Author Interviews, Boehringer Ingelheim, Pharmacology, Pulmonary Disease / 02.10.2017

MedicalResearch.com Interview with: Professor Carlo Vancheri Professor of Respiratory Medicine, University of Catania, Italy and Director of the Regional Referral Centre for Rare Lung Diseases and the Laboratory of Experimental Respiratory Medicine. MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The aim of Boehringer Ingelheim’s INJOURNEY trial was to investigate the safety profile of Ofev (nintedanib) in combination with pirfenidone in treating patients with idiopathic pulmonary fibrosis (IPF). Nintedanib and pirfenidone, the only two FDA-approved drugs for the treatment of IPF, are able to slow down the progression of the disease, reducing the forced vital capacity (FVC) decline of about 50%, but this is not a cure. The target for the future is to have even more effective treatments. In the meanwhile, it is necessary to optimize the use of the available drugs. The medical treatment of other pulmonary diseases such as COPD, asthma or pulmonary hypertension is already based on different combinations of drugs. This 12-week, open-label, randomized study was designed to evaluate the safety, tolerability and pharmacokinetics of nintedanib with add-on pirfenidone, compared with nintedanib alone in patients with IPF. Change in FVC, the established efficacy endpoint in IPF trials, was evaluated as an exploratory endpoint. The primary endpoint of the INJOURNEY trial was the percentage of patients with on-treatment gastrointestinal adverse events from baseline to week 12 of randomized treatment, and the results showed that the combination of nintedanib and add-on pirfenidone resulted in a manageable safety and tolerability profile, similar to the profile of each drug individually in the majority of patients. Results also indicated there may be a slower decline in FVC in patients treated with pirfenidone along with nintedanib compared with nintedanib alone, suggesting a potential benefit of the combination. However, further research will be necessary to fully evaluate the efficacy of the combination. (more…)
Author Interviews, Boehringer Ingelheim, Columbia, Heart Disease, J&J-Janssen, Merck, NEJM / 14.09.2017

MedicalResearch.com Interview with: Professor Christopher P. Cannon MD Executive Director, Cardiometabolic Trials, Baim Institute Cardiologist Brigham and Women's Hospital Baim Institute for Clinical Research Columbia University College of Physicians and Surgeons MedicalResearch.com: What is the background for this study? What are the main findings? Response: The trial explored whether a dual therapy approach of anticoagulation and P2Y12 antagonist - without aspirin - in non-valvular atrial fibrillation (AF) patients following percutaneous coronary intervention (PCI) and stent placement would be as safe, and still efficacious, as the current standard treatment – triple therapy. For more detailed background on the study, readers may want to review the first paragraph of the article in the New England Journal of Medicine. Results showed significantly lower rates of major or clinically relevant non-major bleeding events for dual therapy with dabigatran, when compared to triple therapy with warfarin. In the study, the risk for the primary safety endpoint (time to major or clinically relevant non-major bleeding event) was 48 percent lower for dabigatran 110 mg dual therapy and 28 percent lower for dabigatran 150 mg dual therapy (relative difference), with similar rates of overall thromboembolic events. (more…)
Annals Internal Medicine, Author Interviews, Flu - Influenza, Merck, Technology / 11.09.2017

MedicalResearch.com Interview with: Jesse Papenburg, MD MSc FRCPC FRQS Clinical Research Scholar Assistant Professor of Pediatrics, McGill University Div. of Pediatric Infectious Diseases, Dept. of Microbiology Montreal Children’s Hospital Montreal, QC  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Influenza viruses cause yearly epidemics of acute respiratory illness affecting 5 to 30 percent of the population. Diagnosing influenza on the basis of only clinical symptoms is difficult because its manifestations vary and are nonspecific. Reverse transcriptase polymerase chain reaction (RT-PCR) is the gold standard for flu diagnosis, but these tests must be sent to a laboratory and have turnaround times that extend beyond the clinical encounter. Rapid and accurate diagnosis of influenza has the potential to improve patient outcomes and decrease health care costs. Since 2011, two novel classes of rapid influenza diagnostic assays i.e., with results available in <30 minutes, have been commercialized with claims of improved sensitivities based on technological improvements: 1) automated immunochromatographic antigen detection tests (digital immunoassays, DIAs) and 2) rapid nucleic acid amplification tests (NAATs). Our systematic review and meta-analysis synthesized the available evidence and compared the diagnostic accuracy of commercially available rapid tests for the detection of influenza A and B infection:
  • Overall, the rapid tests displayed very high specificities (≥98%). Physicians can therefore diagnose influenza with confidence on the basis of a positive RIDT, DIA, or rapid NAAT result.
  • The pooled sensitivities for DIAs (80.0% for influenza A and 76.8% for influenza B) and rapid NAATs (91.6% for influenza A and 95.4% for influenza B) are markedly higher than those for RIDTs (54.4% for influenza A and 53.2% for influenza B).
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AstraZeneca, Author Interviews, Eli Lilly, Merck / 07.09.2017

MedicalResearch.com Interview with: Dragana Radovanovic, MD  Head of AMIS Plus Data Center Hirschengraben Zürich MedicalResearch.com: What is the background for this study? What are the main findings? Response: What we know so far? When a woman suffers a heart attack she is older, has consequently more cardiovascular risk factors such as hypertension, has more comorbidities, is less likely to receive the same therapies and more likely to die in hospital. Furthermore, we know from many hospital statistics and administrative data bases that in-hospital mortality of acute myocardial infarction patients has been on the decrease from 1970 to the early 2000’s. We then wanted to know what the situation looks like in Switzerland and therefore analyzed in-hospital mortality over the last 20 years with regard to gender, age and therapies. For this study we used the data of the nationwide AMIS Plus registry (Acute Myocardial Infarction in Switzerland) which exists since 1997 and continuously prospectively collects clinical data of patients hospitalized with acute myocardial infarction. We have found that during the last 20 years (from 1997 to the end of 2016) in-hospital mortality of patients with acute myocardial infarction in Switzerland has halved. Although in-hospital mortality was consistently higher in women, overall age-adjusted mortality has decreased more prominently in women compared to men. Especially in patients aged below 60 years a significant decrease in in-hospital mortality was observed in women but not in men. (more…)
Author Interviews, Boehringer Ingelheim, Heart Disease, PAD / 03.09.2017

MedicalResearch.com Interview with: John Eikelboom MBBS Associate Professor, Division of Hematology & Thromboembolism Department of Medicine Canada Research Chair in Cardiovascular Medicine Canadian Institutes for Health Research McMaster University MedicalResearch.com: What is the background for this study? Response: Cardiovascular disease affects 1 in 25 persons around the world and a total of more than 300 million individuals. Thrombus formation at the site of a ruptured atherosclerotic plaque is the commonest mechanism of myocardial infarction and ischemic stroke in patients with cardiovascular disease. Aspirin is effective for the prevention of these complications but reduces the risk by only 19% during long term therapy. Rivaroxaban has previously been tested in the ATLAS ACS-2 TIMI 51 trial at doses of 2.5 mg twice daily or 5 mg twice daily on top of background antiplatelet therapy and has been shown to reduce major adverse cardiovascular events as well as mortality. We tested these same doses of rivaroxaban for the prevention of cardiovascular death, stroke or myocardial infarction in patients with stable cardiovascular disease. (more…)
Author Interviews, Flu - Influenza, Kaiser Permanente, Merck, NEJM, Vaccine Studies / 10.08.2017

MedicalResearch.com Interview with: Michael Jackson  PhD, MPH Kaiser Permanente Washington Health Research Institute (KPWHRI) principal investigator for the United States Influenza Vaccine Effectiveness Network  MedicalResearch.com: What is the background for this study?
  • Response: Each year, Kaiser Permanente Washington is one of five sites across the country that participate in the United States Influenza Vaccine Effectiveness Network. The Network reports its early interim results in the MMWRand presents additional interim results to the Advisory Committee on Immunization Practices (ACIP). This New England Journal of Medicine publication is an update of those interim results.
  • The findings in this New England Journal of Medicine are special because prior randomized controlled trials indicated that the nasal spray vaccine (FluMist)—also called live attenuated influenza vaccine (LAIV)—would work well to protect children and teens from the flu, whereas in actual practice we found that the flu shot worked much better, particularly against the predominant strain, A(H1N1)pdm09.
  • The nasal spray vaccine was first seen to be less effective for young children than the flu shot in 2013-2014 for the A(H1N1)pdm09 virus strain. In response, the A(H1N1)pdm09 virus strain used in the nasal spray vaccine was changed for the 2015-2016 influenza season. The 2016/17 season was the first since 2015-2016 to be dominated by the A(H1N1)pdm09 virus, making this our first opportunity to evaluate the updated nasal spray vaccine.
  • The Influenza Vaccine Effectiveness Network evaluated the impact of this change as part of our estimates of influenza vaccine effectiveness in 2015-2016. Preliminary findings from this study were presented to the ACIP in June 2016, which led to the nasal spray vaccine not being recommended in 2016-2017 in the US, although the nasal spray vaccine remains licensed in the US. In 2016-2017, the LAIV A(H1N1)pdm09 vaccine strain was unchanged from 2015-2016.
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Author Interviews, HIV, J&J-Janssen, Merck, Pharmacology / 26.07.2017

MedicalResearch.com Interview with: Dr. Kathleen Squires MD Professor and Director of Infectious Diseases Thomas Jefferson University Philadelphia, PA  MedicalResearch.com: What is the background for this study? What are the main findings?
  • The pivotal Phase 3 DRIVE-AHEAD study evaluated the safety and efficacy of a once-daily, single tablet, fixed-dose combination containing doravirine, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infection, compared to a fixed-dose combination containing efavirenz.
    • After 48 weeks of treatment, 84 percent of the 364 treatment-naïve patients taking once-daily DOR/3TC/TDF achieved levels of HIV-1 RNA <50 copies/mL compared to 81 percent of the 364 patients taking once-daily EFV/FTC/TDF, with an estimated treatment difference of 3.5 percent.
    • Increases in mean CD4+ T-cell counts from baseline for the DOR/3TC/TDF and EFV/FTC/TDF groups were 198 and 188 cells/mm3, respectively, with an estimated treatment difference of 10.1.
    • In addition, comparable efficacy was observed across both treatment groups among individuals with high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, which consisted of 69 patients in the DOR/3TC/TDF group and 73 patients in the EFV/FTC/TDF group (Observed Failure approach).
      • Of those patients with a high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, 81 percent in the DOR/3TC/TDF group and 81 percent in the EFV/FTC/TDF group achieved the study’s primary endpoint of <50 copies/mL of HIV-1 RNA, with a treatment difference of 1.0 percent.
    • The study also met its primary safety endpoint, showing that treatment with DOR/3TC/TDF resulted in fewer patients reporting events of several pre-specified neuropsychiatric adverse events compared to EFV/FTC/TDF by Week 48, including dizziness (8.8 percent versus 37.1 percent); sleep disorders and disturbances (12.1 percent versus 25.5 percent); and inability to think clearly or concentrate (4.4 percent versus 8.2 percent).
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Author Interviews, HIV, Merck, Pharmacology / 25.07.2017

MedicalResearch.com Interview with: Dr. Pedro Cahn Chief of the infectious disease unit at Juan A. Fernandez Hospital Buenos Aires, Argentina, and ONCEMRK lead study investigator MedicalResearch.com: What is the background for this study? What are the main findings? The ONCEMRK Phase 3 study was conducted to evaluate the efficacy and safety of once-daily ISENTRESS (raltegravir) HD 1200 mg (given as two 600 mg oral tablets) compared to twice daily raltegravir 400 mg, each in combination therapy with emtricitabine plus tenofovir disoproxil fumarate in previously untreated adults with HIV-1 infection with levels of HIV-1 RNA ≥ 1,000 copies/mL.
  • Week 96 data showed:
    • 5 percent of the 531 patients taking once-daily raltegravir 1200 mg (2 x 600 mg) achieved viral suppression of less than 40 copies/mL of HIV-1 RNA, compared to 80.1 percent of the 266 patients taking twice-daily raltegravir 400 mg, both in combination therapy with emtricitabine plus tenofovir disoproxil fumarate, with a treatment difference of 1.4 percent.
    • Increases in CD4+T-cell counts from baseline were comparable for the two treatment regimens, with an average increase of 261.6 cells/mm3 for once-daily raltegravir (1200 mg) and 262.2 cells/mm3 for twice-daily raltegravir (400 mg).
    • Efficacy was consistent across a variety of patient populations, including those with high viral load at baseline (HIV-1 RNA >100,000 copies/mL).
    • Treatment-emergent viral mutations leading to any drug resistance were detected in less than 1 percent of patients in both treatment arms, with 4/531 (0.8 percent) in the once-daily raltegravir (1200 mg) treatment arm, and 2/266 (0.8 percent) in the twice-daily raltegravir (400 mg) treatment arm through 96 weeks.
    • The rate of discontinuation of therapy due to adverse events through 96 weeks was low (1.3 percent in patients receiving once-daily raltegravir (1200 mg) and 2.3 percent in patients receiving twice-daily raltegravir (400 mg).
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Annals Internal Medicine, AstraZeneca, Author Interviews, Brigham & Women's - Harvard, Heart Disease, Merck, Pharmacology / 25.07.2017

MedicalResearch.com Interview with: Alexander Turchin, MD,MS Director of Quality in Diabetes Associate Professor, Harvard Medical School Brigham and Women's Hospital Boston, MA MedicalResearch.com: What is the background for this study? Response: Cardiovascular disease is the # 1 cause of death in the U.S. and worldwide. Statins are some of the most effective medications available for prevention of cardiovascular events. However, many patients stop statins, frequently because of adverse reactions. In our study we aimed to assess the risk-benefit balance of trying a statin again after experiencing an adverse reaction. (more…)
Author Interviews, Boehringer Ingelheim, Heart Disease, JAMA / 18.07.2017

MedicalResearch.com Interview with: Javed Butler, MD, PhD Chief of the Cardiology Division Dr. Vincent Yang, Simons Chair in Internal Medicine Stony Brook University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF. We therefore studies high dose spironolactone in patients with AHF. Unfortunately all of our primary and secondary endpoints were not different between spironolactone and placebo arms. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Dermatology, HIV, JAMA, Kaiser Permanente, Merck / 13.07.2017

MedicalResearch.com Interview with: Maryam M. Asgari, MD, MPH Department of Dermatology Massachusetts General Hospital, Department of Population Medicine Harvard Medical School, Boston, Massachusetts Division of Research, Kaiser Permanente Northern California, Oakland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nonmelanoma skin cancer – defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) – is a common malignant condition, affecting more than 2 million Americans every year. BCCs are more common than SCCs among individuals with healthy immune systems, while SCCs are more predominate than BCCs among people who are immunocompromised. We examined how laboratory markers used to evaluate HIV disease progression may be associated with subsequent nonmelanoma skin cancer risk in white patients previously diagnosed with at least one such cancer from 1996 to 2008.  We measured CD4 count, viral load and subsequent nonmelanoma skin cancer. The study included 455 participants with HIV and 1,952 without HIV. All were members of the Kaiser Permanente Northern California health care plan. (more…)
AACR, Abuse and Neglect, Boehringer Ingelheim, Cancer Research / 11.07.2017

MedicalResearch.com Interview with: Dr. Jordi Bruix, MD Professor of Medicine University of Barcelona Director of the Barcelona Clinic Liver Cancer (BCLC) Group Liver Unit Hospital Clinic of Barcelona MedicalResearch.com: What is the background for this study? What are the main findings? Response: The RESORCE Phase III pivotal trial is an international, multicenter, placebo-controlled trial which investigated the efficacy of Stivarga (regorafenib) in adults with Child-Pugh A and Barcelona Clinic Liver Cancer Stage Category B or C hepatocellular carcinoma (HCC) who had documented disease progression following first-line treatment with Nexavar (sorafenib). Trial participants were administered a daily oral 160mg dose (three weeks on/ one week off) of regorafenib plus best supportive care (BSC), or placebo plus BSC. Results from the trial demonstrated that participants treated with regorafenib experienced a statistically significant and clinically meaningful improvement in the study’s primary endpoint—overall survival (OS). Participants treated with regorafenib demonstrated a median overall survival of 10.6 months vs. 7.8 months with placebo. At ASCO 2017, an exploratory analysis evaluated the impact of baseline alpha-fetoprotein (AFP) and c-Met as predictors of poor prognosis in patients enrolled in the RESORCE trial (Abstract #4078). (more…)
Abuse and Neglect, Boehringer Ingelheim, Diabetes, Endocrinology, Lipids / 22.06.2017

MedicalResearch.com Interview with: Robert R. Henry, M.D. Professor of Medicine Member of the ODYSSEY DM Steering Committee and Director of the Center for Metabolic Research VA San Diego Healthcare System MedicalResearch.com: What is the background for this study? What are the main findings? Response: The ODYSSEY DM-DYSLIPIDEMIA trial was a randomized, open-label, parallel-group study designed to evaluate the superiority of Praluent versus usual care in 413 patients with type 2 diabetes with mixed dyslipidemia at high cardiovascular (CV) risk, not adequately controlled with maximally tolerated dose (MTD) statins. The primary endpoint was percent change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to week 24. In ODYSSEY DM-DYSLIPIDEMIA, Praluent 75 mg was added to MTD statins, with dose adjusted at week 12 to 150 mg every two weeks if their non-HDL-C was greater than or equal to 100 mg/dL at week 8. Approximately 64 percent of patients reached their lipid goals with the Praluent 75 mg dose. Results from the ODYSSEY DM-DYSLIPIDEMIA study found that Praluent added to MTD statins showed significant reduction in non-HDL-C and other lipid parameters compared to those on usual care. Praluent was superior to usual care in lowering non-HDL-C (37.3 percent and 4.7 percent, for the usual care arm). The mean difference between the two treatment arms was -32.5 percent (p<0.0001). Praluent in combination with MTD statins reduced LDL-C by 43 percent from baseline compared to a 0.3 percent increase for usual care (p<0.0001). Treatment with Praluent also improved the overall lipid profile. There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Furthermore, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk. (more…)
AstraZeneca, Author Interviews, Boehringer Ingelheim, Diabetes, Eli Lilly, J&J-Janssen, Lipids, Merck / 19.06.2017

MedicalResearch.com Interview with: Lawrence Leiter, M.D. MDCM, FRCPC, FACP FACE, FAHA Chair of the ODYSSEY DM Steering Committee and Director of the Lipid Clinic at the Li Ka Shing Knowledge Institute St. Michael’s Hospital University of Toronto, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: The ODYSSEY DM-INSULIN trial was a randomized, double-blind, placebo-controlled, multicenter study that evaluated alirocumab (Praluent) in 517 patients with insulin treated type 1 and type 2 diabetes with high cardiovascular (CV) risk and hypercholesterolemia despite maximally tolerated dose (MTD) statins. The primary endpoint was percent change in calculated LDL-C from baseline to week 24. Alirocumab 75 mg every two weeks was added to MTD statins, with the dose increased at week 12 to 150 mg every two weeks if the LDL-C at week 8 was greater than or equal to 70 mg/dL. In fact, only about 20% of the alirocumab treated participants required the higher dose. Results of the type 2 diabetes study population (n=441) showed that the addition of alirocumab to MTD statin therapy, reduced LDL-C by 48.2 percent from baseline compared to a 0.8 percent increase for placebo. The mean difference between the two treatment arms was -49 percent (p<0.0001). Treatment with alirocumab also improved the overall lipid profile. Furthermore, no new safety issues were identified. There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Additionally, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk. (more…)
Author Interviews, Merck, Pharmacology / 13.06.2017

MedicalResearch.com Interview with: Roy F Chemaly, M.D., M.P.H., F.A.C.P., F.I.D.S.A Professor, Department of Infectious Diseases, Director, Infection Control and Employee Health, Division of Internal Medicine Director of the clinical virology research program,Department of infectious diseases Infection control and employee health The University of Texas MD Anderson MedicalResearch.com: Would you briefly explain the significance of CMV infections? What is the background for this study? Response: Cytomegalovirus (CMV) is one of the most important causes of infectious complications following organ transplantation and is a significant cause of illness and death in patients who have undergone allogeneic hematopoietic cell transplantation (allo-HCT). For more than 20 years, we have been managing this infection and trying to develop effective strategies to control it, but to no one’s satisfaction; CMV infection is still associated with significant morbidity and mortality in this high-risk population. Most transplant centers have adopted preemptive antiviral therapy as the strategy of choice for HCT patients.1 While anti-CMV drugs have decreased the incidence of CMV diseases, their use for prophylaxis has not been associated with improved outcomes.1 Demographic and transplant trends heighten the need for new anti-CMV agents. In the U.S, 83% of people aged 60 and older are CMV seropositive. These older patients received 8% of all hematopoietic-cell transplants in 2000-2006, a figure that jumped to 22% in 2007-2013. As Baby Boomers age, many more allogeneic transplant patients will be CMV seropositive. Therefore, prophylactic antiviral compounds that could effectively control viral replication, and restrict some pathologic processes of CMV diseases, could potentially lessen the complications associated with CMV infection and possibly reduce all-cause mortality. (more…)
Author Interviews, Boehringer Ingelheim, Cost of Health Care, Heart Disease / 12.06.2017

MedicalResearch.com Interview with: Sabine Luik, M.D. Senior vice president, Medicine & Regulatory Affairs Boehringer Ingelheim Pharmaceuticals, Inc. MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study is the first real-world, matched head-to-head study comparing all cause healthcare costs and healthcare resource utilization (HCRU) among novel oral anticoagulants (NOACs). The study analyzed claims data from 70,898 newly-diagnosed NVAF patients who were newly treated with Pradaxa, rivaroxaban or apixaban. The analysis found that Pradaxa was associated with lower all-cause costs and HCRU compared to rivaroxaban. Compared to apixaban, Pradaxa was associated with similar all-cause costs and hospitalizations, but higher all-cause outpatient and pharmacy HCRU. (more…)
ASCO, Author Interviews, Breast Cancer, Merck, NYU / 10.06.2017

MedicalResearch.com Interview with: Sylvia Adams, MD Associate Professor of Medicine Breast Cancer and Cancer Immunotherapy Programs NYU Langone Medical Center Cancer Institute/Clinical Cancer Center New York, NY 10016   MedicalResearch.com: What is the background for the Keynote-086 trial ? What are the main findings? Response: This study is the largest immunotherapy study to date presented in metastatic triple negative breast cancer. This phase 2 trial studied the efficacy and safety of pembrolizumab (P) as single agent in a very aggressive disease and had two cohorts, a cohort of previously untreated patients (Cohort B) and a cohort with patients who had received prior chemotherapy lines in the metastatic setting (Cohort A). The study showed that single agent pembrolizumab can elicit durable responses in a subset of patients. This was found regardless of tumoral PD-L1 expression but appeared to be much more frequent in women without prior chemotherapy treatments in the metastatic setting. Survival is especially promising for patients responding to therapy. (more…)
Author Interviews, Infections, Merck / 08.06.2017

MedicalResearch.com Interview with: Sanjay Merchant, PhD Executive Director Center for Observational and Real-world Evidence (CORE) Merck MedicalResearch.com: What is the background for this study? What are the main findings? Response: In February, the World Health Organization (WHO) published its first ever list of antibiotic-resistant “priority pathogens” that pose the greatest threat to human health. The list highlights in particular the threat of gram-negative bacteria that are resistant to multiple antibiotics, referred to as multidrug-resistant (MDR) bacteria, which have built-in abilities to find new ways to resist treatment. MDR Pseudomonas aeruginosa (MDR PsA) is listed as one of the pathogens in the Critical category in terms of need for new therapies. It poses an urgent threat. We set out to better understand the clinical and economic burden associated with hospital-onset MDR PsA so that appropriate treatment strategies can be employed to mitigate resistance. Our findings were presented at ASM Microbe 2017. Mortality rates for hospital-onset MDR PsA patients (20.1%) were almost twice as high compared to patients who did not have MDR PsA (11.5%). The MDR PsA patient group had a significantly higher odds ratio for mortality even after controlling for various factors that may impact mortality. Hospital-onset MDR PsA patients spent six additional days in the hospital when compared to patients who did not have MDR PsA infections. These findings highlight the public health threat of MDR PsA among hospitalized patients and the need for timely and effective therapy. (more…)
Author Interviews, Hepatitis - Liver Disease, Kidney Disease, Lancet, Merck / 01.06.2017

MedicalResearch.com Interview with: Annette Bruchfeld MD, PhD Senior Consultant Associate Professor Karolinska Institute Dept of Renal Medicine, M99 Karolinska University Hospital Huddinge Stockholm, Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: In patients with stage 4–5 chronic kidney disease(CKD), hepatitis C virus (HCV) infection can accelerate the decline in kidney function, impair health-related quality of life (HRQOL), and decrease survival chances of both patients and grafts in transplantation recipients. In this study additional data from patients with stage 4–5 chronic kidney disease undergoing treatment for HCV infection in the C-SURFER study, including HRQOL and resistance analyses was presented not previously reported for this patient population with gwnotype 1 infection. The final virological analysis of this study indicated a high cure rate with sustained virological response at 12 weeks after the end of treatment (SVR12) in more than 98% of all treated patients. Even in patients with resistance-associated substitutions (RASs) the SVR was high in 11 (84·6%) of 13 patients genotype 1a infection. (more…)
Author Interviews, Baylor College of Medicine Houston, Merck, Rheumatology / 07.05.2017

MedicalResearch.com Interview with: Grace H. Lo MD MSc Department of Medicine, Baylor College of Medicine Medical Care Line and Research Care Line, Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety Michael E. DeBakey Medical Center, Houston, TX MedicalResearch.com: What is the background for this study? What are the main findings? Response: Osteoarthritis is the most common form of arthritis. Many people who have signs of osteoarthritis on x-rays do not necessarily complain of pain. Presently, there are no known strategies for preventing the development of pain in this group of people. This study suggests that if these people have noisy knees (otherwise known as “crepitus”), they are at higher risk for developing pain within the next year compared to the people who do not have noisy knees. Future studies that target people who have x-ray signs of osteoarthritis, who do not complain of pain, but do report noisy knees, hold the promise of identifying interventions that can prevent knee pain. (more…)
Author Interviews, Boehringer Ingelheim, Immunotherapy, Pulmonary Disease / 27.04.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Biomarkers, Hepatitis - Liver Disease, Lancet, Merck / 25.04.2017

MedicalResearch.com Interview with: Jason Grebely PhD Associate Professor Senior Research Fellow (UNSW) Viral Hepatitis Clinical Research Program MedicalResearch.com: What is the background for this study? What are the main findings? Response: Globally, testing and diagnosis of hepatitis C virus infection remain low. Although point of care tests for HCV infection exist, but many of these tests only measure HCV antibodies (previous exposure), not HCV RNA (active infection). Given that 25% of individuals spontaneously clear HCV infection, efforts to enhance diagnosis of chronic HCV infection and improve the HCV care cascade requires enhanced uptake of HCV RNA testing. We conducted the first evaluation of the Xpert HCV Viral Load test (manufactured by Cepheid) - a point-of-care hepatitis C virus test that can detect active infection - from a finger-stick sample of blood. We established that there is good sensitivity and specificity of the Xpert HCV Viral Load point-of-care test using blood samples collected by finger-stick in participants attending drug health and homelessness services in Australia. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Merck / 24.04.2017

MedicalResearch.com Interview with: Eilish McCann, PhD Director, Outcomes Research (Center for Observational and Real-World Evidence) Merck MedicalResearch.com: What is the background for this study? Response: One of the most pressing challenges facing medicine today is the emergence of bacterial resistance to antibiotics. One area of high concern is the increasing prevalence of resistance to powerful antibiotics like carbapenems, as patients with infections due to carbapenem-resistant bacteria have very few alternate effective treatment options. In this study we used real-world data from a Becton, Dickinson and Company electronic research data set to analyze over 140,000 bacterial isolates from patients at 342 hospitals across the United States, so that we could investigate where the burden of carbapenem resistance is most acute. Importantly analysis of real-world data in this way allows us to gain insights from a large number of hospitals, giving a broad and nationally representative picture of the resistance burden. (more…)
AstraZeneca, Author Interviews, Autism, Boehringer Ingelheim, Depression, Eli Lilly, J&J-Janssen, JAMA, Merck, OBGYNE / 17.04.2017

MedicalResearch.com Interview with: Florence Gressier MD PhD Insermk Department of psychiatry CHU de Bicêtrem Le Kremlin Bicêtre France MedicalResearch.com: What is the background for this study? What are the main findings? Response: Results from recent studies have suggested an increased risk for Autism Spectrum Disorders (ASDs) in children exposed to antidepressants in utero. We performed a systematic review of and a meta-analysis of published studies to assess the association between ASDs and fetal exposure to antidepressants during pregnancy for each trimester of pregnancy and preconception. Our systematic review and meta-analysis suggests a significant association between increased ASD risk and maternal use of antidepressants during pregnancy; however, it appears to be more consistent during the preconception period than during each trimester. In addition, the association was weaker when controlled for past maternal mental illness. Maternal psychiatric disorders in treatment before pregnancy rather than antenatal exposure to antidepressants could have a major role in the risk for Autism Spectrum Disorders. (more…)
Author Interviews, Boehringer Ingelheim, Diabetes, JAMA, Ophthalmology / 13.04.2017

MedicalResearch.com Interview with: Marco A Zarbin, MD, PhD, FACS Alfonse Cinotti, MD/Lions Eye Research Professor and Chair Institute of Ophthalmology & Visual Science Rutgers-New Jersey Medical School Rutgers University Newark, NJ 0710  MedicalResearch.com: What is the background for this study? What are the main findings?
  1. Most large, randomized clinical trials are powered to assess the efficacy of drugs or interventions, but they usually do not enroll enough patients to accurately assess the frequency of uncommon, undesirable side effects.
  2. In order to compensate for this deficiency in trial design, investigators aggregate the results of numerous studies all of which address the same clinical question with the same (or similar) drugs/interventions to increase the power to detect uncommon side effects. These aggregate studies can be meta-analyses.
  3. Unfortunately, most meta-analyses do not have the ability to answer some critical questions such as the timing of an adverse event relative to the last exposure to the drug, nor can they compensate fully for differences among the aggregated studies in trial design, length of patient follow-up, or presence pre-existing risk factors for the side effects in question.
  4. A pooled analysis of combined clinical trials using patient level data, however, allows a more in depth analysis of side effects than study level data, which are usually used for most published meta-analyses, because patient level data allow one to incorporate the per-patient duration of exposure to treatment, adjust for imbalances in predefined baseline risk factors, and adjust for the effect of results of single studies on the overall result.
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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…)
ASCO, Author Interviews, Boehringer Ingelheim, Journal Clinical Oncology, NYU, Prostate Cancer, Testosterone / 16.03.2017

MedicalResearch.com Interview with: Dr. Stacy Loeb MD Msc Assistant Professor of Urology and Population Health New York University Langone Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The association between exposure to testosterone replacement therapy and prostate cancer risk is controversial.  The purpose of our study was to examine this issue using national registries from Sweden, with complete records on prescription medications and prostate cancer diagnoses.  Overall, we found no association between testosterone use and overall prostate cancer risk. There was an early increase in favorable cancers which is likely due to a detection bias, but long-term users actually had a significantly reduced risk of aggressive disease. (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…)