medicine
Clinical Director, Melanoma Research Program
Melanoma, clinical and translational studies
Vanderbilt University Medical Center

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

Response: Immune checkpoint inhibitors produce long-lasting responses in patients with many different types of cancer. However, they may cause serious autoimmune-like side effects that may affect any organ. We used several large databases to determine how often these side effects were fatal, when they occurred, and which types of side effects were responsible.

We found that overall, fatal side effects were uncommon, ranging from 0.3 – 1.3%. However, they tended to occur early on treatment (on average within the first 6 weeks), and affected a variety of organs, including the heart, lungs, colon, liver, and brain. There was a dramatic increase in reporting of fatal toxicities since 2017, likely reflecting the increased use of immune checkpoint inhibitors.  Continue reading

IMPRES Score Predicts Melanoma Response to Immunotherapy

MedicalResearch.com Interview with:

Melanoma CDC/ Carl Washington, M.D., Emory Univ. School of Medicine; Mona Saraiya, MD, MPH

This image depicts the gross appearance of a cutaneous pigmented lesion, which had been diagnosed as superficial spreading malignant melanoma (SSMM).  Reminder: Melanoma can take many forms. Not all look like this. Have your skin examined for skin cancer.

Dr. Noam Auslander PhD
National Cancer institute and the Center for Bioinformatics and Computational Biology University of Maryland, College Park

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

Response: Immunotherapy – specifically immune checkpoint blockage (ICB) therapy – has been shown to be very effective in treating melanoma. However, only some patients with advanced tumors currently benefit from ICB therapies, while others are completely resistant and hence can be spared from the associated side effects and costs. Hence, predicting which patients are most likely to respond is an important challenge that can have great clinical benefits.   Continue reading

Two Studies Evaluate Monoclonal Antibody Tralokinumab For Asthma

MedicalResearch.com Interview with:

Reynold A. Panettieri, Jr., M.D. Professor of Medicine, Robert Wood Johnson Medical School Vice Chancellor, Clinical & Translational Science Director, Rutgers Institute for Translational Medicine & Science Emeritus Professor of Medicine, University of Pennsylvania Child Health Institute of New Jersey Rutgers, The State University of New Jersey New Brunswick, NJ  08901

Dr. Panettieri

Reynold A. Panettieri, Jr., M.D.
Professor of Medicine, Robert Wood Johnson Medical School
Vice Chancellor, Clinical & Translational Science
Director, Rutgers Institute for Translational Medicine & Science
Emeritus Professor of Medicine, University of Pennsylvania
Child Health Institute of New Jersey
Rutgers, The State University of New Jersey
New Brunswick, NJ  08901

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

Response: Severe asthma is characterized by Type 2 inflammation manifested by increases in IL-13, IL-4 and Il-5 levels in the airways that promotes airway hyperresponsiveness and in part irreversible airway obstruction.  These clinical manifestations profoundly increase asthma morbidity and mortality.

To address an unmet therapeutic need, Tralokinumab was developed as a monoclonal antibody targeting soluble IL-13 with the goal of improving lung function and patient reported outcomes while decreasing annual exacerbation rates.  Stratus 1 and 2 represent two identical randomized, double-blind, placebo-controlled, phase 3 clinical trials in severe asthma.  These international trials enrolled approximately 2000 subjects with severe asthma and examined whether Tralokinumab decreased annualized exacerbation rates (AER) as compared with placebo (primary outcome).

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Recombinant Polio Vaccine Improved Survival Rate Among Some With Aggressive Recurrent Brain Tumor

MedicalResearch.com Interview with:

Dr. Annick Desjardins, Assistant Professor of Medicine, photographed on October 2, 2013.

Dr. Desjardins

Annick Desjardins, M.D., F.R.C.P.C.
Associate Professor of Neurology
Associate Professor of Neurosurgery
Director of Clinical Research
The Preston Robert Tisch Brain Tumor Center at Duke
Duke University School of Medicine
Durham, NC 27710

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

Response: The poliovirus receptor (CD155) is an onco-fetal cell adhesion molecule with widespread expression in all solid tumors and particularly in primary CNS tumors (adult and pediatric).

Recombinant nonpathogenic polio–rhinovirus chimera (PVSRIPO) was generated by replacing a critical piece of the genetic information from the Sabin type 1 polio vaccine, making PVSRIPO incapable of harming or killing normal brain cells, but toxic/lethal in cancer cells. In preclinical models, it has been demonstrated that the infection of tumor cells, leads to the release of danger signals, which triggers a recruitment of dendritic/CD4/CD8 T cells and a destruction of tumor cells by anti-tumor T cells.

The manuscript reports the results of the phase 1 trial of PVSRSIPO in recurrent WHO grade IV malignant glioma patients. Adult patients with recurrence of a single glioblastoma lesion, 1-5.5cm in dimension, in a non-eloquent area of the brain, were enrolled on study. PVSRIPO is injected slowly over 6.5 hours directly into the tumor via a small catheter inserted via a small bur hole. Once intratumoral injection is completed, the catheter is removed and patients are observed for localized tumor inflammation, followed by tumor contraction. A total of 61 patients were treated on study, 9 patients in a dose escalation phase and 52 in a dose expansion phase. Side effects observed were in relation to the localized inflammation of the tumor and depending on the cerebral functions in close proximity to the tumor: headaches, visual field changes, hemiparesis, etc.

One patient experienced a brain hemorrhage at the time of catheter removal, which triggered right sided weakness and aphasia. The patient remained alive 57.5 months after PVSRIPO infusion at data cutoff of March 20th, 2018. Two on-study death were observed, a patient died from cerebral edema and seizures, which was later found to be due to tumor progression, and one patient died from the complications of an intracranial hemorrhage while receiving anticoagulation and bevacizumab.

The median overall survival among all 61 patients who received PVSRIPO was 12.5 months (95% CI, 9.9 to 15.2), comparatively to 11.3 months (95% CI, 9.8 to 12.5) in a historical control group of patients treated at Duke and who would have met eligibility on trial, would have the trial been available to them.

At 24 months, the survival plateaued in patients treated with PVSRIPO with an overall survival rate of 21% (95% CI, 11 to 33) at 24 months and 36 months in PVSRIPO treated patients, while overall survival in the historical control group continued to decline, with an overall survival rates of 14% (95% CI, 8 to 21) at 24 months and 4% (95% CI, 1 to 9) at 36 months in the historical control group.  Continue reading

Anti-PD1 Immunotherapy May Work Better in Older Melanoma Patients

MedicalResearch.com Interview with:

Ashani Weeraratna, Ph.D. The Ira Brind professor and  Co-program leader of the Immunology, Microenvironment and Metastasis Program  The Wistar Institute Member of Wistar’s Melanoma Research Center Philadelphia 

Dr. Weeraratna

Ashani Weeraratna, Ph.D.
The Ira Brind professor and
Co-program leader of the Immunology, Microenvironment and Metastasis Program
The Wistar Institute
Member of Wistar’s Melanoma Research Center
Philadelphia 

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

Response:  This study shows for the first time that older patients, especially those who have had prior MAPKi therapy fare better than younger patients when treated with anti-PD1. We found that tumors in younger patients and younger mice have higher levels of Tregulatory cells, the cells that regulate other immune cells. This is not true systemically, only within the tumor microenvironment.

We were surprised because we expected that, as with targeted therapy, older patients would have a poorer response to immunotherapy, given what we perceive as a poorer immune system in older patients.  Continue reading

Study Reports Hair Repigmentation During Immunotherapy For Lung Cancer

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.

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Report of Benign Moles Undergoing Immune Reaction During Nivolumab Therapy in a Patient With Melanoma

MedicalResearch.com Interview with:

Yasuhiro Nakamura, M.D., Ph.D. Associate Professor Department of Skin Oncology/Dermatology Comprehensive Cancer Center Saitama Medical University International Medical Center Hidaka, Saitama

Dr. Nakamura

Yasuhiro Nakamura, M.D., Ph.D.
Associate Professor
Department of Skin Oncology/Dermatology
Comprehensive Cancer Center
Saitama Medical University International Medical Center
Hidaka, Saitama

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

Response: Regressing nevi, which are frequently associated with halo phenomenon, occur in approximately 1% of the general population. In patients with melanoma, spontaneous or treatment-related depigmentation of the skin (vitiligo) is sometimes observed. Although humoral and cellular immune responses may play a crucial role in their development, immune reactions to benign melanocytic nevi (BMN) without a halo are extremely rare in both the general population and in patients with melanoma.

This publication reports a rare case with multiple metastatic melanomas who showed a remarkable clinical response to nivolumab with a simultaneous prominent immune reaction to multiple BMN without halo phenomenon. This rare phenomenon may be associated with dramatic efficacy of nivolumab in melanoma patients.

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Tofacitinib -XELJANZ: Potential New Treatment Option For Moderate To Severe Ulcerative Colitis

MedicalResearch.com Interview with:

William J. Sandborn, MD Professor of Medicine and Adjunct Professor of Surgery Chief, Division of Gastroenterology Vice Chair for Clinical Operations, Department of Medicine Director, UCSD IBD Center University of California San Diego and UC San Diego Health System

Dr. Sandborn

William J. Sandborn, MD
Professor of Medicine and Adjunct Professor of Surgery
Chief, Division of Gastroenterology
Vice Chair for Clinical Operations, Department of Medicine
Director, UCSD IBD Center
University of California San Diego and
UC San Diego Health System

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

Response: There is still a substantial unmet need for new treatments for patients with ulcerative colitis.

A previous Phase II study had suggested that tofacitinib might be effective for short term therapy of ulcerative colitis. The patients in that study for the most part had not failed anti-TNF therapy. Now we report the findings from 3 large Phase III trials, two short term trials and one long term trial, demonstrating that tofacitinib 10 mg twice daily is effective for short term therapy, and that both 5 mg and 10 mg twice daily is effective for long term therapy. We also demonstrated that tofacitinib is effective both in patients who have not failed anti-TNF therapy and patients who have failed anti-TNF therapy.

The study demonstrated induction of clinical remission, clinical response and mucosal healing (flexible sigmoidoscopy improvement) over the short term, and maintenance of clinical remission, clinical response, and mucosal healing over the long term.

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Granzyme B Probe Plus PET Scanning Helps Determine Response To Immunotherapy

MedicalResearch.com Interview with:

Ben Larimer, PhD research fellow in lab of Umar Mahmood, MD, PhD Massachusetts General Hospital Professor, Radiology, Harvard Medical School

Dr. Ben Larimer

Ben Larimer, PhD research fellow in lab of
Umar Mahmood, MD, PhD

Massachusetts General Hospital
Professor, Radiology, Harvard Medical School

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

Response:
Although immunotherapies such as checkpoint inhibitors have revolutionized cancer treatment, unfortunately they only work in a minority of patients. This means that most people who are put on a checkpoint inhibitor will not benefit but still have the increased risk of side effects. They also lose time they could have spent on other therapies. The ability to differentiate early in the course of treatment patients who are likely to benefit from immunotherapy from those who will not greatly improves individual patient care and helps accelerate the development of new therapies.

The main purpose of our study was to find a way to separate immunotherapy responders from non-responders at the earliest time point possible, and develop an imaging probe that would allow us to distinguish this non-invasively.

Granzyme B is a protein that immune cells use to actually kill their target. They keep it locked up in special compartments until they get the right signal to kill, after which they release it along with another protein called perforin that allows it to go inside of tumor cells and kill them. We designed a probe that only binds to granzyme B after it is released from immune cells, so that we could directly measure immune cell killing. We then attached it to a radioactive atom that quickly decays, so we could use PET scanning to noninvasively image the entire body to see where immune cells were actively releasing tumor-killing granzyme B.

We took genetically identical mice and gave them identical cancer and then treated every mouse with checkpoint inhibitors, which we knew would result in roughly half of the mice responding, but we wouldn’t know which ones until their tumors began to shrink. A little over a week after giving therapy to the mice, and before any of the tumors started to shrink, we injected our imaging probe and performed PET scans. When we looked at the mice by PET imaging, they fell into two groups. One group had high PET uptake, meaning high levels of granzyme B in the tumors, the other group had low levels of PET signal in the tumors. When we then followed out the two groups, all of the mice with high granzyme B PET uptake ended up responding to the therapy and their tumors subsequently disappeared, whereas those with low uptake had their tumors continue to grow.

We were very excited about this and so we expanded our collaboration with co-authors Keith Flaherty and Genevieve Boland to get patient samples from patients who were on checkpoint inhibitor therapy to see if the same pattern held true in humans. When we looked at the human melanoma tumor samples we saw the same pattern, high secreted granzyme levels in responders and much lower levels in non-responders.

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First Patients Enrolled in Study of Nintedanib For Progressive Fibrosing Lung Conditions

MedicalResearch.com Interview with:

Thomas Leonard, Ph.D. Executive director, Clinical Development and Medical Affairs, Specialty Care Boehringer Ingelheim Pharmaceuticals, Inc.

Dr. Thomas Leonard

Thomas Leonard, Ph.D.
Executive director, Clinical Development and Medical Affairs, Specialty Care
Boehringer Ingelheim Pharmaceuticals, Inc.

MedicalResearch.com: What is the background for this study? Would you tell us a little more about IPF?

Response: Boehringer Ingelheim’s Phase III PF-ILD (progressive fibrosing interstitial lung disease) trial will investigate the safety and efficacy of nintedanib, in a range of progressive fibrosing lung conditions other than idiopathic pulmonary fibrosis, or IPF. The PF-ILD trial is the first time that patients with different fibrosing lung diseases will be included in one single clinical trial assessing the efficacy of nintedanib as a potential treatment, and the trial is the first in the field of fibrosing lung diseases to group patients based on the clinical characteristics of their disease, rather than the diagnosis.

There are more than 200 conditions that affect the tissue and space around the air sacs of the lungs, or interstitium, and, collectively, these conditions are called interstitial lung diseases — or ILDs. Based on clinical observations, there is a group of patients with ILD who, independent from the classification of the ILD, exhibit progressive fibrosis. The proposed terminology for describing this group of patients is PF-ILD. In these patients, the disease appears to follow a course similar to IPF with worsening of respiratory symptoms, lung function, quality of life and ability to perform daily activities, as well as early mortality despite treatment.

There is currently no efficacious treatment available for PF-ILD. This trial is exploring how fibrosis in the lungs is treated and whether nintedanib is a potential treatment, based on the efficacy and safety of nintedanib in IPF, a rare and serious lung disease that causes permanent scarring of the lungs, making it difficult to breathe. IPF affects as many as 132,000 Americans, typically men over the age of 65. On average, people with IPF live only three to five years after diagnosis, and approximately 40,000 people die from this disease every year.

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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.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

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Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

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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