Day: March 25, 2021

AstraZeneca Updates its US Trial Results

AstraZeneca issued updated phase III trial data for its COVID vaccine on Wednesday after facing questions on its accuracy of its preliminary US study.

The company now says its vaccine is 76% effective in protecting against symptomatic cases of virus. A release issued on Monday reported a symptomatic efficacy rate of 79%, but the next day, the National Institute of Allergy and Infectious Diseases said it had been informed the company may have included information from its US results that provided an “incomplete view of the efficacy data.”

The updated report still says that the vaccine is 100% effective against severe disease and hospitalisation. A number of US health officials have criticised the company for what seemed like cherry-picking of data in an effort to improve the results’ appearance.

At the time, AstraZeneca said the figures were based on a “pre-specified interim analysis” and promised it would share an updated analysis in the coming days.

Dr Anthony Fauci, White House chief medical advisor and director at the NIAID, was more supportive of the company, calling the situation “unfortunate” and said it was likely AstraZeneca would issue a modified statement.

“This is really what you call an unforced error because the fact is this is very likely a very good vaccine,” Fauci told ABC’s Robin Roberts on “Good Morning America” on Tuesday. “This kind of thing does … really cast some doubt about the vaccines and maybe contribute to the hesitancy. It was not necessary.”

The BBC’s medical editor, Fergus Walsh, was told the results may have been rushed out of a desire to address the safety concerns surrounding possible blood clots. These had resulted in AstraZeneca vaccines being withdrawn from circulation in some European countries.

The updated results include 190 symptomatic cases out of over 32 000 participants — about 50 more symptomatic cases than the data set released on Monday.

The findings suggest the vaccine is more effective in patients aged 65 and older, with a newly reported efficacy rate of 85% for that population, up from 80% stated earlier.

AstraZeneca reiterated that there were no safety concerns with the vaccine and that it was well tolerated.

Source: NBC News

Low-dose Radiation May be Beneficial to Humans

A study has found that cancer rates go down and life expectancy increases in areas of the US with high natural background radiation, flying in the face of decades of accepted theory that low-dose radiation is still harmful.

Natural background radiation exists from sources in the environment. This is the first large-scale study looking at terrestrial radiation (coming from radioactive elements in rocks, which vary across regions) and cosmic radiation (which increases with altitude). The Ben-Gurion University of the Negev (BGU) researchers found that life expectancy is approximately 2.5 years longer for those who live in areas of naturally high background radiation vs those who live in areas of low radiation.

The linear no-threshold (LNT) hypothesis has guided radiation protection policy in the US since the 1960s. This assumes that health risk from radiation is linear and incremental, meaning that there is no safe minimum dose – all ionising radiation is assumed to be harmful. However, numerous studies have contended that radiation at low doses initiates a protective hormesis effect.

Reduced levels of a number of types of cancers were found when in areas of high background radiation levels as opposed to lower. In both sexes, there was a significant decrease in lung, pancreatic, colon and rectal cancers. Among men, there were additional decreases in brain and bladder cancers. However, no decreases in cervix, breast or prostate cancers or leukaemia were observed.

“Decades of scientific theory are potentially being disproven by the remarkable researchers at BGU. These findings might even provide a sense of relief for those who reside in areas in the U.S. with higher-than-average background radiation,” said Doug Seserman, Chief Executive Officer, American Associates, BGU.

Using the United States Environmental Protection Agency’s radiation dose calculator, the researchers retrieved data background radiation on all 3,29 US counties. Cancer rate data were retrieved from the United States Cancer Statistics, while life expectancy data were retrieved from the Institute for Health Metrics and Evaluation at the University of Washington Medical Center.

“It is reasonable to suggest that a radiation threshold does exist, yet it is higher than the upper limit of the natural background radiation levels in the US (227 mrem/year),” the researchers wrote. “These findings provide clear indications for re-considering the linear no-threshold paradigm, at least within the natural range of low-dose radiation.”

Source: News-Medical.Net

Journal information: David, E., et al. (2021) Background radiation impacts human longevity and cancer mortality: reconsidering the linear no-threshold paradigm. Biogerontology.

Common Preservative May Interfere with Immune Functions

A common preservative may hamper immune functions, along with other chemicals, warns the Environmental Working Group (EWG).

Using the Environmental Protection Agency’s Toxicity Forecaster, or ToxCast, the EWG assessed the potential human health impact of a number of chemicals including those commonly added to food and those that can be transferred to food from packaging.

Particularly concerning in the pandemic era, EWG’s analysis found that the preservative tertiary butylhydroquinone (TBHQ), has been found to harm the immune system both in both animal tests and in high-throughput in vitro toxicology testing.

“The pandemic has focused public and scientific attention on environmental factors that can impact the immune system,” said study lead author Olga Naidenko, PhD, and EWG Vice President for Science Investigations.”Before the pandemic, chemicals that may harm the immune system’s defense against infection or cancer did not receive sufficient attention from public health agencies. To protect public health, this must change.”

Using new non-animal test results from ToxCast, TBHQ was found to affect immune cell proteins at doses considered to cause harm. Previous studies have also found that TBHQ could influence flu vaccine effectiveness and may be associated with a rise in food allergies.

In the United States, the Food and Drug Administration often entrusts food companies to ensure that chemicals added to the foods they produce are safe. Additives such as TBHQ were approved decades ago, and the FDA does not consider new science.

Per- and polyfluoroalkyl substances (PFAS), which are used in food packaging, were found to be in many types of food packaging, and can migrate to food. Human epidemiological studies have found that PFAS is linked to reduced immune function and vaccine effectiveness. Recent research also links bloodstream PFAS levels to COVID severity. 

“Food manufacturers have no incentive to change their formulas,” explained Scott Faber, senior vice president for government affairs at EWG. “Too often, the FDA allows the food and chemical industry to determine which ingredients are safe for consumption. Our research shows how important it is that the FDA take a second look at these ingredients and test all food chemicals for safety.”

The EWG is calling on the FDA to close the food additive loophole, and to conduct immunotoxicity testing of chemicals in food and food packaging.

Source: News-Medical.Net

Journal information: Naidenko, O. V., et al. (2021) Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food. International Journal of Environmental Research and Public Health.

Positive Safety News for Important Diabetes Drugs

A systematic review and meta-analysis showed that GLP-1 receptor agonists weren’t associated with increased risk for incident breast cancer.

Giovana Fagundes Piccoli, MD, of the Hospital de Clínicas de Porto Alegre in Brazil presented the findings at the Endocrine Society’s virtual ENDO 2021 meeting.

Out of 48 267 patients treated with a GLP-1 receptor agonist there were 130 cases of incident breast cancer among versus 107 cases out of 40 755 controls. Control participants received either placebo or active treatment with a non-GLP-1 receptor agonist. 
There was also no difference in risk of benign breast neoplasms for patients on GLP-1 receptor agonists versus other drug types (RR 0.99).

No difference was seen among individual GLP-1 receptor agonists, including each of the four major drugs in the class — liraglutide, dulaglutide, semaglutide, and albiglutide  — with exendin-4 mimetic agents including exenatide and lixisenatide.

No difference in incident breast cancer risk was seen when comparing trials with an open-label design versus double-blinded trials.

Dr Piccoli explained that her team wanted to investigate the issue further following the 2015 SCALE Obesity and Prediabetes trial, which found more breast neoplasms in patients receiving liraglutide than with placebo (4.36 vs 1.80 per 1000 person years). In that study, most of those neoplasms developed in the first year of treatment with GLP-1 receptor agonist, and were more common in participants with greater weight loss on the agent.

“I think that the results of our meta-analysis adds more security and safety information about this treatment,” said Dr Piccoli during a press conference. “Patients, doctors, and other health professionals can be more secure of the safety of these drugs.”

For this analysis, her team searched a variety of medical journal databases for randomised trials assessing GLP-1 receptor agonists in adults with overweight, obesity, prediabetes, or type 2 diabetes that also reported breast cancer or benign breast neoplasm incidence.

Participant ages ranged from 45 to 70 years old and follow-up lasted between 24 weeks to 7.5 years.

Piccoli emphasised that these findings only apply to patients treated with a GLP-1 receptor agonist for diabetes control or weight loss in the absence of pre-existing breast cancer. She added that patients with a history of breast or any other cancer were usually excluded from the trials in this meta-analysis.

“We can say in a general population with type 2 diabetes and obesity, [GLP-1 receptor agonists] are safe,” Piccoli said. But the class’s safety in patients with a history of breast cancer is less certain, she added.

Source: MedPage Today

Presentation information: Piccoli G, et al “Do GLP-1 receptor agonists increase the risk of breast cancer? A systematic review and meta- analysis” ENDO 2021.

New JAK1 Inhibitor Abrocitinib Effective in Atopic Dermatitis

A phase III trial showed that a new oral Janus kinase 1 (JAK1) inhibitor, abrocitinib, bettered placebo, at higher doses, also outperformed dupilumab in treating signs and symptoms of atopic dermatitis.

More patients on the higher dose of abrocitinib had an Eczema Area and Severity Index 75 (EASI-75) response (75% improvement from baseline) as compared with the other three randomised groups, reported Hernan Valdez, MD, of Pfizer in New York City, and colleagues.

“In the JADE COMPARE trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo on the basis of IGA and EASI-75 responses at weeks 12 and 16,” the authors stated. “The 100-mg dose of abrocitinib was not significantly different from dupilumab with respect to the three key secondary endpoints of the trial.”

“The 200-mg dose of abrocitinib was superior to dupilumab with respect to itch response at week 2 but not to an EASI-75 response at week 16; no conclusion could be drawn regarding the difference between the 200-mg dose of abrocitinib and dupilumab with respect to an IGA response… . Longer and larger trials are necessary to determine the efficacy and safety of abrocitinib and to compare it with other JAK inhibitors and with biologic agents used for the treatment of atopic dermatitis,” they added.

Several oral JAK inhibitors besides abrocitinib being clinically evaluatied for AD. According to the authors, targeting JAK1 results in inhibition of signaling by interleukin (IL)-4, IL-13, and other cytokines involved in AD. However, there is a lack of data on head-to-head trials of JAK inhibitors.

Despite the very positive reception of JAK inhibitors for the treatment of AD, there have been some studies which raised safety concerns. Tofacitinib, for example, has been associated with a higher rate of malignancies and major adverse cardiovascular events.

In this phase III trial, 838 patients with moderate or severe AD were randomised to abrocitinib 100 mg or 200 mg, dupilumab, or placebo. The trial had two primary endpoints: investigator’s global assessment (IGA) response at week 12 and EASI-75 response at week 12. Both endpoints were compared versus placebo. Secondary analyses included comparisons of itch response at week 2 versus placebo and dupilumab and IGA and EASI-75 responses versus placebo at week 16.

More patients on either of the two doses of abrocitinib had IGA responses at week 12 compared to placebo. The proportion of patients with an EASI-75 response at 12 weeks was 70.3% with abrocitinib 200mg, 58.7% for abrocitinib 100mg, 58.1% for dupilumab, and 27.1% for placebo. All treatment groups performed significantly better than placebo.

At week 2, 49.1% of patients had itch response with the higher dose of abrocitinib, 31.8% with the lower dose, 26.4% with dupilumab, and 13.8% with placebo. The 200-mg abrocitinib group was superior to dupilumab. 

Adverse events (AEs) occurred more often with 200-mg abrocitinib as compared with the other three groups (61.9% vs 50.0% to 53.4%), the most common of which was nausea.

Source: MedPage Today

Journal information:  Bieber T, et al “Abrocitinib versus placebo or dupilumab for atopic dermatitis” N Engl J Med 2021; DOI: 10.1056/NEJM0a2019380.

A Dozen Accounts Responsible for Majority of COVID Misinformation

Photo by Connor Danylenko from Pexels

According to a report from the Center for Countering Digital Hate (CCDH), the majority of COVID and vaccine misinformation posts emanate from a dozen accounts.

Out of 812 000 anti-vaccine messages shared or posted on social media platforms between Feb 1 and March 16, 2021, 65% were attributed to just a handful of individuals, whom the report authors have dubbed the “Disinformation Dozen”, 13 users spread across 12 accounts (one of the accounts refers to a couple, Ty and Charlene Bollinger, who are alternative medicine activists).

Some of the individuals named include entrepreneur Joseph Mercola, author Robert F Kennedy Jr and chiropractor Ben Tapper, with the report including examples of the COVID misinformation that they shared on various social media platforms.

Mercola for example has shared his views on unproven COVID cures in various anti-vaxxer groups on Facebook, including one article saying “hydrogen peroxide treatment can successfully treat most viral respiratory illnesses, including coronavirus” getting 4600 shares.

The report notes that Robert Kennedy Jr often shares misinformation linked COVID vaccines to deaths, and his organisation, Children’s Health Defense, released a film in March that targeted American black and Latino communities with anti-vaccine messages. 

“According to our recent report, anti-vaccine activists on Facebook, YouTube, Instagram and Twitter reach more than 59 million followers, making these the largest and most important social media platforms for anti-vaxxers,” said CCDH CEO Imran Ahmed.

“Despite repeatedly violating Facebook, Instagram and Twitter’s terms of service agreements, nine of the Disinformation Dozen remain on all three platforms, while just three have been comprehensively removed from just one platform,” the report added.

To combat the disinformation problem, the CCDH urged social media companies to deplatform the Disinformation Dozen, along with key organisations associated with the 12 individuals.

In a statement to Engadet, Facebook took issue with the report, claiming that “it taken action against some of the group”. However, the report contends that Facebook’s algorithm struggle to identify COVID misinformation.

Source: The Star