Chronic Lymphocytic Lymphoma drug trial of Zydelig combined with Rituxan and Treanda unblinded early due to success.

“Sing praises for another medical breakthrough of research by a publicly traded American company. Gilead is in Foster City, California. Many of us have been with loved ones as they died with a leukemia and it brings tears for years. Yes, it still does, as I write this. “Bill Chesnut, MD

Chronic Lymphocytic Lymphoma drug trial of Zydelig combined with Rituxan and Treanda unblinded early due to success.

Reuters (11/17, Berkrot) reports that a Phase III clinical trial of Gilead Sciences’ chronic lymphocytic leukemia (CLL) treatment was unblinded after independent observers concluded the drug was significantly effective at slowing the progression of the disease. The study tested Gilead’s Zydelig (idelalisib) in combination with Rituxan (rituximab) and Treanda (bendamustine), compared to Rituxan and Treanda alone.

 

AMA News, November, 2015.

Hospitals turning to new ways to control pain

“This is happy news. Help spread the word.” Bill Chesnut, MD

 Hospitals turning to new ways to control pain

 On the front of its Personal Journal section, the Wall Street Journal (9/29, D1, Landro, Subscription Publication) reports that hospitals are increasingly turning to new devices to minimize pain, such as needleless blood drawing devices, hand-held vein finders, topical numbing agents, and fast-acting pain control nasal sprays. Pain control has become a bigger priority than in the past due to its high ranking on patient satisfaction surveys.

AMA Wire newsletter, October 2015.

 

High-dose vitamin D3 may modulate immune system in patients with MS

AMA News 12.31.15 reports that vitamin D3 taken as a supplement to patients with multiple sclerosis showed a decrease of harmful cell activity at 10,400 international units a day. This finding is important because MS touches many of us and its effects are profound. It is easy to check possible overdoing the Vit D3 with a simple blood test. You want your blood level of Vit. D3 to be < 100 ng/dl.” Bill Chesnut, MD.

High-dose vitamin D3 may modulate immune system in patients with MS

Newsweek (12/31, Main) reports that in a study published online Dec. 30 in Neurology, researchers “tested the impact of two levels of vitamin D supplementation among 80 patients” with multiple sclerosis. Half the patients “were given 10,400 international units of Vitamin D, and the other 40 took 800 IUs of the supplement per day.” Researchers found that patients “in the high-dose group had significantly reduced levels of activity among a certain type of immune cell thought to be involved in multiple sclerosis, compared with those in the low-dose group.”

According to MedPage Today (12/31, Jackson), in patients taking high-dose vitamin D3 (cholecalciferol), researchers found “in vivo pleiotropic immunomodulatory effects” as evidenced by the “significant reduction in the proportion of interleukin-17+CD4+ T cells (P=0.016), CD161+CD4+ T cells (P=0.03), and effector memory CD4+ T cells (P=0.021),” as well as “a concomitant increase in the proportion of central memory CD4+ T cells

AMA Wire newsletter January, 2016.

Gene test, Oncotype DX, may reveal which women with early-stage breast cancer can skip chemo

“Oncotype DX may help a lot of women avoid chemotherapy with the comfort of confidence that they do not need it. Pass the information along and follow the development in Europe and as it becomes used in the US.” Bill Chesnut, MD.

Gene test may reveal which women with early-stage breast cancer can skip chemo.

The Wall Street Journal (9/28, Winslow, Subscription Publication) reports that research presented at the European Cancer Congress in Vienna and published online in the New England Journal of Medicine suggests that a gene test known as Oncotype DX may help certain women with early-stage breast cancer skip chemotherapy.

The AP (9/28, Marchione) reports that “the test accurately identified a group of women whose cancers are so likely to respond to hormone-blocking drugs that adding chemo would do little if any good while exposing them to side effects and other health risks.” Researchers found that “women who skipped chemo based on the test had less than a 1 percent chance of cancer recurring far away, such as the liver or lungs, within the next five years.”

AMA Newsletter 9.28.15

Gastric balloon swallowed like a tablet may help patients lose excess weight

“Anything that helps our epidemic of obesity is welcome news. There are so many hidden medical consequences of obesity. I hope someday we will have an affordable effective help for obese children, the critical time of opportunity. “Bill Chesnut, MD

Gastric balloon swallowed like a tablet may help patients lose excess weight

 The Los Angeles Times (11/6, Healy) reports in “Science Now” that the Elipse device, an encapsulated “gastric balloon that’s swallowed like a [tablet] and then sits in the stomach filled with fluid, helped patients lose more than a third of their excess weight over a four-month period,” according to the results of a study presented at Obesity Week. The study of “34 overweight and obese subjects who got the balloon lost an average of 22 pounds after four months – roughly 37% of their excess weight,” the study found. The device has yet to be approved by the FDA, however.

HealthDay (11/6, Mozes) points out that the Elipse device “is intended for patients with a BMI as low as 27,” whereas “invasive approaches are typically reserved for severely obese patients – those with a body-mass index (BMI) of 35 and up.” The device is not permanent. After a period of “about four months, the balloon automatically deflates, at which point its thin shell is naturally excreted.”

AMA newsletter_10.06.15

Sparing ovaries and removing fallopian tubes may cut cancer risk, but few have procedure

“This is important for women and their families to understand. They might think that removing the Fallopian tubes is an unnecessary additional surgery. There is an important reason patients facing hysterectomy should research this more. For the average person to be able to go to the Internet and find good explanations of complicated medical advances is another blessing of these last 20 years.” Bill Chesnut, MD

  • Sparing ovaries and removing fallopian tubes may cut cancer risk, but few have the procedure.

During hysterectomies for non-cancerous conditions, removing both fallopian tubes while keeping the ovaries may help protect against ovarian cancer while preserving hormonal levels, but few women receive this surgical option, according to a new study by Yale School of Medicine researchers.

Published in the February issue of the journal Obstetrics & Gynecology, the study was led by Xiao Xu, assistant professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine.

In hysterectomies to treat benign conditions, removing both of the ovaries in addition to the fallopian tubes has been used as a way to reduce ovarian cancer risk. But this practice can induce surgical menopause, which adversely affects cardiovascular, bone, cognitive, and sexual health. New evidence suggests that ovarian cancer often originates from the fallopian tube, rather than from the ovaries. This led the American College of Obstetricians and Gynecologists (ACOG) to issue a statement in 2015 suggesting that the practice of bilateral salpingectomy with ovarian conservation — surgical removal of both fallopian tubes while retaining the ovaries — may be a better option for ovarian cancer prevention in women at low risk for ovarian cancer.

Xu and her co-author, Dr. Vrunda Bhavsar Desai, conducted the study using data from the 2012 National Inpatient Sample. The team studied 20,635 adult women undergoing hysterectomy for benign conditions who were at low risk for ovarian cancer or future ovarian surgery.

“We found that among women undergoing inpatient hysterectomies in 2012 who were at low risk for ovarian cancer, very few of them received bilateral salpingectomy  with preservation of the ovaries,” said Xu. “The rate of bilateral salpingectomy with ovarian conservation was 5.9% in this population. This study provides important baseline information on national practice patterns prior to the ACOG recommendation.”

Xu added that the rate of bilateral salpingectomy with ovarian conservation varied widely among 744 hospitals across the country, ranging from 0% to 72.2%.

“The wide variation in hospital practice may result in differential access to prophylactic procedures depending on where patients access care,” said Xu. “This can have longer-term health implications given the benefits of ovarian conservation.”

 

FDA approves long-acting injectable schizophrenia treatment

“This is the kind of news that makes you want to stand up and dance when you read it. I am eager to learn more about the details of Aristada. Imagine the future mental health management with injectable long-lasting psychosis medications.” Bill Chesnut, MD

 FDA approves long-acting injectable schizophrenia treatment

 The Wall Street Journal (10/6, Armental, Subscription Publication) reports that the Food and Drug Administration approved Aristada (aripiprazole lauroxil), Alkermes PLC’s drug to treat schizophrenia.

Bloomberg News (10/6, Chen) reports that Aristada is “a long-acting injectable medicine with options to be taken once monthly or every six weeks,” and is “intended as an alternative to oral anti-psychotic medications taken daily.”

AMA newsletter October, 2015.

 

FDA approves new hepatitis C medication

Zepatier, a new hep C treatment is $54,000. For a 12-week treatment course. The Associated Press reports that the approval is “good news for patients because the growing competition should crimp the sky-high prices for hepatitis C drugs!” Bill Chesnut, MD

 FDA approves new hepatitis C medication

The Wall Street Journal (1/28, Loftus, Subscription Publication) reports that the Food and Drug Administration has approved Merck & Co.’s Zepatier (elbasvir and grazoprevir), a once-daily, single-tablet combination therapy for hepatitis C. The drug is approved for patients with the most common type of hepatitis C in the US, genotype 1, as well as genotype 4. Zepatier has a list price of $54,000 for a 12-week course of treatment.

The AP (1/29, Johnson) reports that the approval is “good news for patients, because the growing competition should crimp the sky-high prices for hepatitis C drugs, and the additional option means there’s one that will work for nearly every subgroup of people with hepatitis C.”

AMA Wire newsletter January, 2016.

Children conceived using infertility treatment at no greater risk of developmental problems

“This is happy news to broadcast. Wanting children and considering infertility treatment causes concerns that, maybe, are not really a concern. Yeah for babies and for the parents who want them desperately. My heart goes out to them each and every one.” Bill Chesnut, MD

 Children conceived using infertility treatment at no greater risk of developmental problems, study suggests

Reuters (1/5, Doyle) reports that a new study conducted at the Eunice Kennedy Shriver National Institute of Child Health and Human Development suggests that “children conceived with assisted reproductive technology have similar early childhood development as other children.” However, researchers found that those conceived using fertility treatments were more often born as twins or multiple births prompting lead author Edwina H. Yeung to encourage fertility specialist to use techniques that decrease the risk of multiple births.

HealthDay (1/5, Norton) reports that for the study, Yeung’s team “followed over 5,800 children born in New York state between 2008 and 2010,” including 1,830 children conceived using fertility treatments. Overall, the researchers found that those conceived using reproductive technology “were no more likely to show developmental delays at the age of 3 than their peers whose parents conceived naturally.” The findings were published in JAMA Pediatrics.

AMA Wire newsletter, January 2015.

 

New blood test may help determine if a patient with a respiratory illness is suffering from a virus or bacterial infection

This is a pivot of research investigation in the effort to see if a respiratory illness is viral and will not respond to antibiotics, versus bacterial and needing antibiotics. “The test…flips bacteria and virus testing on its head.” Rather than “searching for hallmark signs of specific bugs, it scans the infected person’s genetic reaction to the microbe.” Bill Chesnut, MD

New blood test may help determine if a patient with a respiratory illness is suffering from a virus or bacterial infection

CBS News (1/20, Marcus) reports that “a new blood test is in the works that could help” physicians determine whether “a patient with a respiratory illness is suffering from a virus or a bacterial infection, or even a non-infectious condition with similar symptoms.” This “test could help cut back on the serious problem of antibiotic overuse, say the” researchers “who developed it.”

TIME (1/20, Park) reports that “the test…flips bacteria and virus testing on its head.” Rather than “searching for hallmark signs of specific bugs, it scans the infected person’s genetic reaction to the microbe.” The test “takes advantage of the fact that our bodies react differently to bacteria and viruses by activating different genes that are part of the immune system.” Research on the test was published in Science Translational Medicine.

HealthDay (1/20, Dotinga) reports that the researchers “tried the test out on 273 people with respiratory infections and 44 healthy people.” Altogether, “the test was accurate 87 percent of the time in distinguishing between bacterial and viral infections, and infections caused by something else.”

AMA Morning Rounds 1.21.16

Researchers develop blood test to detect concussions in children

“This development of a blood test for concussion needs wider dissemination as a part of our cultural discussion about head impact sports.” Bill Chesnut, MD

Researchers develop blood test to detect concussions in children

CBS News (11/11, Welch) website reports that “a simple blood test can accurately detect concussions in children, a new study finds, and researchers hope one day it could be used on the field to help coaches, trainers and parents develop a plan of action on the spot.” The test “accurately identified the presence of brain injuries 94 percent of the time.” Lead study author Dr. Linda Papa, an emergency medicine physician said in a statement that this blood test “could ultimately change the way we diagnose concussions, not only in children, but in anyone who sustains a head injury.” The study was published in the journal Academic Emergency Medicine.

HealthDay (11/11, Reinberg) reports that the blood test measures levels of glial fibrillary acidic protein (GFAP), which is “found in cells that surround neurons in the brain,” and is released into the bloodstream when the brain is injured.

JAMA 11.11.15

Adults with who take hypertension medications at bedtime may be less likely to develop Type 2 diabetes

“Hypertension is serious, complicated and there is a lot to know. I posted elsewhere on this site a video of how to take your blood pressure correctly. I recommend reviewing that. This article associates type 2 diabetes with your control of hypertension. This finding is an important finding and needs wider dissemination than I have seen in my reading.” Bill Chesnut, MD

Adults with who take hypertension medications at bedtime may be less likely to develop Type 2 diabetes

The Los Angeles Times (9/24, Healy) “Science Now” reports that research published in Diabetologia suggests that “adults with high blood pressure who take all of their hypertension medications before they go to bed, rather than in the morning, are less likely to develop Type 2 diabetes.” Another study, “also published in Diabetologia” yesterday “and conducted by the same…researchers, found that subjects whose blood pressure did not dip, and those whose readings dipped more briefly or shallowly, were more likely to develop Type 2 diabetes than those whose sleep-time blood pressure saw a deep and sustained drop from daytime levels.”

AMA Wire 9.26.15

A new drug is showing remarkable efficacy in treating allergic conditions

“A new drug is showing remarkable efficacy in treating allergic conditions, primarily eczema.  The side effects are trivial considering the morbidity of atopic eczema.  This publication demonstrates that it’s also effective in nasal polyps for people who are affected by allergies and have sinus polyps develop.

Dupilumab is in clinical trials now.  The government site for clinical trials, clinical trials.gov, predicts release in November 2016.

I anticipate that there will the other uses of this remarkable technique of inhibiting the blood cells involved in the inflammatory response of allergies.” Bill Chesnut, MD

 

Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal PolyposisA Randomized Clinical Trial

Claus Bachert, MD, PhD1,2; Leda Mannent, MD3; Robert M. Naclerio, MD4; Joaquim Mullol, MD, PhD5; Berrylin J. Ferguson, MD6; Philippe Gevaert, MD, PhD1; Peter Hellings, MD, PhD7; Lixia Jiao, PhD8; Lin Wang, PhD8; Robert R. Evans, PharmD9; Gianluca Pirozzi, MD, PhD8; Neil M. Graham, MD, MPH9; Brian Swanson, PhD8; Jennifer D. Hamilton, PhD9; Allen Radin, MD9; Namita A. Gandhi, PhD9; Neil Stahl, PhD9; George D. Yancopoulos, MD, PhD9; E. Rand Sutherland, MD, MPH10

ABSTRACT

Importance  Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell–mediated diseases.

Objective  To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis.

Design, Setting, and Participants  A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up.

Interventions  Subcutaneous dupilumab (a 600 mg loading dose followed by 300 mg weekly; n = 30) or placebo (n = 30) plus mometasone furoate nasal spray for 16 weeks.

Main Outcomes and Measures  Change in endoscopic nasal polyp score (range, 0-8; higher scores indicate worse status) at 16 weeks (primary end point). Secondary end points included Lund-Mackay computed tomography (CT) score (range, 0-24; higher scores indicate worse status), 22-item SinoNasal Outcome Test score (range, 0-110; higher scores indicating worse quality of life; minimal clinically important difference ≥8.90), sense of smell assessed using the University of Pennsylvania Smell Identification Test (UPSIT) score (range, 0-40; higher scores indicate better status), symptoms, and safety.

Results  Among the 60 patients who were randomized (mean [SD] age, 48.4 years [9.4 years]; 34 men [56.7%]; 35 with comorbid asthma), 51 completed the study. The least squares (LS) mean change in nasal polyp score was −0.3 (95% CI, −1.0 to 0.4) with placebo and −1.9 (95% CI, −2.5 to −1.2) with dupilumab (LS mean difference, −1.6 [95% CI, −2.4 to −0.7]; P < .001). The LS mean difference between the 2 groups for the Lund-Mackay CT total score was −8.8 (95% CI, −11.1 to −6.6; P < .001). Significant improvements with dupilumab were also observed for the 22-item SinoNasal Outcome Test (LS mean difference between groups, −18.1 [95% CI, −25.6 to −10.6]; P < .001) and sense of smell assessed by UPSIT (LS mean difference, 14.8 [95% CI, 10.9 to 18.7]; P < .001). The most common adverse events were nasopharyngitis (33% in the placebo group vs 47% in the dupilumab group), injection site reactions (7% vs 40%, respectively), and headache (17% vs 20%).

Conclusions and Relevance  Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometasone alone reduced endoscopic nasal polyp burden after 16 weeks. Further studies are needed to assess longer treatment duration, larger samples, and direct comparison with other medications.

Trial Registration  clinicaltrials.gov Identifier: NCT01920893

Chronic sinusitis, an inflammatory condition of the sinuses, is common with estimates of prevalence as high as 12% in Western populations.1,2 It is characterized by specific symptoms often lasting for many years including nasal congestion, discharge and postnasal drip, decreased or lost sense of smell, facial pain and pressure, headache, and the consequences thereof.3 Based on endoscopic findings, the condition can be divided into chronic sinusitis with or without nasal polyposis. Typically observed in the context of eosinophilic inflammation of the upper airways, nasal polyps originate in the sinuses and obstruct the sinus and nasal passages.

Medical management of chronic sinusitis with nasal polyposis focuses on controlling tissue inflammation and, depending on severity, includes use of intranasal corticosteroids, nasal saline irrigation, antibiotics, or short-course oral steroids.3 In patients in whom polyps and symptoms persist despite medical treatment, surgical excision is considered. However, disease recurrence after surgery approaches 50% in patients with tissue eosinophilia,4 and resolution of symptoms, including sense of smell loss, is often incomplete.

Epidemiological data from a large European cohort indicate that chronic sinusitis is associated with a 3.5-fold increase in comorbid asthma prevalence.5 Although type 2 helper T-cell inflammation is implicated in this association, the mechanisms of this association have not been fully elucidated.6– 8

Dupilumab is a fully human monoclonal antibody to the interleukin 4 (IL-4) receptor α subunit, which inhibits signaling of IL-4 and IL-13, 2 cytokines central to type 2 helper T-cell–mediated inflammation. Dupilumab has demonstrated clinical efficacy in the type 2 helper T-cell–mediated diseases of asthma and atopic dermatitis,9– 11 and also improved sinonasal symptoms in patients with asthma.9

We hypothesized that the addition of dupilumab to intranasal corticosteroids would improve endoscopic, radiographic, and patient-reported measures of disease activity in those with chronic sinusitis and nasal polyposis, while also improving lung function and disease control in patients with comorbid asthma.

Association of Bullying Behavior at 8 Years of Age and Use of Specialized Services for Psychiatric Disorders by 29 Years of Age

“This is a pressing report of 5,034 children. The authors address childhood experiences that are associated with mental and behavioral health problems as your adults. Exposure to bullying, even in the absence of childhood psychiatric symptoms, is associated with severe adulthood psychiatric outcomes that require treatment in specialized services.  This deserves wide dissemination.” Bill Chesnut, MD

 Association of Bullying Behavior at 8 Years of Age and Use of Specialized Services for Psychiatric Disorders by 29 Years of Age

Andre Sourander, MD, PhD1,2; David Gyllenberg, MD, PhD1; Anat Brunstein Klomek, PhD3,4; Lauri Sillanmäki, Stud SocSc1; Anna-Marja Ilola, MD1; Kirsti Kumpulainen, MD, PhD5

JAMA Psychiatry. 2016;73(2):159-165. doi:10.1001/jamapsychiatry.2015.2419.

 Importance. Bullying and being exposed to bullying among children is prevalent, especially among children with psychiatric symptoms, and constitutes a major concern worldwide. Whether childhood bullying or exposure to bullying in the absence of childhood psychiatric symptoms is associated with psychiatric outcomes in adulthood remains unclear.

Objective.  To study the associations between bullying behavior at 8 years of age and adult psychiatric outcomes by 29 years of age.

Design, Setting, and Participants.  Nationwide birth cohort study of 5034 Finnish children with complete information about childhood bullying behavior was followed up from 8 to 29 years of age. Follow-up was completed on December 31, 2009, and data were analyzed from January 15, 2013, to February 15, 2015.

Main Outcomes and Measures.  Information about bullying, exposure to bullying, and psychiatric symptoms were obtained from parents, teachers, and child self-reports when children were 8 years of age. Use of specialized services for psychiatric disorders from 16 to 29 years of age was obtained from a nationwide hospital register, including outpatient and inpatient treatment.

Results.  Among the 5034 study participants, 4540 (90.2%) did not engage in bullying behavior; of these, 520 (11.5%) had received a psychiatric diagnosis at follow-up; 33 of 166 (19.9%) who engaged in frequent bullying, 58 of 251 (23.1%) frequently exposed to bullying, and 24 of 77 (31.2%) who both frequently engaged in and were frequently exposed to bullying had received psychiatric diagnoses at follow-up. When analyses were adjusted by sex, family factors, and child psychiatric symptoms at 8 years of age, we found independent associations of treatment of any psychiatric disorder with frequent exposure to bullying (hazard ratio [HR], 1.9; 95% CI, 1.4-2.5) and being a bully and exposed to bullying (HR, 2.1; 95% CI, 1.3-3.4). Exposure to bullying was specifically associated with depression (HR, 1.9; 95% CI, 1.2-2.9). Bullying was associated with psychiatric outcomes only in the presence of psychiatric problems at 8 years of age. Participants who were bullies and exposed to bullying at 8 years of age had a high risk for several psychiatric disorders requiring treatment in adulthood. However, the associations with specific psychiatric disorders did not remain significant after controlling for concurrent psychiatric symptoms.

Conclusions and RelevanceExposure to bullying, even in the absence of childhood psychiatric symptoms, is associated with severe adulthood psychiatric outcomes that require treatment in specialized services. Early intervention among those involved in bullying can prevent long-term consequences.

 

Brain scans to catch depression before it starts.

“This brief article is about the neuroimaging research at the McGovern Institute for Brain Research at M.I.T. Functional MRI shows the patterns of activity in the brain. It is revealing differences in brain patterns that are predictive. This link is the research at McGovern; the whole area is astonishing.” Bill Chesnut, MD   http://mcgovern.mit.edu/brain-disorders/psychiatric

Brain scans to catch depression before it starts

By Ben Gruber, 2.4.16.

CAMBRIDGE, MASS. (Reuters) – Researchers at MIT’s McGovern Institute are using the latest advances in brain imaging to identify children at high risk of depression before the debilitating and sometimes deadly disorder sets in.

According to the World Health Organization an estimated 350 million people of all ages suffer from depression. It’s a serious mental disorder that affects every aspect of a person’s life and in severe cases could lead to suicide.

The study involved two groups of children, one at high risk of depression due to family history and a control group with kids at low risk.

Kids from both groups were scanned to map the network pathways in their brains. The question was if the researchers could find differences in brain activity that would be an indicator for a higher risk of depression.

“They answer is there are very great differences. We saw differences that were striking in a number of circuits including those that change in depression, including those involved in feelings, other parts that are involved in thinking. The additional thing besides seeing these differences were that the differences were so strong child by child that that we were very close to perfect with being able to categorize from a brain scan itself whether a child was at risk or not,” said John Gabrieli, a professor of Brain and Cognitive Sciences at MIT.

The goal going forward is to follow these children and see who among the high risk group goes on to develop depression, tracking changes in their brain function along the way .

“Obviously the children that go on to depression the more we can identify them well the more we are hopeful that we can get preventive treatments going. Not waiting for them to be suffering but helping them beforehand,” said Gabrieli

“So we want to learn both to identify early children who are at true risk, help them before they struggle and learn from those that are resilient what is different about them because that might be a hint about how to help the children that are not resilient,” he added.

The researchers say a better understanding of how depression affects the brain will ultimately lead to better treatment options for those that are most at risk.

Here is the McGovern Institute for Brain Research at MIT: http://mcgovern.mit.edu/

This is some of the brain research they do: http://mcgovern.mit.edu/research

Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal PolyposisA Randomized Clinical Trial

“A new drug is showing remarkable efficacy in treating allergic conditions, primarily eczema. The side effects are trivial considering the morbidity of atopic eczema. This publication shows that it’s also effective in nasal polyps for people who are affected with allergies and have sinus polyps develop.   Dupilumab is in clinical trials now. The government site for clinical trials, clinical trials.gov, predicts t will be release in November 2016.

I anticipate that there will the other uses of this remarkable technique of inhibiting the blood cells involved in the inflammatory response of allergies.” Bill Chesnut, MD.

Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal PolyposisA Randomized Clinical Trial

Claus Bachert, MD, PhD1,2; Leda Mannent, MD3; Robert M. Naclerio, MD4; Joaquim Mullol, MD, PhD5; Berrylin J. Ferguson, MD6; Philippe Gevaert, MD, PhD1; Peter Hellings, MD, PhD7; Lixia Jiao, PhD8; Lin Wang, PhD8; Robert R. Evans, PharmD9; Gianluca Pirozzi, MD, PhD8; Neil M. Graham, MD, MPH9; Brian Swanson, PhD8; Jennifer D. Hamilton, PhD9; Allen Radin, MD9; Namita A. Gandhi, PhD9; Neil Stahl, PhD9; George D. Yancopoulos, MD, PhD9; E. Rand Sutherland, MD, MPH10

ABSTRACT

Importance  Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell–mediated diseases.

Objective  To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis.

Design, Setting, and Participants  A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up.

Interventions  Subcutaneous dupilumab (a 600 mg loading dose followed by 300 mg weekly; n = 30) or placebo (n = 30) plus mometasone furoate nasal spray for 16 weeks.

Main Outcomes and Measures  Change in endoscopic nasal polyp score (range, 0-8; higher scores indicate worse status) at 16 weeks (primary end point). Secondary end points included Lund-Mackay computed tomography (CT) score (range, 0-24; higher scores indicate worse status), 22-item SinoNasal Outcome Test score (range, 0-110; higher scores indicating worse quality of life; minimal clinically important difference ≥8.90), sense of smell assessed using the University of Pennsylvania Smell Identification Test (UPSIT) score (range, 0-40; higher scores indicate better status), symptoms, and safety.

Results  Among the 60 patients who were randomized (mean [SD] age, 48.4 years [9.4 years]; 34 men [56.7%]; 35 with comorbid asthma), 51 completed the study. The least squares (LS) mean change in nasal polyp score was −0.3 (95% CI, −1.0 to 0.4) with placebo and −1.9 (95% CI, −2.5 to −1.2) with dupilumab (LS mean difference, −1.6 [95% CI, −2.4 to −0.7]; P < .001). The LS mean difference between the 2 groups for the Lund-Mackay CT total score was −8.8 (95% CI, −11.1 to −6.6; P < .001). Significant improvements with dupilumab were also observed for the 22-item SinoNasal Outcome Test (LS mean difference between groups, −18.1 [95% CI, −25.6 to −10.6]; P < .001) and sense of smell assessed by UPSIT (LS mean difference, 14.8 [95% CI, 10.9 to 18.7]; P < .001). The most common adverse events were nasopharyngitis (33% in the placebo group vs 47% in the dupilumab group), injection site reactions (7% vs 40%, respectively), and headache (17% vs 20%).

Conclusions and Relevance  Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometasone alone reduced endoscopic nasal polyp burden after 16 weeks. Further studies are needed to assess longer treatment duration, larger samples, and direct comparison with other medications.

Chronic sinusitis, an inflammatory condition of the sinuses, is common with estimates of prevalence as high as 12% in Western populations.1,2 It is characterized by specific symptoms often lasting for many years including nasal congestion, discharge and postnasal drip, decreased or lost sense of smell, facial pain and pressure, headache, and the consequences thereof.3 Based on endoscopic findings, the condition can be divided into chronic sinusitis with or without nasal polyposis. Typically observed in the context of eosinophilic inflammation of the upper airways, nasal polyps originate in the sinuses and obstruct the sinus and nasal passages.

Medical management of chronic sinusitis with nasal polyposis focuses on controlling tissue inflammation and, depending on severity, includes use of intranasal corticosteroids, nasal saline irrigation, antibiotics, or short-course oral steroids.3 In patients in whom polyps and symptoms persist despite medical treatment, surgical excision is considered. However, disease recurrence after surgery approaches 50% in patients with tissue eosinophilia,4 and resolution of symptoms, including sense of smell loss, is often incomplete.

Epidemiological data from a large European cohort indicate that chronic sinusitis is associated with a 3.5-fold increase in comorbid asthma prevalence.5 Although type 2 helper T-cell inflammation is implicated in this association, the mechanisms of this association have not been fully elucidated.6– 8

Dupilumab is a fully human monoclonal antibody to the interleukin 4 (IL-4) receptor α subunit, which inhibits signaling of IL-4 and IL-13, 2 cytokines central to type 2 helper T-cell–mediated inflammation. Dupilumab has demonstrated clinical efficacy in the type 2 helper T-cell–mediated diseases of asthma and atopic dermatitis,9– 11 and also improved sinonasal symptoms in patients with asthma.9

We hypothesized that the addition of dupilumab to intranasal corticosteroids would improve endoscopic, radiographic, and patient-reported measures of disease activity in those with chronic sinusitis and nasal polyposis, while also improving lung function and disease control in patients with comorbid asthma.