Asthma, Author Interviews, Immunotherapy, Pediatrics / 31.10.2015

MedicalResearch.com Interview with: Stephen J. Teach, MD, MPH Chair, Department of Pediatrics Children's National Health System Washington, DC  Medical Research: What is the background for this study? What are the main findings? Dr. Teach: Inner-city children aged 6 to 17 years with moderate to severe asthma continue to experience exacerbations at high rates during the fall season despite therapy which follows the guidelines of the National Institutes of Health. These exacerbations are most common among children with a history of prior exacerbations and sensitivities to common indoor allergens who develop an upper respiratory infection with the common cold virus (rhinovirus). The PROSE study found that treatment with omalizumab begun 4 to 6 weeks before the children return to school, significantly reduced exacerbations of asthma in the first 90 days of the school year. This effect was most dramatic among those children who had experienced an exacerbation in the months preceding the beginning of the school year. Omalizumab is an antibody which binds and deactivates the IgE antibody. The IgE antibody serves as the basis for allergic sensitivity. (more…)
Author Interviews, FDA, Immunotherapy, Lung Cancer / 24.10.2015

MedicalResearch.com Interview with: Dickran Kazandjian, MD Office of Hematology and Oncology Products Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Kazandjian: Nivolumab is the first approved immunotherapy, for the treatment of metastatic squamous non–small-cell lung cancer (NSCLC) after platinum-based chemotherapy.  FDA initiated an expedited review after obtaining the data monitoring committee report of a planned interim analysis of a second-line squamous NSCLC trial demonstrating a large overall survival benefit (CheckMate 017). Nivolumab efficacy in metastatic Squamous (SQ) NSCLC has been previously reported in two studies.  CheckMate 063 was a single-arm trial in 117 patients with metastatic SQ NSCLC who had progressed after previous treatment with 2 systemic regimens including platinum-based doublet chemotherapy (Rizvi et al)  CheckMate 017 was a randomized study of nivolumab compared to docetaxel in 272 patients with metastatic SQ NSCLC who had progressed after prior platinum-based doublet chemotherapy (Brahmer et al).  The median survival of patients randomized to nivolumab was 9.2 months vs 6.0 months for docetaxel (hazard ratio, 0.59; 95%CI, 0.44-0.79; P < .001) a 41% improvement in the risk of death. Approval was supported by the single-arm study which demonstrated an objective response rate of 15% and at the time of analysis, 10 of the 17 responding patients (59%) had response  durations of 6 months or longer. The FDA approved nivolumab on March 4, 2015, saving 6 months by not waiting for formal preparation of data by the sponsor and 2.5 months by expediting review. (more…)
Author Interviews, Immunotherapy, Melanoma, Nature / 19.06.2015

MedicalResearch.com Interview with: Chiara Martinoli, PhD Medical Oncology of Melanoma European Institute of Oncology Milan, Italy MedicalResearch: What is the background for this study? What are the main findings? Dr. Martinoli: The recent advent of new immunomodulatory drugs and targeted therapies is changing the therapeutic algorithm for metastatic melanoma patients. Immunomodulation with the anti-CTLA-4 antibody ipilimumab improves survival but is not devoid of potential risks. There is an urgent need for biomarkers to identify patients best suited to receive this therapy, in order to maximize treatment benefit and spare toxicities. In this study, by analyzing pre-therapy hematological parameters of a large group of metastatic melanoma patients treated with ipilimumab, we showed that neutrophil-to-lymphocyte ratio is strongly and independently associated to patient outcome. Patients with a low baseline neutrophil-to-lymphocyte ratio had a double-reduced risk of disease progression and a two-to-four-fold reduced risk of death, regardless of age, sex and LDH. (more…)
Author Interviews, Diabetes, Immunotherapy, Kidney Disease, University of Michigan / 13.06.2015

MedicalResearch.com Interview with: Frank C. Brosius, MD Professor, Internal Medicine and Physiology Chief, Division of Nephrology University of Michigan Ann Arbor, MI Dr. Matthias Kretzler MD Professor, Internal Medicine Research Professor, Computational Medicine and Biology University of Michigan Ann Arbor, MI Katherine R. Tuttle MD Clinical Professor of Medicine, Division of Nephrology Medical & Scientific Director, Providence Medical Research Center/Sacred Heart Center Professor of Basic Medical Sciences, WWAMI Program Washington State University Medical Research: What is the background for this study? Response: Our University of Michigan team had found that JAK-STAT gene expression was increased in kidneys in patients with diabetic kidney disease and that these changes correlated with progression of kidney disease.  We subsequently substantiated these changes in other studies and have found that by increasing expression of just one of these genes, JAK2, in a single kidney cell type (podocytes) in mice that we can make their diabetic kidney disease much worse. At around the same time, investigators at Eli Lilly and Co. had FDA approval to test a JAK1-2 inhibitor, baricitinib, in patients with rheumatoid arthritis.  The Lilly scientists saw our human results and thought about using baricitinib in patients with diabetic kidney disease.  After initial discussions with Dr. Kretzler and myself they concluded that there was good reason to move ahead with this study and just 14 months after the initial meeting the phase 2 clinical trial of baricitinib in the treatment of patients with diabetic kidney disease was initiated. (more…)
Author Interviews, BMJ, Gastrointestinal Disease, Immunotherapy / 11.06.2015

MedicalResearch.com Interview with: Nynne Nyboe Andersen, MD, PhD student Department of Epidemiology Research Statens Serum Institut Copenhagen, Denmark Medical Research: What is the background for this study? What are the main findings? Dr. Andersen: The use of TNF-α inhibitors, including infliximab, adalimumab and certolizumab pegol to treat people with inflammatory bowel disease is increasing worldwide and has upgraded the medical treatment modalities. However, concerns about their safety, including an increased risk of serious infections have persisted because they suppress the immune system. Previous meta-analyses based on randomized controlled trials did not suggest an increased risk of serious infections in people with inflammatory bowel disease treated with TNF-α inhibitors compared to placebo. However, the trials included in the meta-analyses were designed to investigate efficacy, and not to analyze risk of rare adverse events such as serious infections and often represent selected populations. Therefore, observational studies are essential to evaluate safety in a real world setting; however, results from these studies have been conflicting. Thus, as the risk of infections associated with TNF-α inhibitor treatment in people with inflammatory bowel disease is unclear we aimed at investigating this potential risk in a population-based setting based on the entire Danish inflammatory bowel disease population. In a propensity score matched cohort we found a significant 63% increased risk of serious infections within 90 days after treatment initiation. When we prolonged follow-up to 356 days the risk was attenuated and no longer significant.  For site-specific serious infections, we found increased point estimates for sepsis, urological/gynecological infections, and skin and soft tissue infections; but these results should be interpreted cautiously because of limited power. (more…)
Author Interviews, Immunotherapy, Melanoma / 02.06.2015

Prof. Ze'ev Ronai Ph.D Scientific Director Sanford-Burnham's La JollaMedicalResearch.com Interview with: Prof. Ze'ev Ronai Ph.D Scientific Director Sanford-Burnham's La Jolla Medical Research: What is the background for this study? What are the main findings? Prof. Ronai: There is an urgent need to find new approaches to treat melanoma in patients that are resistant to current therapeutic regimes—and this represents a significant percent of melanoma patients.  We used  samples from patients with drug resistant tumors  to study the molecular basis of resistance and screened for genes involved in the process. We have identified a new player in melanoma resistance to therapy—a molecular target, which provides the basis for clinical trials with drugs currently available to these targets. We found that JAK1 kinase is one target that  is upregulated in the resistant tumors. Inhibiting JAK1 kinase can effectively overcome such resistance.  (more…)